start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=15
article-no=
start-page=2557
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250802
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Concept of “Platinum Sensitivity” in Endometrial Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies.
en-copyright=
kn-copyright=

en-aut-name=NagaoShoji
en-aut-sei=Nagao
en-aut-mei=Shoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FujikawaAtsushi
en-aut-sei=Fujikawa
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ImataniRyoko
en-aut-sei=Imatani
en-aut-mei=Ryoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TaniYoshinori
en-aut-sei=Tani
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MatsuokaHirofumi
en-aut-sei=Matsuoka
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IdaNaoyuki
en-aut-sei=Ida
en-aut-mei=Naoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HaragaJunko
en-aut-sei=Haraga
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OgawaChikako
en-aut-sei=Ogawa
en-aut-mei=Chikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NakamuraKeiichiro
en-aut-sei=Nakamura
en-aut-mei=Keiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MasuyamaHisashi
en-aut-sei=Masuyama
en-aut-mei=Hisashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=endometrial cancer
kn-keyword=endometrial cancer
en-keyword=platinum sensitivity
kn-keyword=platinum sensitivity
en-keyword=platinum free interval
kn-keyword=platinum free interval
END

start-ver=1.4
cd-journal=joma
no-vol=104
cd-vols=
no-issue=2
article-no=
start-page=151495
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Tri-culture model of intestinal epithelial cell, macrophage, and bacteria for the triggering of inflammatory bowel disease on a microfluidic device
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Inflammatory bowel disease (IBD) involves gastrointestinal inflammation, due to intestinal epithelial barrier destruction caused by excessive immune activation. Conventional cell culture systems do not provide a model system that can recapitulate the complex interactions between epithelial cells, immune cells, and intestinal bacteria. To address this, we developed a microfluidic device that mimics the inflammatory response associated with microbial invasion of the intestinal mucosa. The device consisted of two media channels, an upper and a lower channel, and a porous membrane between these channels on which C2BBe1 intestinal epithelial cells were seeded to form a tight junction layer. Each electrode was placed in contact with both channels to continuously monitor the tight junction state. Fresh medium flow allowed bacterial numbers to be controlled and bacterial toxins to be removed, allowing co-culture of mammalian cells and bacteria. In addition, RAW264 macrophage cells were attached to the bottom of the lower channel. By introducing E. coli into the lower channel, the RAW264 cells were activated and produced TNF-α, successfully recapitulating a culture model of inflammation in which the C2BBe1cell tight junction layer was destroyed. The main structure of the device was initially made of polydimethylsiloxane to facilitate its widespread use, but with a view to introducing anaerobic bacteria in the future, a similar phenomenon was successfully reproduced using polystyrene. When TPCA-1, an IκB kinase 2 inhibitor was added into this IBD culture model, the tight junction destruction was significantly suppressed. The results suggest that this IBD culture model also is useful as a screening system for anti-IBD drugs.
en-copyright=
kn-copyright=

en-aut-name=TamuraShiori
en-aut-sei=Tamura
en-aut-mei=Shiori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=PasangClarissa Ellice Talitha
en-aut-sei=Pasang
en-aut-mei=Clarissa Ellice Talitha
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TsudaMinami
en-aut-sei=Tsuda
en-aut-mei=Minami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MaShilan
en-aut-sei=Ma
en-aut-mei=Shilan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShindoHiromasa
en-aut-sei=Shindo
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NagaokaNoriyuki
en-aut-sei=Nagaoka
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OhkuboTomoki
en-aut-sei=Ohkubo
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=FujiyamaYoichi
en-aut-sei=Fujiyama
en-aut-mei=Yoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TamaiMiho
en-aut-sei=Tamai
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TagawaYoh-ichi
en-aut-sei=Tagawa
en-aut-mei=Yoh-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=School of Life Science and Technology, Institute of Science Tokyo
kn-affil=

affil-num=2
en-affil=School of Life Science and Technology, Tokyo Institute of Technology
kn-affil=

affil-num=3
en-affil=School of Life Science and Technology, Tokyo Institute of Technology
kn-affil=

affil-num=4
en-affil=School of Life Science and Technology, Institute of Science Tokyo
kn-affil=

affil-num=5
en-affil=School of Life Science and Technology, Tokyo Institute of Technology
kn-affil=

affil-num=6
en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation
kn-affil=

affil-num=8
en-affil=Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation
kn-affil=

affil-num=9
en-affil=School of Life Science and Technology, Tokyo Institute of Technology
kn-affil=

affil-num=10
en-affil=School of Life Science and Technology, Institute of Science Tokyo
kn-affil=
en-keyword=Intestine chip
kn-keyword=Intestine chip
en-keyword=Inflammatory bowel disease
kn-keyword=Inflammatory bowel disease
en-keyword=Co-culture
kn-keyword=Co-culture
en-keyword=Tri-culture
kn-keyword=Tri-culture
en-keyword=Fluidic device
kn-keyword=Fluidic device
en-keyword=Disease model
kn-keyword=Disease model
en-keyword=Macrophage
kn-keyword=Macrophage
en-keyword=Inflammation
kn-keyword=Inflammation
END

start-ver=1.4
cd-journal=joma
no-vol=638
cd-vols=
no-issue=8049
article-no=
start-page=225
end-page=236
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250122
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immune evasion through mitochondrial transfer in the tumour microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2,3,4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies.
en-copyright=
kn-copyright=

en-aut-name=IkedaHideki
en-aut-sei=Ikeda
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawaseKatsushige
en-aut-sei=Kawase
en-aut-mei=Katsushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishiTatsuya
en-aut-sei=Nishi
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WatanabeTomofumi
en-aut-sei=Watanabe
en-aut-mei=Tomofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakenagaKeizo
en-aut-sei=Takenaga
en-aut-mei=Keizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=InozumeTakashi
en-aut-sei=Inozume
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IshinoTakamasa
en-aut-sei=Ishino
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AkiSho
en-aut-sei=Aki
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=LinJason
en-aut-sei=Lin
en-aut-mei=Jason
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=SuzukiShinichiro
en-aut-sei=Suzuki
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=MakinoshimaHideki
en-aut-sei=Makinoshima
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ItamiMakiko
en-aut-sei=Itami
en-aut-mei=Makiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=NakamuraYuki
en-aut-sei=Nakamura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=TatsumiYasutoshi
en-aut-sei=Tatsumi
en-aut-mei=Yasutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=SuenagaYusuke
en-aut-sei=Suenaga
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=MorinagaTakao
en-aut-sei=Morinaga
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=Honobe-TabuchiAkiko
en-aut-sei=Honobe-Tabuchi
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=OhnumaTakehiro
en-aut-sei=Ohnuma
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=KawamuraTatsuyoshi
en-aut-sei=Kawamura
en-aut-mei=Tatsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=UmedaYoshiyasu
en-aut-sei=Umeda
en-aut-mei=Yoshiyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=NakamuraYasuhiro
en-aut-sei=Nakamura
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=KiniwaYukiko
en-aut-sei=Kiniwa
en-aut-mei=Yukiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=

en-aut-name=HayashiHidetoshi
en-aut-sei=Hayashi
en-aut-mei=Hidetoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
ORCID=

en-aut-name=IkedaJun-ichiro
en-aut-sei=Ikeda
en-aut-mei=Jun-ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=28
ORCID=

en-aut-name=HanazawaToyoyuki
en-aut-sei=Hanazawa
en-aut-mei=Toyoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=29
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=30
ORCID=

en-aut-name=ManoHiroyuki
en-aut-sei=Mano
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=31
ORCID=

en-aut-name=SuzukiTakuji
en-aut-sei=Suzuki
en-aut-mei=Takuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=32
ORCID=

en-aut-name=OsawaTsuyoshi
en-aut-sei=Osawa
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=33
ORCID=

en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=34
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=35
ORCID=

affil-num=1
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=2
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=3
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Division of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute
kn-affil=

affil-num=6
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=7
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo
kn-affil=

affil-num=9
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=10
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan Department of Dermatology, Graduate School of Medicine, Chiba University
kn-affil=

affil-num=11
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=12
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine
kn-affil=

affil-num=14
en-affil=Tsuruoka Metabolomics Laboratory, National Cancer Center
kn-affil=

affil-num=15
en-affil=Department of Surgical Pathology, Chiba Cancer Center
kn-affil=

affil-num=16
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=17
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=18
en-affil=Laboratory of Evolutionary Oncology, Chiba Cancer Center Research Institute
kn-affil=

affil-num=19
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=20
en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi
kn-affil=

affil-num=21
en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi
kn-affil=

affil-num=22
en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi
kn-affil=

affil-num=23
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=

affil-num=24
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=

affil-num=25
en-affil=Department of Dermatology, Shinshu University School of Medicine
kn-affil=

affil-num=26
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=27
en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine
kn-affil=

affil-num=28
en-affil=Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University
kn-affil=

affil-num=29
en-affil=Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine
kn-affil=

affil-num=30
en-affil=Department of General Thoracic Surgery and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=31
en-affil=Division of Cellular Signalling, National Cancer Center Research Institute
kn-affil=

affil-num=32
en-affil=Department of Respirology, Graduate School of Medicine, Chiba University
kn-affil=

affil-num=33
en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo
kn-affil=

affil-num=34
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=35
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=27502
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250728
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Autoantibody spark response predicts treatment outcome in patients receiving chemoradiation followed by durvalumab therapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The PACIFIC regimen, comprising chemoradiotherapy (CRT) followed by maintenance with the immune checkpoint inhibitor (ICI) durvalumab, has become the standard of care for patients with unresectable non-small cell lung cancer (NSCLC). Although ICI is used to prevent recurrence by targeting residual microtumors, biomarkers capable of monitoring immune activity during this phase remain lacking. Here, we evaluated whether temporal changes in serum autoantibody levels can predict treatment efficacy. This retrospective study included 20 patients with unresectable stage II or III NSCLC who received the PACIFIC regimen. Serum autoantibodies against 130 antigens were quantified before CRT, after CRT, and two weeks after the first ICI dose. The primary outcome was progression-free survival (PFS), and its association with autoantibody dynamics was examined. We observed an immediate and strong autoantibody response (spark response [SR]) after ICI initiation in patients with favorable treatment outcomes. Patients with SR and programmed death ligand 1 (PD-L1) expression ≥ 50% showed better PFS (two-year PFS; 72.9% vs. 18.2%, p = 0.0021). These findings suggest that serial monitoring of serum autoantibodies can provide a noninvasive approach to assess immune activity and predict treatment outcomes in patients receiving CRT or ICI therapy.
en-copyright=
kn-copyright=

en-aut-name=MoriTakeru
en-aut-sei=Mori
en-aut-mei=Takeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KitagawaMio
en-aut-sei=Kitagawa
en-aut-mei=Mio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HasegawaTomokazu
en-aut-sei=Hasegawa
en-aut-mei=Tomokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SomeyaMasanori
en-aut-sei=Someya
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TsuchiyaTakaaki
en-aut-sei=Tsuchiya
en-aut-mei=Takaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=GochoToshio
en-aut-sei=Gocho
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HonjoTomoko
en-aut-sei=Honjo
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=DateMirei
en-aut-sei=Date
en-aut-mei=Mirei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MoriiMariko
en-aut-sei=Morii
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MiyamotoAi
en-aut-sei=Miyamoto
en-aut-mei=Ai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Radiology, Sapporo Medical University School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Radiology, Sapporo Medical University School of Medicine
kn-affil=

affil-num=4
en-affil=Department of Radiology, Sapporo Medical University School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Radiology, Sapporo Medical University School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Radiology, Sapporo Medical University School of Medicine
kn-affil=

affil-num=7
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=8
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=9
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=10
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=11
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=Autoantibodies
kn-keyword=Autoantibodies
en-keyword=PACIFIC regimen
kn-keyword=PACIFIC regimen
en-keyword=ICIs
kn-keyword=ICIs
en-keyword=Immune monitoring
kn-keyword=Immune monitoring
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=6
article-no=
start-page=e00110-25
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250519
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblasts
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)−1β, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1β, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection.
en-copyright=
kn-copyright=

en-aut-name=TakiiTakemasa
en-aut-sei=Takii
en-aut-mei=Takemasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YamadaHiroyuki
en-aut-sei=Yamada
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MotozonoChihiro
en-aut-sei=Motozono
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YamasakiSho
en-aut-sei=Yamasaki
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TorrellesJordi B.
en-aut-sei=Torrelles
en-aut-mei=Jordi B.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TurnerJoanne
en-aut-sei=Turner
en-aut-mei=Joanne
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KimishimaAoi
en-aut-sei=Kimishima
en-aut-mei=Aoi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AsamiYukihiro
en-aut-sei=Asami
en-aut-mei=Yukihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OharaNaoya
en-aut-sei=Ohara
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HidaShigeaki
en-aut-sei=Hida
en-aut-mei=Shigeaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=HayashiHidetoshi
en-aut-sei=Hayashi
en-aut-mei=Hidetoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=OnozakiKikuo
en-aut-sei=Onozaki
en-aut-mei=Kikuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association
kn-affil=

affil-num=2
en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association
kn-affil=

affil-num=3
en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka
kn-affil=

affil-num=4
en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka
kn-affil=

affil-num=5
en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE)
kn-affil=

affil-num=6
en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE)
kn-affil=

affil-num=7
en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University
kn-affil=

affil-num=8
en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University
kn-affil=

affil-num=9
en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University
kn-affil=

affil-num=11
en-affil=Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University
kn-affil=

affil-num=12
en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University
kn-affil=
en-keyword=Mycobacterium tuberculosis
kn-keyword=Mycobacterium tuberculosis
en-keyword=pyroptosis
kn-keyword=pyroptosis
en-keyword=caspase
kn-keyword=caspase
en-keyword=RNA-Seq
kn-keyword=RNA-Seq
en-keyword=cytokine
kn-keyword=cytokine
en-keyword=fibroblasts
kn-keyword=fibroblasts
END

start-ver=1.4
cd-journal=joma
no-vol=779
cd-vols=
no-issue=
article-no=
start-page=152453
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250912
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=1,2-naphthoquinone enhances IFN-γ-induced MHC-I expression in dendritic cells, thereby inducing CD8 T cell activation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Dendritic cells play a crucial role in immune responses by capturing pathogens and presenting antigens to T cells via major histocompatibility complex (MHC) molecules, thus triggering adaptive immune responses. 1,2-naphthoquinone (1,2-NQ), a quinone found in diesel exhaust and cigarette smoke, has various physiological functions. In this study, we investigated the effect of 1,2-NQ on the expression of antigen presentation-related molecules in the dendritic cell line DC2.4. The results revealed that 1,2-NQ enhanced the IFN-γ-induced upregulation of MHC-I expression at the transcriptional level. Moreover, it upregulated the expression of NLRC5, a transcriptional activator of MHC-I. 1,2-NQ is a reactive oxygen species (ROS) producing reagent. The 1,2-NQ-induced upregulation of MHC-I expression and downregulation of MHC-II expression were abolished by the ROS scavenger N-acetylcysteine. Similar effects on MHC expression were also observed with ROS-inducing reagents, such as paraquat and diethyl maleate. In addition, dendritic cells stimulated with 1,2-NQ exhibited enhanced efficacy in CD8 T cell activation, which was accompanied by increased IFN-γ production by T cells. These findings demonstrate that 1,2-NQ enhances the IFN-γ-induced activation of dendritic cells and promotes the activation of CD8 T cells.
en-copyright=
kn-copyright=

en-aut-name=FurutaKazuyuki
en-aut-sei=Furuta
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MiyazatoKanon
en-aut-sei=Miyazato
en-aut-mei=Kanon
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KobataKai
en-aut-sei=Kobata
en-aut-mei=Kai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IshikawaKazuya
en-aut-sei=Ishikawa
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KaitoChikara
en-aut-sei=Kaito
en-aut-mei=Chikara
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=1,2-Napthoquinone
kn-keyword=1,2-Napthoquinone
en-keyword=Dendritic cell
kn-keyword=Dendritic cell
en-keyword=IFN-γ
kn-keyword=IFN-γ
en-keyword=MHC-I
kn-keyword=MHC-I
en-keyword=CD8 T cell
kn-keyword=CD8 T cell
END

start-ver=1.4
cd-journal=joma
no-vol=33
cd-vols=
no-issue=3
article-no=
start-page=99
end-page=117
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240429
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Generation and characterization of cerebellar granule neurons specific knockout mice of Golli-MBP
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Golli–myelin basic proteins, encoded by the myelin basic protein gene, are widely expressed in neurons and oligodendrocytes in the central nervous system. Further, prior research has shown that Golli–myelin basic protein is necessary for myelination and neuronal maturation during central nervous system development. In this study, we established Golli–myelin basic protein-floxed mice to elucidate the cell-type-specific effects of Golli–myelin basic protein knockout through the generation of conditional knockout mice (Golli–myelin basic proteinsfl/fl; E3CreN), in which Golli–myelin basic proteins were specifically deleted in cerebellar granule neurons, where Golli–myelin basic proteins are expressed abundantly in wild-type mice. To investigate the role of Golli–myelin basic proteins in cerebellar granule neurons, we further performed histopathological analyses of these mice, with results indicating no morphological changes or degeneration of the major cellular components of the cerebellum. Furthermore, behavioral analysis showed that Golli–myelin basic proteinsfl/fl; E3CreN mice were healthy and did not display any abnormal behavior. These results suggest that the loss of Golli–myelin basic proteins in cerebellar granule neurons does not lead to cerebellar perturbations or behavioral abnormalities. This mouse model could therefore be employed to analyze the effect of Golli–myelin basic protein deletion in specific cell types of the central nervous system, such as other neuronal cells and oligodendrocytes, or in lymphocytes of the immune system.
en-copyright=
kn-copyright=

en-aut-name=MiyazakiHaruko
en-aut-sei=Miyazaki
en-aut-mei=Haruko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishiokaSaki
en-aut-sei=Nishioka
en-aut-mei=Saki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YamanakaTomoyuki
en-aut-sei=Yamanaka
en-aut-mei=Tomoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AbeManabu
en-aut-sei=Abe
en-aut-mei=Manabu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ImamuraYukio
en-aut-sei=Imamura
en-aut-mei=Yukio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MiyasakaTomohiro
en-aut-sei=Miyasaka
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KakudaNobuto
en-aut-sei=Kakuda
en-aut-mei=Nobuto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ShimogoriTomomi
en-aut-sei=Shimogori
en-aut-mei=Tomomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=YamakawaKazuhiro
en-aut-sei=Yamakawa
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=IkawaMasahito
en-aut-sei=Ikawa
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=NukinaNobuyuki
en-aut-sei=Nukina
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University
kn-affil=

affil-num=3
en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University
kn-affil=

affil-num=4
en-affil=Department of Animal Model Development, Brain Research Institute, Niigata University
kn-affil=

affil-num=5
en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University
kn-affil=

affil-num=6
en-affil=Faculty of Life and Medical Sciences, Doshisha University
kn-affil=

affil-num=7
en-affil=Faculty of Life and Medical Sciences, Doshisha University
kn-affil=

affil-num=8
en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Laboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain Science
kn-affil=

affil-num=10
en-affil=Laboratory for Neurogenetics, RIKEN Center for Brain Science
kn-affil=

affil-num=11
en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University
kn-affil=

affil-num=12
en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University
kn-affil=
en-keyword=Golli-MBP
kn-keyword=Golli-MBP
en-keyword=Cerebellar granule neuron
kn-keyword=Cerebellar granule neuron
en-keyword=CRISPR/Cas9
kn-keyword=CRISPR/Cas9
en-keyword=Conditional knockout
kn-keyword=Conditional knockout
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=158
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250719
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs.
en-copyright=
kn-copyright=

en-aut-name=YamadaMotohiko
en-aut-sei=Yamada
en-aut-mei=Motohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SuemoriKanto
en-aut-sei=Suemori
en-aut-mei=Kanto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OkadaNaohiro
en-aut-sei=Okada
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KajiwaraYoshinori
en-aut-sei=Kajiwara
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShojiRyohei
en-aut-sei=Shoji
en-aut-mei=Ryohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NagaiYasuo
en-aut-sei=Nagai
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=InoueHiroaki
en-aut-sei=Inoue
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HashimotoNaoyuki
en-aut-sei=Hashimoto
en-aut-mei=Naoyuki
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MichiueHiroyuki
en-aut-sei=Michiue
en-aut-mei=Hiroyuki
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Neutron Therapy Research Center, Okayama University Hospital
kn-affil=

affil-num=14
en-affil=Oncolys BioPharma, Inc
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=199
cd-vols=
no-issue=
article-no=
start-page=108027
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202501
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.<br>
Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan–Meier method.<br>
Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy—61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group—42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group—37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).<br>
Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era.

en-copyright=
kn-copyright=

en-aut-name=HorinouchiHidehito
en-aut-sei=Horinouchi
en-aut-mei=Hidehito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MurakamiHaruyasu
en-aut-sei=Murakami
en-aut-mei=Haruyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HaradaHideyuki
en-aut-sei=Harada
en-aut-mei=Hideyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SobueTomotaka
en-aut-sei=Sobue
en-aut-mei=Tomotaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KatoTomohiro
en-aut-sei=Kato
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AtagiShinji
en-aut-sei=Atagi
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KozukiToshiyuki
en-aut-sei=Kozuki
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TokitoTakaaki
en-aut-sei=Tokito
en-aut-mei=Takaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OizumiSatoshi
en-aut-sei=Oizumi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SeikeMasahiro
en-aut-sei=Seike
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=MioTadashi
en-aut-sei=Mio
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=SoneTakashi
en-aut-sei=Sone
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=IwaoChikako
en-aut-sei=Iwao
en-aut-mei=Chikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=IwaneTakeshi
en-aut-sei=Iwane
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KotoRyo
en-aut-sei=Koto
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=TsuboiMasahiro
en-aut-sei=Tsuboi
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

affil-num=1
en-affil=Department of Thoracic Oncology, National Cancer Center Hospital
kn-affil=

affil-num=2
en-affil=Department of Thoracic Oncology, Shizuoka Cancer Center
kn-affil=

affil-num=3
en-affil=Division of Radiation Therapy, Shizuoka Cancer Center
kn-affil=

affil-num=4
en-affil=Division of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University
kn-affil=

affil-num=5
en-affil=Department of Respiratory Medicine, National Hospital Organization Himeji Medical Cente
kn-affil=

affil-num=6
en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center
kn-affil=

affil-num=7
en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center
kn-affil=

affil-num=8
en-affil=Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University Hospital
kn-affil=

affil-num=9
en-affil=Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center
kn-affil=

affil-num=10
en-affil=Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital
kn-affil=

affil-num=11
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=12
en-affil=Department of Respiratory Medicine, National Hospital Organization Kyoto Medical Center
kn-affil=

affil-num=13
en-affil=Department of Respiratory Medicine, Kanazawa University Hospital
kn-affil=

affil-num=14
en-affil=Department of Medical, AstraZeneca K.K.
kn-affil=

affil-num=15
en-affil=Department of Medical, AstraZeneca K.K.
kn-affil=

affil-num=16
en-affil=Department of Medical, AstraZeneca K.K.
kn-affil=

affil-num=17
en-affil=Department of Thoracic Surgery, National Cancer Center Hospital East
kn-affil=
en-keyword=Non-small cell lung cancer
kn-keyword=Non-small cell lung cancer
en-keyword=Surgery
kn-keyword=Surgery
en-keyword=Adjuvant therapy
kn-keyword=Adjuvant therapy
en-keyword=Neoadjuvant therapy
kn-keyword=Neoadjuvant therapy
en-keyword=Chemoradiotherapy
kn-keyword=Chemoradiotherapy
en-keyword=Observational study
kn-keyword=Observational study
en-keyword=Retrospective study
kn-keyword=Retrospective study
END

start-ver=1.4
cd-journal=joma
no-vol=106
cd-vols=
no-issue=7
article-no=
start-page=002112
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250725
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(−) Viruses Subcommittee, 2025
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=RNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(−) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses.
en-copyright=
kn-copyright=

en-aut-name=HughesHolly R.
en-aut-sei=Hughes
en-aut-mei=Holly R.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=BallingerMatthew J.
en-aut-sei=Ballinger
en-aut-mei=Matthew J.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=BaoYiming
en-aut-sei=Bao
en-aut-mei=Yiming
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=BejermanNicolas
en-aut-sei=Bejerman
en-aut-mei=Nicolas
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=BlasdellKim R.
en-aut-sei=Blasdell
en-aut-mei=Kim R.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=BrieseThomas
en-aut-sei=Briese
en-aut-mei=Thomas
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=BrignoneJulia
en-aut-sei=Brignone
en-aut-mei=Julia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=CarreraJean Paul
en-aut-sei=Carrera
en-aut-mei=Jean Paul
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=De ConinckLander
en-aut-sei=De Coninck
en-aut-mei=Lander
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=de SouzaWilliam Marciel
en-aut-sei=de Souza
en-aut-mei=William Marciel
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=DebatHumberto
en-aut-sei=Debat
en-aut-mei=Humberto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=DietzgenRalf G.
en-aut-sei=Dietzgen
en-aut-mei=Ralf G.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=DürrwaldRalf
en-aut-sei=Dürrwald
en-aut-mei=Ralf
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=ErdinMert
en-aut-sei=Erdin
en-aut-mei=Mert
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=FooksAnthony R.
en-aut-sei=Fooks
en-aut-mei=Anthony R.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=ForbesKristian M.
en-aut-sei=Forbes
en-aut-mei=Kristian M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=Freitas-AstúaJuliana
en-aut-sei=Freitas-Astúa
en-aut-mei=Juliana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=GarciaJorge B.
en-aut-sei=Garcia
en-aut-mei=Jorge B.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=GeogheganJemma L.
en-aut-sei=Geoghegan
en-aut-mei=Jemma L.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=GrimwoodRebecca M.
en-aut-sei=Grimwood
en-aut-mei=Rebecca M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=HorieMasayuki
en-aut-sei=Horie
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=HyndmanTimothy H.
en-aut-sei=Hyndman
en-aut-mei=Timothy H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=JohneReimar
en-aut-sei=Johne
en-aut-mei=Reimar
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=KlenaJohn D.
en-aut-sei=Klena
en-aut-mei=John D.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=KondoHideki
en-aut-sei=Kondo
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

en-aut-name=KooninEugene V.
en-aut-sei=Koonin
en-aut-mei=Eugene V.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=

en-aut-name=KostygovAlexei Y.
en-aut-sei=Kostygov
en-aut-mei=Alexei Y.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
ORCID=

en-aut-name=KrupovicMart
en-aut-sei=Krupovic
en-aut-mei=Mart
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=28
ORCID=

en-aut-name=KuhnJens H.
en-aut-sei=Kuhn
en-aut-mei=Jens H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=29
ORCID=

en-aut-name=LetkoMichael
en-aut-sei=Letko
en-aut-mei=Michael
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=30
ORCID=

en-aut-name=LiJun-Min
en-aut-sei=Li
en-aut-mei=Jun-Min
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=31
ORCID=

en-aut-name=LiuYiyun
en-aut-sei=Liu
en-aut-mei=Yiyun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=32
ORCID=

en-aut-name=MartinMaria Laura
en-aut-sei=Martin
en-aut-mei=Maria Laura
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=33
ORCID=

en-aut-name=MullNathaniel
en-aut-sei=Mull
en-aut-mei=Nathaniel
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=34
ORCID=

en-aut-name=NazarYael
en-aut-sei=Nazar
en-aut-mei=Yael
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=35
ORCID=

en-aut-name=NowotnyNorbert
en-aut-sei=Nowotny
en-aut-mei=Norbert
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=36
ORCID=

en-aut-name=NunesMárcio Roberto Teixeira
en-aut-sei=Nunes
en-aut-mei=Márcio Roberto Teixeira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=37
ORCID=

en-aut-name=ØklandArnfinn Lodden
en-aut-sei=Økland
en-aut-mei=Arnfinn Lodden
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=38
ORCID=

en-aut-name=RubbenstrothDennis
en-aut-sei=Rubbenstroth
en-aut-mei=Dennis
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=39
ORCID=

en-aut-name=RussellBrandy J.
en-aut-sei=Russell
en-aut-mei=Brandy J.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=40
ORCID=

en-aut-name=SchottEric
en-aut-sei=Schott
en-aut-mei=Eric
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
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ORCID=

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affil-num=2
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kn-affil=

affil-num=3
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affil-num=4
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affil-num=5
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kn-affil=

affil-num=6
en-affil=Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University
kn-affil=

affil-num=7
en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS
kn-affil=

affil-num=8
en-affil=Instituto Conmemorativo Gorgas de Estudios de la Salud
kn-affil=

affil-num=9
en-affil=Division of Clinical and Epidemiological Virology, KU Leuven
kn-affil=

affil-num=10
en-affil=Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky
kn-affil=

affil-num=11
en-affil=Instituto Nacional de Tecnología Agropecuaria (INTA)
kn-affil=

affil-num=12
en-affil=QAAFI, The University of Queensland
kn-affil=

affil-num=13
en-affil=Robert Koch Institut
kn-affil=

affil-num=14
en-affil=Department of Virology, University of Helsinki
kn-affil=

affil-num=15
en-affil=Animal and Plant Health Agency (APHA)
kn-affil=

affil-num=16
en-affil=Department of Biological Sciences, University of Arkansas
kn-affil=

affil-num=17
en-affil=Embrapa Cassava and Fruits
kn-affil=

affil-num=18
en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS
kn-affil=

affil-num=19
en-affil=Department of Microbiology and Immunology, University of Otago
kn-affil=

affil-num=20
en-affil=Department of Microbiology and Immunology, University of Otago
kn-affil=

affil-num=21
en-affil=Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University
kn-affil=

affil-num=22
en-affil=School of Veterinary Medicine, Murdoch University
kn-affil=

affil-num=23
en-affil=German Federal Institute for Risk Assessment
kn-affil=

affil-num=24
en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention
kn-affil=

affil-num=25
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=26
en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health
kn-affil=

affil-num=27
en-affil=University of Ostrava
kn-affil=

affil-num=28
en-affil=Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit
kn-affil=

affil-num=29
en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health
kn-affil=

affil-num=30
en-affil=Paul G. Allen School for Global Health, Washington State University
kn-affil=

affil-num=31
en-affil=Institute of Plant Virology, Ningbo University
kn-affil=

affil-num=32
en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences
kn-affil=

affil-num=33
en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS
kn-affil=

affil-num=34
en-affil=Department of Natural Sciences, Shawnee State University
kn-affil=

affil-num=35
en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS
kn-affil=

affil-num=36
en-affil=College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health
kn-affil=

affil-num=37
en-affil=Universidade Federal do Pará
kn-affil=

affil-num=38
en-affil=Pharmaq Analytiq
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affil-num=39
en-affil=Institute of Diagnostic Virology, Friedrich-Loeffler-Institut
kn-affil=

affil-num=40
en-affil=Centers for Disease Control and Prevention
kn-affil=

affil-num=41
en-affil=Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science
kn-affil=

affil-num=42
en-affil=Paul G. Allen School for Global Health, Washington State University
kn-affil=

affil-num=43
en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS
kn-affil=

affil-num=44
en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention
kn-affil=

affil-num=45
en-affil=Department of Virology, University of Helsinki
kn-affil=

affil-num=46
en-affil=Department of Virology, University of Helsinki
kn-affil=

affil-num=47
en-affil=Integrated Group of Aquaculture and Environmental Studies, Federal University of Paraná
kn-affil=

affil-num=48
en-affil=Department of Pathology, The University of Texas Medical Branch
kn-affil=

affil-num=49
en-affil=Department of Microbiology and Immunology, Indiana University School of Medicine
kn-affil=

affil-num=50
en-affil=Institut Pasteur
kn-affil=

affil-num=51
en-affil=Department of Pathology, The University of Texas Medical Branch
kn-affil=

affil-num=52
en-affil=University of Queensland
kn-affil=

affil-num=53
en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences
kn-affil=

affil-num=54
en-affil=North Carolina State University
kn-affil=

affil-num=55
en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention
kn-affil=

affil-num=56
en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health
kn-affil=

affil-num=57
en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences
kn-affil=

affil-num=58
en-affil=Institute of Insect Sciences, Zhejiang University
kn-affil=

affil-num=59
en-affil=Institute of Plant Virology, Ningbo University
kn-affil=

affil-num=60
en-affil=University of Ostrava
kn-affil=

affil-num=61
en-affil=Department of Pathobiology and Population Sciences, Royal Veterinary College
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=27163
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250725
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Eosinophils as a predictive marker of treatment-related adverse events in mRCC patients treated with first-line immune-checkpoint inhibitor combination therapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade ≥ 3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of ≥ 2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23–4.54, p = 0.01) and a low neutrophil/eosinophil ratio (NER) of ≤ 40.0 (OR: 2.78, 95% CI 1.39–5.53, p = 0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade ≥ 3 TRAEs and help determine individualized treatment strategies in patients with mRCC.
en-copyright=
kn-copyright=

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affil-num=1
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affil-num=2
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kn-affil=

affil-num=3
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kn-affil=

affil-num=4
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affil-num=5
en-affil=Department of Urology, The Jikei University School of Medicine
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affil-num=6
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affil-num=7
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affil-num=8
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affil-num=9
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affil-num=10
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affil-num=11
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affil-num=12
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affil-num=13
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kn-affil=

affil-num=14
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affil-num=15
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affil-num=16
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affil-num=17
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affil-num=18
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affil-num=19
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affil-num=20
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affil-num=21
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affil-num=22
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affil-num=23
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affil-num=24
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affil-num=25
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affil-num=26
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affil-num=27
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=28
en-affil=Department of Urology, The Jikei University School of Medicine
kn-affil=

affil-num=29
en-affil=Department of Urology, Osaka Medical and Pharmaceutical University
kn-affil=

affil-num=30
en-affil=Department of Urology, Fujita Health University School of Medicine
kn-affil=

affil-num=31
en-affil=Department of Urology, Kindai University Faculty of Medicine
kn-affil=

affil-num=32
en-affil=Department of Urology, Tokyo Medical University
kn-affil=

affil-num=33
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Renal cell carcinoma
kn-keyword=Renal cell carcinoma
en-keyword=Immune checkpoint inhibitor
kn-keyword=Immune checkpoint inhibitor
en-keyword=ICI
kn-keyword=ICI
en-keyword=Eosinophil
kn-keyword=Eosinophil
en-keyword=Immune-related adverse event
kn-keyword=Immune-related adverse event
en-keyword=Treatment-related adverse event
kn-keyword=Treatment-related adverse event
END

start-ver=1.4
cd-journal=joma
no-vol=135
cd-vols=
no-issue=13
article-no=
start-page=e172988
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250513
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=LAG3 regulates antibody responses in a murine model of kidney transplantation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Lymphocyte activation gene 3 (LAG3) is a coinhibitory receptor expressed by various immune cells. Although the immunomodulatory potential of LAG3 is being explored in cancer and autoimmunity, there is no information on its role after organ transplantation. Our study investigated the functions of LAG3 in a mouse model of renal allograft rejection. LAG3–/– recipients rapidly rejected MHC-mismatched renal allografts that were spontaneously accepted by WT recipients, with graft histology characteristic of antibody-mediated rejection. Depletion of recipient B cells but not CD8+ T cells significantly extended kidney allograft survival in LAG3–/– recipients. Treatment of WT recipients with an antagonistic LAG3 antibody enhanced anti-donor immune responses and induced kidney damage associated with chronic rejection. The studies of conditional LAG3–/– recipients and mixed bone marrow chimeras demonstrated that LAG3 expression on either T or B cells is sufficient to regulate anti-donor humoral immunity but not to induce acute allograft rejection. The numbers and proinflammatory functions of graft-infiltrating NK cells were markedly increased in LAG3–/– recipients, suggesting that LAG3 also regulates the effector stage of antibody-mediated rejection. These findings identified LAG3 as a regulator of immune responses to kidney allografts and a potential therapeutic target for antibody-mediated rejection prevention and treatment.
en-copyright=
kn-copyright=

en-aut-name=NicosiaMichael
en-aut-sei=Nicosia
en-aut-mei=Michael
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FanRan
en-aut-sei=Fan
en-aut-mei=Ran
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LeeJuyeun
en-aut-sei=Lee
en-aut-mei=Juyeun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AllGabriella
en-aut-sei=All
en-aut-mei=Gabriella
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=GorbachevaVictoria
en-aut-sei=Gorbacheva
en-aut-mei=Victoria
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ValenzuelaJosé I.
en-aut-sei=Valenzuela
en-aut-mei=José I.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YamamotoYosuke
en-aut-sei=Yamamoto
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=BeaversAshley
en-aut-sei=Beavers
en-aut-mei=Ashley
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=DvorinaNina
en-aut-sei=Dvorina
en-aut-mei=Nina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=BaldwinWilliam M.
en-aut-sei=Baldwin
en-aut-mei=William M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ChuluyanEduardo
en-aut-sei=Chuluyan
en-aut-mei=Eduardo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ArakiMotoo
en-aut-sei=Araki
en-aut-mei=Motoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=GaudetteBrian T.
en-aut-sei=Gaudette
en-aut-mei=Brian T.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FairchildRobert L.
en-aut-sei=Fairchild
en-aut-mei=Robert L.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=MinBooki
en-aut-sei=Min
en-aut-mei=Booki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=ValujskikhAnna
en-aut-sei=Valujskikh
en-aut-mei=Anna
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=2
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=4
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=5
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=6
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=7
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=8
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=9
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=10
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=11
en-affil=Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina
kn-affil=

affil-num=12
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=14
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=15
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=

affil-num=16
en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=25
cd-vols=
no-issue=1
article-no=
start-page=107
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250428
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Impact of concomitant medications on the oncologic efficacy of systemic therapy in patients with advanced or metastatic urothelial carcinoma: a systematic review and meta-analysis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Immune checkpoint inhibitors (ICI) and chemotherapy, including antibody-drug conjugates, are widely used for the treatment of patients with advanced unresectable or metastatic urothelial carcinoma (UC). The majority of elderly patients receive concomitant medications to address various comorbidities. We aimed to evaluate the impact of concomitant medications on oncological outcomes in patients with advanced unresectable or metastatic UC treated with systemic therapy.<br>
Material & methods: In August 2024, three datasets were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic UC. The review protocol was registered in PROSPERO (CRD42024547335). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis depending on the heterogeneity.<br>
Results: We identified 16 eligible studies (3 prospective and 13 retrospective) comprising 4,816 patients. Most reported concomitant medications included proton pump inhibitors (PPIs), antibiotics, steroids, and opioids. The use of concomitant PPIs, antibiotics, steroids or opioids during ICI therapy was associated with worsened OS (PPIs: HR: 1.43, 95% CI: 1.31–1.57, p < 0.001; antibiotics: HR: 1.2, 95% CI: 1.04–1.38, p = 0.01; steroids: HR: 1.45, 95% CI: 1.25–1.67, p < 0.001; and opioids: HR: 1.74, 95% CI: 1.46–2.07, p < 0.001). Concomitant use of antibiotics during chemotherapy did not impact OS (HR: 1.01, 95% CI: 0.67–1.51).<br>
Conclusions: When treating advanced unresectable or metastatic UC with ICI therapy, we need to pay attention to concomitant medications, such as PPIs and antibiotics to avoid reducing the efficacy of ICI therapy. The mechanism of action of these drugs on ICI efficacy requires further examination.
en-copyright=
kn-copyright=

en-aut-name=TsuboiIchiro
en-aut-sei=Tsuboi
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=PariziMehdi Kardoust
en-aut-sei=Parizi
en-aut-mei=Mehdi Kardoust
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MiszczykMarcin
en-aut-sei=Miszczyk
en-aut-mei=Marcin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FazekasTamás
en-aut-sei=Fazekas
en-aut-mei=Tamás
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SchulzRobert J
en-aut-sei=Schulz
en-aut-mei=Robert J
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=LaukhtinaEkaterina
en-aut-sei=Laukhtina
en-aut-mei=Ekaterina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KawadaTatsushi
en-aut-sei=Kawada
en-aut-mei=Tatsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KatayamaSatoshi
en-aut-sei=Katayama
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=IwataTakehiro
en-aut-sei=Iwata
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=BekkuKensuke
en-aut-sei=Bekku
en-aut-mei=Kensuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=RajwaPawel
en-aut-sei=Rajwa
en-aut-mei=Pawel
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=WadaKoichiro
en-aut-sei=Wada
en-aut-mei=Koichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=ObernederKatharina
en-aut-sei=Oberneder
en-aut-mei=Katharina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ChlostaPiotr
en-aut-sei=Chlosta
en-aut-mei=Piotr
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KarakiewiczPierre I.
en-aut-sei=Karakiewicz
en-aut-mei=Pierre I.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=ArakiMotoo
en-aut-sei=Araki
en-aut-mei=Motoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=ShariatShahrokh F.
en-aut-sei=Shariat
en-aut-mei=Shahrokh F.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

affil-num=1
en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=3
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=4
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=5
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=6
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=7
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=8
en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=10
en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=13
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=14
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=15
en-affil=Department of Urology, Medical College, Jagiellonian University
kn-affil=

affil-num=16
en-affil=Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre
kn-affil=

affil-num=17
en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=18
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=
en-keyword=Concomitant medications
kn-keyword=Concomitant medications
en-keyword=Proton pump inhibitors
kn-keyword=Proton pump inhibitors
en-keyword=Antibiotics
kn-keyword=Antibiotics
en-keyword=steroids
kn-keyword=steroids
en-keyword=Opioids
kn-keyword=Opioids
en-keyword=Histamine type-2 receptor antagonists
kn-keyword=Histamine type-2 receptor antagonists
en-keyword=Immune checkpoint inhibitors
kn-keyword=Immune checkpoint inhibitors
en-keyword=Urothelial carcinoma
kn-keyword=Urothelial carcinoma
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=10
article-no=
start-page=2401783
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241010
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Biocompatibility of Water-Dispersible Pristine Graphene and Graphene Oxide Using a Close-to-Human Animal Model: A Pilot Study on Swine
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Graphene-based materials (GBMs) are of considerable interest for biomedical applications, and the pilot study on the toxicological and immunological impact of pristine graphene (GR) and graphene oxide (GO) using swine as a close-to-human provides valuable insights. First, ex vivo experiments are conducted on swine blood cells, then GBMs are injected intraperitoneally (i.p.) into swine. Hematological and biochemical analyses at various intervals indicate that neither GO nor GR cause systemic inflammation, pro-coagulant responses, or renal or hepatic dysfunction. Importantly, no systemic toxicity is observed. Analysis of a panel of 84 immune-related genes shows minimal impact of GO and GR. The animals are sacrificed 21 days post-injection, and transient absorption imaging and Raman mapping show the presence of GO and GR in the mesentery only. Histological evaluation reveals no signs of alterations in other organs. Thus, clusters of both materials are detected in the mesentery, and GO aggregates are surrounded only by macrophages with the formation of granulomas. In contrast, modest local reactions are observed around the GR clusters. Overall, these results reveal that i.p. injection of GBMs resulted in a modest local tissue reaction without systemic toxicity. This study, performed in swine, provides essential guidance for future biomedical applications of graphene.
en-copyright=
kn-copyright=

en-aut-name=NicolussiPaola
en-aut-sei=Nicolussi
en-aut-mei=Paola
kn-aut-name=
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kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=PiloGiovannantonio
en-aut-sei=Pilo
en-aut-mei=Giovannantonio
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=CanceddaMaria Giovanna
en-aut-sei=Cancedda
en-aut-mei=Maria Giovanna
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=PengGuotao
en-aut-sei=Peng
en-aut-mei=Guotao
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ChauNgoc Do Quyen
en-aut-sei=Chau
en-aut-mei=Ngoc Do Quyen
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=De la CadenaAlejandro
en-aut-sei=De la Cadena
en-aut-mei=Alejandro
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kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=VannaRenzo
en-aut-sei=Vanna
en-aut-mei=Renzo
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kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SamadYarjan Abdul
en-aut-sei=Samad
en-aut-mei=Yarjan Abdul
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=AhmedTanweer
en-aut-sei=Ahmed
en-aut-mei=Tanweer
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MarcellinoJeremia
en-aut-sei=Marcellino
en-aut-mei=Jeremia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TeddeGiuseppe
en-aut-sei=Tedde
en-aut-mei=Giuseppe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=GiroLinda
en-aut-sei=Giro
en-aut-mei=Linda
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=YlmazerAcelya
en-aut-sei=Ylmazer
en-aut-mei=Acelya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=LoiFederica
en-aut-sei=Loi
en-aut-mei=Federica
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=CartaGavina
en-aut-sei=Carta
en-aut-mei=Gavina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=SecchiLoredana
en-aut-sei=Secchi
en-aut-mei=Loredana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=Dei GiudiciSilvia
en-aut-sei=Dei Giudici
en-aut-mei=Silvia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=MacciocuSimona
en-aut-sei=Macciocu
en-aut-mei=Simona
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=PolliDario
en-aut-sei=Polli
en-aut-mei=Dario
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=NishinaYuta
en-aut-sei=Nishina
en-aut-mei=Yuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=LigiosCiriaco
en-aut-sei=Ligios
en-aut-mei=Ciriaco
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=CerulloGiulio
en-aut-sei=Cerullo
en-aut-mei=Giulio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=FerrariAndrea
en-aut-sei=Ferrari
en-aut-mei=Andrea
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=BiancoAlberto
en-aut-sei=Bianco
en-aut-mei=Alberto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=FadeelBengt
en-aut-sei=Fadeel
en-aut-mei=Bengt
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

en-aut-name=FranzoniGiulia
en-aut-sei=Franzoni
en-aut-mei=Giulia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=

en-aut-name=DeloguLucia Gemma
en-aut-sei=Delogu
en-aut-mei=Lucia Gemma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
ORCID=

affil-num=1
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=2
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=3
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=4
en-affil=Institute of Environmental Medicine, Karolinska Institutet
kn-affil=

affil-num=5
en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry
kn-affil=

affil-num=6
en-affil=Dipartimento di Fisica, Politecnico di Milano
kn-affil=

affil-num=7
en-affil=Istituto di Fotonica e Nanotecnologie – CNR
kn-affil=

affil-num=8
en-affil=Cambridge Graphene Centre, University of Cambridge
kn-affil=

affil-num=9
en-affil=Cambridge Graphene Centre, University of Cambridge
kn-affil=

affil-num=10
en-affil=Cambridge Graphene Centre, University of Cambridge
kn-affil=

affil-num=11
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=12
en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences
kn-affil=

affil-num=13
en-affil=Department of Biomedical Engineering, Ankara University
kn-affil=

affil-num=14
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=15
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=16
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=17
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=18
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=19
en-affil=Dipartimento di Fisica, Politecnico di Milano
kn-affil=

affil-num=20
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=21
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=22
en-affil=Dipartimento di Fisica, Politecnico di Milano
kn-affil=

affil-num=23
en-affil=Cambridge Graphene Centre, University of Cambridge
kn-affil=

affil-num=24
en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry
kn-affil=

affil-num=25
en-affil=Institute of Environmental Medicine, Karolinska Institutet
kn-affil=

affil-num=26
en-affil=Istituto Zooprofilattico Sperimentale della Sardegna
kn-affil=

affil-num=27
en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences
kn-affil=
en-keyword=2D materials
kn-keyword=2D materials
en-keyword=biocompatibility
kn-keyword=biocompatibility
en-keyword=immune system
kn-keyword=immune system
en-keyword=porcine model
kn-keyword=porcine model
en-keyword=toxicity
kn-keyword=toxicity
END

start-ver=1.4
cd-journal=joma
no-vol=36
cd-vols=
no-issue=12
article-no=
start-page=4932
end-page=4951
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241021
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The leucine-rich repeat receptor kinase QSK1 regulates PRR-RBOHD complexes targeted by the bacterial effector HopF2Pto
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Plants detect pathogens using cell-surface pattern recognition receptors (PRRs) such as ELONGATION Factor-TU (EF-TU) RECEPTOR (EFR) and FLAGELLIN SENSING 2 (FLS2), which recognize bacterial EF-Tu and flagellin, respectively. These PRRs belong to the leucine-rich repeat receptor kinase (LRR-RK) family and activate the production of reactive oxygen species via the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD). The PRR-RBOHD complex is tightly regulated to prevent unwarranted or exaggerated immune responses. However, certain pathogen effectors can subvert these regulatory mechanisms, thereby suppressing plant immunity. To elucidate the intricate dynamics of the PRR-RBOHD complex, we conducted a comparative coimmunoprecipitation analysis using EFR, FLS2, and RBOHD in Arabidopsis thaliana. We identified QIAN SHOU KINASE 1 (QSK1), an LRR-RK, as a PRR-RBOHD complex-associated protein. QSK1 downregulated FLS2 and EFR abundance, functioning as a negative regulator of PRR-triggered immunity (PTI). QSK1 was targeted by the bacterial effector HopF2Pto, a mono-ADP ribosyltransferase, reducing FLS2 and EFR levels through both transcriptional and transcription-independent pathways, thereby inhibiting PTI. Furthermore, HopF2Pto transcriptionally downregulated PROSCOOP genes encoding important stress-regulated phytocytokines and their receptor MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2. Importantly, HopF2Pto requires QSK1 for its accumulation and virulence functions within plants. In summary, our results provide insights into the mechanism by which HopF2Pto employs QSK1 to desensitize plants to pathogen attack.
en-copyright=
kn-copyright=

en-aut-name=GotoYukihisa
en-aut-sei=Goto
en-aut-mei=Yukihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KadotaYasuhiro
en-aut-sei=Kadota
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MbengueMalick
en-aut-sei=Mbengue
en-aut-mei=Malick
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=LewisJennifer D
en-aut-sei=Lewis
en-aut-mei=Jennifer D
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MatsuiHidenori
en-aut-sei=Matsui
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MakiNoriko
en-aut-sei=Maki
en-aut-mei=Noriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NgouBruno Pok Man
en-aut-sei=Ngou
en-aut-mei=Bruno Pok Man
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SklenarJan
en-aut-sei=Sklenar
en-aut-mei=Jan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=DerbyshirePaul
en-aut-sei=Derbyshire
en-aut-mei=Paul
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ShibataArisa
en-aut-sei=Shibata
en-aut-mei=Arisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=IchihashiYasunori
en-aut-sei=Ichihashi
en-aut-mei=Yasunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=GuttmanDavid S
en-aut-sei=Guttman
en-aut-mei=David S
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=NakagamiHirofumi
en-aut-sei=Nakagami
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=SuzukiTakamasa
en-aut-sei=Suzuki
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=MenkeFrank L H
en-aut-sei=Menke
en-aut-mei=Frank L H
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=RobatzekSilke
en-aut-sei=Robatzek
en-aut-mei=Silke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=DesveauxDarrell
en-aut-sei=Desveaux
en-aut-mei=Darrell
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=ZipfelCyril
en-aut-sei=Zipfel
en-aut-mei=Cyril
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=ShirasuKen
en-aut-sei=Shirasu
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

affil-num=1
en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) 
kn-affil=

affil-num=2
en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) 
kn-affil=

affil-num=3
en-affil=The Sainsbury Laboratory, University of East Anglia
kn-affil=

affil-num=4
en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto
kn-affil=

affil-num=5
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=6
en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) 
kn-affil=

affil-num=7
en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) 
kn-affil=

affil-num=8
en-affil=The Sainsbury Laboratory, University of East Anglia
kn-affil=

affil-num=9
en-affil=The Sainsbury Laboratory, University of East Anglia
kn-affil=

affil-num=10
en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) 
kn-affil=

affil-num=11
en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) 
kn-affil=

affil-num=12
en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto
kn-affil=

affil-num=13
en-affil=Plant Proteomics Research Unit, RIKEN CSRS
kn-affil=

affil-num=14
en-affil=College of Bioscience and Biotechnology, Chubu University
kn-affil=

affil-num=15
en-affil=The Sainsbury Laboratory, University of East Anglia
kn-affil=

affil-num=16
en-affil=The Sainsbury Laboratory, University of East Anglia
kn-affil=

affil-num=17
en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto
kn-affil=

affil-num=18
en-affil=Institute of Plant and Microbial Biology, Zurich-Basel Plant Science Center, University of Zurich
kn-affil=

affil-num=19
en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) 
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=177
cd-vols=
no-issue=4
article-no=
start-page=e70396
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202507
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=CNGC2 Negatively Regulates Stomatal Closure and Is Not Required for flg22- and H2O2-Induced Guard Cell [Ca2+]cyt Elevation in Arabidopsis thaliana
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=In guard cells, cytosolic Ca2+ acts as a second messenger that mediates abscisic acid (ABA)- and pathogen-associated molecular pattern (PAMP)-induced stomatal closure. It was reported that Arabidopsis cyclic nucleotide-gated ion channel 2 (CNGC2) functions as hydrogen peroxide (H2O2)- and PAMP-activated Ca2+-permeable channels at the plasma membrane of mesophyll cells and mediates Ca2+-dependent PAMP-triggered immunity. In this study, we examined the role of CNGC2 in the regulation of stomatal movement because CNGC2 is also expressed in guard cells. We found that stomata of the CNGC2 disruption mutant cngc2-3 are constitutively closed even in the absence of ABA or the flagellar-derived PAMP, flg22. Consistently, leaf temperatures of the cngc2-3 mutant were higher than those of wild-type (WT) plants. The stomatal phenotype of the cngc2-3 mutant was restored by complementation with wild-type CNGC2 under the control of the guard cell preferential promoter, pGC1. Elevation of cytosolic free Ca2+ concentration in guard cells induced by flg22 and H2O2 remained intact in the cngc2-3 mutant. The introduction of the ost1-3 mutation into the cngc2-3 background did not alter the stomatal phenotype. However, the stomatal phenotype of the cngc2-3 mutant was successfully rescued in the double disruption mutant cngc2-3aba2-2. Taken together, these results suggest that CNGC2 negatively regulates stomatal closure response and does not function as flg22– and H2O2-activated Ca2+ channels in guard cells. Though CNGC2 is responsive for H2O2- and flg22-induced [Ca2+]cyt elevation in mesophyll cells, the involvement of CNGC2 in the response to H2O2 and flg22 in guard cells is questionable.
en-copyright=
kn-copyright=

en-aut-name=AkterRojina
en-aut-sei=Akter
en-aut-mei=Rojina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=InoueYasuhiro
en-aut-sei=Inoue
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MasumotoSaori
en-aut-sei=Masumoto
en-aut-mei=Saori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MimataYoshiharu
en-aut-sei=Mimata
en-aut-mei=Yoshiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MatsuuraTakakazu
en-aut-sei=Matsuura
en-aut-mei=Takakazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MoriIzumi C.
en-aut-sei=Mori
en-aut-mei=Izumi C.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NakamuraToshiyuki
en-aut-sei=Nakamura
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NakamuraYoshimasa
en-aut-sei=Nakamura
en-aut-mei=Yoshimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MurataYoshiyuki
en-aut-sei=Murata
en-aut-mei=Yoshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MunemasaShintaro
en-aut-sei=Munemasa
en-aut-mei=Shintaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=3
en-affil=Faculty of Agriculture, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=5
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=6
en-affil=
kn-affil=

affil-num=7
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=8
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=9
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=10
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=
en-keyword=calcium signaling
kn-keyword=calcium signaling
en-keyword=CNGC
kn-keyword=CNGC
en-keyword=stomata
kn-keyword=stomata
END

start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=5
article-no=
start-page=733
end-page=747
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202503
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A PRA-Rab trafficking machinery modulates NLR immune receptor plasma membrane microdomain anchoring and blast resistance in rice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Nucleotide-binding leucine-rich repeat (NLR) receptors mediate pathogen effector-triggered immunity (ETI) in plants, and a subclass of NLRs are hypothesized to function at the plasma membrane (PM). However, how NLR traffic and PM delivery are regulated during immune responses remains largely unknown. The rice NLR PigmR confers broad-spectrum resistance to the blast fungus Magnaporthe oryzae. Here, we report that a PRA (Prenylated Rab acceptor) protein, PIBP4 (PigmR-INTERACTING and BLAST RESISTANCE PROTEIN 4), interacts with both PigmR and the active form of the Rab GTPase, OsRab5a, thereby loads a portion of PigmR on trafficking vesicles that target to PM microdomains. Microdomain-localized PigmR interacts with and activates the small GTPase OsRac1, which triggers reactive oxygen species signaling and hypersensitive response, leading to immune responses against blast infection. Thus, our study discovers a previously unknown mechanism that deploys a PRA-Rab protein delivering hub to ensure ETI, linking the membrane trafficking machinery with NLR function and immune activation in plants.
en-copyright=
kn-copyright=

en-aut-name=LiangDi
en-aut-sei=Liang
en-aut-mei=Di
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YangDongyong
en-aut-sei=Yang
en-aut-mei=Dongyong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LiTai
en-aut-sei=Li
en-aut-mei=Tai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZhuZhe
en-aut-sei=Zhu
en-aut-mei=Zhe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YanBingxiao
en-aut-sei=Yan
en-aut-mei=Bingxiao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HeYang
en-aut-sei=He
en-aut-mei=Yang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=LiXiaoyuan
en-aut-sei=Li
en-aut-mei=Xiaoyuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ZhaiKeran
en-aut-sei=Zhai
en-aut-mei=Keran
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=LiuJiyun
en-aut-sei=Liu
en-aut-mei=Jiyun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KawanoYoji
en-aut-sei=Kawano
en-aut-mei=Yoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=DengYiwen
en-aut-sei=Deng
en-aut-mei=Yiwen
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=WuXu Na
en-aut-sei=Wu
en-aut-mei=Xu Na
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=LiuJunzhong
en-aut-sei=Liu
en-aut-mei=Junzhong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=HeZuhua
en-aut-sei=He
en-aut-mei=Zuhua
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
kn-affil=

affil-num=2
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
kn-affil=

affil-num=3
en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University
kn-affil=

affil-num=4
en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University
kn-affil=

affil-num=5
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
kn-affil=

affil-num=6
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
kn-affil=

affil-num=7
en-affil=School of Life Science and Technology, ShanghaiTech University
kn-affil=

affil-num=8
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
kn-affil=

affil-num=9
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
kn-affil=

affil-num=10
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=11
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
kn-affil=

affil-num=12
en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University
kn-affil=

affil-num=13
en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University
kn-affil=

affil-num=14
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
kn-affil=
en-keyword=Prenylated Rab acceptor
kn-keyword=Prenylated Rab acceptor
en-keyword=PigmR
kn-keyword=PigmR
en-keyword=Trafficking vesicles
kn-keyword=Trafficking vesicles
en-keyword=OsRab5a
kn-keyword=OsRab5a
en-keyword=Blast resistance
kn-keyword=Blast resistance
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=CTLA-4阻害の抗腫瘍効果はTreg細胞のCTLA-4非依存性免疫抑制機構の活性化によって減弱する
kn-title=Activated CTLA-4-independent immunosuppression of Treg cells disturbs CTLA-4 blockade-mediated antitumor immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=WATANABETomofumi
en-aut-sei=WATANABE
en-aut-mei=Tomofumi
kn-aut-name=渡部智文
kn-aut-sei=渡部
kn-aut-mei=智文
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=樹状細胞の成熟は、腫瘍由来エクソソームを介してp53搭載腫瘍融解アデノウイルスによって誘導され、全身の抗腫瘍免疫を誘導する
kn-title=Dendritic cell maturation is induced by p53‑armed oncolytic adenovirus via tumor‑derived exosomes enhancing systemic antitumor immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=OTANITomoko
en-aut-sei=OTANI
en-aut-mei=Tomoko
kn-aut-name=大谷朋子
kn-aut-sei=大谷
kn-aut-mei=朋子
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=腫瘍融解アデノウイルスによる腹腔内マクロファージの機能的再構築により、胃癌腹膜播種に対する抗腫瘍免疫が回復する
kn-title=Functional remodeling of intraperitoneal macrophages by oncolytic adenovirus restores anti-tumor immunity for peritoneal metastasis of gastric cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=TABUCHIMotoyasu
en-aut-sei=TABUCHI
en-aut-mei=Motoyasu
kn-aut-name=田渕幹康
kn-aut-sei=田渕
kn-aut-mei=幹康
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=79
cd-vols=
no-issue=3
article-no=
start-page=167
end-page=176
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Promising Effectiveness of Combined Chemotherapy and Immunotherapy in Patients with Advanced Non-small Cell Lung Cancer: A Real-World Prospective Observational Study (CS-Lung-003)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=This prospective observational study investigated the clinical status of patients with advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy+an immune checkpoint inhibitor (chemo + IO) as first-line treatment in a real-world setting. The cases of 98 patients treated with chemo + IO were prospectively collected and analyzed for effectiveness and safety. The response rate to chemo + IO was 46.9%, and the disease control rate was 76.5%. The median progression-free survival and overall survival (OS) in the total population were 5.2 and 22.3 months, respectively. The patients positive for PD-L1 (≥ 1%) showed significantly longer OS than the negative group (<1%) (median 26.7 vs. 18.7 months, p=0.04). Pre-existing interstitial lung disease (ILD) was associated with shorter OS than the absence of ILD (median 9.0 vs. 22.6 months, p<0.01). Immunerelated adverse events (irAEs) were observed in 28 patients (28.6%). The most frequent irAE was ILD (n=11); Grade 1 (n=1 patient), G2 (n=5), G3 (n=4), and only a single patient with a G5 irAE. In this CS-Lung-003 study, first-line chemo + IO in a real-world setting showed good effectiveness, comparable to that observed in international clinical trials. In real-world practice, chemo + IO is a promising and steadfast strategy.
en-copyright=
kn-copyright=

en-aut-name=KanajiNobuhiro
en-aut-sei=Kanaji
en-aut-mei=Nobuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TsubataYukari
en-aut-sei=Tsubata
en-aut-mei=Yukari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NakaoMika
en-aut-sei=Nakao
en-aut-mei=Mika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OkunoTakae
en-aut-sei=Okuno
en-aut-mei=Takae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakataKenji
en-aut-sei=Takata
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KodaniMasahiro
en-aut-sei=Kodani
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YamasakiMasahiro
en-aut-sei=Yamasaki
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujitakaKazunori
en-aut-sei=Fujitaka
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KubotaTetsuya
en-aut-sei=Kubota
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=InoueMasaaki
en-aut-sei=Inoue
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=WatanabeNaoki
en-aut-sei=Watanabe
en-aut-mei=Naoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=CS-Lung-003 Investigator
en-aut-sei=CS-Lung-003 Investigator
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

affil-num=1
en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University
kn-affil=

affil-num=2
en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center
kn-affil=

affil-num=3
en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine
kn-affil=

affil-num=4
en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine
kn-affil=

affil-num=5
en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine
kn-affil=

affil-num=6
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University
kn-affil=

affil-num=9
en-affil=Department of Respiratory Disease, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital
kn-affil=

affil-num=10
en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
kn-affil=

affil-num=11
en-affil=Department of Respiratory Medicine and Allergology, Kochi University
kn-affil=

affil-num=12
en-affil=Department of Chest Surgery, Shimonoseki City Hospital
kn-affil=

affil-num=13
en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University
kn-affil=

affil-num=14
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=15
en-affil=
kn-affil=
en-keyword=non-small cell lung cancer
kn-keyword=non-small cell lung cancer
en-keyword=real-world
kn-keyword=real-world
en-keyword=first-line
kn-keyword=first-line
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=combined immunotherapy
kn-keyword=combined immunotherapy
END

start-ver=1.4
cd-journal=joma
no-vol=79
cd-vols=
no-issue=3
article-no=
start-page=157
end-page=166
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 μg/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3.
en-copyright=
kn-copyright=

en-aut-name=HatipogluOmer Faruk
en-aut-sei=Hatipoglu
en-aut-mei=Omer Faruk
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishinakaTakashi
en-aut-sei=Nishinaka
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YaykasliKursat Oguz
en-aut-sei=Yaykasli
en-aut-mei=Kursat Oguz
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MoriShuji
en-aut-sei=Mori
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WatanabeMasahiro
en-aut-sei=Watanabe
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ToyomuraTakao
en-aut-sei=Toyomura
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HirohataSatoshi
en-aut-sei=Hirohata
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TakahashiHideo
en-aut-sei=Takahashi
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University
kn-affil=

affil-num=2
en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University
kn-affil=

affil-num=3
en-affil=Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
kn-affil=

affil-num=4
en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University
kn-affil=

affil-num=5
en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University
kn-affil=

affil-num=6
en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University
kn-affil=

affil-num=7
en-affil=Department of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University
kn-affil=

affil-num=10
en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University
kn-affil=
en-keyword=advanced glycation end product
kn-keyword=advanced glycation end product
en-keyword=aging
kn-keyword=aging
en-keyword=cartilage
kn-keyword=cartilage
en-keyword=collagen
kn-keyword=collagen
en-keyword=aggrecan
kn-keyword=aggrecan
END

start-ver=1.4
cd-journal=joma
no-vol=79
cd-vols=
no-issue=3
article-no=
start-page=147
end-page=155
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immunometabolic Regulation of Innate Immunity in Systemic Lupus Erythematosus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pathogens or their components can induce long-lasting changes in the behavior of innate immune cells, a process analogous to “training” for future threats or environmental adaptation. However, such training can sometimes have unintended consequences, such as the development of autoimmunity. Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease characterized by the production of autoantibodies and progressive organ damage. Innate immunity plays a central role in its pathogenesis, contributing through impaired clearance of apoptotic cells, excessive type I interferon production, and dysregulated formation of neutrophil extracellular traps. Recent studies have revealed that metabolites and nucleic acids derived from mitochondria, a crucial energy production site, directly regulate type I interferon and anti-inflammatory cytokine production. These insights have fueled interest in targeting metabolic pathways as a novel therapeutic approach for SLE, offering promise for improving long-term patient outcomes.
en-copyright=
kn-copyright=

en-aut-name=WatanabeHaruki
en-aut-sei=Watanabe
en-aut-mei=Haruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MatsumotoYoshinori
en-aut-sei=Matsumoto
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=systemic lupus erythematosus
kn-keyword=systemic lupus erythematosus
en-keyword=interferon
kn-keyword=interferon
en-keyword=tricarboxylic acid cycle
kn-keyword=tricarboxylic acid cycle
en-keyword=innate immune memory
kn-keyword=innate immune memory
en-keyword=trained immunity
kn-keyword=trained immunity
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250501
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Xenopus laevis as an infection model for human pathogenic bacteria
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Animal infection models are essential for understanding bacterial pathogenicity and corresponding host immune responses. In this study, we investigated whether juvenile Xenopus laevis could be used as an infection model for human pathogenic bacteria. Xenopus frogs succumbed to intraperitoneal injection containing the human pathogenic bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Listeria monocytogenes. In contrast, non-pathogenic bacteria Bacillus subtilis and Escherichia coli did not induce mortality in Xenopus frogs. The administration of appropriate antibiotics suppressed mortality caused by S. aureus and P. aeruginosa. Strains lacking the agr locus, cvfA (rny) gene, or hemolysin genes in S. aureus, LIPI-1-deleted mutant of L. monocytogenes, which attenuate virulence within mammals, exhibited reduced virulence in Xenopus frogs compared with their respective wild-type counterparts. Bacterial distribution analysis revealed that S. aureus persisted in the blood, liver, heart, and muscles of Xenopus frogs until death. These results suggested that intraperitoneal injection of human pathogenic bacteria induces sepsis-like symptoms in Xenopus frogs, supporting their use as a valuable animal model for evaluating antimicrobial efficacy and identifying virulence genes in various human pathogenic bacteria.
en-copyright=
kn-copyright=

en-aut-name=KuriuAyano
en-aut-sei=Kuriu
en-aut-mei=Ayano
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IshikawaKazuya
en-aut-sei=Ishikawa
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TsuchiyaKohsuke
en-aut-sei=Tsuchiya
en-aut-mei=Kohsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FurutaKazuyuki
en-aut-sei=Furuta
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KaitoChikara
en-aut-sei=Kaito
en-aut-mei=Chikara
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Division of Immunology and Molecular Biology, Cancer Research Institute, Kanazawa University
kn-affil=

affil-num=4
en-affil=Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=animal infection model
kn-keyword=animal infection model
en-keyword=Staphylococcus aureus
kn-keyword=Staphylococcus aureus
en-keyword=Listeria monocytogenes
kn-keyword=Listeria monocytogenes
en-keyword=Pseudomonas aeruginosa
kn-keyword=Pseudomonas aeruginosa
en-keyword=antibiotics efficacy
kn-keyword=antibiotics efficacy
en-keyword=virulence genes
kn-keyword=virulence genes
en-keyword=hemolysin
kn-keyword=hemolysin
END

start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=7
article-no=
start-page=192
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250509
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1 alpha, thereby augmenting antitumor effector functions. HIF-1 alpha upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response.<br>
Methods The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms.<br>
Results HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4+ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8+ T cells.<br>
Conclusion Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC.
en-copyright=
kn-copyright=

en-aut-name=ChenYuehua
en-aut-sei=Chen
en-aut-mei=Yuehua
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HamadaYusuke
en-aut-sei=Hamada
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WangYuze
en-aut-sei=Wang
en-aut-mei=Yuze
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TianMiao
en-aut-sei=Tian
en-aut-mei=Miao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=8
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Colorectal cancer
kn-keyword=Colorectal cancer
en-keyword=Microsatellite stable
kn-keyword=Microsatellite stable
en-keyword=Hypoxia-inducible factor
kn-keyword=Hypoxia-inducible factor
en-keyword=Immune checkpoint inhibitors
kn-keyword=Immune checkpoint inhibitors
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=10462
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250326
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) is believed to possess immune evasion capabilities, but it remains unclear whether this immune evasion is related to host gene alternative splicing (AS). In this study, RNA-sequencing revealed significant changes in both AS landscape and transcriptomic profile of macrophages following P. gingivalis infection with/without knockout of gingipain (a unique toxic protease of P. gingivalis). P. gingivalis infection increased the PD-L1 transcripts expression and selectively upregulated a specific coding isoform that more effectively binds to PD-1 on T cells, thereby inhibiting immune function. Biological experiments also detected AS switch of PD-L1 in P. gingivalis-infected or gingipain-treated macrophages. AlphaFold 3 predictions indicated that the protein docking compatibility between PD-1 and P. gingivalis-upregulated PD-L1 isoform was over 80% higher than another coding isoform. These findings suggest that P. gingivalis employs gingipain to modulate the AS of PD-L1, facilitating immune evasion.
en-copyright=
kn-copyright=

en-aut-name=ZhengYilin
en-aut-sei=Zheng
en-aut-mei=Yilin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WangZiyi
en-aut-sei=Wang
en-aut-mei=Ziyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WengYao
en-aut-sei=Weng
en-aut-mei=Yao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SitosariHeriati
en-aut-sei=Sitosari
en-aut-mei=Heriati
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HeYuhan
en-aut-sei=He
en-aut-mei=Yuhan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ZhangXiu
en-aut-sei=Zhang
en-aut-mei=Xiu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ShiotsuNoriko
en-aut-sei=Shiotsu
en-aut-mei=Noriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=FukuharaYoko
en-aut-sei=Fukuhara
en-aut-mei=Yoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IkegameMika
en-aut-sei=Ikegame
en-aut-mei=Mika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OkamuraHirohiko
en-aut-sei=Okamura
en-aut-mei=Hirohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University
kn-affil=

affil-num=7
en-affil=Comprehensive Dental Clinic, Okayama University Hospital, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University
kn-affil=
en-keyword=Porphyromonas gingivalis
kn-keyword=Porphyromonas gingivalis
en-keyword=Gingipain
kn-keyword=Gingipain
en-keyword=Macrophage
kn-keyword=Macrophage
en-keyword=Alternative splicing
kn-keyword=Alternative splicing
en-keyword=PD-L1
kn-keyword=PD-L1
en-keyword=Immune evasion
kn-keyword=Immune evasion
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=
article-no=
start-page=1537615
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250311
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PARylation-mediated post-transcriptional modifications in cancer immunity and immunotherapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Poly-ADP-ribosylation (PARylation) is a post-translational modification in which ADP-ribose is added to substrate proteins. PARylation is mediated by a superfamily of ADP-ribosyl transferases known as PARPs and influences a wide range of cellular functions, including genome integrity maintenance, and the regulation of proliferation and differentiation. We and others have recently reported that PARylation of SH3 domain-binding protein 2 (3BP2) plays a role in bone metabolism, immune system regulation, and cytokine production. Additionally, PARylation has recently gained attention as a target for cancer treatment. In this review, we provide an overview of PARylation, its involvement in several signaling pathways related to cancer immunity, and the potential of combination therapies with PARP inhibitors and immune checkpoint inhibitors.
en-copyright=
kn-copyright=

en-aut-name=MatsumotoKazuya
en-aut-sei=Matsumoto
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MatsumotoYoshinori
en-aut-sei=Matsumoto
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=PARylation
kn-keyword=PARylation
en-keyword=cancer
kn-keyword=cancer
en-keyword=post-transcriptional regulation
kn-keyword=post-transcriptional regulation
en-keyword=ubiquitylation
kn-keyword=ubiquitylation
en-keyword=immune system
kn-keyword=immune system
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=e70053
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250323
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Association of blood carboxyhemoglobin levels with mortality and neurological outcomes in out-of-hospital cardiac arrest
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Carbon monoxide (CO), produced endogenously by heme oxygenase-1, plays a crucial role in the immune system by mitigating cellular damage under stress. However, the significance of carboxyhemoglobin (COHb) levels after out-of-hospital cardiac arrest (OHCA) is not well understood. This study aimed to explore the association between COHb levels at hospital arrival and within the first 24 h post-arrival with 30-day mortality and neurological outcomes in patients who experienced OHCA.<br>
Methods: This single-center, retrospective study analyzed data from adult patients who experienced OHCA seen at Okayama University Hospital from 2019 to 2023. The patients were assigned to one of two study groups based on COHb levels (0.0% or >= 0.1%) upon hospital arrival. The primary outcome was 30-day mortality.<br>
Results: Among the 560 eligible patients who experienced OHCA, 284 (50.7%) were in the COHb 0.0% group and 276 (49.3%) were in the COHb >= 0.1% group. The 30-day mortality was significantly higher in the COHb 0.0% group compared to the COHb >= 0.1% group (264 [92.9%] vs. 233 [84.4%]). Multivariable logistic regression showed that the COHb 0.0% group was associated with 30-day mortality (adjusted ORs: 2.24, 95% CIs: 1.10-4.56). Non-survivors at 30 days who were admitted to the intensive care unit had lower COHb levels at hospital arrival (0.0% vs. 0.2%) and lower mean COHb levels during the first 24 h post-arrival (0.7% vs. 0.9%) compared to survivors.<br>
Conclusions: COHb levels of 0.0% were linked to worse outcomes in patients experiencing OHCA, warranting further research on the prognostic implications of COHb in this context.
en-copyright=
kn-copyright=

en-aut-name=HongoTakashi
en-aut-sei=Hongo
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YumotoTetsuya
en-aut-sei=Yumoto
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NaitoHiromichi
en-aut-sei=Naito
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HiraokaTomohiro
en-aut-sei=Hiraoka
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MurakamiYuya
en-aut-sei=Murakami
en-aut-mei=Yuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ObaraTakafumi
en-aut-sei=Obara
en-aut-mei=Takafumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NojimaTsuyoshi
en-aut-sei=Nojima
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AokageToshiyuki
en-aut-sei=Aokage
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NakaoAtsunori
en-aut-sei=Nakao
en-aut-mei=Atsunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=brain injury
kn-keyword=brain injury
en-keyword=carbon monoxide
kn-keyword=carbon monoxide
en-keyword=carboxyhemoglobin
kn-keyword=carboxyhemoglobin
en-keyword=cardiac arrest
kn-keyword=cardiac arrest
en-keyword=resuscitation
kn-keyword=resuscitation
END

start-ver=1.4
cd-journal=joma
no-vol=85
cd-vols=
no-issue=6
article-no=
start-page=1082
end-page=1096
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250314
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Brain metastasis is a poor prognostic factor in patients with cancer. Despite showing efficacy in many extracranial tumors, immunotherapy with anti–PD-1 mAb or anti–CTLA4 mAb seems to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti–PD-1 and anti–CTLA4 mAbs has a potent antitumor effect on brain metastasis, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. In this study, we analyzed the tumor-infiltrating lymphocytes in murine models of brain metastasis that responded to anti–CTLA4 and anti–PD-1 mAbs. Activated CD4+ T follicular helper (TFH) cells with high CTLA4 expression characteristically infiltrated the intracranial TME, which were activated by combination anti–CTLA4 and anti–PD-1 treatment. The loss of TFH cells suppressed the additive effect of CTLA4 blockade on anti–PD-1 mAb. B-cell–activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo proinflammatory M1-like macrophages, in the intracranial TME induced B-cell and TFH-cell infiltration and activation. Furthermore, the intracranial TME of patients with non–small cell lung cancer featured TFH- and B-cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell cross-talk in the intracranial TME that facilitates an additive antitumor effect of CTLA4 blockade with anti–PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for brain metastases.<br>
Significance: B-cell and CD4+ T follicular helper cell activation via BAFF/APRIL from abundant myeloid cells in the intracranial tumor microenvironment enables a combinatorial effect of CTLA4 and PD-1 blockade in brain metastases.
en-copyright=
kn-copyright=

en-aut-name=NinomiyaToshifumi
en-aut-sei=Ninomiya
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KemmotsuNaoya
en-aut-sei=Kemmotsu
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MukoharaFumiaki
en-aut-sei=Mukohara
en-aut-mei=Fumiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MagariMasaki
en-aut-sei=Magari
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MiyamotoAi
en-aut-sei=Miyamoto
en-aut-mei=Ai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IshinoTakamasa
en-aut-sei=Ishino
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FujiwaraTomohiro
en-aut-sei=Fujiwara
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=YamamotoHidetaka
en-aut-sei=Yamamoto
en-aut-mei=Hidetaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=HayashiHidetoshi
en-aut-sei=Hayashi
en-aut-mei=Hidetoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TachibanaKota
en-aut-sei=Tachibana
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=IshidaJoji
en-aut-sei=Ishida
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=OtaniYoshihiro
en-aut-sei=Otani
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=TanakaShota
en-aut-sei=Tanaka
en-aut-mei=Shota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=OkamotoIsamu
en-aut-sei=Okamoto
en-aut-mei=Isamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

affil-num=1
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Medical Protein Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine
kn-affil=

affil-num=12
en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=14
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=15
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=16
en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=

affil-num=17
en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University
kn-affil=

affil-num=18
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=31
cd-vols=
no-issue=3
article-no=
start-page=102660
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202503
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Intention and potential determinants of COVID-19 vaccination among healthcare workers at a single university hospital in Japan, 2024–2025 pre-season
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Financial accessibility has emerged as a significant barrier to vaccine uptake following the cessation of universal public funding for coronavirus disease 2019 (COVID-19) vaccination programs. This investigation assessed the intention and determinant factors of COVID-19 vaccination among healthcare workers in Japan in the 2024–2025 pre-season.<br>
Methods: A retrospective survey was conducted utilizing data collected from hospital staff at Okayama University Hospital, Japan, to inform the COVID-19 vaccination strategy in October 2024. The analysis evaluated demographic characteristics, vaccine intention, perceived barriers to vaccination, and maximum acceptable out-of-pocket expenditure.<br>
Results: The study population of 3417 respondents comprised 843 medical doctors (24.7 %), 1131 nurses (33.1 %), 320 other medical staff (9.4 %), 286 dental doctors (8.4 %), and 627 administrative officers (18.3 %). At full cost, 2109 (61.7 %) indicated no intention to receive vaccination, while only 4.4 % expressed willingness to be vaccinated and 33.9 % remained undecided. With total self-payment, the vaccination acceptance rates were the highest and lowest among medical doctors (11.4 %) and nurses (1.0 %), respectively. Cost (38.1 %), followed by safety issues (29.5 %) and concerns regarding efficacy or medical necessity (20.3 %), emerged as the primary barrier. The projected vaccination intention increased to 43.9 % and 54.9 % at reduced self-pay costs of 3000 JPY and 5000 JPY, respectively.<br>
Conclusions: Addressing financial constraints through policy interventions could be effective strategies in increasing overall vaccination coverage among healthcare workers. In addition, providing tailored education on vaccine safety, efficacy, and necessity may further facilitate increased vaccine uptake within this critical population.
en-copyright=
kn-copyright=

en-aut-name=HagiyaHideharu
en-aut-sei=Hagiya
en-aut-mei=Hideharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FujitaYasushi
en-aut-sei=Fujita
en-aut-mei=Yasushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KiguchiTakashi
en-aut-sei=Kiguchi
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ManabeYohei
en-aut-sei=Manabe
en-aut-mei=Yohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Infectious Diseases, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Division of Infection Prevention and Control, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Division of Infection Prevention and Control, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Division of Infection Prevention and Control, Okayama University Hospital
kn-affil=
en-keyword=COVID-19
kn-keyword=COVID-19
en-keyword=Immunization
kn-keyword=Immunization
en-keyword=Reimbursement
kn-keyword=Reimbursement
en-keyword=Healthcare workers
kn-keyword=Healthcare workers
en-keyword=Financial support
kn-keyword=Financial support
END

start-ver=1.4
cd-journal=joma
no-vol=79
cd-vols=
no-issue=1
article-no=
start-page=51
end-page=58
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202502
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Photoinitiators Induce Histamine Production in Human Mast Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4´-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro.
en-copyright=
kn-copyright=

en-aut-name=MiuraTaro
en-aut-sei=Miura
en-aut-mei=Taro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawasakiYoichi
en-aut-sei=Kawasaki
en-aut-mei=Yoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HamanoHirofumi
en-aut-sei=Hamano
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZamamiYoshito
en-aut-sei=Zamami
en-aut-mei=Yoshito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SendoToshiaki
en-aut-sei=Sendo
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Laboratory of Clinical Pharmacology and Therapeutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University
kn-affil=

affil-num=3
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=photoinitiator
kn-keyword=photoinitiator
en-keyword=ink
kn-keyword=ink
en-keyword=injection
kn-keyword=injection
en-keyword=histamine
kn-keyword=histamine
en-keyword=inflammation
kn-keyword=inflammation
END

start-ver=1.4
cd-journal=joma
no-vol=79
cd-vols=
no-issue=1
article-no=
start-page=1
end-page=7
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202502
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Endothelial Cell Polarity in Health and Disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Endothelial cell polarity is fundamental to the organization and function of blood vessels, influencing processes such as angiogenesis, vascular stability, and response to shear stress. This review elaborates on the molecular mechanisms that regulate endothelial cell polarity, focusing on key players like the PAR polarity complex and Rho family GTPases. These pathways coordinate the front–rear, apical–basal and planar polarity of endothelial cells, which are essential for the proper formation and maintenance of vascular structures. In health, endothelial polarity ensures not only the orderly development of blood vessels, with tip cells adopting distinct polarities during angiogenesis, but also ensures proper vascular integrity and function. In disease states, however, disruptions in polarity contribute to pathologies such as coronary artery disease, where altered planar polarity exacerbates atherosclerosis, and cancer, where disrupted polarity in tumor vasculature leads to abnormal vessel growth and function. Understanding cell polarity and its disruption is fundamental not only to comprehending how cells interact with their microenvironment and organize themselves into complex, organ-specific tissues but also to developing novel, targeted, and therapeutic strategies for a range of diseases, from cardiovascular disorders to malignancies, ultimately improving patient outcomes.
en-copyright=
kn-copyright=

en-aut-name=ThihaMoe
en-aut-sei=Thiha
en-aut-mei=Moe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HikitaTakao
en-aut-sei=Hikita
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakayamaMasanori
en-aut-sei=Nakayama
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=blood vessel
kn-keyword=blood vessel
en-keyword=endothelial cell
kn-keyword=endothelial cell
en-keyword=cell polarity
kn-keyword=cell polarity
en-keyword=atherosclerosis
kn-keyword=atherosclerosis
en-keyword=cancer
kn-keyword=cancer
END

start-ver=1.4
cd-journal=joma
no-vol=121
cd-vols=
no-issue=35
article-no=
start-page=e2320189121
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240821
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell–specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets.
en-copyright=
kn-copyright=

en-aut-name=MukoharaFumiaki
en-aut-sei=Mukohara
en-aut-mei=Fumiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IwataKazuma
en-aut-sei=Iwata
en-aut-mei=Kazuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IshinoTakamasa
en-aut-sei=Ishino
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InozumeTakashi
en-aut-sei=Inozume
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UenoToshihide
en-aut-sei=Ueno
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IkedaHideki
en-aut-sei=Ikeda
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KawaseKatsushige
en-aut-sei=Kawase
en-aut-mei=Katsushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=SaekiYuka
en-aut-sei=Saeki
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=YamashitaKazuo
en-aut-sei=Yamashita
en-aut-mei=Kazuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KawaharaYu
en-aut-sei=Kawahara
en-aut-mei=Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=NakamuraYasuhiro
en-aut-sei=Nakamura
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=Honobe-TabuchiAkiko
en-aut-sei=Honobe-Tabuchi
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=WatanabeHiroko
en-aut-sei=Watanabe
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=DansakoHiromichi
en-aut-sei=Dansako
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=KawamuraTatsuyoshi
en-aut-sei=Kawamura
en-aut-mei=Tatsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=SuzukiYutaka
en-aut-sei=Suzuki
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=HondaHiroaki
en-aut-sei=Honda
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=ManoHiroyuki
en-aut-sei=Mano
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

affil-num=1
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Dermatology, Chiba University Graduate School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University
kn-affil=

affil-num=8
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=

affil-num=9
en-affil=Division of Cell Therapy, Chiba Cancer Research Institute
kn-affil=

affil-num=10
en-affil=Division of Cell Therapy, Chiba Cancer Research Institute
kn-affil=

affil-num=11
en-affil=Department of Dermatology, Chiba University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Department of Dermatology, Chiba University Graduate School of Medicine
kn-affil=

affil-num=13
en-affil=KOTAI Biotechnologies, Inc.
kn-affil=

affil-num=14
en-affil=Department of Dermatology, Chiba University Graduate School of Medicine
kn-affil=

affil-num=15
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=

affil-num=16
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=17
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=18
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=19
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=20
en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa
kn-affil=

affil-num=21
en-affil=Department of Pathology, Tokyo Women's Medical University
kn-affil=

affil-num=22
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=

affil-num=23
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University
kn-affil=

affil-num=24
en-affil=Division of Cell Therapy, Chiba Cancer Research Institute
kn-affil=

affil-num=25
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=cancer immunology
kn-keyword=cancer immunology
en-keyword=somatic mutation
kn-keyword=somatic mutation
en-keyword=T cell
kn-keyword=T cell
en-keyword=tumor-infiltrating lymphocytes
kn-keyword=tumor-infiltrating lymphocytes
END

start-ver=1.4
cd-journal=joma
no-vol=145
cd-vols=
no-issue=1
article-no=
start-page=7
end-page=14
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250101
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Precision Medicine for Patients with Renal Cell Carcinoma Based on Drug-metabolizing Enzyme Expression Levels
kn-title=薬物代謝酵素の発現情報を活用した腎がん治療の個別適正化
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Notable advances have recently been achieved in drug therapies for renal cell carcinoma (RCC). Several tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have been approved for metastatic RCC (mRCC). The current first-line treatment for mRCC involves combination therapies using TKIs and ICIs. However, there is no consensus on which TKI+ICI therapy is best or how to select the appropriate therapy for individual patients with RCC. The kidney expresses various metabolic enzymes, including CYP and uridine diphosphate glucose (UDP)-glucuronosyltransferase (UGT). Although information on CYP and UGT expression in the kidney is limited compared to our understanding of liver expression, the main CYP and UGT subtypes expressed at high levels in the kidney are estimated to be CYP2B6, CYP3A5, CYP4A11, CYP4F2, UGT1A6, UGT1A9, and UGT2B7. In RCC, the expression profiles and levels of these enzymes are somewhat altered compared with normal kidney. The main known subtypes of CYP and UGT in RCC are CYP1B1, CYP3A5, CYP4A11, UGT1A6, UGT1A9, UGT1A10, and UGT2B7. High CYP expression has been reported in several cancers, possibly conferring resistance to anti-cancer drugs including TKIs, due to extensive drug metabolism. Additionally, CYP and UGT expression levels may possibly affect cancer prognosis by metabolizing endogenous substrates, regardless of their role in anti-cancer drug metabolism. In this review, I discuss CYP and UGT expression level profiles in RCC based on previously published papers, including ours, and examine possible relationships between these enzyme expression profiles and treatment outcomes for patients with RCC.
en-copyright=
kn-copyright=

en-aut-name=MatsumotoJun
en-aut-sei=Matsumoto
en-aut-mei=Jun
kn-aut-name=松本准
kn-aut-sei=松本
kn-aut-mei=准
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学学術研究院医歯薬学域（薬学系）疾患薬理制御科学分野
en-keyword=renal cell carcinoma (RCC)
kn-keyword=renal cell carcinoma (RCC)
en-keyword=kidney
kn-keyword=kidney
en-keyword=CYP
kn-keyword=CYP
en-keyword=uridine diphosphate glucose (UDP)-glucuronosyltransferase
kn-keyword=uridine diphosphate glucose (UDP)-glucuronosyltransferase
en-keyword=metabolism
kn-keyword=metabolism
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=2577
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250120
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Plasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital. The pre-treatment plasma levels of S100A8/A9 were analyzed. Eighty-one eligible patients were included (median age, 69 years). Sixty-two patients were men, 54 had adenocarcinoma, 74 had performance status (PS) 0–1, and 47 received ICIs as first-line treatment. The median time to treatment failure (TTF) for ICIs was 5.7 months, and the median overall survival (OS) was 19.6 months. The TTF and OS were worse in patients with high plasma S100A8/A9 levels (≥ 2.475 µg/mL) (median TTF: 4.3 vs. 8.5 months, p = 0.009; median OS: 15.4 vs. 38.0 months, p = 0.001). Multivariate analysis revealed that PS ≥ 2, liver metastasis, and high plasma S100A8/A9 levels were significantly associated with short TTF and OS. In conclusion, plasma S100A8/A9 level may have a limited effect on ICI therapy for NSCLC.
en-copyright=
kn-copyright=

en-aut-name=KuribayashiTadahiro
en-aut-sei=Kuribayashi
en-aut-mei=Tadahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=12
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=S100A8/A9
kn-keyword=S100A8/A9
en-keyword=Lung cancer
kn-keyword=Lung cancer
en-keyword=Immune checkpoint inhibitors
kn-keyword=Immune checkpoint inhibitors
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=21
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241225
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Gut-Kidney Axis in Chronic Kidney Diseases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The gut-kidney axis represents the complex interactions between the gut microbiota and kidney, which significantly impact the progression of chronic kidney disease (CKD) and overall patient health. In CKD patients, imbalances in the gut microbiota promote the production of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which impair renal function and contribute to systemic inflammation. Mechanisms like endotoxemia, immune activation and oxidative stress worsen renal damage by activating pro-inflammatory and oxidative pathways. Insights into these mechanisms highlight the impact of gut-derived metabolites, bacterial translocation, and immune response changes on kidney health, suggesting new potential approaches for CKD treatment. Clinical applications, such as dietary interventions, prebiotics, probiotics and fecal microbiota transplantation, are promising in adjusting the gut microbiota to alleviate CKD symptoms and slow disease progression. Current research highlights the clinical relevance of the gut-kidney axis, but further study is essential to clarify these mechanisms' diagnostic biomarkers and optimize therapeutic interventions. This review emphasizes the importance of an integrated approach to CKD management, focusing on the gut microbiota as a therapeutic target to limit kidney injury.
en-copyright=
kn-copyright=

en-aut-name=TsujiKenji
en-aut-sei=Tsuji
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=UchidaNaruhiko
en-aut-sei=Uchida
en-aut-mei=Naruhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakanohHiroyuki
en-aut-sei=Nakanoh
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FukushimaKazuhiko
en-aut-sei=Fukushima
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HaraguchiSoichiro
en-aut-sei=Haraguchi
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KitamuraShinji
en-aut-sei=Kitamura
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=gut-kidney axis
kn-keyword=gut-kidney axis
en-keyword=chronic kidney disease
kn-keyword=chronic kidney disease
en-keyword=uremic toxin
kn-keyword=uremic toxin
en-keyword=dysbiosis
kn-keyword=dysbiosis
en-keyword=gut microbiota
kn-keyword=gut microbiota
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=
article-no=
start-page=1439705
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241211
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=HOMA-beta independently predicts survival in patients with advanced cancer on treatment with immune checkpoint inhibitors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Although immune checkpoint inhibitors (ICIs) are effective cancer drugs, ICI-induced diabetes is a rare but a life-threatening adverse event for patients. The deleterious action of ICI on pancreatic beta-cell function is a concern. However, the influence of ICI on insulin synthesis and secretion in patients with cancer without diabetes remains unknown. <br>
Methods: This study included 87 patients diagnosed with advanced cancer. Glucose metabolism markers (HbA1c, HOMA-IR) and indicators of insulin secretory capacity (HOMA-beta, C-peptide) were prospectively evaluated in patients with ICI-treated cancers to determine their association with cancer prognosis. <br>
Results: Patients with overall survival (OS) >= 7 months had substantially higher HOMA-beta levels at baseline (p=0.008) and 1 month after ICI administration (p=0.006) compared to those with OS <7 months. The median OS was significantly longer in patients with HOMA-beta >= 64.24 (13 months, 95%CI: 5.849-20.151, 37 events) than in those with HOMA-beta < 64.24 (5 months, 95%CI: 3.280-6.720, 50 events) (p=0.013). Further, the median progression-free survival (PFS) was significantly longer in patients with HOMA-beta >= 66.43 (4 months, 95%CI: 3.073-4.927, 33 events) than in those with HOMA-beta < 66.43 (2 months, 95%CI: 1.410-2.590, 54 events) (p=0.025). Additionally, multivariable logistic regression analysis revealed that a HOMA-beta value >= 64.24 independently predicted longer OS in ICI-treated patients. <br>
Conclusions: Pre-ICI HOMA-beta level is linked to longer OS in ICI-treated patients. This connection is significant and shows that insulin secretory capacity may predict ICI efficacy.
en-copyright=
kn-copyright=

en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakamotoAtsushi
en-aut-sei=Takamoto
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KanzakiHiromitsu
en-aut-sei=Kanzaki
en-aut-mei=Hiromitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NodaYohei
en-aut-sei=Noda
en-aut-mei=Yohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KagawaSyunsuke
en-aut-sei=Kagawa
en-aut-mei=Syunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Urology, Fukuyama City Hospital
kn-affil=

affil-num=4
en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital
kn-affil=

affil-num=5
en-affil=Department of Urology, Fukuyama City Hospital
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=anti-PD1 immune checkpoint inhibitors
kn-keyword=anti-PD1 immune checkpoint inhibitors
en-keyword= insulin secretory capacity
kn-keyword= insulin secretory capacity
en-keyword= cancer prognosis
kn-keyword= cancer prognosis
en-keyword= insulin secretion
kn-keyword= insulin secretion
en-keyword= glucose metabolism markers
kn-keyword= glucose metabolism markers
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=24
article-no=
start-page=2045
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241211
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=iPSC-Derived Biological Pacemaker-From Bench to Bedside
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node's natural pacemaking function, providing a more physiological approach to rhythm control. These cells can differentiate into cardiomyocytes capable of autonomous electrical activity, integrating into heart tissue. However, challenges such as achieving cellular maturity, long-term functionality, and immune response remain significant barriers to clinical translation. Future research should focus on refining gene-editing techniques, optimizing differentiation, and developing scalable production processes to enhance the safety and effectiveness of these biological pacemakers. With further advancements, iPSC-derived pacemakers could offer a patient-specific, durable alternative for cardiac rhythm management. This review discusses key advancements in differentiation protocols and preclinical studies, demonstrating their potential in treating dysrhythmias.
en-copyright=
kn-copyright=

en-aut-name=VoQuan Duy
en-aut-sei=Vo
en-aut-mei=Quan Duy
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NakamuraKazufumi
en-aut-sei=Nakamura
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SaitoYukihiro
en-aut-sei=Saito
en-aut-mei=Yukihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IidaToshihiro
en-aut-sei=Iida
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YoshidaMasashi
en-aut-sei=Yoshida
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AmiokaNaofumi
en-aut-sei=Amioka
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AkagiSatoshi
en-aut-sei=Akagi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MiyoshiToru
en-aut-sei=Miyoshi
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YuasaShinsuke
en-aut-sei=Yuasa
en-aut-mei=Shinsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular Medicine, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Cardiovascular Medicine, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=sinoatrial node
kn-keyword=sinoatrial node
en-keyword=HCN channels
kn-keyword=HCN channels
en-keyword=induced pluripotent stem cell
kn-keyword=induced pluripotent stem cell
END

start-ver=1.4
cd-journal=joma
no-vol=169
cd-vols=
no-issue=1
article-no=
start-page=e16291
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241222
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Exploring the Role of Ccn3 in Type III Cell of Mice Taste Buds
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Different taste cells express unique cell-type markers, enabling researchers to distinguish them and study their functional differentiation. Using single-cell RNA-Seq of taste cells in mouse fungiform papillae, we found that Cellular Communication Network Factor 3 (Ccn3) was highly expressed in Type III taste cells but not in Type II taste cells. Ccn3 is a protein-coding gene involved in various biological processes, such as cell proliferation, angiogenesis, tumorigenesis, and wound healing. Therefore, in this study, we aimed to explore the expression and function of Ccn3 in mouse taste bud cells. Using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry (IHC), we confirmed that Ccn3 was predominantly expressed in Type III taste cells. Through IHC, quantitative real-time RT-PCR, gustatory nerve recordings, and short-term lick tests, we observed that Ccn3 knockout (Ccn3-KO) mice did not exhibit any significant differences in the expression of taste cell markers and taste responses compared to wild-type controls. To explore the function of Ccn3 in taste cells, bioinformatics analyses were conducted and predicted possible roles of Ccn3 in tissue regeneration, perception of pain, protein secretion, and immune response. Among them, an immune function is the most plausible based on our experimental results. In summary, our study indicates that although Ccn3 is strongly expressed in Type III taste cells, its knockout did not influence the basic taste response, but bioinformatics provided valuable insights into the possible role of Ccn3 in taste buds and shed light on future research directions.
en-copyright=
kn-copyright=

en-aut-name=WangKuanyu
en-aut-sei=Wang
en-aut-mei=Kuanyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MitohYoshihiro
en-aut-sei=Mitoh
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HorieKengo
en-aut-sei=Horie
en-aut-mei=Kengo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YoshidaRyusuke
en-aut-sei=Yoshida
en-aut-mei=Ryusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=bioinformatics
kn-keyword=bioinformatics
en-keyword=Ccn3
kn-keyword=Ccn3
en-keyword=Type III taste cell
kn-keyword=Type III taste cell
END

start-ver=1.4
cd-journal=joma
no-vol=31
cd-vols=
no-issue=2
article-no=
start-page=102554
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241105
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Human Papillomavirus vaccination awareness and uptake among healthcare students in Japan
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: The vaccination rate for HPV (Human Papillomavirus) has remained significantly low in Japan because of the administrative suspension of active recommendation. This study investigates the awareness and uptake of the HPV vaccine among healthcare students in Japan following the reinstatement of active recommendation for young women in April 2022.<br>
Methods: A web-based survey was administered to 2567 healthcare students from Okayama and Shujitsu Universities in Japan in July 2023. The survey assessed participants' backgrounds, immunization status, awareness of vaccine recommendations, and knowledge of cervical cancer across various demographics, including sex, academic year, and department (Medicine, Health Science, Pharmaceutical, and Dentistry).<br>
Results: The response rate was 36.3 % (933 students; 181 male, 739 female, and 13 unspecified gender). The overall immunization rate among female students was 55.6 %, with higher rates observed in medical (73.8 %) and dental (63.0 %) students. Awareness of the government's change in vaccine recommendation was notably high among female and senior male students. Over half of the female students (54.7 %) reported receiving vaccinations based on their parents' advice. Among those unvaccinated but interested in future immunization, concerns about adverse reactions (47.4 %) and challenges in scheduling vaccinations (29.1 %) were predominant.<br>
Conclusion: Healthcare students exhibited a higher HPV vaccination rate than the general population. Ongoing education to improve vaccine literacy is crucial for augmenting HPV vaccination rates in Japan.
en-copyright=
kn-copyright=

en-aut-name=ShimbeMadoka
en-aut-sei=Shimbe
en-aut-mei=Madoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OtsukaYuki
en-aut-sei=Otsuka
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HagiyaHideharu
en-aut-sei=Hagiya
en-aut-mei=Hideharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YamadaYoichi
en-aut-sei=Yamada
en-aut-mei=Yoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OtsukaFumio
en-aut-sei=Otsuka
en-aut-mei=Fumio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Infectious Diseases, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=School of Pharmacy, Shujitsu University
kn-affil=

affil-num=5
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Cervical cancer
kn-keyword=Cervical cancer
en-keyword=Human Papillomavirus
kn-keyword=Human Papillomavirus
en-keyword=Immunization
kn-keyword=Immunization
en-keyword=Vaccine literacy
kn-keyword=Vaccine literacy
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=1
article-no=
start-page=28
end-page=36
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202501
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Local Control of Conjunctival Malignant Melanoma by Proton Beam Therapy in a Patient With No Metastasis in Six Years From in Situ to Nodular Lesions
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Conjunctival malignant melanoma is extremely rare, with no standard of care established at moment. Here we report a 65-year-old woman, as a hepatitis B virus (HBV) carrier, who presented concurrently a liver mass and lower bulbar conjunctival pigmented lesions in the right eye. Needle liver biopsy and excisional conjunctival biopsy showed hepatocellular carcinoma and conjunctival malignant melanoma in situ, respectively. The priority was given to segmental liver resection for hepatocellular carcinoma after transcatheter arterial chemoembolization. In 1 year, she underwent second and third resection of bulbar conjunctival pigmented lesions, and the pathological examinations constantly showed melanoma in situ. In the course, she showed gradual widening of pigmented lesions to upper bulbar conjunctiva and lower palpebral conjunctiva and lower eyelid. About 2.5 years from the initial visit, the lower eyelid lesion was resected for a genomic DNA-based test of BRAF mutations which turned out to be absent, and then, she began to have intravenous anti-programmed cell death-1 (PD-1), nivolumab every 3 or 4 weeks. She developed iritis in the right eye with conjunctival melanoma as an immune-related adverse event, 3 months after the beginning of nivolumab, and so she used daily topical 0.1% betamethasone eye drops to control the intraocular inflammation. She showed no metastasis in 6 years of follow-up, but later in the course, 5 years from the initial visit, she developed abruptly a non-pigmented nodular lesion on the temporal side of the bulbar conjunctiva along the corneal limbus, accompanied by two pigmented nodular lesions in the upper and lower eyelids in a few months. She thus, underwent proton beam therapy toward the conjunctival melanoma and achieved the successful local control. Proton beam therapy is a treatment option in place of orbital exenteration, and multidisciplinary team collaboration is desirable to achieve better cosmetic and functional outcomes in conjunctival malignant melanoma.
en-copyright=
kn-copyright=

en-aut-name=MatsuoToshihiko
en-aut-sei=Matsuo
en-aut-mei=Toshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OgataTakeshi
en-aut-sei=Ogata
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WakiTakahiro
en-aut-sei=Waki
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TachibanaKota
en-aut-sei=Tachibana
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujiTomokazu
en-aut-sei=Fuji
en-aut-mei=Tomokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AdachiTakuya
en-aut-sei=Adachi
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YamasakiOsamu
en-aut-sei=Yamasaki
en-aut-mei=Osamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Regenerative and Reconstructive Medicine (Ophthalmology), Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital
kn-affil=

affil-num=3
en-affil=Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital
kn-affil=

affil-num=4
en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Ocular surface
kn-keyword=Ocular surface
en-keyword=Conjunctiva
kn-keyword=Conjunctiva
en-keyword=Malignant melanoma
kn-keyword=Malignant melanoma
en-keyword=Proton beam therapy
kn-keyword=Proton beam therapy
en-keyword=Nivolumab
kn-keyword=Nivolumab
en-keyword=PD-1 inhibitor
kn-keyword=PD-1 inhibitor
en-keyword=Immune checkpoint inhibitor
kn-keyword=Immune checkpoint inhibitor
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=23
article-no=
start-page=4089
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241206
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Frequency and Significance of Body Weight Loss During Immunochemotherapy in Patients with Advanced Non-Small Cell Lung Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Limited data are available on the frequency and significance of body weight loss during cancer therapy. This study investigated the frequency of patients who experienced body weight loss during immune checkpoint inhibitor (ICI) plus chemotherapy for advanced non-small cell lung cancer (NSCLC) and the impact of weight loss on treatment outcomes. Methods: Using the clinical data of 370 patients with NSCLC who received a combination of ICI and chemotherapy at 13 institutions, this study investigated the frequency of body weight loss > 5% during treatment and determined the impact of body weight loss on patient outcomes. Results: Of the 370 included patients, 141 (38.1%) lost more than 5% of their body weight during ICI plus chemotherapy (WL group). The 2-month landmark analysis showed that patients who experienced body weight loss of >5% during treatment had worse overall survival (OS) and progression-free survival (PFS) than those who did not (OS 14.0 and 31.1 months in the WL non-WL groups, respectively, p < 0.001; PFS 6.8 and 10.9 months in the WL non-WL groups, respectively, p = 0.002). Furthermore, a negative impact of body weight loss on survival was observed even in those who had obesity (body mass index [BMI] >= 25.0) at the start of therapy (OS 12.8 and 25.4 months in the WL non-WL groups, respectively, p < 0.001; PFS 5.7 and 10.7 months in the WL non-WL groups, respectively, p = 0.038). Conclusions: In conclusion, weight loss of >5% during ICI plus chemotherapy negatively influenced patient outcomes. Further and broader studies should investigate the role of nutritional status, specifically weight change and nutritional support, in responsiveness to ICI plus chemotherapy.
en-copyright=
kn-copyright=

en-aut-name=TaokaMasataka
en-aut-sei=Taoka
en-aut-mei=Masataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YokoyamaToshihide
en-aut-sei=Yokoyama
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InoueKoji
en-aut-sei=Inoue
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TamuraTomoki
en-aut-sei=Tamura
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SatoAkiko
en-aut-sei=Sato
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NakamuraKayo
en-aut-sei=Nakamura
en-aut-mei=Kayo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KawaiHaruyuki
en-aut-sei=Kawai
en-aut-mei=Haruyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=InoueMasaaki
en-aut-sei=Inoue
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=OchiNobuaki
en-aut-sei=Ochi
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujimotoNobukazu
en-aut-sei=Fujimoto
en-aut-mei=Nobukazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=IchikawaHirohisa
en-aut-sei=Ichikawa
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=OzeIsao
en-aut-sei=Oze
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

affil-num=1
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital
kn-affil=

affil-num=4
en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital
kn-affil=

affil-num=5
en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center
kn-affil=

affil-num=6
en-affil=Department of Internal Medicine, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=7
en-affil=Department of Respiratory Medicine, Fukuyama City Hospital
kn-affil=

affil-num=8
en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
kn-affil=

affil-num=9
en-affil=Department of Respiratory Medicine, Japanese Red Cross Himeji Hospital
kn-affil=

affil-num=10
en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital
kn-affil=

affil-num=11
en-affil=Department of Chest Surgery, Shimonoseki City Hospital
kn-affil=

affil-num=12
en-affil=Department of General Internal Medicine 4 , Kawasaki Medical School
kn-affil=

affil-num=13
en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital
kn-affil=

affil-num=14
en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital
kn-affil=

affil-num=15
en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
kn-affil=

affil-num=16
en-affil=Division of Cancer Information and Control, Aichi Cancer Center Research Institute
kn-affil=

affil-num=17
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=18
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
en-keyword=non-small cell lung cancer
kn-keyword=non-small cell lung cancer
en-keyword=body weight loss
kn-keyword=body weight loss
en-keyword=immune checkpoint inhibitors
kn-keyword=immune checkpoint inhibitors
en-keyword=chemotherapy
kn-keyword=chemotherapy
END

start-ver=1.4
cd-journal=joma
no-vol=32
cd-vols=
no-issue=2
article-no=
start-page=292
end-page=305
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241128
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The role of C1orf50 in breast cancer progression and prognosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50’s involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness, and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer.
en-copyright=
kn-copyright=

en-aut-name=OtaniYusuke
en-aut-sei=Otani
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TanakaAtsushi
en-aut-sei=Tanaka
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MaekawaMasaki
en-aut-sei=Maekawa
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=PeñaTirso
en-aut-sei=Peña
en-aut-mei=Tirso
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=RogachevskayaAnna
en-aut-sei=Rogachevskaya
en-aut-mei=Anna
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AndoTeruhiko
en-aut-sei=Ando
en-aut-mei=Teruhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ItanoTakuto
en-aut-sei=Itano
en-aut-mei=Takuto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KatayamaHaruyoshi
en-aut-sei=Katayama
en-aut-mei=Haruyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NakataEiji
en-aut-sei=Nakata
en-aut-mei=Eiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=DoiharaHiroyoshi
en-aut-sei=Doihara
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=RoehrlMichael H.
en-aut-sei=Roehrl
en-aut-mei=Michael H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujimuraAtsushi
en-aut-sei=Fujimura
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School
kn-affil=

affil-num=2
en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School
kn-affil=

affil-num=3
en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School
kn-affil=

affil-num=4
en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School
kn-affil=

affil-num=5
en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School
kn-affil=

affil-num=6
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center
kn-affil=

affil-num=13
en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School
kn-affil=

affil-num=14
en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=C1orf50
kn-keyword=C1orf50
en-keyword=Luminal A breast cancer
kn-keyword=Luminal A breast cancer
en-keyword=Cell cycle
kn-keyword=Cell cycle
en-keyword=Immune evasion
kn-keyword=Immune evasion
en-keyword=YAP/TAZ
kn-keyword=YAP/TAZ
END

start-ver=1.4
cd-journal=joma
no-vol=24
cd-vols=
no-issue=22
article-no=
start-page=7382
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241119
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Microdetection of Nucleocapsid Proteins via Terahertz Chemical Microscope Using Aptamers
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=In the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several methods have been employed, including the detection of viral ribonucleic acid (RNA), nucleocapsid (N) proteins, spike proteins, and antibodies. RNA detection, primarily through polymerase chain reaction tests, targets the viral genetic material, whereas antigen tests detect N and spike proteins to identify active infections. In addition, antibody tests are performed to measure the immune response, indicating previous exposure or vaccination. Here, we used the developed terahertz chemical microscope (TCM) to detect different concentrations of N protein in solution by immobilizing aptamers on a semiconductor substrate (sensing plate) and demonstrated that the terahertz amplitude varies as the concentration of N proteins increases, exhibiting a highly linear relationship with a coefficient of determination (R2 = 0.9881), indicating that a quantitative measurement of N proteins is achieved. By optimizing the reaction conditions, we confirmed that the amplitude of the terahertz wave was independent of the solution volume. Consequently, trace amounts (0.5 μL) of the N protein were successfully detected, and the detection process only took 10 min. Therefore, this study is expected to develop a rapid and sensitive method for the detection and observation of the SARS-CoV-2 virus at a microdetection level. It is anticipated that this research will significantly contribute to reducing the spread of novel infectious diseases in the future.
en-copyright=
kn-copyright=

en-aut-name=DingXue
en-aut-sei=Ding
en-aut-mei=Xue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MurakamiMana
en-aut-sei=Murakami
en-aut-mei=Mana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WangJin
en-aut-sei=Wang
en-aut-mei=Jin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InoueHirofumi
en-aut-sei=Inoue
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KiwaToshihiko
en-aut-sei=Kiwa
en-aut-mei=Toshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=terahertz chemical microscope
kn-keyword=terahertz chemical microscope
en-keyword=aptamers
kn-keyword=aptamers
en-keyword=N protein
kn-keyword=N protein
en-keyword=microdetection
kn-keyword=microdetection
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=免疫不全/調節異常に起因する古典的ホジキンリンパ腫における9p24.1のコピー数解析
kn-title=Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=OHSAWAKumiko
en-aut-sei=OHSAWA
en-aut-mei=Kumiko
kn-aut-name=大澤久美子
kn-aut-sei=大澤
kn-aut-mei=久美子
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=岡山大学大学院保健学研究科
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=非小細胞肺癌における腫瘍免疫状態の指標としての好中球リンパ球比の有用性
kn-title=Utility of neutrophil-to-lymphocyte ratio as an indicator of tumor immune status in non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=IWATAKazuma
en-aut-sei=IWATA
en-aut-mei=Kazuma
kn-aut-name=岩田一馬
kn-aut-sei=岩田
kn-aut-mei=一馬
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=癌関連線維芽細胞を標的とした光免疫療法は腫瘍免疫の再構築に寄与する
kn-title=Fibroblast activation protein-targeted near-infrared photoimmunotherapy depletes immunosuppressive cancer-associated fibroblasts and remodels local tumor immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=AKAIMasaaki
en-aut-sei=AKAI
en-aut-mei=Masaaki
kn-aut-name=赤井正明
kn-aut-sei=赤井
kn-aut-mei=正明
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=p53搭載テロメラーゼ特異的腫瘍溶解アデノウイルスによる膵臓癌における長期抗腫瘍免疫の活性化
kn-title=Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=HASHIMOTOMasashi
en-aut-sei=HASHIMOTO
en-aut-mei=Masashi
kn-aut-name=橋本将志
kn-aut-sei=橋本
kn-aut-mei=将志
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=26
cd-vols=
no-issue=1
article-no=
start-page=198
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241112
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis. <br>
Methods This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage. <br>
Results Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 <= PSL < 7.5 mg, 5.2 for 7.5 <= PSL < 10 mg, 9.0 for 10 <= PSL < 20 mg, and 43.1 for PSL >= 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis. <br>
Conclusion This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use.
en-copyright=
kn-copyright=

en-aut-name=OnishiTakahisa
en-aut-sei=Onishi
en-aut-mei=Takahisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SadaKen-Ei
en-aut-sei=Sada
en-aut-mei=Ken-Ei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HayashiKeigo
en-aut-sei=Hayashi
en-aut-mei=Keigo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MiyawakiYoshia
en-aut-sei=Miyawaki
en-aut-mei=Yoshia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YoshimiRyusuke
en-aut-sei=Yoshimi
en-aut-mei=Ryusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShimojimaYasuhiro
en-aut-sei=Shimojima
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OhnoShigeru
en-aut-sei=Ohno
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KajiyamaHiroshi
en-aut-sei=Kajiyama
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IchinoseKunihiro
en-aut-sei=Ichinose
en-aut-mei=Kunihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SatoShuzo
en-aut-sei=Sato
en-aut-mei=Shuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=FujiwaraMichio
en-aut-sei=Fujiwara
en-aut-mei=Michio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=YajimaNobuyuki
en-aut-sei=Yajima
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KidaTakashi
en-aut-sei=Kida
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=MatsuoYusuke
en-aut-sei=Matsuo
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=NishimuraKeisuke
en-aut-sei=Nishimura
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=YamaneTakashi
en-aut-sei=Yamane
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=Department of Rheumatology, Kakogawa Central City Hospital
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
kn-affil=

affil-num=7
en-affil=Center for Rheumatic Diseases, Yokohama City University Medical Center
kn-affil=

affil-num=8
en-affil=Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University
kn-affil=

affil-num=9
en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences
kn-affil=

affil-num=10
en-affil=Department of Rheumatology, Fukushima Medical University School of Medicine
kn-affil=

affil-num=11
en-affil=Department of Rheumatology, Yokohama Rosai Hospital
kn-affil=

affil-num=12
en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine
kn-affil=

affil-num=13
en-affil=Infammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=14
en-affil=Department of Rheumatology, Tokyo Kyosai Hospital
kn-affil=

affil-num=15
en-affil=Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine
kn-affil=

affil-num=16
en-affil=Department of Rheumatology, Kakogawa Central City Hospital
kn-affil=
en-keyword=Systemic lupus erythematosus
kn-keyword=Systemic lupus erythematosus
en-keyword=Pneumocystis jirovecii pneumonia
kn-keyword=Pneumocystis jirovecii pneumonia
en-keyword=Glucocorticoid
kn-keyword=Glucocorticoid
en-keyword=Immunosuppressant
kn-keyword=Immunosuppressant
en-keyword=Practice pattern
kn-keyword=Practice pattern
END

start-ver=1.4
cd-journal=joma
no-vol=26
cd-vols=
no-issue=1
article-no=
start-page=195
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241111
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Association between discontinuity of care and patient trust in the usual rheumatologist among patients with systemic lupus erythematosus: a cross-sectional study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Patient trust plays a central role in the patient-physician relationship. This study aimed to determine whether the number of outpatient visits with a covering rheumatologist is associated with patient trust in their usual rheumatologist.<br>
Methods Japanese adults with systemic lupus erythematosus (SLE) who met the 1997 revised classification criteria of the American College of Rheumatology and had outpatient visits with a covering rheumatologist in the past year were included.<br>
We used the 11-item Japanese version of the modified Trust in Physician Scale (range 0–100) to assess patient trust. A general linear model with cluster-robust variance estimation was used to evaluate the association between the number of outpatient visits with covering rheumatologists and the patient’s trust in their usual rheumatologist.<br>
Results Of the 515 enrolled participants, 421 patients with SLE were included in our analyses. Patients were divided into groups according to the number of outpatient visits with a covering rheumatologist in the past year as follows: no visits (59.9%; reference group), one to three visits (24.2%; low-frequency group), and four or more visits (15.9%; high-frequency group). The median Trust in Physician Scale score was 81.8 (interquartile range: 72.7–93.2). Both the low-frequency group (mean difference: -3.03; 95% confidence interval [CI] -5.93 to -0.80) and high-frequency group (mean difference: -4.17; 95% CI -7.77 to -0.58) exhibited lower trust in their usual rheumatologist.<br>
Conclusion This study revealed that the number of outpatient visits with a covering rheumatologist was associated with lower trust in a patient’s usual rheumatologist.
en-copyright=
kn-copyright=

en-aut-name=KatayamaYu
en-aut-sei=Katayama
en-aut-mei=Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MiyawakiYoshia
en-aut-sei=Miyawaki
en-aut-mei=Yoshia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ShidaharaKenta
en-aut-sei=Shidahara
en-aut-mei=Kenta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NawachiShoichi
en-aut-sei=Nawachi
en-aut-mei=Shoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AsanoYosuke
en-aut-sei=Asano
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KatsuyamaEri
en-aut-sei=Katsuyama
en-aut-mei=Eri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KatsuyamaTakayuki
en-aut-sei=Katsuyama
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=Takano-NarazakiMariko
en-aut-sei=Takano-Narazaki
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MatsumotoYoshinori
en-aut-sei=Matsumoto
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OguroNao
en-aut-sei=Oguro
en-aut-mei=Nao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YajimaNobuyuki
en-aut-sei=Yajima
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=IshikawaYuichi
en-aut-sei=Ishikawa
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=SakuraiNatsuki
en-aut-sei=Sakurai
en-aut-mei=Natsuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=HidekawaChiharu
en-aut-sei=Hidekawa
en-aut-mei=Chiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=YoshimiRyusuke
en-aut-sei=Yoshimi
en-aut-mei=Ryusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=OhnoShigeru
en-aut-sei=Ohno
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=IchikawaTakanori
en-aut-sei=Ichikawa
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=KishidaDai
en-aut-sei=Kishida
en-aut-mei=Dai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=ShimojimaYasuhiro
en-aut-sei=Shimojima
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=SadaKen-Ei
en-aut-sei=Sada
en-aut-mei=Ken-Ei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=ThomDavid H.
en-aut-sei=Thom
en-aut-mei=David H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=KuritaNoriaki
en-aut-sei=Kurita
en-aut-mei=Noriaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine
kn-affil=

affil-num=11
en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine
kn-affil=

affil-num=12
en-affil=The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health
kn-affil=

affil-num=13
en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine
kn-affil=

affil-num=14
en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine
kn-affil=

affil-num=15
en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine
kn-affil=

affil-num=16
en-affil=Centre for Rheumatic Disease, Yokohama City University Medical Centre
kn-affil=

affil-num=17
en-affil=Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University
kn-affil=

affil-num=18
en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
kn-affil=

affil-num=19
en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
kn-affil=

affil-num=20
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=21
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=22
en-affil=Department of Medicine, Stanford University School of Medicine
kn-affil=

affil-num=23
en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine
kn-affil=
en-keyword=Systemic lupus erythematosus
kn-keyword=Systemic lupus erythematosus
en-keyword=Patient-physician relationship
kn-keyword=Patient-physician relationship
en-keyword=Outpatient visits
kn-keyword=Outpatient visits
en-keyword=Patient trust
kn-keyword=Patient trust
en-keyword=Discontinuity of care
kn-keyword=Discontinuity of care
END

start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=1
article-no=
start-page=12
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241105
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Dendritic cells (DCs) are crucial in cancer immunity, because they activate cytotoxic T cells by presenting tumor antigens. Recently, oncolytic virus therapy has been recognized as a systemic immune stimulator. We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. However, their effects on DCs remained unclear. In the present study, the aim was to elucidate the mechanisms of DC activation by OBP-702, focusing particularly on tumor-derived exosomes. Exosomes (Exo53, Exo301, or Exo702) were isolated from conditioned media of human or murine pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and PAN02) after treatment with Ad-p53, OBP-301, or OBP-702. Exo702 derived from Panc-1 and MiaPaCa-2 cells significantly upregulated CD86, CD80, CD83 (markers of DC maturation), and IFN-γ in DCs in vitro. Similarly, Exo702 derived from PAN02 cells upregulated CD86 and IFN-γ in bone marrow-derived DCs in a bilateral PAN02 subcutaneous tumor model. This DC maturation was inhibited by GW4869, an inhibitor of exosome release, and anti-CD63, an antibody targeting the exosome marker. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect.
en-copyright=
kn-copyright=

en-aut-name=OhtaniTomoko
en-aut-sei=Ohtani
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KumonKento
en-aut-sei=Kumon
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YagiChiaki
en-aut-sei=Yagi
en-aut-mei=Chiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SugimotoRyoma
en-aut-sei=Sugimoto
en-aut-mei=Ryoma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Oncolys BioPharma, Inc
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Oncolytic adenovirus
kn-keyword=Oncolytic adenovirus
en-keyword=p53
kn-keyword=p53
en-keyword=Dendritic cells
kn-keyword=Dendritic cells
en-keyword=Anti-tumor immunity
kn-keyword=Anti-tumor immunity
en-keyword=Exosome
kn-keyword=Exosome
END

start-ver=1.4
cd-journal=joma
no-vol=63
cd-vols=
no-issue=19
article-no=
start-page=2655
end-page=2660
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241001
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Prompt Diagnosis and Treatment of a Case of Nuclear Protein of the Testis Carcinoma Characterized by a Bronchial Lesion and High Serum Alpha-fetoprotein Level Following Genomic Testing
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Nuclear protein of the testis carcinoma (NUTC) is a rare and aggressive malignancy. We herein report a case of NUTC in the lung characterized by a bronchial lesion and elevated alpha-fetoprotein levels. A 35-year-old Japanese man presented to our institution with suspected advanced lung cancer based on a histological examination. Subsequently, next-generation sequencing (NGS) yielded a positive BRD4-NUTM1 fusion. In addition, positive NUT immunostaining of the lung biopsy specimen confirmed NUTC in the lungs. Systemic chemotherapy and radiotherapy showed a temporary response, with decreased serum alpha-fetoprotein levels. We highlight this case of a prompt diagnosis by NGS of NUTC in a young individual with a rapidly progressing tumor.
en-copyright=
kn-copyright=

en-aut-name=MatsuuraHiroaki
en-aut-sei=Matsuura
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Respiratory Medicine, Fukuyama City Hospital
kn-affil=

affil-num=4
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=

affil-num=12
en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=NUT carcinoma
kn-keyword=NUT carcinoma
en-keyword=BRD4-NUTM1
kn-keyword=BRD4-NUTM1
en-keyword=lung cancer
kn-keyword=lung cancer
en-keyword=alpha-fetoprotein (AFP)
kn-keyword=alpha-fetoprotein (AFP)
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=4
article-no=
start-page=557
end-page=564
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241019
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Clinical Significance of Prior Ramucirumab Use on the Effectiveness of Nivolumab as the Third-Line Regimen in Gastric Cancer: A Multicenter Retrospective Study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background and Objective Because vascular endothelial growth factor inhibition has been suggested to improve immune cell function in the cancer microenvironment, we examined whether using ramucirumab (RAM) before nivolumab usage is more effective in advanced gastric cancer. <br>
Methods This was a multicenter retrospective observational study. We analyzed patients who received nivolumab monotherapy as the third-line regimen for unresectable advanced or recurrent gastric cancer between October 2017 and December 2022. They were divided into the RAM (RAM-treated) group and the non-RAM (non-treated) group according to the RAM usage in the second-line regimen. The primary outcome was to compare the overall survival after nivolumab administration in the third-line regimen between the RAM and non-RAM groups. <br>
Results Fifty-two patients were included in the present study: 42 patients in the RAM group and ten patients in the non-RAM group. The median overall survival was significantly longer in the RAM group than in the non-RAM group (8.5 months vs 6.9 months, p < 0.05). In the RAM group, patients without peritoneal metastasis had significantly better median overall survival than those with peritoneal metastasis (23.8 months vs 7.7 months, p = 0.0033). Multivariate Cox-proportional hazards analyses showed that the presence of peritoneal metastasis (hazard ratio, 2.4; 95% confidence interval 1.0-5.7) alone was significantly associated with overall survival in the RAM group. <br>
Conclusions The use of RAM prior to nivolumab monotherapy may contribute to prolonged survival in patients with gastric cancer, especially those without peritoneal metastasis.
en-copyright=
kn-copyright=

en-aut-name=ObayashiYuka
en-aut-sei=Obayashi
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HirataShoichiro
en-aut-sei=Hirata
en-aut-mei=Shoichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KonoYoshiyasu
en-aut-sei=Kono
en-aut-mei=Yoshiyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AbeMakoto
en-aut-sei=Abe
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MiyaharaKoji
en-aut-sei=Miyahara
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NakagawaMasahiro
en-aut-sei=Nakagawa
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IshidaMichihiro
en-aut-sei=Ishida
en-aut-mei=Michihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ChodaYasuhiro
en-aut-sei=Choda
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HamadaKenta
en-aut-sei=Hamada
en-aut-mei=Kenta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=IwamuroMasaya
en-aut-sei=Iwamuro
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KawanoSeiji
en-aut-sei=Kawano
en-aut-mei=Seiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KawaharaYoshiro
en-aut-sei=Kawahara
en-aut-mei=Yoshiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OtsukaMotoyuki
en-aut-sei=Otsuka
en-aut-mei=Motoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital
kn-affil=

affil-num=2
en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital
kn-affil=

affil-num=5
en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital
kn-affil=

affil-num=6
en-affil=Department of Endoscopy, Hiroshima City Hiroshima Citizens Hospital
kn-affil=

affil-num=7
en-affil=Department of Surgery, Hiroshima City Hiroshima Citizens Hospital
kn-affil=

affil-num=8
en-affil=Department of Surgery, Hiroshima City Hiroshima Citizens Hospital
kn-affil=

affil-num=9
en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Gastroenterology, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Department of Gastroenterology, Okayama University Hospital
kn-affil=

affil-num=12
en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=5
article-no=
start-page=407
end-page=412
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202410
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The First Report of Bickerstaff Brainstem Encephalitis Induced by Atezolizumab for Metastatic Breast Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but they have been known to cause immune-related adverse events (irAEs) by promoting T-cell activation. Neurological irAEs are rare (1%) but have a high fatality rate (11.5%). Here we report the first case of Bickerstaff brainstem encephalitis (BBE) induced by an ICI. A woman in her 60s with metastatic breast cancer was treated with atezolizumab plus nab-paclitaxel once intravenously. Eighteen days later, she lost consciousness with ophthalmoplegia and was diagnosed with a neurological irAE. She recovered consciousness immediately with the administration of intravenous immunoglobulin (IVIG) but suffered severe permanent peripheral neuropathy. Although it is just one case, this experience shows that BBE occurring as a neurological irAE of ICI cancer treatment may be associated with more severe outcomes than conventional BBE in metastatic cancer. Creating a system for multidisciplinary treatment is essential for ICI therapy.
en-copyright=
kn-copyright=

en-aut-name=ShimoyamaKyoko
en-aut-sei=Shimoyama
en-aut-mei=Kyoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NakajimaAtsushi
en-aut-sei=Nakajima
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MinariYoshimitsu
en-aut-sei=Minari
en-aut-mei=Yoshimitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Breast Surgery, Takatsuki General Hospital
kn-affil=

affil-num=2
en-affil=Department of Rehabilitation, Aijinkai Rehabilitation Hospital
kn-affil=

affil-num=3
en-affil=Department of Breast Surgery, Takatsuki General Hospital
kn-affil=
en-keyword=Bickerstaff brainstem encephalitis
kn-keyword=Bickerstaff brainstem encephalitis
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=atezolizumab
kn-keyword=atezolizumab
en-keyword=neurological immune-related adverse event
kn-keyword=neurological immune-related adverse event
en-keyword=breast cancer
kn-keyword=breast cancer
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=5
article-no=
start-page=363
end-page=370
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202410
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Small-for-Gestational-Age Status and the Risk of Kawasaki Disease: A Nationwide Birth Cohort in Japan
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Kawasaki disease (KD) is a pediatric disease of unknown etiology that commonly affects infants in East Asia. Infants born small for gestational age (SGA) have weaker immune systems and are more susceptible to infection. Using data from a nationwide Japanese birth cohort study conducted in 2010 (n=34,579), we investigated whether SGA increases the risk of KD. SGA was defined as birth weight below the 10th percentile for gestational age. The outcome was hospitalization for KD between 6 and 30 months of age. The association between SGA and hospitalization for KD, adjusted for child and maternal factors, was examined using logistic regression. Of the 231 children hospitalized for KD, 9.5% were SGA. Further statistical analysis showed that SGA did not increase the odds ratio (OR) of hospitalization for KD (adjusted OR 1.12, 95% confidence interval 0.71-1.75). This result was not changed with stratification by early daycare attendance and preterm status. Reasons for the lack of association may include the multifactorial pathogenesis of KD; in addition, the types of infections to which SGA infants are predisposed may differ from those triggering KD. Overall, our large nationwide study found no association between SGA and KD.
en-copyright=
kn-copyright=

en-aut-name=TakanagaSatoe
en-aut-sei=Takanaga
en-aut-mei=Satoe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MatsumotoNaomi
en-aut-sei=Matsumoto
en-aut-mei=Naomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KadowakiTomoka
en-aut-sei=Kadowaki
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakaoSoshi
en-aut-sei=Takao
en-aut-mei=Soshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YorifujiTakashi
en-aut-sei=Yorifuji
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Kawasaki disease (KD)
kn-keyword=Kawasaki disease (KD)
en-keyword=small for gestational age (SGA)
kn-keyword=small for gestational age (SGA)
en-keyword=cohort
kn-keyword=cohort
en-keyword=epidemiology
kn-keyword=epidemiology
END

start-ver=1.4
cd-journal=joma
no-vol=33
cd-vols=
no-issue=4
article-no=
start-page=294
end-page=301
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202307
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Role of lymphadenectomy during primary surgery for kidney cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose of review <br>
Lymph node dissection (LND) during radical nephrectomy (RN) for renal cell carcinoma (RCC) is not considered as a standard. The emergence of robot-assisted surgery and effective immune checkpoint inhibitors (ICI) in recent years may change this and lymph node (LN) staging has become easier and has a clinical impact. In this review, we aimed to reconsider the role of LND today.<br>
<br>
Recent findings <br>
Although the extent of LND has still not been well established, removal of more LN seems to provide better oncologic outcomes for a select group of patients with high-risk factors such as clinical T3-4. Adjuvant therapy using pembrolizumab has been shown to improve disease free survival if complete resection of metastatic lesions as well as the primary site is obtained in combination. Robot assisted RN for localized RCC has been widespread and the studies regarding LND for RCC has been recently appeared.<br>
<br>
Summary <br>
The staging and surgical benefits and its extent of LND during RN for RCC remains unclear, but it is becoming increasingly important. Technologies that allow an easier LND and adjuvant ICI that improve survival in LN-positive patients are engaging the role of LND, a procedure that was needed, but almost never done, is now indicated sometimes. Now, the goal is to identify the clinical and molecular imaging tools that can help identify with sufficient accuracy who needs a LND and which LNs to remove in a targeted personalized approach.
en-copyright=
kn-copyright=

en-aut-name=BekkuKensuke
en-aut-sei=Bekku
en-aut-mei=Kensuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawadaTatsushi
en-aut-sei=Kawada
en-aut-mei=Tatsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YanagisawaTakafumi
en-aut-sei=Yanagisawa
en-aut-mei=Takafumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KarakiewiczPierre I.
en-aut-sei=Karakiewicz
en-aut-mei=Pierre I.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShariatShahrokh F.
en-aut-sei=Shariat
en-aut-mei=Shahrokh F.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=

affil-num=4
en-affil=Cancer Prognostic and Health Outcomes Unit, Division of Urology, University of Montreal Health Center
kn-affil=

affil-num=5
en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna
kn-affil=
en-keyword=lymph node dissection
kn-keyword=lymph node dissection
en-keyword=lymph node metastasis
kn-keyword=lymph node metastasis
en-keyword=lymphadenectomy
kn-keyword=lymphadenectomy
en-keyword=lymphadenopathy
kn-keyword=lymphadenopathy
en-keyword=Renal cell carcinoma
kn-keyword=Renal cell carcinoma
END

start-ver=1.4
cd-journal=joma
no-vol=65
cd-vols=
no-issue=11
article-no=
start-page=1769
end-page=1786
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240824
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Nutrient Requirements Shape the Preferential Habitat of Allorhizobium vitis VAR03-1, a Commensal Bacterium, in the Rhizosphere of Arabidopsis thaliana
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A diverse range of commensal bacteria inhabit the rhizosphere, influencing host plant growth and responses to biotic and abiotic stresses. While root-released nutrients can define soil microbial habitats, the bacterial factors involved in plant–microbe interactions are not well characterized. In this study, we investigated the colonization patterns of two plant disease biocontrol agents, Allorhizobium vitis VAR03-1 and Pseudomonas protegens Cab57, in the rhizosphere of Arabidopsis thaliana using Murashige and Skoog (MS) agar medium. VAR03-1 formed colonies even at a distance from the roots, preferentially in the upper part, while Cab57 colonized only the root surface. The addition of sucrose to the agar medium resulted in excessive proliferation of VAR03-1, similar to its pattern without sucrose, whereas Cab57 formed colonies only near the root surface. Overgrowth of both bacterial strains upon nutrient supplementation inhibited host growth, independent of plant immune responses. This inhibition was reduced in the VAR03-1 ΔrecA mutant, which exhibited increased biofilm formation, suggesting that some activities associated with the free-living lifestyle rather than the sessile lifestyle may be detrimental to host growth. VAR03-1 grew in liquid MS medium with sucrose alone, while Cab57 required both sucrose and organic acids. Supplementation of sugars and organic acids allowed both bacterial strains to grow near and away from Arabidopsis roots in MS agar. These results suggest that nutrient requirements for bacterial growth may determine their growth habitats in the rhizosphere, with nutrients released in root exudates potentially acting as a limiting factor in harnessing microbiota.
en-copyright=
kn-copyright=

en-aut-name=HemeldaNiarsi Merry
en-aut-sei=Hemelda
en-aut-mei=Niarsi Merry
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=BaoJiyuan
en-aut-sei=Bao
en-aut-mei=Jiyuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WatanabeMegumi
en-aut-sei=Watanabe
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MatsuiHidenori
en-aut-sei=Matsui
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ToyodaKazuhiro
en-aut-sei=Toyoda
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IchinoseYuki
en-aut-sei=Ichinose
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NoutoshiYoshiteru
en-aut-sei=Noutoshi
en-aut-mei=Yoshiteru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=7
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=
en-keyword=Commensal bacteria
kn-keyword=Commensal bacteria
en-keyword=Nutrient requirements
kn-keyword=Nutrient requirements
en-keyword=Organic acids
kn-keyword=Organic acids
en-keyword=Plant-microbe interactions
kn-keyword=Plant-microbe interactions
en-keyword=Rhizosphere
kn-keyword=Rhizosphere
en-keyword=Sugars
kn-keyword=Sugars
END

start-ver=1.4
cd-journal=joma
no-vol=24
cd-vols=
no-issue=1
article-no=
start-page=1099
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240916
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren's syndrome
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Some forms of Sjögren’s syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging.
en-copyright=
kn-copyright=

en-aut-name=Ono-MinagiHitomi
en-aut-sei=Ono-Minagi
en-aut-mei=Hitomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NohnoTsutomu
en-aut-sei=Nohno
en-aut-mei=Tsutomu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakabatakeKiyofumi
en-aut-sei=Takabatake
en-aut-mei=Kiyofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KatsuyamaTakayuki
en-aut-sei=Katsuyama
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MiyawakiKohta
en-aut-sei=Miyawaki
en-aut-mei=Kohta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=IbaragiSoichiro
en-aut-sei=Ibaragi
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IidaSeiji
en-aut-sei=Iida
en-aut-mei=Seiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NagatsukaHitoshi
en-aut-sei=Nagatsuka
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SakaiTakayoshi
en-aut-sei=Sakai
en-aut-mei=Takayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OhuchiHideyo
en-aut-sei=Ohuchi
en-aut-mei=Hideyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Cytology and Histology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Cytology and Histology, Okayama University Medical School
kn-affil=

affil-num=3
en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Division of Precision Medicine, Kyushu University School of Medicine
kn-affil=

affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=12
en-affil=Department of Rehabilitation for Orofacial Disorders, Osaka University Graduate School of Dentistry
kn-affil=

affil-num=13
en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Autoimmune disease
kn-keyword=Autoimmune disease
en-keyword=Xerostomia
kn-keyword=Xerostomia
en-keyword=Multiplex immunostaining
kn-keyword=Multiplex immunostaining
en-keyword=Spatial analysis
kn-keyword=Spatial analysis
en-keyword=Autophagy
kn-keyword=Autophagy
END

start-ver=1.4
cd-journal=joma
no-vol=136
cd-vols=
no-issue=2
article-no=
start-page=69
end-page=73
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=A case of immune checkpoint inhibitor-associated colitis treated with infliximab
kn-title=インフリキシマブが著効した免疫関連有害事象大腸炎の１例
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=　A 52-year-old Japanese man diagnosed with non-small cell lung cancer initiated chemotherapy with tremelimumab, durvalumab, nanoparticle albumin-bound paclitaxel, and carboplatin. On the fourth day of the first treatment course, he developed a fever, followed by watery diarrhea exceeding 10 episodes per day and bloody stools the next day. Immunotherapy-related adverse event colitis was diagnosed through CT scans and colonoscopy examinations. Despite the ineffectiveness of systemic steroid administration, prompt alleviation of symptoms was achieved through the administration of infliximab. In our case, the patient developed Grade 3 diarrhea, prompting the initiation of intravenous prednisolone at 80mg/day in accordance with guidelines. However, symptom improvement was not attained. In situations where symptoms persist beyond three days despite systemic steroid administration, the consideration of adjunctive infliximab use at a dosage of 5mg/kg becomes necessary.
en-copyright=
kn-copyright=

en-aut-name=IwamuroMasaya
en-aut-sei=Iwamuro
en-aut-mei=Masaya
kn-aut-name=岩室雅也
kn-aut-sei=岩室
kn-aut-mei=雅也
aut-affil-num=1
ORCID=

en-aut-name=HiraokaSakiko
en-aut-sei=Hiraoka
en-aut-mei=Sakiko
kn-aut-name=平岡佐規子
kn-aut-sei=平岡
kn-aut-mei=佐規子
aut-affil-num=2
ORCID=

en-aut-name=OtsukaMotoyuki
en-aut-sei=Otsuka
en-aut-mei=Motoyuki
kn-aut-name=大塚基之
kn-aut-sei=大塚
kn-aut-mei=基之
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=岡山大学病院　消化器内科

affil-num=2
en-affil=Inflammatory Bowel Disease Center, Okayama University Hospital
kn-affil=岡山大学病院　炎症性腸疾患センター

affil-num=3
en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学学術研究院医歯薬学域　消化器・肝臓内科学
en-keyword=インフリキシマブ（infliximab）
kn-keyword=インフリキシマブ（infliximab）
en-keyword=免疫関連有害事象（immune-related adverse events）
kn-keyword=免疫関連有害事象（immune-related adverse events）
en-keyword=大腸炎（colitis）
kn-keyword=大腸炎（colitis）
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=
article-no=
start-page=1329162
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240809
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Vaccine and antiviral drug promise for preventing post-acute sequelae of COVID-19, and their combination for its treatment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction: Most healthy individuals recover from acute SARS-CoV-2 infection, whereas a remarkable number continues to suffer from unexplained symptoms, known as Long COVID or post-acute COVID-19 syndrome (PACS). It is therefore imperative that methods for preventing and treating the onset of PASC be investigated with the utmost urgency.<br>
Methods: A mathematical model of the immune response to vaccination and viral infection with SARS-CoV-2, incorporating immune memory cells, was developed.<br>
Results and discussion: Similar to our previous model, persistent infection was observed by the residual virus in the host, implying the possibility of chronic inflammation and delayed recovery from tissue injury. Pre-infectious vaccination and antiviral medication administered during onset can reduce the acute viral load; however, they show no beneficial effects in preventing persistent infection. Therefore, the impact of these treatments on the PASC, which has been clinically observed, is mainly attributed to their role in preventing severe tissue damage caused by acute viral infections. For PASC patients with persistent infection, vaccination was observed to cause an immediate rapid increase in viral load, followed by a temporary decrease over approximately one year. The former was effectively suppressed by the coadministration of antiviral medications, indicating that this combination is a promising treatment for PASC.
en-copyright=
kn-copyright=

en-aut-name=SumiTomonari
en-aut-sei=Sumi
en-aut-mei=Tomonari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HaradaKouji
en-aut-sei=Harada
en-aut-mei=Kouji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Research Institute for Interdisciplinary Science, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Computer Science and Engineering, Toyohashi University of Technology
kn-affil=
en-keyword=post-acute sequelae of SARS-CoV-2 infection
kn-keyword=post-acute sequelae of SARS-CoV-2 infection
en-keyword=PASC
kn-keyword=PASC
en-keyword=long Covid
kn-keyword=long Covid
en-keyword=persistent viruses
kn-keyword=persistent viruses
en-keyword=vaccine
kn-keyword=vaccine
en-keyword=antiviral drug
kn-keyword=antiviral drug
en-keyword=mathematical model
kn-keyword=mathematical model
en-keyword=immune response
kn-keyword=immune response
END

start-ver=1.4
cd-journal=joma
no-vol=115
cd-vols=
no-issue=10
article-no=
start-page=3231
end-page=3247
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240809
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Overcoming immunotherapy resistance and inducing abscopal effects with boron neutron immunotherapy (B-NIT)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8(+) T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44(+) effector memory T cells and CD69(+) early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers.
en-copyright=
kn-copyright=

en-aut-name=FujimotoTakuya
en-aut-sei=Fujimoto
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YamasakiOsamu
en-aut-sei=Yamasaki
en-aut-mei=Osamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanehiraNoriyuki
en-aut-sei=Kanehira
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MatsushitaHirokazu
en-aut-sei=Matsushita
en-aut-mei=Hirokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SakuraiYoshinori
en-aut-sei=Sakurai
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KenmotsuNaoya
en-aut-sei=Kenmotsu
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MizutaRyo
en-aut-sei=Mizuta
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KondoNatsuko
en-aut-sei=Kondo
en-aut-mei=Natsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TakataTakushi
en-aut-sei=Takata
en-aut-mei=Takushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KitamatsuMizuki
en-aut-sei=Kitamatsu
en-aut-mei=Mizuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=IgawaKazuyo
en-aut-sei=Igawa
en-aut-mei=Kazuyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujimuraAtsushi
en-aut-sei=Fujimura
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OtaniYoshihiro
en-aut-sei=Otani
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=ShirakawaMakoto
en-aut-sei=Shirakawa
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=SuzukiMinoru
en-aut-sei=Suzuki
en-aut-mei=Minoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=MichiueHiroyuki
en-aut-sei=Michiue
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute
kn-affil=

affil-num=5
en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University
kn-affil=

affil-num=6
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University
kn-affil=

affil-num=9
en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University
kn-affil=

affil-num=10
en-affil=Faculty of Science and Engineering, Kindai University
kn-affil=

affil-num=11
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=

affil-num=12
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=18
en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University
kn-affil=

affil-num=19
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=20
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=
en-keyword=abscopal effect
kn-keyword=abscopal effect
en-keyword=advanced melanoma
kn-keyword=advanced melanoma
en-keyword=boron neutron capture therapy
kn-keyword=boron neutron capture therapy
en-keyword=boron-neutron immunotherapy
kn-keyword=boron-neutron immunotherapy
en-keyword=immune combination therapy
kn-keyword=immune combination therapy
END

start-ver=1.4
cd-journal=joma
no-vol=42
cd-vols=
no-issue=21
article-no=
start-page=126156
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202408
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Kinetics of SARS-CoV-2 antibody titers after booster vaccinations during an Omicron surge in Japan
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Despite the emergence of SARS-CoV-2 variants and waning immunity after initial vaccination, data on antibody kinetics following booster doses, particularly those adapted to Omicron subvariants like XBB.1.5, remain limited. This study assesses the kinetics of anti-spike protein receptor-binding domain (S-RBD) IgG antibody titers post-booster vaccination in a Japanese population during the Omicron variant epidemic.<br>
Methods: A prospective cohort study was conducted in Bizen City, Japan, from November 2023 to January 2024. Participants included residents and workers aged ≥18 years, with at least three COVID-19 vaccinations. Antibody levels were measured from venous blood samples. The study analyzed 424 participants and 821 antibody measurements, adjusting for variables such as age, sex, underlying conditions, and prior infection status. Mixed-effects models were employed to describe the kinetics of log-transformed S-RBD antibody titers.<br>
Results: The study found that S-RBD antibody titers declined over time but increased with the number of booster vaccinations, particularly those adapted to Omicron and its subvariant XBB.1.5 (Pfizer-BioNTech Omicron-compatible: 0.156, 95%CI −0.032 to 0.344; Pfizer-BioNTech XBB-compatible: 0.226; 95%CI −0.051 to 0.504; Moderna Omicron-compatible: 0.279, 95%CI 0.012 to 0.546; and Moderna XBB-compatible: 0.338, 95%CI −0.052 to 0.728). Previously infected individuals maintained higher antibody titers, which declined more gradually compared to uninfected individuals (coefficient for interaction with time 0.006; 95%CI 0.001 to 0.011). Sensitivity analyses using Generalized Estimating Equations and interval-censored random intercept model confirmed the robustness of these findings.<br>
Conclusions: The study provides specific data on antibody kinetics post-booster vaccination, including the XBB.1.5-adapted vaccine, in a highly vaccinated Japanese population. The results highlight the importance of considering individual demographics and prior infection history in optimizing vaccination strategies.
en-copyright=
kn-copyright=

en-aut-name=MatsumotoNaomi
en-aut-sei=Matsumoto
en-aut-mei=Naomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SasakiAyako
en-aut-sei=Sasaki
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KadowakiTomoka
en-aut-sei=Kadowaki
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MitsuhashiToshiharu
en-aut-sei=Mitsuhashi
en-aut-mei=Toshiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakaoSoshi
en-aut-sei=Takao
en-aut-mei=Soshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YorifujiTakashi
en-aut-sei=Yorifuji
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=SARS-CoV-2
kn-keyword=SARS-CoV-2
en-keyword=Vaccine
kn-keyword=Vaccine
en-keyword=Antibody
kn-keyword=Antibody
en-keyword=Mixed-effects model
kn-keyword=Mixed-effects model
en-keyword=Omicron
kn-keyword=Omicron
END

start-ver=1.4
cd-journal=joma
no-vol=29
cd-vols=
no-issue=10
article-no=
start-page=1594
end-page=1601
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240713
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background We previously demonstrated the applicability of the concept of “platinum sensitivity” in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study.<br>
Methods Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data.<br>
Results In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12–23 months, 18/43 (42%); 24–35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12–23 months, 0/19 (0%); 24–35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)].<br>
Conclusions Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering.
en-copyright=
kn-copyright=

en-aut-name=NagaoShoji
en-aut-sei=Nagao
en-aut-mei=Shoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishioShin
en-aut-sei=Nishio
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakeharaKazuhiro
en-aut-sei=Takehara
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SatoShinya
en-aut-sei=Sato
en-aut-mei=Shinya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SatohToyomi
en-aut-sei=Satoh
en-aut-mei=Toyomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShimadaMuneaki
en-aut-sei=Shimada
en-aut-mei=Muneaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YamaguchiSatoshi
en-aut-sei=Yamaguchi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TanabeHiroshi
en-aut-sei=Tanabe
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TakanoMasashi
en-aut-sei=Takano
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HorieKouji
en-aut-sei=Horie
en-aut-mei=Kouji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TakeiYuji
en-aut-sei=Takei
en-aut-mei=Yuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ImaiYuichi
en-aut-sei=Imai
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=HibinoYumi
en-aut-sei=Hibino
en-aut-mei=Yumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=HasegawaKosei
en-aut-sei=Hasegawa
en-aut-mei=Kosei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=TakekumaMunetaka
en-aut-sei=Takekuma
en-aut-mei=Munetaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=NakamuraKazuto
en-aut-sei=Nakamura
en-aut-mei=Kazuto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=TakanoHirokuni
en-aut-sei=Takano
en-aut-mei=Hirokuni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=FujiwaraKeiichi
en-aut-sei=Fujiwara
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=MasuyamaHisashi
en-aut-sei=Masuyama
en-aut-mei=Hisashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

affil-num=1
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Obstetrics and Gynecology, Kurume University School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center
kn-affil=

affil-num=4
en-affil=Department of Obstetrics and Gynecology, Tottori University
kn-affil=

affil-num=5
en-affil=Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba
kn-affil=

affil-num=6
en-affil=Department of Gynecology, Tohoku University Hospital
kn-affil=

affil-num=7
en-affil=Department of Medical Oncology, Hyogo Cancer Center
kn-affil=

affil-num=8
en-affil=Department of Obstetrics and Gynecology, Jikei University School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Obstetrics and Gynecology, National Defense Medical College
kn-affil=

affil-num=10
en-affil=Department of Gynecologic Oncology, Saitama Cancer Center
kn-affil=

affil-num=11
en-affil=Department of Obstetrics and Gynecology, Jichi Medical University
kn-affil=

affil-num=12
en-affil=Department of Obstetrics and Gynecology, Yokohama City University Hospital
kn-affil=

affil-num=13
en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center
kn-affil=

affil-num=14
en-affil=Department of Gynecologic Oncology, Saitama Medical University International Medical Center
kn-affil=

affil-num=15
en-affil=Department of Gynecology, Shizuoka Cancer Center
kn-affil=

affil-num=16
en-affil=Department of Gynecology, Gunma Prefectural Cancer Center
kn-affil=

affil-num=17
en-affil=Department of Obstetrics and Gynecology, Jikei University School of Medicine
kn-affil=

affil-num=18
en-affil=Department of Gynecologic Oncology, Saitama Medical University International Medical Center
kn-affil=

affil-num=19
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Recurrent endometrial cancer
kn-keyword=Recurrent endometrial cancer
en-keyword=Re-administration of platinum-based chemotherapy
kn-keyword=Re-administration of platinum-based chemotherapy
en-keyword=Platinum-free interval
kn-keyword=Platinum-free interval
en-keyword=Secondary platinum response
kn-keyword=Secondary platinum response
END

start-ver=1.4
cd-journal=joma
no-vol=51
cd-vols=
no-issue=8
article-no=
start-page=1108
end-page=1112
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240619
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The treatment effect of endovascular therapy for chronic limb‐threatening ischemia with systemic sclerosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Systemic sclerosis (SSc) is a collagen disease with immune abnormalities, vasculopathy, and fibrosis. Ca blockers and prostaglandins are used to treat peripheral circulatory disturbances. Chronic limb-threatening ischemia (CLTI) is a disease characterized by extremity ulcers, necrosis, and pain due to limb ischemia. Since only a few patients present with coexistence of CLTI and SSc, the treatment outcomes of revascularization in these cases are unknown. In this study, we evaluated the clinical characteristics and treatment outcomes of seven patients with CLTI and SSc, and 35 patients with uncomplicated CLTI who were hospitalized from 2012 to 2022. A higher proportion of patients with uncomplicated CLTI had diabetes and male. There were no significant differences in the age at which ischemic ulceration occurred, other comorbidities, or in treatments, including antimicrobial agents, revascularization and amputation, improvement of pain, and the survival time from ulcer onset between the two subgroups. EVT or amputation was performed in six or two of the seven patients with CLTI and SSc, respectively. Among those who underwent EVT, 33% (2/6) achieved epithelialization and 67% (4/6) experienced pain relief. These results suggest that the revascularization in cases with CLTI and SSc should consider factors such as infection and general condition, since revascularization improve the pain of these patients.
en-copyright=
kn-copyright=

en-aut-name=MatsudaYoshihiro
en-aut-sei=Matsuda
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MiyakeTomoko
en-aut-sei=Miyake
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TodaHironobu
en-aut-sei=Toda
en-aut-mei=Hironobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TachibanaKota
en-aut-sei=Tachibana
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NomuraHayato
en-aut-sei=Nomura
en-aut-mei=Hayato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HiraiYoji
en-aut-sei=Hirai
en-aut-mei=Yoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KawakamiYoshio
en-aut-sei=Kawakami
en-aut-mei=Yoshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SakodaNaoya
en-aut-sei=Sakoda
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MorizaneShin
en-aut-sei=Morizane
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=chronic limb-threatening ischemia (CLTI)
kn-keyword=chronic limb-threatening ischemia (CLTI)
en-keyword=endovascular therapy (EVT)
kn-keyword=endovascular therapy (EVT)
en-keyword=revascularization
kn-keyword=revascularization
en-keyword=systemic sclerosis (SSc)
kn-keyword=systemic sclerosis (SSc)
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=4610
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240530
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=An NLR paralog Pit2 generated from tandem duplication of Pit1 fine-tunes Pit1 localization and function
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=NLR family proteins act as intracellular receptors. Gene duplication amplifies the number of NLR genes, and subsequent mutations occasionally provide modifications to the second gene that benefits immunity. However, evolutionary processes after gene duplication and functional relationships between duplicated NLRs remain largely unclear. Here, we report that the rice NLR protein Pit1 is associated with its paralogue Pit2. The two are required for the resistance to rice blast fungus but have different functions: Pit1 induces cell death, while Pit2 competitively suppresses Pit1-mediated cell death. During evolution, the suppression of Pit1 by Pit2 was probably generated through positive selection on two fate-determining residues in the NB-ARC domain of Pit2, which account for functional differences between Pit1 and Pit2. Consequently, Pit2 lost its plasma membrane localization but acquired a new function to interfere with Pit1 in the cytosol. These findings illuminate the evolutionary trajectory of tandemly duplicated NLR genes after gene duplication.
en-copyright=
kn-copyright=

en-aut-name=LiYuying
en-aut-sei=Li
en-aut-mei=Yuying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WangQiong
en-aut-sei=Wang
en-aut-mei=Qiong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=JiaHuimin
en-aut-sei=Jia
en-aut-mei=Huimin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IshikawaKazuya
en-aut-sei=Ishikawa
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KosamiKen-Ichi
en-aut-sei=Kosami
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=UebaTakahiro
en-aut-sei=Ueba
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TsujimotoAtsumi
en-aut-sei=Tsujimoto
en-aut-mei=Atsumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YamanakaMiki
en-aut-sei=Yamanaka
en-aut-mei=Miki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YabumotoYasuyuki
en-aut-sei=Yabumoto
en-aut-mei=Yasuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MikiDaisuke
en-aut-sei=Miki
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=SasakiEriko
en-aut-sei=Sasaki
en-aut-mei=Eriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FukaoYoichiro
en-aut-sei=Fukao
en-aut-mei=Yoichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraMasayuki
en-aut-sei=Fujiwara
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=Kaneko-KawanoTakako
en-aut-sei=Kaneko-Kawano
en-aut-mei=Takako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=TanLi
en-aut-sei=Tan
en-aut-mei=Li
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KojimaChojiro
en-aut-sei=Kojima
en-aut-mei=Chojiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=WingRod A.
en-aut-sei=Wing
en-aut-mei=Rod A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=SebastianAlfino
en-aut-sei=Sebastian
en-aut-mei=Alfino
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=NishimuraHideki
en-aut-sei=Nishimura
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=FukadaFumi
en-aut-sei=Fukada
en-aut-mei=Fumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=NiuQingfeng
en-aut-sei=Niu
en-aut-mei=Qingfeng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=ShimizuMotoki
en-aut-sei=Shimizu
en-aut-mei=Motoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=YoshidaKentaro
en-aut-sei=Yoshida
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=TerauchiRyohei
en-aut-sei=Terauchi
en-aut-mei=Ryohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=ShimamotoKo
en-aut-sei=Shimamoto
en-aut-mei=Ko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

en-aut-name=KawanoYoji
en-aut-sei=Kawano
en-aut-mei=Yoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=

affil-num=1
en-affil=Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences
kn-affil=

affil-num=2
en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences
kn-affil=

affil-num=3
en-affil=College of Agronomy, Jiangxi Agricultural University
kn-affil=

affil-num=4
en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences
kn-affil=

affil-num=5
en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences
kn-affil=

affil-num=6
en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology
kn-affil=

affil-num=7
en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology
kn-affil=

affil-num=8
en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology
kn-affil=

affil-num=9
en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology
kn-affil=

affil-num=10
en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences
kn-affil=

affil-num=11
en-affil=Faculty of Science, Kyushu University
kn-affil=

affil-num=12
en-affil=Department of Bioinformatics, Ritsumeikan University
kn-affil=

affil-num=13
en-affil=YANMAR HOLDINGS Co., Ltd.
kn-affil=

affil-num=14
en-affil=College of Pharmaceutical Sciences, Ritsumeikan University
kn-affil=

affil-num=15
en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences
kn-affil=

affil-num=16
en-affil=Graduate School of Engineering Science, Yokohama National University
kn-affil=

affil-num=17
en-affil=Arizona Genomics Institute, School of Plant Sciences, University of Arizona
kn-affil=

affil-num=18
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=19
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=20
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=21
en-affil=Advanced Academy, Anhui Agricultural University, Research Centre for Biological Breeding Technology
kn-affil=

affil-num=22
en-affil=Iwate Biotechnology Research Center
kn-affil=

affil-num=23
en-affil=Graduate School of Agriculture, Kyoto University 
kn-affil=

affil-num=24
en-affil=Iwate Biotechnology Research Center
kn-affil=

affil-num=25
en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology
kn-affil=

affil-num=26
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=3
article-no=
start-page=259
end-page=270
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202406
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol–disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients’ sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol–disulfide homeostasis and ischaemia-modified albumin were measured.<br>
We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol–disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol–disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol–disulfide homeostasis in multiple sclerosis patients.
en-copyright=
kn-copyright=

en-aut-name=VuralGonul
en-aut-sei=Vural
en-aut-mei=Gonul
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=DemirEsra
en-aut-sei=Demir
en-aut-mei=Esra
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=GumusyaylaSadiye
en-aut-sei=Gumusyayla
en-aut-mei=Sadiye
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ErenFunda
en-aut-sei=Eren
en-aut-mei=Funda
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=BarakliSerdar
en-aut-sei=Barakli
en-aut-mei=Serdar
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NeseliogluSalim
en-aut-sei=Neselioglu
en-aut-mei=Salim
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ErelOzcan
en-aut-sei=Erel
en-aut-mei=Ozcan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University
kn-affil=

affil-num=2
en-affil=Department of Neurology, Ankara City Hospital
kn-affil=

affil-num=3
en-affil=Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University
kn-affil=

affil-num=4
en-affil=Department of Clinical Biochemistry, Ankara City Hospital
kn-affil=

affil-num=5
en-affil=Department of Neurology, Ankara City Hospital
kn-affil=

affil-num=6
en-affil=Department of Clinical Biochemistry, Ankara City Hospital
kn-affil=

affil-num=7
en-affil=Department of Clinical Biochemistry, Ankara City Hospital
kn-affil=
en-keyword=multiple sclerosis
kn-keyword=multiple sclerosis
en-keyword=dysfunctional HDL
kn-keyword=dysfunctional HDL
en-keyword=thiol–disulfide homeostasis
kn-keyword=thiol–disulfide homeostasis
en-keyword=cognitive decline
kn-keyword=cognitive decline
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=3
article-no=
start-page=227
end-page=235
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202406
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effect of Lipopolysaccharide on the Duration of Zolpidem-Induced Loss of Righting Reflex in Mice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Zolpidem, a non-benzodiazepine hypnotic, is primarily used to treat insomnia. In a previous study, pior treatment with non-benzodiazepine receptor agonists was associated with inflammation. The present study aimed to clarify the association between the effects of zolpidem and inflammation in mice treated with lipopolysaccharide (LPS), a known model of inflammation. We assessed the zolpidem-induced loss of righting reflex (LORR) duration 24 h after LPS treatment in mice. Additionally, the expressions of γ-aminobutyric acid (GABA)A receptor subunit and K+-Cl− cotransporter isoform 2 (KCC2) mRNA in the hippocampus and frontal cortex were examined in LPS-treated mice. Pretreatment with LPS was associated with significantly prolonged duration of zolpidem-induced LORR compared to control mice. This effect was significantly attenuated by administering bicuculline, a GABAA receptor antagonist, or flumazenil, a benzodiazepine receptor antagonist, in LPS-treated mice. Compared to controls, LPS-treated mice showed no significant change in the expression of GABAA receptor subunits in the hippocampus or frontal cortex. Bumetanide, an Na+-K+-2Cl− cotransporter isoform 1 blocker, attenuated the extended duration of zolpidem-induced LORR observed in LPS-treated mice. LPS significantly decreased Kcc2 mRNA expression in the hippocampus and the frontal cortex. These findings suggest that inflammation increases zolpidem-induced LORR, possibly through a reduction in KCC2 expression.
en-copyright=
kn-copyright=

en-aut-name=WadaYudai
en-aut-sei=Wada
en-aut-mei=Yudai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=UshioSoichiro
en-aut-sei=Ushio
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KitamuraYoshihisa
en-aut-sei=Kitamura
en-aut-mei=Yoshihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZamamiYoshito
en-aut-sei=Zamami
en-aut-mei=Yoshito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SendoToshiaki
en-aut-sei=Sendo
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=lipopolysaccharide
kn-keyword=lipopolysaccharide
en-keyword=zolpidem
kn-keyword=zolpidem
en-keyword=GABAA receptor
kn-keyword=GABAA receptor
en-keyword=K+-Cl− cotransporters
kn-keyword=K+-Cl− cotransporters
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=10
article-no=
start-page=1811
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240509
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Impact of Nutritional Status on Neutrophil-to-Lymphocyte Ratio as a Predictor of Efficacy and Adverse Events of Immune Check-Point Inhibitors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to nutritional status, this study examined whether the usefulness of NLR varies in ICI treatment due to changes in nutritional status. A retrospective analysis was performed on 1234 patients who received ICI treatment for malignant tumors at our hospital. Progression-free survival (PFS) was significantly prolonged in patients with NLR < 4. Multivariate analysis revealed that the factors associated with the occurrence of irAE were NLR < 4 and the use of ipilimumab. However, when limited to cases with serum albumin levels <3.8 g/dL, lymphocyte counts significantly decreased, and the associations between NLR and PFS and between NLR and irAE occurrence disappeared. In contrast, when limited to the cases with serum albumin levels ≥3.8 g/dL, the associations remained, with significantly prolonged PFS and significantly increased irAE occurrence at NLR < 4. NLR may be a good predictive tool for PFS and irAE occurrence during ICI treatment when a good nutritional status is maintained.
en-copyright=
kn-copyright=

en-aut-name=SueMasahiko
en-aut-sei=Sue
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakeuchiYasuto
en-aut-sei=Takeuchi
en-aut-mei=Yasuto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HirataShoichiro
en-aut-sei=Hirata
en-aut-mei=Shoichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakakiAkinobu
en-aut-sei=Takaki
en-aut-mei=Akinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OtsukaMotoyuki
en-aut-sei=Otsuka
en-aut-mei=Motoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=
en-keyword=immune-related adverse events
kn-keyword=immune-related adverse events
en-keyword=serum albumin
kn-keyword=serum albumin
en-keyword=real-world practice
kn-keyword=real-world practice
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=10
article-no=
start-page=807
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240509
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial-mesenchymal cell co-culture models in the air-liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism.
en-copyright=
kn-copyright=

en-aut-name=MuXindi
en-aut-sei=Mu
en-aut-mei=Xindi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OnoMitsuaki
en-aut-sei=Ono
en-aut-mei=Mitsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NguyenHa Thi Thu
en-aut-sei=Nguyen
en-aut-mei=Ha Thi Thu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WangZiyi
en-aut-sei=Wang
en-aut-mei=Ziyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ZhaoKun
en-aut-sei=Zhao
en-aut-mei=Kun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KomoriTaishi
en-aut-sei=Komori
en-aut-mei=Taishi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YonezawaTomoko
en-aut-sei=Yonezawa
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KubokiTakuo
en-aut-sei=Kuboki
en-aut-mei=Takuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=
kn-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Oral Rehabilitation and Implantology, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cell differentiation
kn-keyword=cell differentiation
en-keyword=epithelia
kn-keyword=epithelia
en-keyword=growth factor(s)
kn-keyword=growth factor(s)
en-keyword=bioinformatics
kn-keyword=bioinformatics
en-keyword=extracellular matrix (ECM)
kn-keyword=extracellular matrix (ECM)
en-keyword=mucocutaneous disorders
kn-keyword=mucocutaneous disorders
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=10
article-no=
start-page=e174618
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240522
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro -tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph -circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC.
en-copyright=
kn-copyright=

en-aut-name=EainHtoo Shwe
en-aut-sei=Eain
en-aut-mei=Htoo Shwe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawaiHotaka
en-aut-sei=Kawai
en-aut-mei=Hotaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakayamaMasaaki
en-aut-sei=Nakayama
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OoMay Wathone
en-aut-sei=Oo
en-aut-mei=May Wathone
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FukuharaYoko
en-aut-sei=Fukuhara
en-aut-mei=Yoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakabatakeKiyofumi
en-aut-sei=Takabatake
en-aut-mei=Kiyofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ShanQuisheng
en-aut-sei=Shan
en-aut-mei=Quisheng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SoeYamin
en-aut-sei=Soe
en-aut-mei=Yamin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OnoKisho
en-aut-sei=Ono
en-aut-mei=Kisho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NakanoKeisuke
en-aut-sei=Nakano
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=MizukawaNobuyoshi
en-aut-sei=Mizukawa
en-aut-mei=Nobuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=IidaSeiji
en-aut-sei=Iida
en-aut-mei=Seiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=NagatsukaHitoshi
en-aut-sei=Nagatsuka
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Universit
kn-affil=

affil-num=6
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=12
en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=14
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=63
cd-vols=
no-issue=9
article-no=
start-page=1261
end-page=1267
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240501
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Severe Cytokine Release Syndrome and Immune Effector Cell-associated Neurotoxicity Syndrome in a Man Receiving Immune Checkpoint Inhibitors for Lung Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 55-year-old man with stage IV lung adenocarcinoma was treated with cisplatin, pemetrexed, nivolumab, and ipilimumab. Approximately 100 days after treatment initiation, he became disoriented and presented to the emergency department with a high fever. Blood tests revealed liver and kidney dysfunctions. Subsequently, the patient developed generalized convulsions that required intensive care. He was clinically diagnosed with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Organ damage was gradually controlled with immunosuppressive drugs, including steroids, and the patient was discharged. Successful treatment is rare in patients with CRS, including ICANS, during immune checkpoint inhibitor treatment for solid tumors.
en-copyright=
kn-copyright=

en-aut-name=TanakaTakaaki
en-aut-sei=Tanaka
en-aut-mei=Takaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TaokaMasataka
en-aut-sei=Taoka
en-aut-mei=Masataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=nivolumab
kn-keyword=nivolumab
en-keyword=ipilimumab
kn-keyword=ipilimumab
en-keyword=cytokine release syndrome
kn-keyword=cytokine release syndrome
en-keyword=immune effector cell-associated neurotoxicity syndrome
kn-keyword=immune effector cell-associated neurotoxicity syndrome
END

start-ver=1.4
cd-journal=joma
no-vol=73
cd-vols=
no-issue=2
article-no=
start-page=323
end-page=331
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Topical application of activator protein-1 inhibitor T-5224 suppresses inflammation and improves skin barrier function in a murine atopic dermatitis-like dermatitis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders. <br>
Methods: Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the in vivo study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice. Baricitinib, a conventional therapeutic agent Janus kinase (JAK) inhibitor, was also topically applied. In the in vitro study, human epidermal keratinocytes were treated with T-5224 and stimulated with AD-related cytokines. <br>
Results: AP-1/c-Jun was phosphorylated at skin lesions in AD patients. In vivo, topical T-5224 application inhibited ear swelling (P < 0.001), restored filaggrin (Flg) expression (P < 0.01), and generally suppressed immune-related pathways. T-5224 significantly suppressed Il17a and l17f expression, whereas baricitinib did not.Baricitinib suppressed Il4, Il19, Il33 and Ifnb expression, whereas T-5224 did not. Il1a, Il1b, Il23a, Ifna, S100a8, and S100a9 expression was cooperatively downregulated following the combined use of T5224 and baricitinib. In vitro, T-5224 restored the expression of FLG and loricrin (LOR) (P < 0.05) and suppressed IL33 expression (P < 0.05) without affecting cell viability and cytotoxicity. <br>
Conclusions: Topical T-5224 ameliorates clinical manifestations of AD-like dermatitis in mice. The effect of this inhibitor is amplified via combined use with JAK inhibitors.
en-copyright=
kn-copyright=

en-aut-name=SasakuraMinori
en-aut-sei=Sasakura
en-aut-mei=Minori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=UrakamiHitoshi
en-aut-sei=Urakami
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TachibanaKota
en-aut-sei=Tachibana
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IkedaKenta
en-aut-sei=Ikeda
en-aut-mei=Kenta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HasuiKen-Ichi
en-aut-sei=Hasui
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MatsudaYoshihiro
en-aut-sei=Matsuda
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SunagawaKo
en-aut-sei=Sunagawa
en-aut-mei=Ko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=EnnishiDaisuke
en-aut-sei=Ennishi
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MorizaneShin
en-aut-sei=Morizane
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=AP-1 inhibitor
kn-keyword=AP-1 inhibitor
en-keyword=Atopic dermatitis
kn-keyword=Atopic dermatitis
en-keyword=Baricitinib
kn-keyword=Baricitinib
en-keyword=T-5224
kn-keyword=T-5224
en-keyword=Topical application
kn-keyword=Topical application
END

start-ver=1.4
cd-journal=joma
no-vol=30
cd-vols=
no-issue=16
article-no=
start-page=2220
end-page=2232
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240428
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Drug-induced mucosal alterations observed during esophagogastroduodenoscopy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract, i.e., the esophagus, stomach, and duodenum. These include pill-induced esophagitis, desquamative esophagitis, worsening of gastroesophageal reflux, chemotherapy-induced esophagitis, proton pump inhibitor-induced gastric mucosal changes, medication-induced gastric erosions and ulcers, pseudomelanosis of the stomach, olmesartan-related gastric mucosal inflammation, lanthanum deposition in the stomach, zinc acetate hydrate tablet-induced gastric ulcer, immune-related adverse event gastritis, olmesartan-asso-ciated sprue-like enteropathy, pseudomelanosis of the duodenum, and lanthanum deposition in the duodenum. For endoscopists, acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions. This minireview aims to provide essential information on drug-induced mucosal alterations observed on esophagogastroduodenoscopy, along with representative endoscopic images.
en-copyright=
kn-copyright=

en-aut-name=IwamuroMasaya
en-aut-sei=Iwamuro
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawanoSeiji
en-aut-sei=Kawano
en-aut-mei=Seiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OtsukaMotoyuki
en-aut-sei=Otsuka
en-aut-mei=Motoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Diagnosis
kn-keyword=Diagnosis
en-keyword=Esophagogastroduodenoscopy
kn-keyword=Esophagogastroduodenoscopy
en-keyword=Non-neoplastic lesions
kn-keyword=Non-neoplastic lesions
en-keyword=Esophageal lesions
kn-keyword=Esophageal lesions
en-keyword=Gastric lesions
kn-keyword=Gastric lesions
en-keyword=Duodenal lesions
kn-keyword=Duodenal lesions
END

start-ver=1.4
cd-journal=joma
no-vol=120
cd-vols=
no-issue=1
article-no=
start-page=128
end-page=134
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240415
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Spontaneous regression of multiple solitary plasmacytoma harboring Epstein–Barr virus: a case report and literature review
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We report a rare case of spontaneous regression (SR) in an elderly untreated patient with multiple solitary plasmacytoma (MSP). Diagnosis of MSP was confirmed through surgical resection of the left nasal cavity mass and subsequent biopsy of the right humerus. The patient was considered ineligible for chemotherapy due to poor performance status. At 3-month post-diagnosis, the patient’s condition worsened with deteriorating bone lesions and emergence of a new serum monoclonal protein. However, these clinical findings completely disappeared at 6 months, and positron emission tomography–computed tomography at 1 year confirmed complete metabolic remission. Notably, peripheral blood lymphocyte counts were inversely correlated with tumor progression and remission. Pathological re-evaluation of the initial biopsy specimens revealed programmed cell death protein 1 (PD-1) expression in tumor-infiltrating CD8+ T cells. In addition, tumor cells were infected with Epstein–Barr virus (EBV) but were negative for programmed cell death ligand 1 (PD-L1) expression, which is the most potent immune escape mechanism in tumor cells. While the mechanism underlying SR remains unclear, our findings suggest that host immune response as well as EBV infection may contribute to SR. Further studies are needed to elucidate the clinicopathologic mechanisms of tumor regression in plasma cell neoplasms.
en-copyright=
kn-copyright=

en-aut-name=KitamuraWataru
en-aut-sei=Kitamura
en-aut-mei=Wataru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KobayashiHiroki
en-aut-sei=Kobayashi
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NodaMinori
en-aut-sei=Noda
en-aut-mei=Minori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IsekiAkiko
en-aut-sei=Iseki
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SatoYumi
en-aut-sei=Sato
en-aut-mei=Yumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KuyamaShoichi
en-aut-sei=Kuyama
en-aut-mei=Shoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Otorhinolaryngology, National Hospital Organization Iwakuni Clinical Center
kn-affil=

affil-num=4
en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center
kn-affil=

affil-num=5
en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center
kn-affil=

affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center
kn-affil=
en-keyword=Plasmacytoma
kn-keyword=Plasmacytoma
en-keyword=Epstein–Barr virus
kn-keyword=Epstein–Barr virus
en-keyword=Spontaneous regression
kn-keyword=Spontaneous regression
END

start-ver=1.4
cd-journal=joma
no-vol=101
cd-vols=
no-issue=4
article-no=
start-page=431
end-page=447
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The adenovirus-REIC/Dkk-3 expression vector (Ad-REIC) has been the focus of numerous clinical studies due to its potential for the quenching of cancers. The cancer-suppressing mechanisms of the REIC/DKK-3 gene depend on multiple pathways that exert both direct and indirect effects on cancers. The direct effect is triggered by REIC/Dkk-3-mediated ER stress that causes cancer-selective apoptosis, and the indirect effect can be classified in two ways: (i) induction, by Ad-REIC-mis-infected cancer-associated fibroblasts, of the production of IL-7, an important activator of T cells and NK cells, and (ii) promotion, by the secretory REIC/Dkk-3 protein, of dendritic cell polarization from monocytes. These unique features allow Ad-REIC to exert effective and selective cancer-preventative effects in the manner of an anticancer vaccine. However, the question of how the REIC/Dkk-3 protein leverages anticancer immunity has remained to be answered. We herein report a novel function of the extracellular REIC/Dkk-3—namely, regulation of an immune checkpoint via modulation of PD-L1 on the cancer-cell surface. First, we identified novel interactions of REIC/Dkk-3 with the membrane proteins C5aR, CXCR2, CXCR6, and CMTM6. These proteins all functioned to stabilize PD-L1 on the cell surface. Due to the dominant expression of CMTM6 among the proteins in cancer cells, we next focused on CMTM6 and observed that REIC/Dkk-3 competed with CMTM6 for PD-L1, thereby liberating PD-L1 from its complexation with CMTM6. The released PD-L1 immediately underwent endocytosis-mediated degradation. These results will enhance our understanding of not only the physiological nature of the extracellular REIC/Dkk-3 protein but also the Ad-REIC-mediated anticancer effects.
en-copyright=
kn-copyright=

en-aut-name=GoharaYuma
en-aut-sei=Gohara
en-aut-mei=Yuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AudebertLéna
en-aut-sei=Audebert
en-aut-mei=Léna
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KomalasariNi Luh Gede Yoni
en-aut-sei=Komalasari
en-aut-mei=Ni Luh Gede Yoni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=JiangFan
en-aut-sei=Jiang
en-aut-mei=Fan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YoshizawaChikako
en-aut-sei=Yoshizawa
en-aut-mei=Chikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YamamotoKen-ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=WatanabeMasami
en-aut-sei=Watanabe
en-aut-mei=Masami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KumonHiromi
en-aut-sei=Kumon
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=4
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=8
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=10
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=13
en-affil=Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University
kn-affil=

affil-num=14
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
en-keyword=Breast cancer
kn-keyword=Breast cancer
en-keyword=REIC/Dkk-3
kn-keyword=REIC/Dkk-3
en-keyword=PD-L1
kn-keyword=PD-L1
en-keyword=Immune checkpoint
kn-keyword=Immune checkpoint
en-keyword=Cancer therapy
kn-keyword=Cancer therapy
END

start-ver=1.4
cd-journal=joma
no-vol=72
cd-vols=
no-issue=11
article-no=
start-page=3787
end-page=3802
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230905
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.
en-copyright=
kn-copyright=

en-aut-name=KawasakiKento
en-aut-sei=Kawasaki
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TanabeShunsuke
en-aut-sei=Tanabe
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakedaYasushige
en-aut-sei=Takeda
en-aut-mei=Yasushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MatsumotoHijiri
en-aut-sei=Matsumoto
en-aut-mei=Hijiri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NishimuraSeitaro
en-aut-sei=Nishimura
en-aut-mei=Seitaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KunitomoTomoyoshi
en-aut-sei=Kunitomo
en-aut-mei=Tomoyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=AkaiMasaaki
en-aut-sei=Akai
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KobayashiTeruki
en-aut-sei=Kobayashi
en-aut-mei=Teruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=NishiwakiNoriyuki
en-aut-sei=Nishiwaki
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=MaedaNaoaki
en-aut-sei=Maeda
en-aut-mei=Naoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=18
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Esophageal cancer
kn-keyword=Esophageal cancer
en-keyword=Cancer-associated fibroblasts
kn-keyword=Cancer-associated fibroblasts
en-keyword=Programmed cell death 1
kn-keyword=Programmed cell death 1
en-keyword=Program cell death ligand 1
kn-keyword=Program cell death ligand 1
en-keyword=Immune checkpoint inhibitors
kn-keyword=Immune checkpoint inhibitors
END

start-ver=1.4
cd-journal=joma
no-vol=136
cd-vols=
no-issue=1
article-no=
start-page=4
end-page=6
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 2022 Incentive Award of the Okayama Medical Association in General Medical Science (2022 Yuuki Prize)
kn-title=令和４年度岡山医学会賞　総合研究奨励賞（結城賞）
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=MeguriYusuke
en-aut-sei=Meguri
en-aut-mei=Yusuke
kn-aut-name=廻勇輔
kn-aut-sei=廻
kn-aut-mei=勇輔
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Hematology, Oncology and Respitatory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科　血液・腫瘍・呼吸器内科学
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=2
article-no=
start-page=185
end-page=191
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The global pandemic of coronavirus infection 2019 (COVID-19) was an unprecedented public health emergency. Several clinical studies reported that heart disease, lung disease, diabetes, hypertension, dyslipidemia, and obesity are critical risk factors for increased severity of and hospitalization for COVID-19. This is largely because patients with these underlying medical conditions can show poor immune responses to the COVID-19 vaccinations. Diabetes is one of the underlying conditions most highly associated with COVID-19 susceptibility and is considered a predictor of poor prognosis of COVID-19. We therefore investigated factors that influence the anti-SARS-CoV-2 spike IgG antibody titer after three doses of vaccination in patients with type 2 diabetes. We found that obesity was associated with low anti-SARS-CoV-2 spike IgG antibody titers following three-dose vaccination in type 2 diabetics. Obese patients with type 2 diabetes may have attenuated vaccine efficacy and require additional vaccination; continuous infection control should be considered in such patients.
en-copyright=
kn-copyright=

en-aut-name=TakahashiHiroko
en-aut-sei=Takahashi
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NakayamaMasanori
en-aut-sei=Nakayama
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=obesity
kn-keyword=obesity
en-keyword=type 2 diabetes
kn-keyword=type 2 diabetes
en-keyword=COVID-19
kn-keyword=COVID-19
en-keyword=vaccination
kn-keyword=vaccination
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=2
article-no=
start-page=151
end-page=161
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.
en-copyright=
kn-copyright=

en-aut-name=KomatsubaraTadashi
en-aut-sei=Komatsubara
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HaseiJoe
en-aut-sei=Hasei
en-aut-mei=Joe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OmoriToshinori
en-aut-sei=Omori
en-aut-mei=Toshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SugiuKazuhisa
en-aut-sei=Sugiu
en-aut-mei=Kazuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MochizukiYusuke
en-aut-sei=Mochizuki
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=DemiyaKoji
en-aut-sei=Demiya
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YoshidaAki
en-aut-sei=Yoshida
en-aut-mei=Aki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FujiwaraTomohiro
en-aut-sei=Fujiwara
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KunisadaToshiyuki
en-aut-sei=Kunisada
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=soft-tissue sarcoma
kn-keyword=soft-tissue sarcoma
en-keyword=radiotherapy
kn-keyword=radiotherapy
en-keyword=oncolytic adenovirus
kn-keyword=oncolytic adenovirus
en-keyword=p53
kn-keyword=p53
en-keyword=BCL-xL
kn-keyword=BCL-xL
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=7
article-no=
start-page=1298
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240327
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features.
en-copyright=
kn-copyright=

en-aut-name=OhsawaKumiko
en-aut-sei=Ohsawa
en-aut-mei=Kumiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MomoseShuji
en-aut-sei=Momose
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishikoriAsami
en-aut-sei=Nishikori
en-aut-mei=Asami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NishimuraMidori Filiz
en-aut-sei=Nishimura
en-aut-mei=Midori Filiz
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=GionYuka
en-aut-sei=Gion
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SawadaKeisuke
en-aut-sei=Sawada
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HigashiMorihiro
en-aut-sei=Higashi
en-aut-mei=Morihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TokuhiraMichihide
en-aut-sei=Tokuhira
en-aut-mei=Michihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TamaruJun-Ichi
en-aut-sei=Tamaru
en-aut-mei=Jun-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SatoYasuharu
en-aut-sei=Sato
en-aut-mei=Yasuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=2
en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University
kn-affil=

affil-num=3
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=4
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=5
en-affil=Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences
kn-affil=

affil-num=6
en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University
kn-affil=

affil-num=7
en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University
kn-affil=

affil-num=8
en-affil=Department of Hematology, Japan Community Health Care Organization Saitama Medical Center
kn-affil=

affil-num=9
en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University
kn-affil=

affil-num=10
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=
en-keyword=classic Hodgkin lymphoma
kn-keyword=classic Hodgkin lymphoma
en-keyword=methotrexate
kn-keyword=methotrexate
en-keyword=immunodeficiency
kn-keyword=immunodeficiency
en-keyword=programmed cell death-ligand 1
kn-keyword=programmed cell death-ligand 1
en-keyword=rheumatoid arthritis
kn-keyword=rheumatoid arthritis
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=2
article-no=
start-page=123
end-page=134
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT.
en-copyright=
kn-copyright=

en-aut-name=SaekiKyosuke
en-aut-sei=Saeki
en-aut-mei=Kyosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FujiwaraHideaki
en-aut-sei=Fujiwara
en-aut-mei=Hideaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SeikeKeisuke
en-aut-sei=Seike
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KuroiTaiga
en-aut-sei=Kuroi
en-aut-mei=Taiga
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NishimoriHisakazu
en-aut-sei=Nishimori
en-aut-mei=Hisakazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MatsuokaKen-ichi
en-aut-sei=Matsuoka
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=FujiiNobuharu
en-aut-sei=Fujii
en-aut-mei=Nobuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Division of Transfusion, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=GVHD
kn-keyword=GVHD
en-keyword=posttransplant cyclophosphamide
kn-keyword=posttransplant cyclophosphamide
en-keyword=hematopoietic cell transplantation
kn-keyword=hematopoietic cell transplantation
en-keyword=HLA-identical
kn-keyword=HLA-identical
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=2
article-no=
start-page=95
end-page=106
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases.
en-copyright=
kn-copyright=

en-aut-name=ItanoJunko
en-aut-sei=Itano
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=neuropeptide y
kn-keyword=neuropeptide y
en-keyword=Y1 receptor
kn-keyword=Y1 receptor
en-keyword=airway immune response
kn-keyword=airway immune response
en-keyword=bronchial epithelial cells
kn-keyword=bronchial epithelial cells
en-keyword=respiratory disease
kn-keyword=respiratory disease
END

start-ver=1.4
cd-journal=joma
no-vol=53
cd-vols=
no-issue=11
article-no=
start-page=1009
end-page=1018
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230825
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Advances in treatment of alveolar soft part sarcoma: an updated review
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Alveolar soft part sarcoma is a rare neoplasm of uncertain histogenesis that belongs to a newly defined category of ultra-rare sarcomas. The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1–TFE3 gene fusion. The natural history of alveolar soft part sarcoma describes indolent behaviour with slow progression in deep soft tissues of the extremities, trunk and head/neck in adolescents and young adults. A high rate of detection of distant metastasis at presentation has been reported, and the most common metastatic sites in decreasing order of frequency are the lung, bone and brain. Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours. Although alveolar soft part sarcoma is refractory to conventional doxorubicin-based chemotherapy, monotherapy or combination therapy using tyrosine kinase inhibitors and immune checkpoint inhibitors have provided antitumor activity and emerged as new treatment strategies. This article provides an overview of the current understanding of this ultra-rare sarcoma and recent advancements in treatments according to the clinical stage of alveolar soft part sarcoma.
en-copyright=
kn-copyright=

en-aut-name=FujiwaraTomohiro
en-aut-sei=Fujiwara
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KunisadaToshiyuki
en-aut-sei=Kunisada
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakataEiji
en-aut-sei=Nakata
en-aut-mei=Eiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NishidaKenji
en-aut-sei=Nishida
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YanaiHiroyuki
en-aut-sei=Yanai
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NakamuraTomoki
en-aut-sei=Nakamura
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TanakaKazuhiro
en-aut-sei=Tanaka
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Orthopaedic Surgery, Mie University
kn-affil=

affil-num=7
en-affil=Department of Advanced Medical Sciences, Oita University
kn-affil=

affil-num=8
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=alveolar soft part sarcoma
kn-keyword=alveolar soft part sarcoma
en-keyword=surgery
kn-keyword=surgery
en-keyword=chemotherapy
kn-keyword=chemotherapy
en-keyword=targeted therapy
kn-keyword=targeted therapy
en-keyword=immunotherapy
kn-keyword=immunotherapy
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=1
article-no=
start-page=4564
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240225
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Longitudinal antibody dynamics after COVID-19 vaccine boosters based on prior infection status and booster doses
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Global concern over COVID-19 vaccine distribution disparities highlights the need for strategic booster shots. We explored longitudinal antibody responses post-booster during the Omicron wave in a Japanese cohort, emphasizing prior infection and booster doses. This prospective cohort study included 1763 participants aged 18 years and older with at least three vaccine doses (7376 datapoints). Antibody levels were measured every 2 months. We modeled temporal declines in antibody levels after COVID-19 vaccine boosters according to prior infection status and booster doses using a Bayesian linear mixed-effects interval-censored model, considering age, sex, underlying conditions, and lifestyle. Prior infection enhanced post-booster immunity (posterior median 0.346, 95% credible interval [CrI] 0.335-0.355), maintaining antibody levels (posterior median 0.021; 95% CrI 0.019-0.023) over 1 year, in contrast to uninfected individuals whose levels had waned by 8 months post-vaccination. Each additional booster was correlated with higher baseline antibody levels and slower declines, comparing after the third dose. Female sex, older age, immunosuppressive status, and smoking history were associated with lower baseline post-vaccination antibodies, but not associated with decline rates except for older age in the main model. Prior infection status and tailored, efficient, personalized booster strategies are crucial, considering sex, age, health conditions, and lifestyle.
en-copyright=
kn-copyright=

en-aut-name=MatsumotoNaomi
en-aut-sei=Matsumoto
en-aut-mei=Naomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SasakiAyako
en-aut-sei=Sasaki
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KadowakiTomoka
en-aut-sei=Kadowaki
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MitsuhashiToshiharu
en-aut-sei=Mitsuhashi
en-aut-mei=Toshiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakaoSoshi
en-aut-sei=Takao
en-aut-mei=Soshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YorifujiTakashi
en-aut-sei=Yorifuji
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Epidemiology, Graduate School of  Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Epidemiology, Graduate School of  Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Center for Innovative  Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=150
cd-vols=
no-issue=2
article-no=
start-page=89
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240212
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC.<br>
Methods We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003).<br>
Results A total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p < 0.001). Patients who received ICIs for more than 6 months were categorized into the durable clinical benefit (DCB) group (24 patients), and those who received ICIs for less than 6 months into the Non-DCB group (43 patients). The overall survival in the DCB group exhibited longer than the Non-DCB group (69.3 vs. 47.1 months), and an equivalent compared to that in the Non-ICI group (69.3 vs. 68.9 months). Multivariate analysis for time to next treatment (TTNT) of ICIs showed that a poor PS was associated with a shorter TTNT [hazard ratio (HR) 3.309; p < 0.001]. Patients who were treated with ICIs and chemotherapy combination were associated with a longer TTNT (HR 0.389; p = 0.003). In addition, minor EGFR mutation was associated with a long TTNT (HR 0.450; p = 0.046).<br>
Conclusion ICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.<br>
en-copyright=
kn-copyright=

en-aut-name=KuribayashiTadahiro
en-aut-sei=Kuribayashi
en-aut-mei=Tadahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TsubataYukari
en-aut-sei=Tsubata
en-aut-mei=Yukari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IshikawaNobuhisa
en-aut-sei=Ishikawa
en-aut-mei=Nobuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KodaniMasahiro
en-aut-sei=Kodani
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KanajiNobuhiro
en-aut-sei=Kanaji
en-aut-mei=Nobuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YamasakiMasahiro
en-aut-sei=Yamasaki
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujitakaKazunori
en-aut-sei=Fujitaka
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KuyamaShoichi
en-aut-sei=Kuyama
en-aut-mei=Shoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TakigawaNagio
en-aut-sei=Takigawa
en-aut-mei=Nagio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujimotoNobukazu
en-aut-sei=Fujimoto
en-aut-mei=Nobukazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KubotaTetsuya
en-aut-sei=Kubota
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=InoueMasaaki
en-aut-sei=Inoue
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=FujiwaraKeiichi
en-aut-sei=Fujiwara
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=HaritaShingo
en-aut-sei=Harita
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=TakataIchiro
en-aut-sei=Takata
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=TakadaKenji
en-aut-sei=Takada
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Faculty of Medicine, Shimane University
kn-affil=

affil-num=6
en-affil=Department of Respiratory Medicine, Hiroshima Prefectural Hospital
kn-affil=

affil-num=7
en-affil=Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University
kn-affil=

affil-num=8
en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology, and Respiratory Medicine, Faculty of Medicine, Kagawa University
kn-affil=

affil-num=9
en-affil=Department of Respiratory Medicine, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital
kn-affil=

affil-num=10
en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences
kn-affil=

affil-num=11
en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center
kn-affil=

affil-num=12
en-affil=Department of Internal Medicine 4, Kawasaki Medical School
kn-affil=

affil-num=13
en-affil=Department of Medical Oncology, Okayama Rosai Hospital
kn-affil=

affil-num=14
en-affil=Department of Respiratory Medicine and Allergology, Kochi University Hospital
kn-affil=

affil-num=15
en-affil=Department of Chest Surgery, Shimonoseki City Hospital
kn-affil=

affil-num=16
en-affil=Department of Respiratory Medicine, NHO Okayama Medical Center
kn-affil=

affil-num=17
en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital
kn-affil=

affil-num=18
en-affil=Internal Medicine, Fukuyama City Hospital
kn-affil=

affil-num=19
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=20
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=21
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=22
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=EGFR
kn-keyword=EGFR
en-keyword=EGFR-TKI
kn-keyword=EGFR-TKI
en-keyword=Lung cancer
kn-keyword=Lung cancer
en-keyword=Immune checkpoint inhibitors
kn-keyword=Immune checkpoint inhibitors
en-keyword=Performance status
kn-keyword=Performance status
END

start-ver=1.4
cd-journal=joma
no-vol=43
cd-vols=
no-issue=2
article-no=
start-page=113797
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240227
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors exert clinical efficacy against various types of cancer through reinvigoration of exhausted CD8+ T cells that attack cancer cells directly in the tumor microenvironment (TME). Using single-cell sequencing and mouse models, we show that CXCL13, highly expressed in tumor-infiltrating exhausted CD8+ T cells, induces CD4+ follicular helper T (TFH) cell infiltration, contributing to anti-tumor immunity. Furthermore, a part of the TFH cells in the TME exhibits cytotoxicity and directly attacks major histocompatibility complex-II-expressing tumors. TFH-like cytotoxic CD4+ T cells have high LAG-3/BLIMP1 and low TCF1 expression without self-renewal ability, whereas non-cytotoxic TFH cells express low LAG-3/BLIMP1 and high TCF1 with self-renewal ability, closely resembling the relationship between terminally differentiated and stem-like progenitor exhaustion in CD8+ T cells, respectively. Our findings provide deep insights into TFH-like CD4+ T cell exhaustion with helper progenitor and cytotoxic differentiated functions, mediating anti-tumor immunity orchestrally with CD8+ T cells.
en-copyright=
kn-copyright=

en-aut-name=ZhouWenhao
en-aut-sei=Zhou
en-aut-mei=Wenhao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IshinoTakamasa
en-aut-sei=Ishino
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KawaseKatsushige
en-aut-sei=Kawase
en-aut-mei=Katsushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YamashitaKazuo
en-aut-sei=Yamashita
en-aut-mei=Kazuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=WatanabeTomofumi
en-aut-sei=Watanabe
en-aut-mei=Tomofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=DansakoHiromichi
en-aut-sei=Dansako
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SuzukiYutaka
en-aut-sei=Suzuki
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NishikawaHiroyoshi
en-aut-sei=Nishikawa
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=InozumeTakashi
en-aut-sei=Inozume
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Dermatology, Chiba University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=5
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=KOTAI Biotechnologies, Inc. 
kn-affil=

affil-num=7
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Chiba Cancer Center, Research Institute, Division of Cell Therapy
kn-affil=

affil-num=9
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
kn-affil=

affil-num=11
en-affil=Department of Immunology, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Department of Dermatology, Chiba University Graduate School of Medicine
kn-affil=

affil-num=13
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cancer immunology
kn-keyword=cancer immunology
en-keyword=follicular helper T cell
kn-keyword=follicular helper T cell
en-keyword=cytotoxic CD4+ T cell
kn-keyword=cytotoxic CD4+ T cell
en-keyword=CXCL13
kn-keyword=CXCL13
en-keyword=T cell exhaustion
kn-keyword=T cell exhaustion
en-keyword=stem-like progenitor exhaustion
kn-keyword=stem-like progenitor exhaustion
en-keyword=terminally differentiated exhaustion
kn-keyword=terminally differentiated exhaustion
en-keyword=PD-1
kn-keyword=PD-1
en-keyword=LAG-3
kn-keyword=LAG-3
en-keyword=TCF1
kn-keyword=TCF1
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=1
article-no=
start-page=1
end-page=8
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202402
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Role of Macrophages in Liver Fibrosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Liver fibrosis, which ultimately leads to liver cirrhosis and hepatocellular carcinoma, is a major health burden worldwide. The progression of liver fibrosis is the result of the wound-healing response of liver to repeated injury. Hepatic macrophages are cells with high heterogeneity and plasticity and include tissue-resident macrophages termed Kupffer cells, and recruited macrophages derived from circulating monocytes, spleen and peritoneal cavity. Studies have shown that hepatic macrophages play roles in the initiation and progression of liver fibrosis by releasing inflammatory cytokines/chemokines and pro-fibrogenic factors. Furthermore, the development of liver fibrosis has been shown to be reversible. Hepatic macrophages have been shown to alternately regulate both the regression and turnover of liver fibrosis by changing their phenotypes during the dynamic progression of liver fibrosis. In this review, we summarize the role of hepatic macrophages in the progression and regression of liver fibrosis.
en-copyright=
kn-copyright=

en-aut-name=SunCuiming
en-aut-sei=Sun
en-aut-mei=Cuiming
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=ERK-MAPK
kn-keyword=ERK-MAPK
en-keyword=SPRED2
kn-keyword=SPRED2
en-keyword=fibrosis
kn-keyword=fibrosis
en-keyword=macrophages
kn-keyword=macrophages
END

start-ver=1.4
cd-journal=joma
no-vol=130
cd-vols=
no-issue=7
article-no=
start-page=1187
end-page=1195
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240205
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702).<br>
Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps).<br>
Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection.<br>
Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.
en-copyright=
kn-copyright=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KadowakiDaisuke
en-aut-sei=Kadowaki
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YoshidaYusuke
en-aut-sei=Yoshida
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SakamotoMasaki
en-aut-sei=Sakamoto
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HamadaYuki
en-aut-sei=Hamada
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SugimotoRyoma
en-aut-sei=Sugimoto
en-aut-mei=Ryoma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YagiChiaki
en-aut-sei=Yagi
en-aut-mei=Chiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OhtaniTomoko
en-aut-sei=Ohtani
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KumonKento
en-aut-sei=Kumon
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=YasuiKazuya
en-aut-sei=Yasui
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=YagiTakahito
en-aut-sei=Yagi
en-aut-mei=Takahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=18
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=20
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=64
cd-vols=
no-issue=1
article-no=
start-page=1
end-page=9
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=2024
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/ lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.
en-copyright=
kn-copyright=

en-aut-name=OkataniTakeshi
en-aut-sei=Okatani
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishimuraMidori Filiz
en-aut-sei=Nishimura
en-aut-mei=Midori Filiz
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=EgusaYuria
en-aut-sei=Egusa
en-aut-mei=Yuria
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YoshidaSayako
en-aut-sei=Yoshida
en-aut-mei=Sayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NishimuraYoshito
en-aut-sei=Nishimura
en-aut-mei=Yoshito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishikoriAsami
en-aut-sei=Nishikori
en-aut-mei=Asami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YamamotoHidetaka
en-aut-sei=Yamamoto
en-aut-mei=Hidetaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SatoYasuharu
en-aut-sei=Sato
en-aut-mei=Yasuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Pathology and Oncology, Okayama University  Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of  Health Sciences
kn-affil=

affil-num=3
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of  Health Sciences
kn-affil=

affil-num=4
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of  Health Sciences
kn-affil=

affil-num=5
en-affil=Department of General Medicine, Okayama University Graduate School  of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of  Health Sciences
kn-affil=

affil-num=7
en-affil=Department of Pathology and Oncology, Okayama University  Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Pathology and Oncology, Okayama University  Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of  Health Sciences
kn-affil=
en-keyword=methotrexate-associated lymphoproliferative disorders
kn-keyword=methotrexate-associated lymphoproliferative disorders
en-keyword=other iatrogenic immunodeficiency-associated lymphoproliferative disorders
kn-keyword=other iatrogenic immunodeficiency-associated lymphoproliferative disorders
en-keyword=lymphoproliferative disorders arising in immune deficiency/dysregulation
kn-keyword=lymphoproliferative disorders arising in immune deficiency/dysregulation
en-keyword=NOTCH1
kn-keyword=NOTCH1
END

start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=1
article-no=
start-page=1
end-page=12
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240118
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Rhizoviticin is an alphaproteobacterial tailocin that mediates biocontrol of grapevine crown gall disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Tailocins are headless phage tail structures that mediate interbacterial antagonism. Although the prototypical tailocins, R- and F-pyocins, in Pseudomonas aeruginosa, and other predominantly R-type tailocins have been studied, their presence in Alphaproteobacteria remains unexplored. Here, we report the first alphaproteobacterial F-type tailocin, named rhizoviticin, as a determinant of the biocontrol activity of Allorhizobium vitis VAR03-1 against crown gall. Rhizoviticin is encoded by a chimeric prophage genome, one providing transcriptional regulators and the other contributing to tail formation and cell lysis, but lacking head formation genes. The rhizoviticin genome retains a nearly intact early phage region containing an integrase remnant and replication-related genes critical for downstream gene transcription, suggesting an ongoing transition of this locus from a prophage to a tailocin-coding region. Rhizoviticin is responsible for the most antagonistic activity in VAR03-1 culture supernatant against pathogenic A. vitis strain, and rhizoviticin deficiency resulted in a significant reduction in the antitumorigenic activity in planta. We identified the rhizoviticin-coding locus in eight additional A. vitis strains from diverse geographical locations, highlighting a unique survival strategy of certain Rhizobiales bacteria in the rhizosphere. These findings advance our understanding of the evolutionary dynamics of tailocins and provide a scientific foundation for employing rhizoviticin-producing strains in plant disease control.
en-copyright=
kn-copyright=

en-aut-name=IshiiTomoya
en-aut-sei=Ishii
en-aut-mei=Tomoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TsuchidaNatsuki
en-aut-sei=Tsuchida
en-aut-mei=Natsuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HemeldaNiarsi Merry
en-aut-sei=Hemelda
en-aut-mei=Niarsi Merry
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SaitoKirara
en-aut-sei=Saito
en-aut-mei=Kirara
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=BaoJiyuan
en-aut-sei=Bao
en-aut-mei=Jiyuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=WatanabeMegumi
en-aut-sei=Watanabe
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ToyodaAtsushi
en-aut-sei=Toyoda
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MatsubaraTakehiro
en-aut-sei=Matsubara
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SatoMayuko
en-aut-sei=Sato
en-aut-mei=Mayuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ToyookaKiminori
en-aut-sei=Toyooka
en-aut-mei=Kiminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=IshihamaNobuaki
en-aut-sei=Ishihama
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ShirasuKen
en-aut-sei=Shirasu
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MatsuiHidenori
en-aut-sei=Matsui
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=ToyodaKazuhiro
en-aut-sei=Toyoda
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=IchinoseYuki
en-aut-sei=Ichinose
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=HayashiTetsuya
en-aut-sei=Hayashi
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KawaguchiAkira
en-aut-sei=Kawaguchi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=NoutoshiYoshiteru
en-aut-sei=Noutoshi
en-aut-mei=Yoshiteru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

affil-num=1
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Faculty of Agriculture, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Genomics and Evolutionary Biology, National Institute of Genetics
kn-affil=

affil-num=8
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Mass Spectrometry and Microscopy Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=10
en-affil=Mass Spectrometry and Microscopy Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=11
en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=12
en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=13
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=14
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=15
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=16
en-affil=Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University
kn-affil=

affil-num=17
en-affil=Western Region Agricultural Research Center (WARC), National Agricultural and Food Research Organization (NARO)
kn-affil=

affil-num=18
en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=
en-keyword=tailocin
kn-keyword=tailocin
en-keyword=phage tail-like bacteriocin
kn-keyword=phage tail-like bacteriocin
en-keyword=Allorhizobium vitris
kn-keyword=Allorhizobium vitris
en-keyword=Alphaproteobacteria
kn-keyword=Alphaproteobacteria
en-keyword=biocontrol
kn-keyword=biocontrol
en-keyword=crown gall disease
kn-keyword=crown gall disease
en-keyword=interbacterial antagonism
kn-keyword=interbacterial antagonism
en-keyword=grapevine
kn-keyword=grapevine
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=118
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240106
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Hydrogen in Transplantation: Potential Applications and Therapeutic Implications
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and signaling pathways. Furthermore, hydrogen's capacity to activate cytoprotective pathways bolsters cellular resilience against stressors. In recent decades, significant advancements have been made in the critical medical procedure of transplantation. However, persistent challenges such as ischemia-reperfusion injury (IRI) and graft rejection continue to hinder transplant success rates. This comprehensive review explores the potential applications and therapeutic implications of hydrogen in transplantation, shedding light on its role in mitigating IRI, improving graft survival, and modulating immune responses. Through a meticulous analysis encompassing both preclinical and clinical studies, we aim to provide valuable insights into the promising utility of hydrogen as a complementary therapy in transplantation.
en-copyright=
kn-copyright=

en-aut-name=ObaraTakafumi
en-aut-sei=Obara
en-aut-mei=Takafumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NaitoHiromichi
en-aut-sei=Naito
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NojimaTsuyoshi
en-aut-sei=Nojima
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HirayamaTakahiro
en-aut-sei=Hirayama
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HongoTakashi
en-aut-sei=Hongo
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AgetaKohei
en-aut-sei=Ageta
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AokageToshiyuki
en-aut-sei=Aokage
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HisamuraMasaki
en-aut-sei=Hisamura
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YumotoTetsuya
en-aut-sei=Yumoto
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NakaoAtsunori
en-aut-sei=Nakao
en-aut-mei=Atsunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=hydrogen
kn-keyword=hydrogen
en-keyword=organ transplantation
kn-keyword=organ transplantation
en-keyword=ischemia reperfusion
kn-keyword=ischemia reperfusion
END

start-ver=1.4
cd-journal=joma
no-vol=30
cd-vols=
no-issue=3
article-no=
start-page=236
end-page=241
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202403
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Relevance of complement immunity with brain fog in patients with long COVID
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction<br>
This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50).<br>
<br>
Methods<br>
This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors.<br>
<br>
Results<br>
Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33–5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04–2.66).<br>
<br>
Conclusions<br>
High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID.
en-copyright=
kn-copyright=

en-aut-name=HagiyaHideharu
en-aut-sei=Hagiya
en-aut-mei=Hideharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TokumasuKazuki
en-aut-sei=Tokumasu
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OtsukaYuki
en-aut-sei=Otsuka
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SunadaNaruhiko
en-aut-sei=Sunada
en-aut-mei=Naruhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NakanoYasuhiro
en-aut-sei=Nakano
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HondaHiroyuki
en-aut-sei=Honda
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FurukawaMasanori
en-aut-sei=Furukawa
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OtsukaFumio
en-aut-sei=Otsuka
en-aut-mei=Fumio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Infectious Diseases, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Clinical Laboratory, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Complement immunity
kn-keyword=Complement immunity
en-keyword=Complement system
kn-keyword=Complement system
en-keyword=Coronavirus disease 2019
kn-keyword=Coronavirus disease 2019
en-keyword=Inflammation
kn-keyword=Inflammation
END

start-ver=1.4
cd-journal=joma
no-vol=4
cd-vols=
no-issue=10
article-no=
start-page=100573
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202310
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs).<br>
Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II–expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo.<br>
Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti–programmed cell death protein 1 monoclonal antibody.<br>
Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs.
en-copyright=
kn-copyright=

en-aut-name=IkedaHideki
en-aut-sei=Ikeda
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ShimizuDaiki
en-aut-sei=Shimizu
en-aut-mei=Daiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KatsuyaYuki
en-aut-sei=Katsuya
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HorinouchiHidehito
en-aut-sei=Horinouchi
en-aut-mei=Hidehito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HosomiYukio
en-aut-sei=Hosomi
en-aut-mei=Yukio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TanjiEtsuko
en-aut-sei=Tanji
en-aut-mei=Etsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=IwataTakekazu
en-aut-sei=Iwata
en-aut-mei=Takekazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ItamiMakiko
en-aut-sei=Itami
en-aut-mei=Makiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=OheYuichiro
en-aut-sei=Ohe
en-aut-mei=Yuichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SuzukiTakuji
en-aut-sei=Suzuki
en-aut-mei=Takuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=2
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=3
en-affil=Division of Thoracic Surgery, Chiba Cancer Center
kn-affil=

affil-num=4
en-affil=Department of Experimental Therapeutics, National Cancer Center Hospital
kn-affil=

affil-num=5
en-affil=Department of Thoracic Oncology, National Cancer Center Hospital
kn-affil=

affil-num=6
en-affil=Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
kn-affil=

affil-num=7
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=8
en-affil=Division of Thoracic Surgery, Chiba Cancer Center
kn-affil=

affil-num=9
en-affil=Department of Surgical Pathology, Chiba Cancer Center
kn-affil=

affil-num=10
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=11
en-affil=Department of Thoracic Oncology, National Cancer Center Hospital
kn-affil=

affil-num=12
en-affil=Department of Respirology, Graduate School of Medicine, Chiba University
kn-affil=

affil-num=13
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Thymic epithelial tumor
kn-keyword=Thymic epithelial tumor
en-keyword=Cancer immunotherapy
kn-keyword=Cancer immunotherapy
en-keyword=CD80/CD86
kn-keyword=CD80/CD86
en-keyword=MHC
kn-keyword=MHC
en-keyword=Memory precursor effector T cell
kn-keyword=Memory precursor effector T cell
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=12
article-no=
start-page=1706
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231124
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Roles of Human Endogenous Retroviruses and Endogenous Virus-Like Elements in Cancer Development and Innate Immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in the host genome. Although mutations and silencing mechanisms impair their original role in viral replication, HERVs are believed to play roles in various biological processes. Long interspersed nuclear elements (LINEs) are non-LTR retrotransposons that have a lifecycle resembling that of retroviruses. Although LINE expression is typically silenced in somatic cells, it also contributes to various biological processes. The aberrant expression of HERVs and LINEs is closely associated with the development of cancer and/or immunological diseases, suggesting that they are integrated into various pathways related to the diseases. HERVs/LINEs control gene expression depending on the context as promoter/enhancer elements. Some RNAs and proteins derived from HERVs/LINEs have oncogenic potential, whereas others stimulate innate immunity. Non-retroviral endogenous viral elements (nrEVEs) are a novel type of virus-like element in the genome. nrEVEs may also be involved in host immunity. This article provides a current understanding of how these elements impact cellular physiology in cancer development and innate immunity, and provides perspectives for future studies.
en-copyright=
kn-copyright=

en-aut-name=KatohHirokazu
en-aut-sei=Katoh
en-aut-mei=Hirokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HondaTomoyuki
en-aut-sei=Honda
en-aut-mei=Tomoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=HERVs
kn-keyword=HERVs
en-keyword=LINEs
kn-keyword=LINEs
en-keyword=cancer
kn-keyword=cancer
en-keyword=innate immunity
kn-keyword=innate immunity
en-keyword=promoter
kn-keyword=promoter
en-keyword=enhancer
kn-keyword=enhancer
en-keyword=interferon signaling
kn-keyword=interferon signaling
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=24
article-no=
start-page=5873
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231217
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Diagnosis and Treatment Approach for Oligo-Recurrent and Oligo-Progressive Renal Cell Carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=One-third of renal cell carcinomas (RCCs) without metastases develop metastatic disease after extirpative surgery for the primary tumors. The majority of metastatic RCC cases, along with treated primary lesions, involve limited lesions termed “oligo-recurrent” disease. The role of metastasis-directed therapy (MDT), including stereotactic body radiation therapy (SBRT) and metastasectomy, in the treatment of oligo-recurrent RCC has evolved. Although the surgical resection of all lesions alone can have a curative intent, SBRT is a valuable treatment option, especially for patients concurrently receiving systemic therapy. Contemporary immune checkpoint inhibitor (ICI) combination therapies remain central to the management of metastatic RCC. However, one objective of MDT is to delay the initiation of systemic therapies, thereby sparing patients from potentially unnecessary burdens. Undertaking MDT for cases showing progression under systemic therapies, known as “oligo-progression”, can be complex in considering the treatment approach. Its efficacy may be diminished compared to patients with stable disease. SBRT combined with ICI can be a promising treatment for these cases because radiation therapy has been shown to affect the tumor microenvironment and areas beyond the irradiated sites. This may enhance the efficacy of ICIs, although their efficacy has only been demonstrated in clinical trials.
en-copyright=
kn-copyright=

en-aut-name=BekkuKensuke
en-aut-sei=Bekku
en-aut-mei=Kensuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawadaTatsushi
en-aut-sei=Kawada
en-aut-mei=Tatsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SekitoTakanori
en-aut-sei=Sekito
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YoshinagaKasumi
en-aut-sei=Yoshinaga
en-aut-mei=Kasumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MaruyamaYuki
en-aut-sei=Maruyama
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YamanoiTomoaki
en-aut-sei=Yamanoi
en-aut-mei=Tomoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TominagaYusuke
en-aut-sei=Tominaga
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SadahiraTakuya
en-aut-sei=Sadahira
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KatayamaSatoshi
en-aut-sei=Katayama
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=IwataTakehiro
en-aut-sei=Iwata
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NishimuraShingo
en-aut-sei=Nishimura
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=EdamuraKohei
en-aut-sei=Edamura
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KobayashiTomoko
en-aut-sei=Kobayashi
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KobayashiYasuyuki
en-aut-sei=Kobayashi
en-aut-mei=Yasuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ArakiMotoo
en-aut-sei=Araki
en-aut-mei=Motoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=NiibeYuzuru
en-aut-sei=Niibe
en-aut-mei=Yuzuru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=12
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=14
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=15
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=16
en-affil=Department of Public Health, School of Medicine, Kurume University
kn-affil=
en-keyword=renal cell carcinoma
kn-keyword=renal cell carcinoma
en-keyword=oligo-metastasis
kn-keyword=oligo-metastasis
en-keyword=oligo-recurrence
kn-keyword=oligo-recurrence
en-keyword=oligo-progression
kn-keyword=oligo-progression
en-keyword=metastasectomy
kn-keyword=metastasectomy
en-keyword=stereotactic body radiation therapy
kn-keyword=stereotactic body radiation therapy
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=6
article-no=
start-page=567
end-page=575
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202312
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Review of a Series of Surveys on Adverse Reactions to the COVID-19 mRNA-1273 Vaccine at Okayama University
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=This paper presents the results of a series of surveys conducted from July 2021 to March 2023 to investigate the post-vaccination adverse reactions to the mRNA-1273 (Moderna) vaccine among faculty, staff, and students at Okayama University. These studies complement the official surveys conducted by the Ministry of Health, Labour and Welfare (MHLW) and provide a more representative picture of adverse reactions in the general population including large numbers of healthy young people. Pain, swelling, redness at the injection site, fever, headache, and malaise were the main adverse reactions reported. The proportion of adverse reactions was generally higher after the second vaccination and decreased with each additional vaccination. No statistically significant differences in the adverse reactions were found for males and females and those with/without a history of allergy, but a lower proportion of fever was observed in older participants and those with underlying medical conditions. We also evaluated the association between adverse reactions and antibody titers after the third vaccination and found no significant differences in antibody levels one month after vaccination. This series of studies highlights the importance of conducting surveys in diverse populations to provide a more representative picture of post-vaccination adverse reactions during a pandemic.
en-copyright=
kn-copyright=

en-aut-name=MatsumotoNaomi
en-aut-sei=Matsumoto
en-aut-mei=Naomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HiguchiChigusa
en-aut-sei=Higuchi
en-aut-mei=Chigusa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MiyajiChikara
en-aut-sei=Miyaji
en-aut-mei=Chikara
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MitsuhashiToshiharu
en-aut-sei=Mitsuhashi
en-aut-mei=Toshiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HagiyaHideharu
en-aut-sei=Hagiya
en-aut-mei=Hideharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakaoSoshi
en-aut-sei=Takao
en-aut-mei=Soshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YorifujiTakashi
en-aut-sei=Yorifuji
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Okayama University Health Service Center
kn-affil=

affil-num=3
en-affil=Okayama University Health Service Center
kn-affil=

affil-num=4
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Infectious Diseases, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=coronavirus disease 2019
kn-keyword=coronavirus disease 2019
en-keyword=adverse reactions
kn-keyword=adverse reactions
en-keyword=mRNA vaccine
kn-keyword=mRNA vaccine
en-keyword=antibody titers
kn-keyword=antibody titers
en-keyword=young adults
kn-keyword=young adults
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=1
article-no=
start-page=204
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231116
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Geriatric nutritional risk index as a prognostic marker of first-line immune checkpoint inhibitor combination therapy in patients with renal cell carcinoma: a retrospective multi-center study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose This study aimed to investigate the effectiveness of the Geriatric Nutritional Risk Index (GNRI) in predicting the efficacy of first-line immune checkpoint inhibitor (ICI) combination therapy for metastatic or unresectable renal cell carcinoma (RCC) and associated patient prognosis.<br>
Methods A retrospective study was conducted using data from 19 institutions. The GNRI was calculated using body mass index and serum albumin level, and patients were classified into two groups using the GNRI values, with 98 set as the cutoff point.<br>
Results In all, 119 patients with clear cell RCC who received first-line drug therapy with ICIs were analyzed. Patients with GNRI >= 98 had significantly better overall survival (OS) (p = 0.008) and cancer-specific survival (CSS) (p = 0.001) rates than those with GNRI < 98; however, progression-free survival (PFS) did not differ significantly. Inverse probability of treatment weighting analysis showed that low GNRI scores were significantly associated with poor OS (p = 0.004) and CSS (p = 0.015). Multivariate analysis showed that the Karnofsky performance status (KPS) score was a better predictor of prognosis (OS; HR 5.17, p < 0.001, CSS; HR 4.82, p = 0.003) than GNRI (OS; HR 0.36, p = 0.066, CSS; HR 0.35, p = 0.072). In a subgroup analysis of patients with a good KPS and GNRI >= 98 vs < 98, the 2-year OS rates were 91.4% vs 66.9% (p = 0.068), 2-year CSS rates were 91.4% vs 70.1% (p = 0.073), and PFS rates were 39.7% vs 21.4 (p = 0.27), respectively.<br>
Conclusion The prognostic efficiency of GNRI was inferior to that of the KPS score at the initiation of the first-line ICI combination therapy for clear cell RCC.
en-copyright=
kn-copyright=

en-aut-name=WatariShogo
en-aut-sei=Watari
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KatayamaSatoshi
en-aut-sei=Katayama
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ShiraishiHiromasa
en-aut-sei=Shiraishi
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TokunagaMoto
en-aut-sei=Tokunaga
en-aut-mei=Moto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KubotaRisa
en-aut-sei=Kubota
en-aut-mei=Risa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KusumiNorihiro
en-aut-sei=Kusumi
en-aut-mei=Norihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IchikawaTakaharu
en-aut-sei=Ichikawa
en-aut-mei=Takaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TsushimaTomoyasu
en-aut-sei=Tsushima
en-aut-mei=Tomoyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KobayashiYasuyuki
en-aut-sei=Kobayashi
en-aut-mei=Yasuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=BekkuKensuke
en-aut-sei=Bekku
en-aut-mei=Kensuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ArakiMotoo
en-aut-sei=Araki
en-aut-mei=Motoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Urology, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=2
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Urology, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=4
en-affil=Department of Urology, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=5
en-affil=Department of Urology, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=6
en-affil=Department of Urology, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=7
en-affil=Department of Urology, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=8
en-affil=Department of Urology, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=9
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Geriatric Nutritional Risk Index
kn-keyword=Geriatric Nutritional Risk Index
en-keyword=Immune checkpoint inhibitor
kn-keyword=Immune checkpoint inhibitor
en-keyword=Renal cell carcinoma
kn-keyword=Renal cell carcinoma
en-keyword=Prognosis
kn-keyword=Prognosis
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=PD-1阻害は、Egfr変異陽性肺癌においてAd-SGE-REICにより誘導されるCD8+T細胞依存性抗腫瘍免疫を増強する
kn-title=PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=NAKASUKATakamasa
en-aut-sei=NAKASUKA
en-aut-mei=Takamasa
kn-aut-name=中須賀崇匡
kn-aut-sei=中須賀
kn-aut-mei=崇匡
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=291
cd-vols=
no-issue=6
article-no=
start-page=1119
end-page=1130
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231020
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Hepatitis C virus NS5B triggers an MDA5-mediated innate immune response by producing dsRNA without the replication of viral genomes
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=During the replication of viral genomes, RNA viruses produce double-stranded RNA (dsRNA), through the activity of their RNA-dependent RNA polymerases (RdRps) as viral replication intermediates. Recognition of viral dsRNA by host pattern recognition receptors – such as retinoic acid-induced gene-I (RIG-I)-like receptors and Toll-like receptor 3 – triggers the production of interferon (IFN)-β via the activation of IFN regulatory factor (IRF)-3. It has been proposed that, during the replication of viral genomes, each of RIG-I and melanoma differentiation-associated gene 5 (MDA5) form homodimers for the efficient activation of a downstream signalling pathway in host cells. We previously reported that, in the non-neoplastic human hepatocyte line PH5CH8, the RdRp NS5B derived from hepatitis C virus (HCV) could induce IFN-β expression by its RdRp activity without the actual replication of viral genomes. However, the exact mechanism by which HCV NS5B produced IFN-β remained unknown. In the present study, we first showed that NS5B derived from another Flaviviridae family member, GB virus B (GBV-B), also possessed the ability to induce IFN-β in PH5CH8 cells. Similarly, HCV NS5B, but not its G317V mutant, which lacks RdRp activity, induced the dimerization of MDA5 and subsequently the activation of IRF-3. Interestingly, immunofluorescence analysis showed that HCV NS5B produced dsRNA. Like HCV NS5B, GBV-B NS5B also triggered the production of dsRNA and subsequently the dimerization of MDA5. Taken together, our results show that HCV NS5B triggers an MDA5-mediated innate immune response by producing dsRNA without the replication of viral genomes in human hepatocytes.
en-copyright=
kn-copyright=

en-aut-name=DansakoHiromichi
en-aut-sei=Dansako
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IkedaMasanori
en-aut-sei=Ikeda
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AriumiYasuo
en-aut-sei=Ariumi
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KatoNobuyuki
en-aut-sei=Kato
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Division of Biological Information Technology, Joint Research Center for Human Retrovirus Infection, Kagoshima University
kn-affil=

affil-num=3
en-affil=Management Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases
kn-affil=

affil-num=4
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=double-stranded RNA
kn-keyword=double-stranded RNA
en-keyword=hepatitis C virus
kn-keyword=hepatitis C virus
en-keyword=innate immunity
kn-keyword=innate immunity
en-keyword=RIG-I-like receptor
kn-keyword=RIG-I-like receptor
en-keyword=RNA virus
kn-keyword=RNA virus
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=
article-no=
start-page=1239598
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231010
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=“Input/output cytokines” in epidermal keratinocytes and the involvement in inflammatory skin diseases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases. The purpose of this review is to provide foundation of knowledge on the cytokines which are recognized or produced by epidermal keratinocytes. Since a number of biologics for skin diseases have appeared, it is necessary to fully understand the relationship between epidermal keratinocytes and the cytokines. In this review, the cytokines recognized by epidermal keratinocytes are specifically introduced as "input cytokines", and the produced cytokines as "output cytokines". Furthermore, we also refer to the existence of biologics against those input and output cytokines, and the target skin diseases. These use results demonstrate how important targeted cytokines are in real skin diseases, and enhance our understanding of the cytokines.
en-copyright=
kn-copyright=

en-aut-name=MorizaneShin
en-aut-sei=Morizane
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MukaiTomoyuki
en-aut-sei=Mukai
en-aut-mei=Tomoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SunagawaKo
en-aut-sei=Sunagawa
en-aut-mei=Ko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TachibanaKota
en-aut-sei=Tachibana
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KawakamiYoshio
en-aut-sei=Kawakami
en-aut-mei=Yoshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OuchidaMamoru
en-aut-sei=Ouchida
en-aut-mei=Mamoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School
kn-affil=

affil-num=3
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=epidermal keratinocytes
kn-keyword=epidermal keratinocytes
en-keyword=input cytokines
kn-keyword=input cytokines
en-keyword=output cytokines
kn-keyword=output cytokines
en-keyword=biologics
kn-keyword=biologics
en-keyword=inflammatory skin diseases
kn-keyword=inflammatory skin diseases
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=19
article-no=
start-page=3038
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Role of Semaphorin 3A in Kidney Development and Diseases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is a secreted and membrane-associated protein, which regulates diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence has revealed that excess SEMA3A expression and the subsequent signaling pathway aggravate kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports have demonstrated that the inhibition of SEMA3A ameliorated kidney injury via a reduction in cell apoptosis, fibrosis and inflammation; thus, SEMA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized the current knowledge regarding the role of SEMA3A in kidney pathophysiology and their potential use in kidney diseases.
en-copyright=
kn-copyright=

en-aut-name=SangYizhen
en-aut-sei=Sang
en-aut-mei=Yizhen
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TsujiKenji
en-aut-sei=Tsuji
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakanohHiroyuki
en-aut-sei=Nakanoh
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FukushimaKazuhiko
en-aut-sei=Fukushima
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KitamuraShinji
en-aut-sei=Kitamura
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=semaphorin 3A
kn-keyword=semaphorin 3A
en-keyword=neuropilin-1
kn-keyword=neuropilin-1
en-keyword=podocyte
kn-keyword=podocyte
en-keyword=diabetic nephropathy
kn-keyword=diabetic nephropathy
en-keyword=acute kidney injury
kn-keyword=acute kidney injury
en-keyword=chronic kidney injury
kn-keyword=chronic kidney injury
en-keyword=lupus nephritis
kn-keyword=lupus nephritis
en-keyword=fibrosis
kn-keyword=fibrosis
en-keyword=apoptosis
kn-keyword=apoptosis
en-keyword=inflammation
kn-keyword=inflammation
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=1
article-no=
start-page=e000772
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220927
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Association of one-point glucocorticoid-free status with chronic damage and disease duration in systemic lupus erythematosus: a cross-sectional study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objective　It is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status.<br>
Methods　Using data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5–20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index.<br>
Results　GC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0<prednisolone (PSL) ≤5 mg/day in 411 (40%); 5<PSL ≤7.5 in 169 (17%); 7.5<PSL ≤10 in 194 (19%) and PSL≥10 in 144 (14%) patients. Of the patients who were not currently using GCs, patients who never used GC more frequently had short disease duration (66% with short, 23% with middle and 17% with long disease duration, p=0.00029). Univariate analysis of patients who underwent GC treatment showed that patients without GCs exhibited older age, lower disease activity, less immunosuppressant and hydroxychloroquine use and higher C3 levels. Among patients with a disease duration of ≥20 years, GC-free status was more frequent in patients without chronic damage (11% vs 4%, p=0.023). After adjusting for age, sex and disease activity, no chronic damage accrual was associated with GC-free status (OR 3.6, 95% CI 1.1 to 11.3).<br>
Conclusion　Even in the patients with long disease duration, one-point GC-free treatment status might be related to no chronic damage accrual.
en-copyright=
kn-copyright=

en-aut-name=SadaKen-ei
en-aut-sei=Sada
en-aut-mei=Ken-ei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KatayamaYu
en-aut-sei=Katayama
en-aut-mei=Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AsanoYosuke
en-aut-sei=Asano
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HayashiKeigo
en-aut-sei=Hayashi
en-aut-mei=Keigo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MiyawakiYoshia
en-aut-sei=Miyawaki
en-aut-mei=Yoshia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OhashiKeiji
en-aut-sei=Ohashi
en-aut-mei=Keiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KatsuyamaEri
en-aut-sei=Katsuyama
en-aut-mei=Eri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KatsuyamaTakayuki
en-aut-sei=Katsuyama
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=Takano-NarazakiMariko
en-aut-sei=Takano-Narazaki
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MatsumotoYoshinori
en-aut-sei=Matsumoto
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YoshimiRyusuke
en-aut-sei=Yoshimi
en-aut-mei=Ryusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ShimojimaYasuhiro
en-aut-sei=Shimojima
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OhnoShigeru
en-aut-sei=Ohno
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KajiyamaHiroshi
en-aut-sei=Kajiyama
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=IchinoseKunihiro
en-aut-sei=Ichinose
en-aut-mei=Kunihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=SatoShuzo
en-aut-sei=Sato
en-aut-mei=Shuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=FujiwaraMichio
en-aut-sei=Fujiwara
en-aut-mei=Michio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=YajimaNobuyuki
en-aut-sei=Yajima
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
kn-affil=

affil-num=13
en-affil=Center for Rheumatic Diseases, Yokohama City University Medical Center
kn-affil=

affil-num=14
en-affil=Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University
kn-affil=

affil-num=15
en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences
kn-affil=

affil-num=16
en-affil=Department of Rheumatology, Fukushima Medical University School of Medicine
kn-affil=

affil-num=17
en-affil=Department of Rheumatology, Yokohama Rosai Hospital
kn-affil=

affil-num=18
en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine
kn-affil=
en-keyword=systemic lupus erythematosus
kn-keyword=systemic lupus erythematosus
en-keyword=glucocorticoids
kn-keyword=glucocorticoids
en-keyword=outcome assessment
kn-keyword=outcome assessment
en-keyword=health care
kn-keyword=health care
en-keyword=epidemiology
kn-keyword=epidemiology
END

start-ver=1.4
cd-journal=joma
no-vol=192
cd-vols=
no-issue=
article-no=
start-page=273
end-page=284
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The function of the plant cell wall in plant–microbe interactions
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The plant cell wall is an interface of plant–microbe interactions. The ability of microbes to decompose cell wall polysaccharides contributes to microbial pathogenicity. Plants have evolved mechanisms to prevent cell wall degradation. However, the role of the cell wall in plant–microbe interactions is not well understood. Here, we discuss four functions of the plant cell wall—physical defence, storage of antimicrobial compounds, production of cell wall-derived elicitors, and provision of carbon sources—in the context of plant–microbe interactions. In addition, we discuss the four families of cell surface receptors associated with plant cell walls (malectin-like receptor kinase family, wall-associated kinase family, leucine-rich repeat receptor-like kinase family, and lysin motif receptor-like kinase family) that have been the subject of several important studies in recent years. This review summarises the findings on both plant cell wall and plant immunity, improving our understanding and may provide impetus to various researchers.
en-copyright=
kn-copyright=

en-aut-name=IshidaKonan
en-aut-sei=Ishida
en-aut-mei=Konan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NoutoshiYoshiteru
en-aut-sei=Noutoshi
en-aut-mei=Yoshiteru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Biochemistry, University of Cambridge
kn-affil=

affil-num=2
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=
en-keyword=Plant cell wall
kn-keyword=Plant cell wall
en-keyword=Plant–microbe interaction
kn-keyword=Plant–microbe interaction
en-keyword=Cell wall integrity
kn-keyword=Cell wall integrity
en-keyword=Receptor-like kinase
kn-keyword=Receptor-like kinase
en-keyword=Plant immunity
kn-keyword=Plant immunity
END

start-ver=1.4
cd-journal=joma
no-vol=2
cd-vols=
no-issue=7
article-no=
start-page=739
end-page=753
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220728
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mixed Response to Cancer Immunotherapy is Driven by Intratumor Heterogeneity and Differential Interlesion Immune Infiltration
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Some patients experience mixed response to immunotherapy, whose biological mechanisms and clinical impact have been obscure. We obtained two tumor samples from lymph node (LN) metastatic lesions in a same patient. Whole exome sequencing for the both tumors and single-cell sequencing for the both tumor-infiltrating lymphocytes (TIL) demonstrated a significant difference in tumor clonality and TILs' characteristics, especially exhausted T-cell clonotypes, although a close relationship between the tumor cell and T-cell clones were observed as a response of an overlapped exhausted T-cell clone to an overlapped neoantigen. To mimic the clinical setting, we generated a mouse model of several clones from a same tumor cell line. Similarly, differential tumor clones harbored distinct TILs, and one responded to programmed cell death protein 1 (PD-1) blockade but the other did not in this model. We further conducted cohort study (n = 503) treated with PD-1 blockade monotherapies to investigate the outcome of mixed response. Patients with mixed responses to PD-1 blockade had a poor prognosis in our cohort. Particularly, there were significant differences in both tumor and T-cell clones between the primary and LN lesions in a patient who experienced tumor response to anti-PD-1 mAb followed by disease progression in only LN metastasis. Our results underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome.<br>
Significance: Several patients experience mixed responses to immunotherapies, but the biological mechanisms and clinical significance remain unclear. Our results from clinical and mouse studies underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome.
en-copyright=
kn-copyright=

en-aut-name=MorinagaTakao
en-aut-sei=Morinaga
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=InozumeTakashi
en-aut-sei=Inozume
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SaxNicolas
en-aut-sei=Sax
en-aut-mei=Nicolas
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YamashitaKazuo
en-aut-sei=Yamashita
en-aut-mei=Kazuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UenoToshihide
en-aut-sei=Ueno
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=LinJason
en-aut-sei=Lin
en-aut-mei=Jason
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=OharaYuuki
en-aut-sei=Ohara
en-aut-mei=Yuuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KuwataTakeshi
en-aut-sei=Kuwata
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=YukamiHiroki
en-aut-sei=Yukami
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KawazoeAkihito
en-aut-sei=Kawazoe
en-aut-mei=Akihito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ShitaraKohei
en-aut-sei=Shitara
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=Honobe-TabuchiAkiko
en-aut-sei=Honobe-Tabuchi
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=OhnumaTakehiro
en-aut-sei=Ohnuma
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=KawamuraTatsuyoshi
en-aut-sei=Kawamura
en-aut-mei=Tatsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=UmedaYoshiyasu
en-aut-sei=Umeda
en-aut-mei=Yoshiyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=KawaharaYu
en-aut-sei=Kawahara
en-aut-mei=Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=NakamuraYasuhiro
en-aut-sei=Nakamura
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=KiniwaYukiko
en-aut-sei=Kiniwa
en-aut-mei=Yukiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=MoritaAyako
en-aut-sei=Morita
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

en-aut-name=EnokidaTomohiro
en-aut-sei=Enokida
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=

en-aut-name=TaharaMakoto
en-aut-sei=Tahara
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
ORCID=

en-aut-name=HasegawaYoshinori
en-aut-sei=Hasegawa
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=28
ORCID=

en-aut-name=ManoHiroyuki
en-aut-sei=Mano
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=29
ORCID=

en-aut-name=SuzukiYutaka
en-aut-sei=Suzuki
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=30
ORCID=

en-aut-name=NishikawaHiroyoshi
en-aut-sei=Nishikawa
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=31
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=32
ORCID=

affil-num=1
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=2
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=3
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=4
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=KOTAI Biotechnologies Inc
kn-affil=

affil-num=6
en-affil=KOTAI Biotechnologies Inc
kn-affil=

affil-num=7
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=8
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=

affil-num=10
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=11
en-affil=Department of Pathology, National Cancer Center Hospital East
kn-affil=

affil-num=12
en-affil=Department of Genetic Medicineand Services, National Cancer Center Hospital East
kn-affil=

affil-num=13
en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East
kn-affil=

affil-num=14
en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East
kn-affil=

affil-num=15
en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East
kn-affil=

affil-num=16
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=17
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=18
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=19
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=

affil-num=20
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=

affil-num=21
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=

affil-num=22
en-affil=Department of Dermatology, Shinshu University School of Medicine 
kn-affil=

affil-num=23
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=24
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=25
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=26
en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East
kn-affil=

affil-num=27
en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East
kn-affil=

affil-num=28
en-affil=Department of Applied Genomics, Kazusa DNA Research Institute
kn-affil=

affil-num=29
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=

affil-num=30
en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
kn-affil=

affil-num=31
en-affil=Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center
kn-affil=

affil-num=32
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=4
article-no=
start-page=395
end-page=405
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202308
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=−0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=−0.258, t=−2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=−0.247, p=0.019) and antipsychotic treatment duration (ρ=−0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia.
en-copyright=
kn-copyright=

en-aut-name=PavlovicMarko
en-aut-sei=Pavlovic
en-aut-mei=Marko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=BabicDragan
en-aut-sei=Babic
en-aut-mei=Dragan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=RastovicPejana
en-aut-sei=Rastovic
en-aut-mei=Pejana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ArapovicJurica
en-aut-sei=Arapovic
en-aut-mei=Jurica
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MartinacMarko
en-aut-sei=Martinac
en-aut-mei=Marko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=JakovacSanja
en-aut-sei=Jakovac
en-aut-mei=Sanja
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=BarbaricRomana
en-aut-sei=Barbaric
en-aut-mei=Romana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=University Hospital Center Mostar, University of Mostar
kn-affil=

affil-num=2
en-affil=University Hospital Center Mostar, University of Mostar
kn-affil=

affil-num=3
en-affil=University Hospital Center Mostar, University of Mostar
kn-affil=

affil-num=4
en-affil=University Hospital Center Mostar, University of Mostar
kn-affil=

affil-num=5
en-affil=Health Care Center Mostar, University of Mostar
kn-affil=

affil-num=6
en-affil=University Hospital Center Mostar, University of Mostar
kn-affil=

affil-num=7
en-affil=University Hospital Center Mostar, University of Mostar
kn-affil=
en-keyword=tumor necrosis factor-alpha
kn-keyword=tumor necrosis factor-alpha
en-keyword=schizophrenia
kn-keyword=schizophrenia
en-keyword=psychopathology
kn-keyword=psychopathology
en-keyword=immune system
kn-keyword=immune system
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=4
article-no=
start-page=347
end-page=357
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202308
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Feasibility of Flow Cytometry Analysis of Gastrointestinal Tract-Residing Lymphocytes in Hematopoietic Stem Cell Transplant Recipients
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The feasibility of lymphocyte isolation and flow cytometry using a single endoscopic biopsy specimen from the gastrointestinal tract of patients who have undergone hematopoietic stem cell transplantation has not been investigated. We acquired 51 endoscopic biopsy specimens from the gastrointestinal tract of 35 patients. We divided the flow cytometry samples into two groups: group A, successful lymphocyte isolation (n=24), and group B, incomplete isolation (n=27). We compared the backgrounds of the samples between the groups to reveal crucial elements in the successful isolation of lymphocytes residing in the gastrointestinal tract. Comparison between the groups revealed lymphocyte isolation success rates differed between biopsy sites. Isolation was most successful in samples from the duodenum (8/9, 88.9%), followed by the ileum (4/8, 50.0%), large intestine (4/11, 36.4%), and stomach (8/23, 34.8%). Tacrolimus was used more frequently in group B (92.6%) than in group A (62.5%) (p=0.015). Logistic regression analysis revealed that isolation from the duodenum or ileum was a significant factor for successful isolation, while tacrolimus use was not statistically significant. In conclusion, the duodenum and ileum are more suitable sites than the stomach and colorectum for acquiring samples for flow cytometry.
en-copyright=
kn-copyright=

en-aut-name=IwamuroMasaya
en-aut-sei=Iwamuro
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KondoTakumi
en-aut-sei=Kondo
en-aut-mei=Takumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=EnnishiDaisuke
en-aut-sei=Ennishi
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FujiiNobuharu
en-aut-sei=Fujii
en-aut-mei=Nobuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MatsuokaKen-ichi
en-aut-sei=Matsuoka
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakahashiTakahide
en-aut-sei=Takahashi
en-aut-mei=Takahide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HirabataAraki
en-aut-sei=Hirabata
en-aut-mei=Araki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OtsukaFumio
en-aut-sei=Otsuka
en-aut-mei=Fumio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=OkadaHiroyuki
en-aut-sei=Okada
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Division of Medical Support, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Division of Medical Support, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=flow cytometry
kn-keyword=flow cytometry
en-keyword=stem cell transplantation
kn-keyword=stem cell transplantation
en-keyword=transplantation-associated microangiopathy
kn-keyword=transplantation-associated microangiopathy
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=4
article-no=
start-page=341
end-page=345
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202308
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Biological Roles of Hepatitis B Viral X Protein in the Viral Replication and Hepatocarcinogenesis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hepatitis B virus is a pathogenic virus that infects 300 million people worldwide and causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Hepatitis B virus encodes four proteins. Among them, the HBx protein plays a central role in the HBV pathogenesis. Because the HBx protein is considered to play a central role in the induction of viral replication and hepatocarcinogenesis, the regulation of its function could be a key factor in the development of new interventions against hepatitis B. In this review, HBx protein-related viral replication and hepatocarcinogenesis mechanisms are described, with a focus on the recently reported viral replication mechanisms related to degradation of the Smc5/6 protein complex. We also discuss our recent discovery of a compound that inhibits HBx protein-induced degradation of the Smc5/6 protein complex, and that exerts inhibitory effects on both viral replication and hepatocarcinogenesis. Finally, prospects for future research on the HBx protein are described.
en-copyright=
kn-copyright=

en-aut-name=OtsukaMotoyuki
en-aut-sei=Otsuka
en-aut-mei=Motoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Academic Field of Medicine, Density and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=HBx
kn-keyword=HBx
en-keyword=Smc5/6
kn-keyword=Smc5/6
en-keyword=DDB1
kn-keyword=DDB1
en-keyword=nitazoxianide
kn-keyword=nitazoxianide
en-keyword=DNA repair
kn-keyword=DNA repair
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=7
article-no=
start-page=895
end-page=908
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230705
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=High Expression of MHC Class I Overcomes Cancer Immunotherapy Resistance Due to IFNγ Signaling Pathway Defects
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=IFNγ signaling pathway defects are well-known mechanisms of resistance to immune checkpoint inhibitors. However, conflicting data have been reported, and the detailed mechanisms remain unclear. In this study, we have demonstrated that resistance to immune checkpoint inhibitors owing to IFNγ signaling pathway defects may be primarily caused by reduced MHC-I expression rather than by the loss of inhibitory effects on cellular proliferation or decreased chemokine production. In particular, we found that chemokines that recruit effector T cells were mainly produced by immune cells rather than cancer cells in the tumor microenvironment of a mouse model, with defects in IFNγ signaling pathways. Furthermore, we found a response to immune checkpoint inhibitors in a patient with JAK-negative head and neck squamous cell carcinoma whose HLA-I expression level was maintained. In addition, CRISPR screening to identify molecules associated with elevated MHC-I expression independent of IFNγ signaling pathways demonstrated that guanine nucleotide-binding protein subunit gamma 4 (GNG4) maintained MHC-I expression via the NF-κB signaling pathway. Our results indicate that patients with IFNγ signaling pathway defects are not always resistant to immune checkpoint inhibitors and highlight the importance of MHC-I expression among the pathways and the possibility of NF-κB–targeted therapies to overcome such resistance.
en-copyright=
kn-copyright=

en-aut-name=KawaseKatsushige
en-aut-sei=Kawase
en-aut-mei=Katsushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InozumeTakashi
en-aut-sei=Inozume
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TanjiEtsuko
en-aut-sei=Tanji
en-aut-mei=Etsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HanazawaToyoyuki
en-aut-sei=Hanazawa
en-aut-mei=Toyoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=2
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=3
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=5
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=6
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=7
en-affil=Department of Otorhinolaryngology/Head & Neck Surgery, Graduate School of Medicine, Chiba University
kn-affil=

affil-num=8
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=114
cd-vols=
no-issue=10
article-no=
start-page=3848
end-page=3856
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230723
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Combination therapy with hydrogen peroxide and irradiation promotes an abscopal effect in mouse models
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hydrogen peroxide (H2O2) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H2O2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H2O2 on antitumor immunity remain unclear. To investigate the effects of H2O2, especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H2O2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H2O2/RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H2O2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor-draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H2O2/RT combination group. In addition, analyses of tumor-infiltrating lymphocytes showed that the number of CD8+ (cluster of differentiation 8) T cells and the frequency of IFN-γ+ (interferon gamma) CD8+ T cells were higher in the noninjected/nonirradiated tumors in the H2O2/RT group compared to those in the other groups. PD-1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H2O2/RT group. Intratumoral injection of H2O2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD-1 blockade. These findings promote the development of H2O2/RT therapy combined with cancer immunotherapies, even for advanced cancers.
en-copyright=
kn-copyright=

en-aut-name=KemmotsuNaoya
en-aut-sei=Kemmotsu
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ZhuLi
en-aut-sei=Zhu
en-aut-mei=Li
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OtaniYoshihiro
en-aut-sei=Otani
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=DansakoHiromichi
en-aut-sei=Dansako
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FangYue
en-aut-sei=Fang
en-aut-mei=Yue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=DateIsao
en-aut-sei=Date
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Microbial and Biochemical Pharmacy, School of Pharmacy, China Medical University
kn-affil=

affil-num=8
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=abscopal effect
kn-keyword=abscopal effect
en-keyword=dendritic cell
kn-keyword=dendritic cell
en-keyword=hydrogen peroxide
kn-keyword=hydrogen peroxide
en-keyword=radiosensitizer
kn-keyword=radiosensitizer
en-keyword=radiotherapy
kn-keyword=radiotherapy
en-keyword=tumor-draining lymph node
kn-keyword=tumor-draining lymph node
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=5
article-no=
start-page=e39466
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230525
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Collagenous Colitis in a Patient With Gastric Cancer Who Underwent Chemotherapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Herein, we present a case of collagenous colitis in a patient who underwent chemotherapy for gastric cancer, comprising five cycles of S-1 plus oxaliplatin and trastuzumab, followed by five cycles of paclitaxel and ramucirumab and seven cycles of nivolumab. The subsequent initiation of trastuzumab deruxtecan chemotherapy led to the development of grade 3 diarrhea after the second cycle of treatment. Collagenous colitis was diagnosed via colonoscopy and biopsy. The patient's diarrhea improved following the cessation of lansoprazole. This case highlights the importance of considering collagenous colitis as a differential diagnosis, in addition to chemotherapy-induced colitis and immune-related adverse event (irAE) colitis, in patients with similar clinical presentations.
en-copyright=
kn-copyright=

en-aut-name=IwamuroMasaya
en-aut-sei=Iwamuro
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InooShoko
en-aut-sei=Inoo
en-aut-mei=Shoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OtsukaMotoyuki
en-aut-sei=Otsuka
en-aut-mei=Motoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=chemotherapy-induced diarrhea
kn-keyword=chemotherapy-induced diarrhea
en-keyword=immune-related adverse event colitis
kn-keyword=immune-related adverse event colitis
en-keyword=colonoscopy
kn-keyword=colonoscopy
en-keyword=collagenous colitis
kn-keyword=collagenous colitis
END

start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=1
article-no=
start-page=7
end-page=20
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220130
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effectiveness of and Immune Responses to SARS-CoV-2 mRNA Vaccines and Their Mechanisms
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Following the online publication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome in January 2020, two lipid nanoparticle-encapsulated mRNA vaccines, BNT162b2 and mRNA-1273, were rapidly developed and are now being used worldwide to prevent coronavirus disease 2019 (COVID-19). The mRNA of both vaccines encodes the full-length spike protein of SARS-CoV-2, which binds to the host cell receptor angiotensin-converting enzyme 2 and is believed to mediate virus entry into cells. After intramuscular injection of the vaccine, the spike protein is produced in the cells. Both humoral and cellular immune responses to the spike protein are elicited for protection against COVID-19. The efficacy of the two mRNA vaccines against COVID-19 with wild-type SARS-CoV-2 is more than 90% and is slightly decreased with the Delta variant, which is currently the predominant variant in many countries. In this review, the effectiveness of and immune responses to COVID-19 mRNA vaccines and their mechanisms are summarized and discussed. Potential waning immunity and an additional dose of COVID-19 mRNA vaccines are also discussed.
en-copyright=
kn-copyright=

en-aut-name=GohdaEiichi
en-aut-sei=Gohda
en-aut-mei=Eiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Okayama University
kn-affil=
en-keyword=COVID-19
kn-keyword=COVID-19
en-keyword=SARS-CoV-2
kn-keyword=SARS-CoV-2
en-keyword=mRNA vaccine
kn-keyword=mRNA vaccine
en-keyword=immune response
kn-keyword=immune response
END

start-ver=1.4
cd-journal=joma
no-vol=299
cd-vols=
no-issue=4
article-no=
start-page=104587
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=ATP and its metabolite adenosine cooperatively upregulate the antigen-presenting molecules on dendritic cells leading to IFN-gamma production by T cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Dendritic cells (DCs) present foreign antigens to T cells via the major histocompatibility complex (MHC), thereby inducing acquired immune responses. ATP accumulates at sites of inflammation or in tumor tissues, which triggers local inflammatory responses. However, it remains to be clarified how ATP modulates the functions of DCs. In this study, we investigated the effects of extracellular ATP on mouse bone marrow- derived dendritic cells (BMDCs) as well as the potential for subsequent T cell activation. We found that high concentrations of ATP (1 mM) upregulated the cell surface expression levels of MHC-I, MHC-II, and co-stimulatory molecules CD80 and CD86 but not those of co-inhibitory molecules PD-L1 and PD-L2 in BMDCs. Increased surface expression of MHC-I, MHC-II, CD80, and CD86 was inhibited by a pan-P2 receptor antagonist. In addition, the upregulation of MHC-I and MHC-II expression was inhibited by an adenosine P1 receptor antagonist and by inhibitors of CD39 and CD73, which metabolize ATP to adenosine. These results suggest that adenosine is required for the ATP-induced upregulation of MHC-I and MHC-II. In the mixed leukocyte reaction assay, ATP-stimulated BMDCs activated CD4 and CD8T cells and induced interferon-gamma (IFN-gamma) production by these T cells. Collectively, these results suggest that high concentrations of extracellular ATP upregulate the expression of antigenpresenting and co-stimulatory molecules but not that of coinhibitory molecules in BMDCs. Cooperative stimulation of ATP and its metabolite adenosine was required for the upregulation of MHC-I and MHC-II. These ATP-stimulated BMDCs induced the activation of IFN-gamma-producing T cells upon antigen presentation.
en-copyright=
kn-copyright=

en-aut-name=FurutaKazuyuki
en-aut-sei=Furuta
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OnishiHiroka
en-aut-sei=Onishi
en-aut-mei=Hiroka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IkadaYuki
en-aut-sei=Ikada
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MasakiKento
en-aut-sei=Masaki
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TanakaSatoshi
en-aut-sei=Tanaka
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KaitoChikara
en-aut-sei=Kaito
en-aut-mei=Chikara
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University
kn-affil=

affil-num=6
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230324
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=乳がんコホートより免疫関連遺伝子シグネチャーの化学療法の効果と予後予測能の検討
kn-title=Predictive value of immune genomic signatures from breast cancer cohorts containing data for both response to neoadjuvant chemotherapy and prognosis after surgery
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=ZHUYIDAN
en-aut-sei=ZHU
en-aut-mei=YIDAN
kn-aut-name=朱一丹
kn-aut-sei=朱
kn-aut-mei=一丹
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230324
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=加齢性難聴マウスの蝸牛における炎症・免疫関連遺伝子の発現解析
kn-title=Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=URAGUCHIKensuke
en-aut-sei=URAGUCHI
en-aut-mei=Kensuke
kn-aut-name=浦口健介
kn-aut-sei=浦口
kn-aut-mei=健介
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230324
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=同種造血幹細胞移植後の低用量IL−２療法が制御性T細胞およびエフェクターT細胞に与える効果はホストの免疫状態に依存する
kn-title=Responses of regulatory and effector T-cells to low-dose interleukin-2 differ depending on the immune environment after allogeneic stem cell transplantation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=MEGURIYusuke
en-aut-sei=MEGURI
en-aut-mei=Yusuke
kn-aut-name=廽勇輔
kn-aut-sei=廽
kn-aut-mei=勇輔
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=62
cd-vols=
no-issue=9
article-no=
start-page=1319
end-page=1322
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230501
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Fulminant Myocarditis for Non-small-cell Carcinoma of the Lung with Nivolumab and Ipilimumab Plus Chemotherapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 59-year-old man with a high level of antinuclear antibody received nivolumab and ipilimumab plus che-motherapy for lung cancer. Two weeks after the second course, he was admitted with a fever and severe fa-tigue. Laboratory studies showed elevated markers of myocardial damage, and a myocardial biopsy showed inflammatory cell infiltration, damaged myocardial fibers. Myocarditis was diagnosed as an immune-related adverse event (irAE), and high-dose corticosteroids were initiated. However, his cardiac function rapidly worsened, and he died on the fifth day after admission. There is no established treatment strategy for fulmi-nant myocarditis as an irAE, and the further exploration of viable treatment strategies is required.
en-copyright=
kn-copyright=

en-aut-name=NishimuraTomoka
en-aut-sei=Nishimura
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakashimaMitsutaka
en-aut-sei=Nakashima
en-aut-mei=Mitsutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AkagiSatoshi
en-aut-sei=Akagi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KuribayashiTadahiro
en-aut-sei=Kuribayashi
en-aut-mei=Tadahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ItoHiroshi
en-aut-sei=Ito
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=myocarditis
kn-keyword=myocarditis
en-keyword=nivolumab plus ipilimumab
kn-keyword=nivolumab plus ipilimumab
en-keyword=irAE
kn-keyword=irAE
en-keyword=case report
kn-keyword=case report
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=8
article-no=
start-page=e162180
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230424
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Hematopoietic stem cell-derived Tregs are essential for maintaining favorable B cell lymphopoiesis following posttransplant cyclophosphamide
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Posttransplant cyclophosphamide (PTCy) is associated with a low incidence of chronic graft -versus-host disease (cGVHD) following hematopoietic stem cell (HSC) transplantation. Previous studies have shown the important roles of B cell immunity in cGVHD development. Here, we investigated the long-term reconstitution of B lymphopoiesis after PTCy using murine models. We first demonstrated that the immune homeostatic abnormality leading to cGVHD is characterized by an initial increase in effector T cells in the bone marrow and subsequent B and Treg cytopenia. PTCy, but not cyclosporine A or rapamycin, inhibits the initial alloreactive T cell response, which restores intra-bone marrow B lymphogenesis with a concomitant vigorous increase in Tregs. This leads to profound changes in posttransplant B cell homeostasis, including decreased B cell activating factors, increased transitional and regulatory B cells, and decreased germinal center B cells. To identify the cells responsible for PTCy-induced B cell tolerance, we selectively depleted Treg populations that were graft or HSC derived using DEREG mice. Deletion of either Treg population without PTCy resulted in critical B cytopenia. PTCy rescued B lymphopoiesis from graft-derived Treg deletion. In contrast, the negative effect of HSC-derived Treg deletion could not be overcome by PTCy, indicating that HSC-derived Tregs are essential for maintaining favorable B lymphopoiesis following PTCy. These findings define the mechanisms by which PTCy restores homeostasis of the B cell lineage and reestablishes immune tolerance.
en-copyright=
kn-copyright=

en-aut-name=SumiiYuichi
en-aut-sei=Sumii
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KondoTakumi
en-aut-sei=Kondo
en-aut-mei=Takumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IkegawaShuntaro
en-aut-sei=Ikegawa
en-aut-mei=Shuntaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FukumiTakuya
en-aut-sei=Fukumi
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=IwamotoMiki
en-aut-sei=Iwamoto
en-aut-mei=Miki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishimuraMidori Filiz
en-aut-sei=Nishimura
en-aut-mei=Midori Filiz
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SugiuraHiroyuki
en-aut-sei=Sugiura
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SandoYasuhisa
en-aut-sei=Sando
en-aut-mei=Yasuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NakamuraMakoto
en-aut-sei=Nakamura
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MeguriYusuke
en-aut-sei=Meguri
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MatsushitaTakashi
en-aut-sei=Matsushita
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TanimineNaoki
en-aut-sei=Tanimine
en-aut-mei=Naoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KimuraMaiko
en-aut-sei=Kimura
en-aut-mei=Maiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=AsadaNoboru
en-aut-sei=Asada
en-aut-mei=Noboru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=EnnishiDaisuke
en-aut-sei=Ennishi
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=MatsuokaKen-Ichi
en-aut-sei=Matsuoka
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of  Dermatology, Faculty of Medicine, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and  Health Sciences, Hiroshima University
kn-affil=

affil-num=13
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Hematology and Oncology, Okayama  University Hospital
kn-affil=

affil-num=15
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=4
article-no=
start-page=488
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230419
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Recent Advances in Apical Periodontitis Treatment: A Narrative Review
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Apical periodontitis is an inflammatory response caused by pulp infection. It induces bone resorption in the apical and periapical regions of the tooth. The most conservative approach to treat this condition is nonsurgical endodontic treatment. However, clinical failure has been reported with this approach; thus, alternative procedures are required. This review highlights recent literature regarding advanced approaches for the treatment of apical periodontitis. Various therapies, including biological medications, antioxidants, specialized pro-resolving lipid mediators, and stem cell therapy, have been tested to increase the success rate of treatment for apical periodontitis. Some of these approaches remain in the in vivo phase of research, while others have just entered the translational research phase to validate clinical application. However, a detailed understanding of the molecular mechanisms that occur during development of the immunoinflammatory reaction in apical periodontitis remains unclear. The aim of this review was to summarize advanced approaches for the treatment of apical periodontitis. Further research can confirm the potential of these alternative nonsurgical endodontic treatment approaches.
en-copyright=
kn-copyright=

en-aut-name=AriasZulema
en-aut-sei=Arias
en-aut-mei=Zulema
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NizamiMohammed Zahedul Islam
en-aut-sei=Nizami
en-aut-mei=Mohammed Zahedul Islam
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ChenXiaoting
en-aut-sei=Chen
en-aut-mei=Xiaoting
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ChaiXinyi
en-aut-sei=Chai
en-aut-mei=Xinyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=XuBin
en-aut-sei=Xu
en-aut-mei=Bin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KuangCanyan
en-aut-sei=Kuang
en-aut-mei=Canyan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OmoriKazuhiro
en-aut-sei=Omori
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TakashibaShogo
en-aut-sei=Takashiba
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital
kn-affil=

affil-num=3
en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=apical periodontitis
kn-keyword=apical periodontitis
en-keyword=contemporary approaches
kn-keyword=contemporary approaches
en-keyword=nonsurgical endodontic treatment
kn-keyword=nonsurgical endodontic treatment
en-keyword=immune inflammatory disease
kn-keyword=immune inflammatory disease
en-keyword=alternative treatments
kn-keyword=alternative treatments
END

start-ver=1.4
cd-journal=joma
no-vol=134
cd-vols=
no-issue=2
article-no=
start-page=86
end-page=91
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Clusters of coronavirus disease 2019 in medical institutions and elderly care facilities in Okayama Prefecture
kn-title=岡山県内における新型コロナウイルス感染症クラスターの発生時期別特徴について
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=　Coronavirus disease 2019 has spread worldwide and has yet to be contained. The Japanese government has taken measures against the occurrence of clusters. However, there has little evaluation of the occurrence of the clusters and their changes. Therefore, we investigated the occurrence of the clusters in medical institutions and elderly care facilities in Okayama Prefecture.<br>
　We compared the characteristics of the clusters that occurred in each of the wave between October 21, 2020, and September 30, 2021, by using the data published that interval. As a case study, we also evaluated the characteristics of positive patients at a medical institution over where a cluster occurred in case the fourth wave.<br>
　The overall number of cluster outbreaks decreased with the spread of vaccination. In the fourth wave, there was a period in which the vaccination of staff members at medical institutions became widespread, while patients or facility users were unvaccinated, resulting in a longer convergence period and an increase in the number of positive cases among patients relative to the number of staff members.<br>
　The impact of the spread of vaccination and the duration of immunity acquired after vaccination on the occurrence of clusters should be closely monitored in the future.
en-copyright=
kn-copyright=

en-aut-name=KadowakiTomoka
en-aut-sei=Kadowaki
en-aut-mei=Tomoka
kn-aut-name=門脇知花
kn-aut-sei=門脇
kn-aut-mei=知花
aut-affil-num=1
ORCID=

en-aut-name=IrieSaori
en-aut-sei=Irie
en-aut-mei=Saori
kn-aut-name=入江佐織
kn-aut-sei=入江
kn-aut-mei=佐織
aut-affil-num=2
ORCID=

en-aut-name=TakahashiYukari
en-aut-sei=Takahashi
en-aut-mei=Yukari
kn-aut-name=髙橋友香里
kn-aut-sei=髙橋
kn-aut-mei=友香里
aut-affil-num=3
ORCID=

en-aut-name=YakushijiHiromasa
en-aut-sei=Yakushiji
en-aut-mei=Hiromasa
kn-aut-name=薬師寺泰匡
kn-aut-sei=薬師寺
kn-aut-mei=泰匡
aut-affil-num=4
ORCID=

en-aut-name=TakaoSoshi
en-aut-sei=Takao
en-aut-mei=Soshi
kn-aut-name=高尾総司
kn-aut-sei=高尾
kn-aut-mei=総司
aut-affil-num=5
ORCID=

en-aut-name=YorifujiTakashi
en-aut-sei=Yorifuji
en-aut-mei=Takashi
kn-aut-name=賴藤貴志
kn-aut-sei=賴藤
kn-aut-mei=貴志
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科　疫学・衛生学

affil-num=2
en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科　疫学・衛生学

affil-num=3
en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科　疫学・衛生学

affil-num=4
en-affil=Yakushiji jikei Hospital
kn-affil=薬師寺慈恵病院

affil-num=5
en-affil=Deportment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学学術研究院医歯薬学域　疫学・衛生学

affil-num=6
en-affil=Deportment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学学術研究院医歯薬学域　疫学・衛生学
en-keyword=新型コロナウイルス感染症 (coronavirus disease 2019)
kn-keyword=新型コロナウイルス感染症 (coronavirus disease 2019)
en-keyword=岡山県 (Okayama Prefecture)
kn-keyword=岡山県 (Okayama Prefecture)
en-keyword=クラスター (cluster)
kn-keyword=クラスター (cluster)
en-keyword=ワクチン接種 (vaccination)
kn-keyword=ワクチン接種 (vaccination)
en-keyword=疫学 (epidemiology)
kn-keyword=疫学 (epidemiology)
END

start-ver=1.4
cd-journal=joma
no-vol=134
cd-vols=
no-issue=2
article-no=
start-page=73
end-page=75
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 2021 Incentive Award of the Okayama Medical Association in Cancer Research (2021 Hayashibara Prize and Yamada Prize)
kn-title=令和３年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞）
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=NishidaMikako
en-aut-sei=Nishida
en-aut-mei=Mikako
kn-aut-name=西田充香子
kn-aut-sei=西田
kn-aut-mei=充香子
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科　免疫学
END

start-ver=1.4
cd-journal=joma
no-vol=63
cd-vols=
no-issue=1
article-no=
start-page=37
end-page=42
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=2023
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Benefit of prednisolone alone in nodal peripheral T-cell lymphoma with T follicular helper phenotype
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 71-year-old Japanese man presented with severe thrombocytopenia. A whole-body CT at presentation showed small cervical, axillary, and para-aortic lymphadenopathy, leading to suspicion of immune thrombocytopenia due to lymphoma. Biopsy was difficult to perform because of severe thrombocytopenia. Thus, he received prednisolone (PSL) therapy and his platelet count gradually recovered. Two and a half years after PSL therapy initiation, his cervical lymphadenopathy slightly progressed without other clinical symptoms. Hence, a biopsy from the left cervical lymph node was performed, and he was diagnosed with nodal peripheral T-cell lymphoma (PTCL) with T follicular helper (TFH) phenotype. Due to various complications, we continued treatment with prednisolone alone after the diagnosis of lymphoma; however, there was no further increase in lymph node enlargement and no other lymphoma-related symptoms for one and a half years after diagnosis. Although immunosuppressive therapy has been reported to produce a response in some patients with angioimmunoblastic T-cell lymphoma, our experience suggests that a similar subset may exist in patients with nodal PTCL with TFH phenotype, which has the same cellular origin. Immunosuppressive therapies may constitute an alternative treatment option even in the era of novel molecular-targeted therapies, especially for elderly patients who are ineligible for chemotherapy.
en-copyright=
kn-copyright=

en-aut-name=KitamuraWataru
en-aut-sei=Kitamura
en-aut-mei=Wataru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KobayashiHiroki
en-aut-sei=Kobayashi
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=UrataTomohiro
en-aut-sei=Urata
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SatoYumiko
en-aut-sei=Sato
en-aut-mei=Yumiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NaoiYusuke
en-aut-sei=Naoi
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KuyamaShoichi
en-aut-sei=Kuyama
en-aut-mei=Shoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Hematology, National Hospital Organization Iwakuni Clinical Center
kn-affil=

affil-num=2
en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama  University Medical School
kn-affil=

affil-num=3
en-affil=Department of Hematology, National Hospital Organization Iwakuni Clinical Center
kn-affil=

affil-num=4
en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center
kn-affil=

affil-num=5
en-affil=Department of Pathology,  Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Pathology,  Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama  University Medical School
kn-affil=

affil-num=8
en-affil=Department of Respiratory Medicine, National Hospital  Organization Iwakuni Clinical Center
kn-affil=
en-keyword=nodal peripheral T-cell lymphoma with T follicular helper phenotype
kn-keyword=nodal peripheral T-cell lymphoma with T follicular helper phenotype
en-keyword=immune thrombocytopenia
kn-keyword=immune thrombocytopenia
en-keyword=prednisolone
kn-keyword=prednisolone
END

start-ver=1.4
cd-journal=joma
no-vol=178
cd-vols=
no-issue=
article-no=
start-page=1
end-page=10
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objectives: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored.<br>
Materials and methods: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined.<br>
Results: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity.<br>
Conclusion: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME.
en-copyright=
kn-copyright=

en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HirabaeAtsuko
en-aut-sei=Hirabae
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakadaKenji
en-aut-sei=Takada
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KumonHiromi
en-aut-sei=Kumon
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=

affil-num=14
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=15
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=16
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=

affil-num=17
en-affil=Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University
kn-affil=

affil-num=18
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=EGFR mutation
kn-keyword=EGFR mutation
en-keyword=Non-small cell lung cancer
kn-keyword=Non-small cell lung cancer
en-keyword=Antitumor immunity
kn-keyword=Antitumor immunity
en-keyword=Non-inflamed tumor
kn-keyword=Non-inflamed tumor
en-keyword=Ad-SGE-REIC
kn-keyword=Ad-SGE-REIC
en-keyword=Gene therapy
kn-keyword=Gene therapy
en-keyword=PD-1
kn-keyword=PD-1
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=2
article-no=
start-page=227
end-page=232
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Lenvatinib Administration for Anaplastic Thyroid Carcinoma with Brain Metastasis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We describe the use of the tyrosine kinase inhibitor lenvatinib in a patient with brain tumor metastases from anaplastic thyroid carcinoma (ATC). A 52-year-old Japanese male presented with consciousness loss. Imaging revealed a thyroid tumor and multiple brain lesions. After the brain tumor’s resection, pathology results provided the diagnosis of ATC. Total thyroidectomy was performed, followed by whole-brain irradiation. Additional brain lesions later developed, and lenvatinib therapy was initiated with no remarkable complications. However, the treatment effects were limited, and the patient died 2 months after starting lenvatinib, 202 days after the initial brain surgery. Relevant literature is discussed.
en-copyright=
kn-copyright=

en-aut-name=ObayashiAtsuto
en-aut-sei=Obayashi
en-aut-mei=Atsuto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AokiKazuma
en-aut-sei=Aoki
en-aut-mei=Kazuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WadaTadayoshi
en-aut-sei=Wada
en-aut-mei=Tadayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FuruieHiromi 
en-aut-sei=Furuie
en-aut-mei=Hiromi 
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KuraokaKazuya
en-aut-sei=Kuraoka
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HamamotoTakao
en-aut-sei=Hamamoto
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TatsukawaTakaharu
en-aut-sei=Tatsukawa
en-aut-mei=Takaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Otorhinolaryngology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center
kn-affil=

affil-num=2
en-affil=Department of Otorhinolaryngology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center
kn-affil=

affil-num=3
en-affil=Department of Otorhinolaryngology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center
kn-affil=

affil-num=4
en-affil=Department of Otorhinolaryngology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center
kn-affil=

affil-num=5
en-affil=Department of Diagnostic Pathology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center
kn-affil=

affil-num=6
en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Hiroshima University Hospital
kn-affil=

affil-num=7
en-affil=Department of Otorhinolaryngology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center
kn-affil=
en-keyword=anaplastic thyroid carcinoma
kn-keyword=anaplastic thyroid carcinoma
en-keyword=brain metastasis
kn-keyword=brain metastasis
en-keyword=lenvatinib
kn-keyword=lenvatinib
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Activated CTLA-4-independent immunosuppression of Treg cells disturbs CTLA-4 blockade-mediated antitumor immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Combination therapy with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) monoclonal antibodies (mAbs) has dramatically improved the prognosis of patients with multiple types of cancer, including renal cell carcinoma (RCC). However, more than half of RCC patients fail to respond to this therapy. Regulatory T cells (Treg cells) are a subset of highly immunosuppressive CD4(+) T cells that promote the immune escape of tumors by suppressing effector T cells in the tumor microenvironment (TME) through various mechanisms. CTLA-4 is constitutively expressed in Treg cells and is regarded as a key molecule for Treg-cell-mediated immunosuppressive functions, suppressing antigen-presenting cells by binding to CD80/CD86. Reducing Treg cells in the TME with an anti-CTLA-4 mAb with antibody-dependent cellular cytotoxicity (ADCC) activity is considered an essential mechanism to achieve tumor regression. In contrast, we demonstrated that CTLA-4 blockade without ADCC activity enhanced CD28 costimulatory signaling pathways in Treg cells and promoted Treg-cell proliferation in mouse models. CTLA-4 blockade also augmented CTLA-4-independent immunosuppressive functions, including cytokine production, leading to insufficient antitumor effects. Similar results were also observed in human peripheral blood lymphocytes and tumor-infiltrating lymphocytes from patients with RCC. Our findings highlight the importance of Treg-cell depletion to achieve tumor regression in response to CTLA-4 blockade therapies.
en-copyright=
kn-copyright=

en-aut-name=WatanabeTomofumi
en-aut-sei=Watanabe
en-aut-mei=Tomofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IshinoTakamasa
en-aut-sei=Ishino
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SadahiraTakuya
en-aut-sei=Sadahira
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=DansakoHiromichi
en-aut-sei=Dansako
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ArakiMotoo
en-aut-sei=Araki
en-aut-mei=Motoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Urology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Urology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=antibody-dependent cell cytotoxicity
kn-keyword=antibody-dependent cell cytotoxicity
en-keyword=cytotoxic T-lymphocyte-associated antigen 4
kn-keyword=cytotoxic T-lymphocyte-associated antigen 4
en-keyword=immune checkpoint inhibitors
kn-keyword=immune checkpoint inhibitors
en-keyword=regulatory T cell
kn-keyword=regulatory T cell
en-keyword=renal cell carcinoma
kn-keyword=renal cell carcinoma
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=
article-no=
start-page=1120710
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230223
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=E3-ubiquitin ligases and recent progress in osteoimmunology
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Ubiquitin-mediated proteasomal degradation is a post-transcriptional protein modification that is comprised of various components including the 76-amino acid protein ubiquitin (Ub), Ub-activating enzyme (E1), Ub-conjugating enzyme (E2), ubiquitin ligase (E3), deubiquitinating enzyme (DUB) and proteasome. We and others have recently provided genetic evidence showing that E3-ubiquitin ligases are associated with bone metabolism, the immune system and inflammation through ubiquitylation and subsequent degradation of their substrates. Dysregulation of the E3-ubiquitin ligase RNF146-mediated degradation of the adaptor protein 3BP2 (SH3 domain-binding protein 2) causes cherubism, an autosomal dominant disorder associated with severe inflammatory craniofacial dysmorphia syndrome in children. In this review, on the basis of our discoveries in cherubism, we summarize new insights into the roles of E3-ubiquitin ligases in the development of human disorders caused by an abnormal osteoimmune system by highlighting recent genetic evidence obtained in both human and animal model studies.
en-copyright=
kn-copyright=

en-aut-name=AsanoYosuke
en-aut-sei=Asano
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MatsumotoYoshinori
en-aut-sei=Matsumoto
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=RottapelRobert
en-aut-sei=Rottapel
en-aut-mei=Robert
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Princess Margaret Cancer Center, University Health Network, University of Toronto
kn-affil=
en-keyword=E3-ubiquitin ligases
kn-keyword=E3-ubiquitin ligases
en-keyword=ubiquitylation
kn-keyword=ubiquitylation
en-keyword=proteasomal degradation
kn-keyword=proteasomal degradation
en-keyword=osteoimmunology
kn-keyword=osteoimmunology
en-keyword=cherubism
kn-keyword=cherubism
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=1
article-no=
start-page=90
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230213
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Autophagy as a potential mechanism underlying the biological effect of 1,25-Dihydroxyvitamin D3 on periodontitis: a narrative review
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The major active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is known for its wide bioactivity in periodontal tissues. Although the exact mechanisms underlying its protective action against periodontitis remain unclear, recent studies have shown that 1,25D3 regulates autophagy. Autophagy is vital for intracellular pathogen invasion control, inflammation regulation, and bone metabolic balance in periodontal tissue homeostasis, and its regulation could be an interesting pathway for future periodontal studies. Since vitamin D deficiency is a worldwide health problem, its role as a potential regulator of autophagy provides new insights into periodontal diseases. Based on this premise, this narrative literature review aimed to investigate the possible connection between 1,25D3 and autophagy in periodontitis. A comprehensive literature search was conducted on PubMed using the following keywords (e.g., vitamin D, autophagy, periodontitis, pathogens, epithelial cells, immunity, inflammation, and bone loss). In this review, the latest studies on the protective action of 1,25D3 against periodontitis and the regulation of autophagy by 1,25D3 are summarized, and the potential role of 1,25D3-activated autophagy in the pathogenesis of periodontitis is analyzed. 1,25D3 can exert a protective effect against periodontitis through different signaling pathways in the pathogenesis of periodontitis, and at least part of this regulatory effect is achieved through the activation of the autophagic response. This review will help clarify the relationship between 1,25D3 and autophagy in the homeostasis of periodontal tissues and provide perspectives for researchers to optimize prevention and treatment strategies in the future.
en-copyright=
kn-copyright=

en-aut-name=ChenXiaoting
en-aut-sei=Chen
en-aut-mei=Xiaoting
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AriasZulema
en-aut-sei=Arias
en-aut-mei=Zulema
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OmoriKazuhiro
en-aut-sei=Omori
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YamamotoTadashi
en-aut-sei=Yamamoto
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=Shinoda-ItoYuki
en-aut-sei=Shinoda-Ito
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakashibaShogo
en-aut-sei=Takashiba
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Pathophysiology‑Periodontal Science, Graduate School  of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 
kn-affil=

affil-num=2
en-affil=Department of Pathophysiology‑Periodontal Science, Graduate School  of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 
kn-affil=

affil-num=3
en-affil=Department of Periodontics and Endodontics, Okayama University  Hospital
kn-affil=

affil-num=4
en-affil=Department of Pathophysiology‑Periodontal Science, Graduate School  of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Pathophysiology‑Periodontal Science, Graduate School  of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Pathophysiology‑Periodontal Science, Graduate School  of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Vitamin D
kn-keyword=Vitamin D
en-keyword=Autophagy
kn-keyword=Autophagy
en-keyword=Periodontitis
kn-keyword=Periodontitis
en-keyword=Epithelial barrier
kn-keyword=Epithelial barrier
en-keyword=Immunity
kn-keyword=Immunity
en-keyword=Inflammation
kn-keyword=Inflammation
en-keyword=Alveolar bone loss
kn-keyword=Alveolar bone loss
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230202
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Somatic mutations can induce a noninflamed tumour microenvironment via their original gene functions, despite deriving neoantigens
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background<br>
Identifying biomarkers to predict immune checkpoint inhibitor (ICI) efficacy is warranted. Considering that somatic mutation-derived neoantigens induce strong immune responses, patients with a high tumour mutational burden reportedly tend to respond to ICIs. However, there are several conflicting data. Therefore, we focused on the original function of neoantigenic mutations and their impact on the tumour microenvironment (TME).<br>
<br>
Methods<br>
We evaluated 88 high-frequency microsatellite instability (MSI-H) colorectal cancers and analysed the function of the identified neoantigenic mutations and their influence on programmed cell death 1 (PD-1) blockade efficacy. The results were validated using The Cancer Genome Atlas (TCGA) datasets.<br>
<br>
Results<br>
We identified frameshift mutations in RNF43 as a common neoantigenic gene mutation in MSI-H tumours. However, loss-of-function RNF43 mutations induced noninflamed TME by activating the WNT/β-catenin signalling pathway. In addition, loss of RNF43 function induced resistance to PD-1 blockade even in neoantigen-rich tumours. TCGA dataset analyses demonstrated that passenger rather than driver gene mutations were related to the inflamed TME in diverse cancer types.<br>
<br>
Conclusions<br>
We propose a novel concept of “paradoxical neoantigenic mutations” that can induce noninflamed TME through their original gene functions, despite deriving neoantigens, suggesting the significance of qualities as well as quantities in neoantigenic mutations.
en-copyright=
kn-copyright=

en-aut-name=IshinoTakamasa
en-aut-sei=Ishino
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TanjiEtsuko
en-aut-sei=Tanji
en-aut-mei=Etsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=UenoToshihide
en-aut-sei=Ueno
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OgasawaraSadahisa
en-aut-sei=Ogasawara
en-aut-mei=Sadahisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SatoKazuhito
en-aut-sei=Sato
en-aut-mei=Kazuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ManoHiroyuki
en-aut-sei=Mano
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IshiharaSoichiro
en-aut-sei=Ishihara
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KatoNaoya
en-aut-sei=Kato
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=3
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=4
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=

affil-num=5
en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterology, Graduate School of Medicine, Chiba University
kn-affil=

affil-num=7
en-affil=Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo
kn-affil=

affil-num=8
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=

affil-num=9
en-affil=Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo
kn-affil=

affil-num=10
en-affil=Department of Gastroenterology, Graduate School of Medicine, Chiba University
kn-affil=

affil-num=11
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=12
en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=1
article-no=
start-page=105
end-page=109
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202302
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Initial Two Doses of COVID-19 Vaccine mRNA-1273 for an Individual Previously Vaccinated with Two Doses of an Inactivated Vaccine CoronaVac That Has Not Been Approved in Japan
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The inactivated coronavirus disease 2019 vaccine CoronaVac has not been approved in Japan. Little information is available on cases in Japan in which an approved mRNA vaccine was administered as the initial (first or second) dose after two doses of CoronaVac. Furthermore, the safety and efficacy of this combination are not established. We here evaluated the safety and efficacy in a patient who showed an antibody response to an approved vaccine, mRNA-1273, after a previous vaccination with CoronaVac. The adverse events consisted of only mild local and systemic common reactions and were transient. In addition, a strong and persistent antibody response was observed.
en-copyright=
kn-copyright=

en-aut-name=IwasakiYoshiaki
en-aut-sei=Iwasaki
en-aut-mei=Yoshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HiguchiChigusa
en-aut-sei=Higuchi
en-aut-mei=Chigusa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Health Service Center, Okayama University
kn-affil=

affil-num=2
en-affil=Health Service Center, Okayama University
kn-affil=
en-keyword=coronavirus disease 2019
kn-keyword=coronavirus disease 2019
en-keyword=severe acute respiratory syndrome coronavirus 2
kn-keyword=severe acute respiratory syndrome coronavirus 2
en-keyword=vaccine
kn-keyword=vaccine
en-keyword=adverse events
kn-keyword=adverse events
en-keyword=antibody response
kn-keyword=antibody response
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=1
article-no=
start-page=37
end-page=43
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202302
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Efficacy of Inflammatory and Immune Markers for Predicting the Prognosis of Patients with Stage IV Breast Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Systemic therapy for stage IV breast cancer is usually an initial treatment and is based on findings regarding biomarkers (e.g., hormone receptors and human epidermal growth factor receptor-2 [HER2]). However, the response to therapy and outcomes sometime differ among patients with similar prognostic factors including grade, hormone receptor, HER2, and more. We conducted retrospective analyses to evaluate the correlations between the overall survival (OS) of 46 stage IV breast cancer patients and (i) the peripheral absolute lymphocyte count (ALC) and (ii) composite blood cell markers. The peripheral blood cell markers included the neutrophil- to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI), and the most recently introduced indicator, the pan-immune-inflammatory value (PIV). The SIRI and PIV showed prognostic impacts on the patients: those with a low SIRI or a low PIV showed significantly better OS than those with a high SIRI (5-year, 66.0% vs. 35.0%, p<0.05) or high PIV (5-year, 68.1% vs. 38.5%, p<0.05), respectively. This is the first report indicating the possible prognostic value of the PIV for OS in patients with stage IV breast cancer. Further studies with larger numbers of patients are necessary for further clarification.
en-copyright=
kn-copyright=

en-aut-name=YamanouchiKosho
en-aut-sei=Yamanouchi
en-aut-mei=Kosho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MaedaShigeto
en-aut-sei=Maeda
en-aut-mei=Shigeto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Surgery, National Hospital Organization, Nagasaki Medical Center
kn-affil=

affil-num=2
en-affil=Department of Surgery, National Hospital Organization, Nagasaki Medical Center
kn-affil=
en-keyword=breast cancer
kn-keyword=breast cancer
en-keyword=pan-immune-inflammatory value
kn-keyword=pan-immune-inflammatory value
en-keyword=prognosis
kn-keyword=prognosis
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=110
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Extracellular Vesicles: New Classification and Tumor Immunosuppression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Simple Summary Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that carry bioactive molecules and deliver them to recipient cells. Classical EVs are exosomes, microvesicles, and apoptotic bodies. This review classifies classical and additional EV types, including autophagic EVs, matrix vesicles, and stressed EVs. Of note, matrix vesicles are key components interacting with extracellular matrices (ECM) in the tumor microenvironment. We also review how EVs are involved in the communication between cancer cells and tumor-associated cells (TAC), leading to establishing immunosuppressive and chemoresistant microenvironments. These include cancer-associated fibroblasts (CAF), mesenchymal stem cells (MSC), blood endothelial cells (BEC), lymph endothelial cells (LEC), and immune cells, such as tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), dendritic cells, natural killer cells, killer T cells, and immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells (MDSC). Exosomal long noncoding RNA (lncRNA), microRNA, circular RNA, piRNA, mRNA, and proteins are crucial in communication between cancer cells and TACs for establishing cold tumors. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles carrying various types of molecules. These EV cargoes are often used as pathophysiological biomarkers and delivered to recipient cells whose fates are often altered in local and distant tissues. Classical EVs are exosomes, microvesicles, and apoptotic bodies, while recent studies discovered autophagic EVs, stressed EVs, and matrix vesicles. Here, we classify classical and new EVs and non-EV nanoparticles. We also review EVs-mediated intercellular communication between cancer cells and various types of tumor-associated cells, such as cancer-associated fibroblasts, adipocytes, blood vessels, lymphatic vessels, and immune cells. Of note, cancer EVs play crucial roles in immunosuppression, immune evasion, and immunotherapy resistance. Thus, cancer EVs change hot tumors into cold ones. Moreover, cancer EVs affect nonimmune cells to promote cellular transformation, including epithelial-to-mesenchymal transition (EMT), chemoresistance, tumor matrix production, destruction of biological barriers, angiogenesis, lymphangiogenesis, and metastatic niche formation.
en-copyright=
kn-copyright=

en-aut-name=ShetaMona
en-aut-sei=Sheta
en-aut-mei=Mona
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TahaEman A.
en-aut-sei=Taha
en-aut-mei=Eman A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LuYanyin
en-aut-sei=Lu
en-aut-mei=Yanyin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=EguchiTakanori
en-aut-sei=Eguchi
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Biochemistry, Faculty of Science, Ain Shams University
kn-affil=

affil-num=3
en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=extracellular vesicle
kn-keyword=extracellular vesicle
en-keyword=exosome
kn-keyword=exosome
en-keyword=autophagy
kn-keyword=autophagy
en-keyword=amphisome
kn-keyword=amphisome
en-keyword=matrix vesicle
kn-keyword=matrix vesicle
en-keyword=cellular communication
kn-keyword=cellular communication
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
en-keyword=immunosuppression
kn-keyword=immunosuppression
en-keyword=immune evasion
kn-keyword=immune evasion
en-keyword=therapy resistance
kn-keyword=therapy resistance
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=12
article-no=
start-page=e32710
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221219
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Multiple White Plaques in the Esophagus: A Possible Case of Esophageal Mucosal Alteration Associated With Immune-Related Adverse Events of Immune Checkpoint Inhibitors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We report two cases of multiple white plaques in the esophagus that emerged after the administration of immune checkpoint inhibitors. Both patients developed enterocolitis as immune-related adverse events associated with immune checkpoint inhibitors. Esophagogastroduodenoscopy revealed duodenal involvement and multiple white plaques in the esophagus. A biopsy of the esophagus showed predominant CD3+ lymphocyte infiltration, suggesting that esophageal mucosal alterations were associated with immune-related adverse events. In addition, histopathology showed keratinized stratified squamous epithelium in the first case while increased inflammatory cell infiltration in the intraepithelial and subepithelial layers was observed in the second case. These data suggest a different pathogenesis of the multiple esophageal white plaques between the two cases. Although further investigation is needed to elucidate the significance of these observations, recognition of the esophageal plaques may be important for prompt diagnosis of immune-related adverse events when associated with immune checkpoint inhibitors.
en-copyright=
kn-copyright=

en-aut-name=IwamuroMasaya
en-aut-sei=Iwamuro
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KonoYoshiyasu
en-aut-sei=Kono
en-aut-mei=Yoshiyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KawanoSeiji
en-aut-sei=Kawano
en-aut-mei=Seiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OkadaHoroyuki
en-aut-sei=Okada
en-aut-mei=Horoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=nivolumab
kn-keyword=nivolumab
en-keyword=ipilimumab
kn-keyword=ipilimumab
en-keyword=immune -related adverse events
kn-keyword=immune -related adverse events
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=esophagogastroduodenoscopy
kn-keyword=esophagogastroduodenoscopy
END

start-ver=1.4
cd-journal=joma
no-vol=24
cd-vols=
no-issue=1
article-no=
start-page=755
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230101
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Metformin and Its Immune-Mediated Effects in Various Diseases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Metformin has been a long-standing prescribed drug for treatment of type 2 diabetes (T2D) and its beneficial effects on virus infection, autoimmune diseases, aging and cancers are also recognized. Metformin modulates the differentiation and activation of various immune-mediated cells such as CD4+ and CD+8 T cells. The activation of adenosine 5 '-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1) pathway may be involved in this process. Recent studies using Extracellular Flux Analyzer demonstrated that metformin alters the activities of glycolysis, oxidative phosphorylation (OXPHOS), lipid oxidation, and glutaminolysis, which tightly link to the modulation of cytokine production in CD4+ and CD+8 T cells in various disease states, such as virus infection, autoimmune diseases, aging and cancers.
en-copyright=
kn-copyright=

en-aut-name=NojimaIchiro
en-aut-sei=Nojima
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=CD8 T cells
kn-keyword=CD8 T cells
en-keyword=AMPK
kn-keyword=AMPK
en-keyword=mTORC
kn-keyword=mTORC
en-keyword=OXPHOS
kn-keyword=OXPHOS
en-keyword=autoimmune disease
kn-keyword=autoimmune disease
en-keyword=aging
kn-keyword=aging
en-keyword=cancer
kn-keyword=cancer
END

start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=6
article-no=
start-page=e0270569
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220629
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Real-world data on vitamin D supplementation and its impacts in systemic lupus erythematosus: Cross-sectional analysis of a lupus registry of nationwide institutions (LUNA)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Although vitamin D concentration is reportedly associated with the pathogenesis and pathology of systemic lupus erythematosus (SLE), benefits of vitamin D supplementation in SLE patients have not been elucidated, to our knowledge. We investigated the clinical impacts of vitamin D supplementation in SLE. Methods A cross-sectional analysis was performed using data from a lupus registry of nationwide institutions. We evaluated vitamin D supplementation status associated with diseaserelated Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) as a parameter of long-term disease activity control. Results Of the enrolled 870 patients (mean age: 45 years, mean disease duration: 153 months), 426 (49%) received vitamin D supplementation. Patients with vitamin D supplementation were younger (43.2 vs 47.5 years, P < 0.0001), received higher doses of prednisolone (7.6 vs 6.8 mg/day, P= 0.002), and showed higher estimated glomerular filtration rates (79.3 vs 75.3 mL/min/1.73m(2), P= 0.02) than those without supplementation. Disease-related SDI (0.73 +/- 1.12 vs 0.73 +/- 1.10, P = 0.75), total SDI, and SLE Disease Activity Index (SLEDAI) did not significantly differ between patients receiving and not receiving vitamin D supplementation. Even after excluding 136 patients who were highly recommended vitamin D supplementation (with age >= 75 years, history of bone fracture or avascular necrosis, denosumab use, and end-stage renal failure), disease-related SDI, total SDI, and SLEDAI did not significantly differ between the two groups. Conclusions Even with a possible Vitamin D deficiency and a high risk of bone fractures in SLE patients, only half of our cohort received its supplementation. The effect of vitamin D supplementation for disease activity control was not observed.
en-copyright=
kn-copyright=

en-aut-name=HayashiKeigo
en-aut-sei=Hayashi
en-aut-mei=Keigo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SadaKen-Ei
en-aut-sei=Sada
en-aut-mei=Ken-Ei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AsanoYosuke
en-aut-sei=Asano
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KatayamaYu
en-aut-sei=Katayama
en-aut-mei=Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OhashiKeiji
en-aut-sei=Ohashi
en-aut-mei=Keiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MorishitaMichiko
en-aut-sei=Morishita
en-aut-mei=Michiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MiyawakiYoshia
en-aut-sei=Miyawaki
en-aut-mei=Yoshia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=WatanabeHaruki
en-aut-sei=Watanabe
en-aut-mei=Haruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KatsuyamaTakayuki
en-aut-sei=Katsuyama
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NarazakiMariko
en-aut-sei=Narazaki
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MatsumotoYoshinori
en-aut-sei=Matsumoto
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=YajimaNobuyuki
en-aut-sei=Yajima
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=YoshimiRyusuke
en-aut-sei=Yoshimi
en-aut-mei=Ryusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=ShimojimaYasuhiro
en-aut-sei=Shimojima
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=OhnoShigeru
en-aut-sei=Ohno
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KajiyamaHiroshi
en-aut-sei=Kajiyama
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=IchinoseKunihiro
en-aut-sei=Ichinose
en-aut-mei=Kunihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=SatoShuzo
en-aut-sei=Sato
en-aut-mei=Shuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=FujiwaraMichio
en-aut-sei=Fujiwara
en-aut-mei=Michio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Medicine, Division of Rheumatology, Showa University School of Medicine
kn-affil=

affil-num=13
en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine
kn-affil=

affil-num=14
en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
kn-affil=

affil-num=15
en-affil=Center for Rheumatic Diseases, Yokohama City University Medical Center
kn-affil=

affil-num=16
en-affil=Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University
kn-affil=

affil-num=17
en-affil=Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences
kn-affil=

affil-num=18
en-affil=Department of Rheumatology, Fukushima Medical University School of Medicine
kn-affil=

affil-num=19
en-affil=Department of Rheumatology, Yokohama Rosai Hospital
kn-affil=

affil-num=20
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=24
article-no=
start-page=6184
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221214
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Effect of Pleural Effusion on Prognosis in Patients with Non-Small Cell Lung Cancer Undergoing Immunochemotherapy: A Retrospective Observational Study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Simple Summary Minimal data exists on pleural effusion (PE) for non-small cell lung cancer (NSCLC) patients undergoing combined ICI and chemotherapy. We retrospectively investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival and overall survival than those without PE. In addition, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. In conclusion, PE was associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy. Objectives: Combined immune checkpoint inhibitor (ICI) therapy and chemotherapy has become the standard treatment for advanced non-small-cell lung cancer (NSCLC). Pleural effusion (PE) is associated with poor outcomes among patients with NSCLC undergoing chemotherapy. However, minimal data exists on PE for patients undergoing combined ICI and chemotherapy. Therefore, we investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. Methods: We identified patients with advanced NSCLC undergoing chemotherapy and ICI therapy from the Okayama Lung Cancer Study Group-Immune Chemotherapy Database (OLCSG-ICD) between December 2018 and December 2020; the OLCSG-ICD includes the clinical data of patients with advanced NSCLC from 13 institutions. Then, we analyzed the treatment outcomes based on the presence of PE. Results: We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without PE (median PFS: 6.2 months versus 9.1 months; p < 0.001; median OS: 16.4 months versus 27.7 months; p < 0.001). The negative effect of PE differed based on the patient's programmed cell death-ligand 1 (PD-L1) expression status; with the effect being more evident in patients with high PD-L1 expression. In addition, PFS and OS did not differ between patients who did and did not undergo bevacizumab treatment; thus, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. Conclusion: PE is associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy.
en-copyright=
kn-copyright=

en-aut-name=NishimuraTomoka
en-aut-sei=Nishimura
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YokoyamaToshihide
en-aut-sei=Yokoyama
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InoueKoji
en-aut-sei=Inoue
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TamuraTomoki
en-aut-sei=Tamura
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SatoKen
en-aut-sei=Sato
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KishinoDaizo
en-aut-sei=Kishino
en-aut-mei=Daizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KawaiHaruyuki
en-aut-sei=Kawai
en-aut-mei=Haruyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=InoueMasaaki
en-aut-sei=Inoue
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=OchiNobuaki
en-aut-sei=Ochi
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujimotoNobukazu
en-aut-sei=Fujimoto
en-aut-mei=Nobukazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=IchikawaHirohisa
en-aut-sei=Ichikawa
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

affil-num=1
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital
kn-affil=

affil-num=4
en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital
kn-affil=

affil-num=5
en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center
kn-affil=

affil-num=6
en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=7
en-affil=Department of Internal Medicine, Fukuyama City Hospital
kn-affil=

affil-num=8
en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
kn-affil=

affil-num=9
en-affil=Department of Respiratory Medicine, Japanese Red Cross Society Himeji Hospital
kn-affil=

affil-num=10
en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital
kn-affil=

affil-num=11
en-affil=Department of Chest Surgery, Shimonoseki City Hospital
kn-affil=

affil-num=12
en-affil=Department of General Internal Medicine 4, Kawasaki Medical School
kn-affil=

affil-num=13
en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital
kn-affil=

affil-num=14
en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital
kn-affil=

affil-num=15
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=17
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=18
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=pleural effusion
kn-keyword=pleural effusion
en-keyword=non-small cell carcinoma
kn-keyword=non-small cell carcinoma
en-keyword=immune checkpoint inhibitors
kn-keyword=immune checkpoint inhibitors
END

start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=3
article-no=
start-page=1059
end-page=1073
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221116
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The secreted immune response peptide 1 functions as a phytocytokine in rice immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Small signalling peptides play important roles in various plant processes, but information regarding their involvement in plant immunity is limited. We previously identified a novel small secreted protein in rice, called immune response peptide 1 (IRP1). Here, we studied the function of IRP1 in rice immunity. Rice plants overexpressing IRP1 enhanced resistance to the virulent rice blast fungus. Application of synthetic IRP1 to rice suspension cells triggered the expression of IRP1 itself and the defence gene phenylalanine ammonia-lyase 1 (PAL1). RNA-seq results revealed that 84% of genes up-regulated by IRP1, including 13 OsWRKY transcription factors, were also induced by a microbe-associated molecular pattern (MAMP), chitin, indicating that IRP1 and chitin share a similar signalling pathway. Co-treatment with chitin and IRP1 elevated the expression level of PAL1 and OsWRKYs in an additive manner. The increased chitin concentration arrested the induction of IRP1 and PAL1 expression by IRP1, but did not affect IRP1-triggered mitogen-activated protein kinases (MAPKs) activation. Collectively, our findings indicate that IRP1 functions as a phytocytokine in rice immunity regulating MAPKs and OsWRKYs that can amplify chitin and other signalling pathways, and provide new insights into how MAMPs and phytocytokines cooperatively regulate rice immunity.
en-copyright=
kn-copyright=

en-aut-name=WangPingyu
en-aut-sei=Wang
en-aut-mei=Pingyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=JiaHuimin
en-aut-sei=Jia
en-aut-mei=Huimin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=GuoTing
en-aut-sei=Guo
en-aut-mei=Ting
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZhangYuanyuan
en-aut-sei=Zhang
en-aut-mei=Yuanyuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WangWanqing
en-aut-sei=Wang
en-aut-mei=Wanqing
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishimuraHideki
en-aut-sei=Nishimura
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=LiZhengguo
en-aut-sei=Li
en-aut-mei=Zhengguo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KawanoYoji
en-aut-sei=Kawano
en-aut-mei=Yoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Key Laboratory of Plant Hormones and Development Regulation of Chongqing, School of Life Sciences, Chongqing University
kn-affil=

affil-num=2
en-affil=Shanghai Center for Plant Stress Biology and Center of Excellence for Molecular Plant Sciences, Chinese Academy of Sciences
kn-affil=

affil-num=3
en-affil=Shanghai Center for Plant Stress Biology and Center of Excellence for Molecular Plant Sciences, Chinese Academy of Sciences
kn-affil=

affil-num=4
en-affil=Shanghai Center for Plant Stress Biology and Center of Excellence for Molecular Plant Sciences, Chinese Academy of Sciences
kn-affil=

affil-num=5
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=6
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=7
en-affil=Key Laboratory of Plant Hormones and Development Regulation of Chongqing, School of Life Sciences, Chongqing University
kn-affil=

affil-num=8
en-affil=Shanghai Center for Plant Stress Biology and Center of Excellence for Molecular Plant Sciences, Chinese Academy of Sciences
kn-affil=
en-keyword=Immunity
kn-keyword=Immunity
en-keyword=IRP1
kn-keyword=IRP1
en-keyword=pattern-triggered immunity
kn-keyword=pattern-triggered immunity
en-keyword=phytocytokine
kn-keyword=phytocytokine
en-keyword=Pyricularia oryzae
kn-keyword=Pyricularia oryzae
en-keyword=rice
kn-keyword=rice
END

start-ver=1.4
cd-journal=joma
no-vol=67
cd-vols=
no-issue=6
article-no=
start-page=654
end-page=665
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202212
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Neuropeptide Y Antagonizes Development of Pulmonary Fibrosis through IL-1β Inhibition
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Neuropeptide Y (NPY), a 36 amino acid residue polypeptide distributed throughout the nervous system, acts on various immune cells in many organs, including the respiratory system. However, little is known about its role in the pathogenesis of pulmonary fibrosis. This study was performed to determine the effects of NPY on pulmonary fibrosis. NPY-deficient and wild-type mice were intratracheally administered bleomycin. Inflammatory cells, cytokine concentrations, and morphological morphometry of the lungs were analyzed. Serum NPY concentrations were also measured in patients with idiopathic pulmonary fibrosis and healthy control subjects. NPY-deficient mice exhibited significantly enhanced pulmonary fibrosis and higher IL-1 beta concentrations in the lungs compared with wild-type mice. Exogenous NPY treatment suppressed the development of bleomycin-induced lung fibrosis and decreased IL-1 beta concentrations in the lungs. Moreover, IL-1 beta neutralization in NPY-deficient mice attenuated the fibrotic changes. NPY decreased IL-1 beta release, and Y1 receptor antagonists inhibited IL-1 beta release and induced epithelial-mesenchymal transition in human alveolar epithelial cells. Patients with idiopathic pulmonary fibrosis had lower NPY and greater IL-1 beta concentrations in the serums compared with healthy control subjects. NPY expression was mainly observed around bronchial epithelial cells in human idiopathic pulmonary fibrosis lungs. These data suggest that NPY plays a protective role against pulmonary fibrosis by suppressing IL-1 beta release, and manipulating the NPY-Y1 receptor axis could be a potential therapeutic strategy for delaying disease progression.
en-copyright=
kn-copyright=

en-aut-name=ItanoJunko
en-aut-sei=Itano
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SenooSatoru
en-aut-sei=Senoo
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AsadaNoboru
en-aut-sei=Asada
en-aut-mei=Noboru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=GionYuka
en-aut-sei=Gion
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=EgusaYuria
en-aut-sei=Egusa
en-aut-mei=Yuria
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=GuoLili
en-aut-sei=Guo
en-aut-mei=Lili
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ArakiKota
en-aut-sei=Araki
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SatoYasuharu
en-aut-sei=Sato
en-aut-mei=Yasuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=6
en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=7
en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=8
en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=11
en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=13
en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=idiopathic pulmonary fibrosis
kn-keyword=idiopathic pulmonary fibrosis
en-keyword=NPY
kn-keyword=NPY
en-keyword=IL-1 beta; bleomycin
kn-keyword=IL-1 beta; bleomycin
en-keyword=bronchial epithelial cells
kn-keyword=bronchial epithelial cells
END

start-ver=1.4
cd-journal=joma
no-vol=32
cd-vols=
no-issue=3
article-no=
start-page=240
end-page=249
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Resistance to immune checkpoint inhibitors and the tumor microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors (ICIs) have contributed significantly to the treatment of various types of cancer, including skin cancer. However, not all patients respond; some patients do not respond at all (primary resistance), while others experience recurrence after the initial response (acquired resistance). Therefore, overcoming ICI resistance is an urgent priority. Numerous ICI resistance mechanisms have been reported. They are seemingly quite complex, varying from patient to patient. However, most involve T cell activation processes, especially in the tumor microenvironment (TME). ICIs exert their effects in the TME by reactivating suppressed T cells through inhibition of immune checkpoint molecules, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Thus, this review focuses on the resistance mechanisms based on the T cell activation process. Here, we classify the main mechanisms of ICI resistance into three categories based on: (1) antigen recognition, (2) T cell migration and infiltration, and (3) effector functions of T cells. By identifying and understanding these resistance mechanisms individually, including unknown mechanisms, we seek to contribute to the development of novel treatments to overcome ICI resistance.
en-copyright=
kn-copyright=

en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Dermatology, Graduate School of Medicine, Chiba University
kn-affil=

affil-num=2
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=immune checkpoint inhibitors
kn-keyword=immune checkpoint inhibitors
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
en-keyword=antitumor immunity
kn-keyword=antitumor immunity
en-keyword=primary resistance
kn-keyword=primary resistance
en-keyword=acquired resistance
kn-keyword=acquired resistance
END

start-ver=1.4
cd-journal=joma
no-vol=20
cd-vols=
no-issue=1
article-no=
start-page=374
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221130
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Involvement in the tumor-infiltrating CD8(+) T cell expression by the initial disease of remnant gastric cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Remnant gastric cancer (RGC) has been increasing for various reasons such as a longer life span, medical progress, and others. It generally has a poor prognosis, and its mechanism of occurrence is unknown. The purpose of this study was to evaluate the clinicopathological features of and clarify the oncological features of RGC. Methods Between January 2002 and January 2017, 39 patients with RGC following distal gastrectomy underwent curative surgical resection at the Okayama University Hospital; their medical records and immunohistochemically stained extracted specimens were used for retrospective analysis. Results On univariate analysis, initial gastric disease, pathological lymph node metastasis, and pathological stage were the significant factors associated with poor overall survival (p=0.014, 0.0061, and 0.016, respectively). Multivariate analysis of these 3 factors showed that only initial gastric disease caused by malignant disease was an independent factor associated with a poor prognosis (p=0.014, hazard ratio: 4.2, 95% confidence interval: 1.3-13.0). In addition, tumor-infiltrating CD8(+) T cells expression was higher in the benign disease group than in the malignant group (p=0.046). Conclusions Initial gastrectomy caused by malignant disease was an independent poor prognostic factor of RGC, and as one of the causes, lower level of tumor-infiltrating CD8(+) T cells in RGC may involve in.
en-copyright=
kn-copyright=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Remnant gastric cancer
kn-keyword=Remnant gastric cancer
en-keyword=Prognostic factor
kn-keyword=Prognostic factor
en-keyword=Tumor-infiltrating lymphocytes
kn-keyword=Tumor-infiltrating lymphocytes
en-keyword=CD8(+) T cell
kn-keyword=CD8(+) T cell
en-keyword=Tumor immunity
kn-keyword=Tumor immunity
END

start-ver=1.4
cd-journal=joma
no-vol=72
cd-vols=
no-issue=5
article-no=
start-page=1285
end-page=1300
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221127
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pancreatic ductal adenocarcinoma (PDAC) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. However, the precise relationship between GEM-resistant PDAC and development of an immunosuppressive tumor microenvironment (TME) remains unclear. In this study, we investigated the immunosuppressive TME in parental and GEM-resistant PDAC tumors and assessed the therapeutic potential of combination therapy with the telomerase-specific replication-competent oncolytic adenovirus OBP-702, which induces tumor suppressor p53 protein and PD-L1 blockade against GEM-resistant PDAC tumors. Mouse PDAC cells (PAN02) and human PDAC cells (MIA PaCa-2, BxPC-3) were used to establish GEM-resistant PDAC lines. PD-L1 expression and the immunosuppressive TME were analyzed using parental and GEM-resistant PDAC cells. A cytokine array was used to investigate the underlying mechanism of immunosuppressive TME induction by GEM-resistant PAN02 cells. The GEM-resistant PAN02 tumor model was used to evaluate the antitumor effect of combination therapy with OBP-702 and PD-L1 blockade. GEM-resistant PDAC cells exhibited higher PD-L1 expression and produced higher granulocyte-macrophage colony-stimulating factor (GM-CSF) levels compared with parental cells, inducing an immunosuppressive TME and the accumulation of myeloid-derived suppressor cells (MDSCs). OBP-702 significantly inhibited GEM-resistant PAN02 tumor growth by suppressing GM-CSF-mediated MDSC accumulation. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation.
en-copyright=
kn-copyright=

en-aut-name=KajiwaraYoshinori
en-aut-sei=Kajiwara
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YamadaMotohiko
en-aut-sei=Yamada
en-aut-mei=Motohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FushimiTakuro
en-aut-sei=Fushimi
en-aut-mei=Takuro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Oncolys BioPharma Inc.
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Pancreatic cancer
kn-keyword=Pancreatic cancer
en-keyword=Chemoresistance
kn-keyword=Chemoresistance
en-keyword=MDSC
kn-keyword=MDSC
en-keyword=GM-CSF
kn-keyword=GM-CSF
en-keyword=Oncolytic virus
kn-keyword=Oncolytic virus
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=6
article-no=
start-page=689
end-page=694
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202212
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=An Evaluation of the Efficacy of Compression Therapy Using Sleeves and Stockings to Prevent Docetaxel-induced Peripheral Neuropathy in Breast Cancer Patients
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Taxanes are key drugs for patients with breast cancer. A major adverse effect of taxanes is peripheral neuropathy (PN). To investigate the ability of compression therapy using sleeves and stockings to prevent PN due to the taxane docetaxel, we conducted a single-center historical control trial. Patients receiving docetaxel at 75 mg/m2 every 3 weeks for 4 cycles as first-line chemotherapy for breast cancer were eligible. PN was evaluated using the common terminology criteria for adverse events version 4.0. The primary endpoint was the incidence of allgrade PN until 3 weeks after the fourth docetaxel administration. We evaluated 26 patients in the intervention group and compared their data to those collected retrospectively from 52 patients treated with docetaxel without compression. Neither the incidence of all-grade PN until 3 weeks after the fourth docetaxel administration (63.5% in the control group vs. 76.9% in the intervention group, p=0.31) nor that of PN grade ≥ 2 (13.5% vs. 15.4%, p=0.99) differed between the groups. In this study, the efficacy of compression therapy using sleeves and stockings to prevent PN induced by docetaxel was not demonstrated. Further clinical studies including medications or intervention are needed to reduce the incidence and severity of PN induced by chemotherapy.
en-copyright=
kn-copyright=

en-aut-name=YamanouchiKosho
en-aut-sei=Yamanouchi
en-aut-mei=Kosho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KubaSayaka
en-aut-sei=Kuba
en-aut-mei=Sayaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MatsumotoMegumi
en-aut-sei=Matsumoto
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YanoHiroshi
en-aut-sei=Yano
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MoritaMichi
en-aut-sei=Morita
en-aut-mei=Michi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SakimuraChika
en-aut-sei=Sakimura
en-aut-mei=Chika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OtsuboRyota
en-aut-sei=Otsubo
en-aut-mei=Ryota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HidakaMasaaki
en-aut-sei=Hidaka
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NagayasuTakeshi
en-aut-sei=Nagayasu
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=EguchiSusumu
en-aut-sei=Eguchi
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science
kn-affil=

affil-num=2
en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science
kn-affil=

affil-num=3
en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science
kn-affil=

affil-num=4
en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science
kn-affil=

affil-num=5
en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science
kn-affil=

affil-num=6
en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science
kn-affil=

affil-num=7
en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science
kn-affil=

affil-num=8
en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science
kn-affil=

affil-num=9
en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science
kn-affil=

affil-num=10
en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science
kn-affil=
en-keyword=breast cancer
kn-keyword=breast cancer
en-keyword=docetaxel
kn-keyword=docetaxel
en-keyword=neuropathy
kn-keyword=neuropathy
en-keyword=compression
kn-keyword=compression
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=6
article-no=
start-page=635
end-page=643
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202212
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=MiR-338-3p Is a Biomarker in Neonatal Acute Respiratory Distress Syndrome (ARDS) and Has Roles in the Inflammatory Response of ARDS Cell Models
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=To investigate the association between serum miR-338-3p levels and neonatal acute respiratory distress syndrome (ARDS) and its mechanism. The relative miR-338-3p expression in serum was detected by quantitative real-time RT-PCR. Interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) levels were detected by ELISAs. A receiver operating characteristic (ROC) curve analysis of serum miR-338-3p evaluated the diagnosis of miR-338-3p in neonatal ARDS. Pearson’s correlation analysis evaluated the correlation between serum miR-338-3p and neonatal ARDS clinical factors. Flow cytometry evaluated apoptosis, and a CCK-8 assay assessed cell viability. A luciferase assay evaluated the miR-338-3p/AKT3 relationship. The miR- 338-3p expression was decreased in neonatal ARDS patients and in lipopolysaccharide (LPS)-treated cells. The ROC curve showed the accuracy of miR-338-3p for evaluating neonatal ARDS patients. The correlation analysis demonstrated that miR-338-3p was related to PRISM-III, PaO2/FiO2, oxygenation index, IL-1β, IL-6, and TNF-α in neonatal ARDS patients. MiR-338-3p overexpression inhibited the secretion of inflammatory components, stifled cell apoptosis, and LPS-induced advanced cell viability. The double-luciferase reporter gene experiment confirmed that miR-338-3p negatively regulates AKT3 mRNA expression. Serum miR-338-3p levels were related to the diagnosis and severity of neonatal ARDS, which may be attributed to its regulatory effect on inflammatory response in ARDS.
en-copyright=
kn-copyright=

en-aut-name=ZhangCuicui
en-aut-sei=Zhang
en-aut-mei=Cuicui
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=JiYanan
en-aut-sei=Ji
en-aut-mei=Yanan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WangQin
en-aut-sei=Wang
en-aut-mei=Qin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=RuanLianying
en-aut-sei=Ruan
en-aut-mei=Lianying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Pediatric Intensive Care Unit, Xingtai People’s Hospital
kn-affil=

affil-num=2
en-affil=Pediatric Intensive Care Unit, Xingtai People’s Hospital
kn-affil=

affil-num=3
en-affil=Pediatric Intensive Care Unit, Xingtai People’s Hospital
kn-affil=

affil-num=4
en-affil=Pediatric Intensive Care Unit, Xingtai People’s Hospital
kn-affil=
en-keyword=miR-338-3p
kn-keyword=miR-338-3p
en-keyword=AKT3
kn-keyword=AKT3
en-keyword=neonatal ARDS
kn-keyword=neonatal ARDS
en-keyword=inflammation
kn-keyword=inflammation
en-keyword=diagnosis
kn-keyword=diagnosis
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220922
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=肝内胆管癌において、制御性T細胞は、抑制性免疫環境を誘導し、リンパ節転移を促進する
kn-title=Regulatory T cells induce a suppressive immune milieu and promote lymph node metastasis in intrahepatic cholangiocarcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=KONISHIDaisuke
en-aut-sei=KONISHI
en-aut-mei=Daisuke
kn-aut-name=小西大輔
kn-aut-sei=小西
kn-aut-mei=大輔
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=5
article-no=
start-page=609
end-page=615
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Idiopathic Pneumonia Syndrome Refractory to Ruxolitinib after Post-Transplant Cyclophosphamide-based Haploidentical Hematopoietic Stem Cell Transplantation: Lung Pathological Findings from an Autopsy Case
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 69-year-old Japanese man with acute leukemia received post-transplant cyclophosphamide-based haploidentical stem cell transplantation (PTCY-haplo-SCT) but was readmitted with dyspnea and ground-glass-opacities of the lungs. Bronchoscopy showed inflammatory changes with no signs of infection. He received steroids but required intubation as his condition deteriorated. In addition to antithymocyte globulin and cyclophosphamide, we administered ruxolitinib but failed to save him. Autopsy findings revealed fibrotic nonspecific interstitial pneumonia (NSIP) without evidence of organizing pneumonia or infection. Thus, we diagnosed idiopathic pneumonia syndrome (IPS). As far as our knowledge, this is the first case of IPS with NSIP histology after PTCY-haplo-SCT.
en-copyright=
kn-copyright=

en-aut-name=MatsumotoKen
en-aut-sei=Matsumoto
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FujishitaKeigo
en-aut-sei=Fujishita
en-aut-mei=Keigo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MatsudaMasayuki
en-aut-sei=Matsuda
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OkaSatoshi
en-aut-sei=Oka
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujisawaYuka
en-aut-sei=Fujisawa
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ImaiToshi
en-aut-sei=Imai
en-aut-mei=Toshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MachidaTakuya
en-aut-sei=Machida
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center
kn-affil=

affil-num=2
en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center
kn-affil=

affil-num=3
en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center
kn-affil=

affil-num=4
en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center
kn-affil=

affil-num=5
en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center
kn-affil=

affil-num=6
en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center
kn-affil=

affil-num=7
en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center
kn-affil=
en-keyword=idiopathic pneumonia syndrome
kn-keyword=idiopathic pneumonia syndrome
en-keyword=ruxolitinib
kn-keyword=ruxolitinib
en-keyword=post-transplant cyclophosphamide-based haploidentical stem cell transplantation
kn-keyword=post-transplant cyclophosphamide-based haploidentical stem cell transplantation
en-keyword=nonspecific interstitial pneumonia
kn-keyword=nonspecific interstitial pneumonia
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=5
article-no=
start-page=503
end-page=510
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Viral Sequences Are Repurposed for Controlling Antiviral Responses as Non-Retroviral Endogenous Viral Elements
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Eukaryotic genomes contain numerous copies of endogenous viral elements (EVEs), most of which are considered endogenous retrovirus (ERV) sequences. Over the past decade, non-retroviral endogenous viral elements (nrEVEs) derived from ancient RNA viruses have been discovered. Several functions have been proposed for these elements, including antiviral defense. This review summarizes the current understanding of nrEVEs derived from RNA viruses, particularly endogenous bornavirus-like elements (EBLs) and endogenous filovirus-like elements (EFLs). EBLs are one of the most extensively studied nrEVEs. The EBL derived from bornavirus nucleoprotein (EBLN) is thought to function as a non-coding RNA or protein that regulates host gene expression or inhibits virus propagation. Ebolavirus and marburgvirus, which are filoviruses, induce severe hemorrhagic fever in humans and nonhuman primates. Although the ecology of filoviruses remains unclear, bats are believed to be potential reservoirs. Based on the knowledge from EBLs, it is postulated that EFLs in the bat genome help to maintain the balance between filovirus infection and the bat’s defense system, which may partially explain why bats act as potential reservoirs. Further research into the functions of nrEVEs could reveal novel antiviral systems and inspire novel antiviral approaches.
en-copyright=
kn-copyright=

en-aut-name=OgawaHirohito
en-aut-sei=Ogawa
en-aut-mei=Hirohito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HondaTomoyuki
en-aut-sei=Honda
en-aut-mei=Tomoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=EVE
kn-keyword=EVE
en-keyword=nrEVE
kn-keyword=nrEVE
en-keyword=bornavirus
kn-keyword=bornavirus
en-keyword=filovirus
kn-keyword=filovirus
en-keyword=antiviral
kn-keyword=antiviral
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=5
article-no=
start-page=489
end-page=502
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Current Insights into Mesenchymal Signatures in Glioblastoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Glioblastoma (GBM) is a fatal primary malignant brain tumor in adults. Despite decades of research, the prognosis for GBM patients is still disappointing. One major reason for the intense therapeutic resistance of GBM is inter- and intra-tumor heterogeneity. GBM-intrinsic transcriptional profiling has suggested the presence of at least three subtypes of GBM: the proneural, classic, and mesenchymal subtypes. The mesenchymal subtype is the most aggressive, and patients with the mesenchymal subtype of primary and recurrent tumors tend to have a worse prognosis compared with patients with the other subtypes. Furthermore, GBM can shift from other subtypes to the mesenchymal subtype over the course of disease progression or recurrence. This phenotypic transition is driven by diverse tumor-intrinsic molecular mechanisms or microenvironmental factors. Thus, better understanding of the plastic nature of mesenchymal transition in GBM is pivotal to developing new therapeutic strategies. In this review, we provide a comprehensive overview of the current understanding of the elements involved in the mesenchymal transition of GBM and discuss future perspectives.
en-copyright=
kn-copyright=

en-aut-name=MatsumotoYuji
en-aut-sei=Matsumoto
en-aut-mei=Yuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IchikawaTomotsugu
en-aut-sei=Ichikawa
en-aut-mei=Tomotsugu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KurozumiKazuhiko
en-aut-sei=Kurozumi
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=DateIsao
en-aut-sei=Date
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Neurological Surgery, Kagawa Prefectural Central Hospital
kn-affil=

affil-num=3
en-affil=Department of Neurosurgery, Hamamatsu University Hospital
kn-affil=

affil-num=4
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=glioma
kn-keyword=glioma
en-keyword=glioblastoma
kn-keyword=glioblastoma
en-keyword=mesenchymal subtype
kn-keyword=mesenchymal subtype
en-keyword=mesenchymal transition
kn-keyword=mesenchymal transition
en-keyword=heterogeneity
kn-keyword=heterogeneity
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=
article-no=
start-page=992198
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220909
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Recruitment of Irgb6 to the membrane is a direct trigger for membrane deformation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Irgb6 is a member of interferon gamma-induced immunity related GTPase (IRG), and one of twenty "effector" IRGs, which coordinately attack parasitophorous vacuole membrane (PVM), causing death of intracellular pathogen. Although Irgb6 plays a pivotal role as a pioneer in the process of PVM disruption, the direct effect of Irgb6 on membrane remained to be elucidated. Here, we utilized artificial lipid membranes to reconstitute Irgb6-membrane interaction in vitro, and revealed that Irgb6 directly deformed the membranes. Liposomes incubated with recombinant Irgb6 were drastically deformed generating massive tubular protrusions in the absence of guanine nucleotide, or with GMP-PNP. Liposome deformation was abolished by incubating with Irgb6-K275A/R371A, point mutations at membrane targeting residues. The membrane tubules generated by Irgb6 were mostly disappeared by the addition of GTP or GDP, which are caused by detachment of Irgb6 from membrane. Binding of Irgb6 to the membrane, which was reconstituted in vitro using lipid monolayer, was stimulated at GTP-bound state. Irgb6 GTPase activity was stimulated by the presence of liposomes more than eightfold. Irgb6 GTPase activity in the absence of membrane was also slightly stimulated, by lowering ionic strength, or by increasing protein concentration, indicating synergistic stimulation of the GTPase activity. These results suggest that membrane targeting of Irgb6 and resulting membrane deformation does not require GTP, but converting into GTP-bound state is crucial for detaching Irgb6 from the membrane, which might coincident with local membrane disruption.
en-copyright=
kn-copyright=

en-aut-name=YamadaHiroshi
en-aut-sei=Yamada
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AbeTadashi
en-aut-sei=Abe
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NagaokaHikaru
en-aut-sei=Nagaoka
en-aut-mei=Hikaru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakashimaEizo
en-aut-sei=Takashima
en-aut-mei=Eizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NittaRyo
en-aut-sei=Nitta
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YamamotoMasahiro
en-aut-sei=Yamamoto
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakeiKohji
en-aut-sei=Takei
en-aut-mei=Kohji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Division of Malaria Research, Proteo-Science Center, Ehime University
kn-affil=

affil-num=4
en-affil=Division of Malaria Research, Proteo-Science Center, Ehime University
kn-affil=

affil-num=5
en-affil=Division of Structural Medicine and Anatomy, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University
kn-affil=

affil-num=7
en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=IFN-inducible GTPase
kn-keyword=IFN-inducible GTPase
en-keyword=Irgb6
kn-keyword=Irgb6
en-keyword=GTPase
kn-keyword=GTPase
en-keyword=membrane
kn-keyword=membrane
en-keyword=T
kn-keyword=T
en-keyword=gondii
kn-keyword=gondii
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=10
article-no=
start-page=2133
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221013
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Design and Robustness Evaluation of Valley Topological Elastic Wave Propagation in a Thin Plate with Phononic Structure
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Based on the concept of band topology in phonon dispersion, we designed a topological phononic crystal in a thin plate for developing an efficient elastic waveguide. Despite that various topological phononic structures have been actively proposed, a quantitative design strategy of the phononic band and its robustness assessment in an elastic regime are still missing, hampering the realization of topological acoustic devices. We adopted a snowflake-like structure for the crystal unit cell and determined the optimal structure that exhibited the topological phase transition of the planar phononic crystal by changing the unit cell structure. The bandgap width could be adjusted by varying the length of the snow-side branch, and a topological phase transition occurred in the unit cell structure with threefold rotational symmetry. Elastic waveguides based on edge modes appearing at interfaces between crystals with different band topologies were designed, and their transmission efficiencies were evaluated numerically and experimentally. The results demonstrate the robustness of the elastic wave propagation in thin plates. Moreover, we experimentally estimated the backscattering length, which measures the robustness of the topologically protected propagating states against structural inhomogeneities. The results quantitatively indicated that degradation of the immunization against the backscattering occurs predominantly at the corners in the waveguides, indicating that the edge mode observed is a relatively weak topological state.
en-copyright=
kn-copyright=

en-aut-name=KataokaMotoki
en-aut-sei=Kataoka
en-aut-mei=Motoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MisawaMasaaki
en-aut-sei=Misawa
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TsurutaKenji
en-aut-sei=Tsuruta
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Electrical and Electronic Engineering, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Electrical and Electronic Engineering, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Electrical and Electronic Engineering, Okayama University
kn-affil=
en-keyword=phononic crystal
kn-keyword=phononic crystal
en-keyword=topological acoustic
kn-keyword=topological acoustic
en-keyword=elastic waveguide
kn-keyword=elastic waveguide
en-keyword=backscattering length
kn-keyword=backscattering length
en-keyword=lamb wave
kn-keyword=lamb wave
END

start-ver=1.4
cd-journal=joma
no-vol=27
cd-vols=
no-issue=
article-no=
start-page=3
end-page=13
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221215
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) antibody, provide improved clinical outcome in certain cancers. However, pancreatic ductal adeno-carcinoma (PDAC) is refractory to PD-1 blockade therapy due to poor immune response. Oncolytic virotherapy is a novel approach for inducing immunogenic cell death (ICD). We demonstrated the therapeutic potential of p53-expressing telo-merase-specific oncolytic adenovirus OBP-702 to induce ICD and anti-tumor immune responses in human PDAC cells with different p53 status (Capan-2, PK-59, PK-45H, Capan-1, MIA PaCa-2, BxPC-3) and murine PDAC cells (PAN02). OBP-702 significantly enhanced ICD with secretion of extracel-lular adenosine triphosphate and high-mobility group box pro-tein B1 by inducing p53-mediated apoptosis and autophagy. OBP-702 significantly promoted the tumor infiltration of CD8+ T cells and the anti-tumor efficacy of PD-1 blockade in a subcutaneous PAN02 syngeneic tumor model. Our results suggest that oncolytic adenovirus-mediated p53 overexpres-sion augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade.
en-copyright=
kn-copyright=

en-aut-name=ArakiHiroyuki
en-aut-sei=Araki
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KajiwaraYoshinori
en-aut-sei=Kajiwara
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamadaMotohiko
en-aut-sei=Yamada
en-aut-mei=Motohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=19
article-no=
start-page=11035
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220920
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development.
en-copyright=
kn-copyright=

en-aut-name=ShigehiroTsukasa
en-aut-sei=Shigehiro
en-aut-mei=Tsukasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=UenoMaho
en-aut-sei=Ueno
en-aut-mei=Maho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KijihiraMayumi
en-aut-sei=Kijihira
en-aut-mei=Mayumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakahashiRyotaro
en-aut-sei=Takahashi
en-aut-mei=Ryotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UmemuraChiho
en-aut-sei=Umemura
en-aut-mei=Chiho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TahaEman A.
en-aut-sei=Taha
en-aut-mei=Eman A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KurosakaChisaki
en-aut-sei=Kurosaka
en-aut-mei=Chisaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AsayamaMegumi
en-aut-sei=Asayama
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MurakamiHiroshi
en-aut-sei=Murakami
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SatohAyano
en-aut-sei=Satoh
en-aut-mei=Ayano
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NakamuraYoshimasa
en-aut-sei=Nakamura
en-aut-mei=Yoshimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MasudaJunko
en-aut-sei=Masuda
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Research Institute for Biomedical Sciences, Tokyo University of Science
kn-affil=

affil-num=2
en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University
kn-affil=

affil-num=9
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=10
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=11
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=12
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=13
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=breast cancer cells
kn-keyword=breast cancer cells
en-keyword=dendritic cells
kn-keyword=dendritic cells
en-keyword=mesenteric lymph node
kn-keyword=mesenteric lymph node
en-keyword=myeloid-derived suppressor cells
kn-keyword=myeloid-derived suppressor cells
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=
article-no=
start-page=1004184
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220915
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Time-series transcriptome of Brachypodium distachyon during bacterial flagellin-induced pattern-triggered immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Plants protect themselves from microorganisms by inducing pattern-triggered immunity (PTI) via recognizing microbe-associated molecular patterns (MAMPs), conserved across many microbes. Although the MAMP perception mechanism and initial events during PTI have been well-characterized, knowledge of the transcriptomic changes in plants, especially monocots, is limited during the intermediate and terminal stages of PTI. Here, we report a time-series high-resolution RNA-sequencing (RNA-seq) analysis during PTI in the leaf disks of Brachypodium distachyon. We identified 6,039 differentially expressed genes (DEGs) in leaves sampled at 0, 0.5, 1, 3, 6, and 12 hours after treatment (hat) with the bacterial flagellin peptide flg22. The k-means clustering method classified these DEGs into 10 clusters (6 upregulated and 4 downregulated). Based on the results, we selected 10 PTI marker genes in B. distachyon. Gene ontology (GO) analysis suggested a tradeoff between defense responses and photosynthesis during PTI. The data indicated the recovery of photosynthesis started at least at 12 hat. Over-representation analysis of transcription factor genes and cis-regulatory elements in DEG promoters implied the contribution of 12 WRKY transcription factors in plant defense at the early stage of PTI induction.
en-copyright=
kn-copyright=

en-aut-name=OgasaharaTsubasa
en-aut-sei=Ogasahara
en-aut-mei=Tsubasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KouzaiYusuke
en-aut-sei=Kouzai
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WatanabeMegumi
en-aut-sei=Watanabe
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakahashiAkihiro
en-aut-sei=Takahashi
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakahagiKotaro
en-aut-sei=Takahagi
en-aut-mei=Kotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KimJune-Sik
en-aut-sei=Kim
en-aut-mei=June-Sik
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MatsuiHidenori
en-aut-sei=Matsui
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YamamotoMikihiro
en-aut-sei=Yamamoto
en-aut-mei=Mikihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ToyodaKazuhiro
en-aut-sei=Toyoda
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=IchinoseYuki
en-aut-sei=Ichinose
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MochidaKeiichi
en-aut-sei=Mochida
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=NoutoshiYoshiteru
en-aut-sei=Noutoshi
en-aut-mei=Yoshiteru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=5
en-affil=Kihara Institute for Biological Research, Yokohama City University
kn-affil=

affil-num=6
en-affil=Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=7
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=8
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=9
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=10
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=11
en-affil=Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=12
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=
en-keyword=Brachypodium distachyon
kn-keyword=Brachypodium distachyon
en-keyword=monocotyledonous plant
kn-keyword=monocotyledonous plant
en-keyword=microbe-associated molecular pattern
kn-keyword=microbe-associated molecular pattern
en-keyword=time-series transcriptome analysis
kn-keyword=time-series transcriptome analysis
en-keyword=reactive oxygen species
kn-keyword=reactive oxygen species
en-keyword=pattern-triggered immunity
kn-keyword=pattern-triggered immunity
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=
article-no=
start-page=890048
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220812
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Anxiolytic-like effects of hochuekkito in lipopolysaccharide-treated mice involve interleukin-6 inhibition
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hochuekkito (HET) is a Kampo medicine used to treat postoperative and post-illness general malaise and decreased motivation. HET is known to regulate immunity and modulate inflammation. However, the precise mechanism and effects of HET on inflammation-induced central nervous system disorders remain unclear. This study aimed to assess the effect of HET on inflammation-induced anxiety-like behavior and the mechanism underlying anxiety-like behavior induced by lipopolysaccharide (LPS). Institute of Cancer Research mice were treated with LPS (300 mu g/kg, intraperitoneally), a bacterial endotoxin, to induce systemic inflammation. The mice were administered HET (1.0 g/kg, orally) once a day for 2 weeks before LPS treatment. The light-dark box test and the hole-board test were performed 24 h after the LPS injection to evaluate the effects of HET on anxiety-like behaviors. Serum samples were obtained at 2, 5, and 24 h after LPS injection, and interleukin-6 (IL-6) levels in serum were measured. Human and mouse macrophage cells (THP-1 and RAW264.7 cells, respectively) were used to investigate the effect of HET on LPS-induced IL-6 secretion. The repeated administration of HET prevented anxiety-like behavior and decreased serum IL-6 levels in LPS-treated mice. HET significantly suppressed LPS-induced IL-6 secretion in RAW264.7 and THP-1 cells. Similarly, glycyrrhizin, one of the chemical constituents of HET, suppressed LPS-induced anxiety-like behaviors. Our study revealed that HET ameliorated LPS-induced anxiety-like behavior and inhibited IL-6 release in vivo and in vitro. Therefore, we postulate that HET may be useful against inflammation-induced anxiety-like behavior.
en-copyright=
kn-copyright=

en-aut-name=UshioSoichiro
en-aut-sei=Ushio
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WadaYudai
en-aut-sei=Wada
en-aut-mei=Yudai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakamuraMizuki
en-aut-sei=Nakamura
en-aut-mei=Mizuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MatsumotoDaiki
en-aut-sei=Matsumoto
en-aut-mei=Daiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HoshikaKota
en-aut-sei=Hoshika
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShiromizuShoya
en-aut-sei=Shiromizu
en-aut-mei=Shoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IwataNaohiro
en-aut-sei=Iwata
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=EsumiSatoru
en-aut-sei=Esumi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KajizonoMakoto
en-aut-sei=Kajizono
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KitamuraYoshihisa
en-aut-sei=Kitamura
en-aut-mei=Yoshihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=SendoToshiaki
en-aut-sei=Sendo
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
en-keyword=anxiolytic
kn-keyword=anxiolytic
en-keyword=inflammation
kn-keyword=inflammation
en-keyword=immunomodulation
kn-keyword=immunomodulation
en-keyword=macrophages
kn-keyword=macrophages
en-keyword=Kampo medicine
kn-keyword=Kampo medicine
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=18
article-no=
start-page=10300
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Histidine-Rich Glycoprotein Suppresses the S100A8/A9-Mediated Organotropic Metastasis of Melanoma Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The dissection of the complex multistep process of metastasis exposes vulnerabilities that could be exploited to prevent metastasis. To search for possible factors that favor metastatic outgrowth, we have been focusing on secretory S100A8/A9. A heterodimer complex of the S100A8 and S100A9 proteins, S100A8/A9 functions as a strong chemoattractant, growth factor, and immune suppressor, both promoting the cancer milieu at the cancer-onset site and cultivating remote, premetastatic cancer sites. We previously reported that melanoma cells show lung-tropic metastasis owing to the abundant expression of S100A8/A9 in the lung. In the present study, we addressed the question of why melanoma cells are not metastasized into the brain at significant levels in mice despite the marked induction of S100A8/A9 in the brain. We discovered the presence of plasma histidine-rich glycoprotein (HRG), a brain-metastasis suppression factor against S100A8/A9. Using S100A8/A9 as an affinity ligand, we searched for and purified the binding plasma proteins of S100A8/A9 and identified HRG as the major protein on mass spectrometric analysis. HRG prevents the binding of S100A8/A9 to the B16-BL6 melanoma cell surface via the formation of the S100A8/A9 complex. HRG also inhibited the S100A8/A9-induced migration and invasion of A375 melanoma cells. When we knocked down HRG in mice bearing skin melanoma, metastasis to both the brain and lungs was significantly enhanced. The clinical examination of plasma S100A8/A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8/A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis.
en-copyright=
kn-copyright=

en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InoueYusuke
en-aut-sei=Inoue
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=RumaI. Made Winarsa
en-aut-sei=Ruma
en-aut-mei=I. Made Winarsa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=GoharaYuma
en-aut-sei=Gohara
en-aut-mei=Yuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KomalasariNi Luh Gede Yoni
en-aut-sei=Komalasari
en-aut-mei=Ni Luh Gede Yoni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=JiangFan
en-aut-sei=Jiang
en-aut-mei=Fan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YamamotoKen-Ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SumardikaI. Wayan
en-aut-sei=Sumardika
en-aut-mei=I. Wayan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=YamauchiAkira
en-aut-sei=Yamauchi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KuribayashiFutoshi
en-aut-sei=Kuribayashi
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KondoEisaku
en-aut-sei=Kondo
en-aut-mei=Eisaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

affil-num=1
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Pharmacology, Kindai University Faculty of Medicine
kn-affil=

affil-num=4
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=

affil-num=5
en-affil=Faculty of Medicine, Udayana University
kn-affil=

affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Faculty of Medicine, Udayana University
kn-affil=

affil-num=13
en-affil=Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University
kn-affil=

affil-num=14
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=15
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=

affil-num=16
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=

affil-num=17
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

affil-num=18
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=20
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=S100A8/A9
kn-keyword=S100A8/A9
en-keyword=HRG
kn-keyword=HRG
en-keyword=metastasis
kn-keyword=metastasis
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=15391
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220913
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Impact of the cervical cancer awareness months on public interest in Japan: A Google Trends analysis, 2012-2021
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The immunization and screening rates for human papillomavirus in Japan are lower than those in other countries. We aimed to evaluate the impact of cervical cancer awareness months on public attention using Google Trends analysis. Between 2012 and 2021, we analyzed the trends in relative search volumes (RSVs) for "Shikyuu-keigan" (cervical cancer in English) in Japan, during the cervical cancer awareness month (CCAM) in January and cervical cancer prevention awareness enhancement month (CCPAEM) in November. We performed a joinpoint regression analysis to identify a statistically significant trend change point. Additionally, we compared the mean RSVs of each awareness month with the rest of the year. Significant trend change points were observed, but none were found in CCAM and CCPAEM periods. Comparison of mean RSVs among CCAM, CCPAEM, and the rest of the months did not suggest any significant increases in RSVs during these awareness periods. In conclusion, CAM and CCPAEM did not raise public interest in cervical cancer in Japan. Although the results are based on internet users, the findings might suggest a need to develop a more effective and attractive approach to achieve the 90-70-90 targets of cervical cancer prevention by 2030.
en-copyright=
kn-copyright=

en-aut-name=HagiyaHideharu
en-aut-sei=Hagiya
en-aut-mei=Hideharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KoyamaToshihiro
en-aut-sei=Koyama
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OtsukaFumio
en-aut-sei=Otsuka
en-aut-mei=Fumio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,  Okayama University
kn-affil=

affil-num=2
en-affil=Department of Health Data Science, Graduate School of  Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,  Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=19
cd-vols=
no-issue=17
article-no=
start-page=10632
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220826
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immunomodulatory Effects of Radon Inhalation on Lipopolysaccharide-Induced Inflammation in Mice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Typical indications for radon therapy include autoimmune diseases such as rheumatoid arthritis (RA). We had previously reported that radon inhalation inhibits Th17 immune responses in RA mice by activating Th1 and Th2 immune responses. However, there are no reports on how radon inhalation affects the activated Th1 and Th17 immune responses, and these findings may be useful for identifying new indications for radon therapy. Therefore, in this study, we investigated the effect of radon inhalation on the lipopolysaccharide (LPS)-induced inflammatory response, focusing on the expression of related cytokines and antioxidant function. Male BALB/c mice were exposed to 2000 Bq/m(3) radon for one day. Immediately after radon inhalation, LPS was administered intraperitoneally at 1.0 mg/kg body weight for 4 h. LPS administration increased the levels of Th1- and Th17-prone cytokines, such as interleukin-2, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor, compared to no treatment control (sham). However, these effects were suppressed by radon inhalation. IL-10 levels were significantly increased by LPS administration, with or without radon inhalation, compared to sham. However, radon inhalation did not inhibit oxidative stress induced by LPS administration. These findings suggest that radon inhalation has immunomodulatory but not antioxidative functions in LPS-induced injury.
en-copyright=
kn-copyright=

en-aut-name=KataokaTakahiro
en-aut-sei=Kataoka
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NaoeShota
en-aut-sei=Naoe
en-aut-mei=Shota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MurakamiKaito
en-aut-sei=Murakami
en-aut-mei=Kaito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FujimotoYuki
en-aut-sei=Fujimoto
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YukimineRyohei
en-aut-sei=Yukimine
en-aut-mei=Ryohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TanakaAyumi
en-aut-sei=Tanaka
en-aut-mei=Ayumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YamaokaKiyonori
en-aut-sei=Yamaoka
en-aut-mei=Kiyonori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Faculty of Health Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Faculty of Health Sciences, Okayama University
kn-affil=
en-keyword=autoimmune diseases
kn-keyword=autoimmune diseases
en-keyword=cytokine
kn-keyword=cytokine
en-keyword=antioxidant function
kn-keyword=antioxidant function
en-keyword=lipopolysaccharide
kn-keyword=lipopolysaccharide
en-keyword=radon inhalation
kn-keyword=radon inhalation
END

start-ver=1.4
cd-journal=joma
no-vol=25
cd-vols=
no-issue=8
article-no=
start-page=104723
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220819
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immune response to SARS-CoV-2 in severe disease and long COVID-19
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=COVID-19 is mild to moderate in otherwise healthy individuals but may nonetheless cause life-threatening disease and/or a wide range of persistent symptoms. The general determinant of disease severity is age mainly because the immune response declines in aging patients. Here, we developed a mathematical model of the immune response to SARS-CoV-2 and revealed that typical age-related risk factors such as only a several 10% decrease in innate immune cell activity and inhibition of type-I interferon signaling by autoantibodies drastil ally increased the viral load. It was reported that the numbers of certain dendritic cell subsets remained less than half those in healthy donors even seven months after infection. Hence, the inflammatory response was ongoing. Our model predicted the persistent DC reduction and showed that certain patients with severe and even mild symptoms could not effectively eliminate the virus and could potentially develop long COVID.
en-copyright=
kn-copyright=

en-aut-name=SumiTomonari
en-aut-sei=Sumi
en-aut-mei=Tomonari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HaradaKouji
en-aut-sei=Harada
en-aut-mei=Kouji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Research Institute for Interdisciplinary Science, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Computer Science and Engineering, Toyohashi University of Technology
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=4
article-no=
start-page=399
end-page=408
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Gene Expression Profiling between Patient Groups with High and Low Ki67 Levels after Short-term Preoperative Aromatase Inhibitor Treatment for Breast Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=According to a recent report, a low Ki67 level after short-term preoperative hormone therapy (post-Ki67) might suggest a more favorable prognosis compared with a high post-Ki67 level in patients with hormone receptorpositive/human epidermal growth factor 2-negative (HR+/HER2−) breast cancer with high levels of Ki67. This study aimed to evaluate the pre-treatment genetic differences between these two patient groups. Forty-five luminal B-like patients were stratified into two groups, namely, a group with high (H→H) and one with low (H→L) Ki67 levels after short-term preoperative aromatase inhibitor (AI) treatment. We compared pre-treatmentgene expression profiles between the two groups. In gene level analysis, there was no significant difference between the two groups by the class comparison test. In pathway analysis, five metabolism-related gene sets were significantly upregulated in the H→L group (p≤0.05). In the search for novel targets, five genes (PARP, BRCA2, FLT4, CDK6, and PDCD1LG2) showed significantly higher expression in the H→H group (p≤0.05). Several metabolism-related pathways were associated with sensitivity to AI. In the future, it will be necessary to seek out new therapeutic strategies for the poor prognostic group with high post-Ki67.
en-copyright=
kn-copyright=

en-aut-name=KajiwaraYukiko
en-aut-sei=Kajiwara
en-aut-mei=Yukiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IwamotoTakayuki
en-aut-sei=Iwamoto
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ZhuYidan
en-aut-sei=Zhu
en-aut-mei=Yidan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KochiMariko
en-aut-sei=Kochi
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShienTadahiko
en-aut-sei=Shien
en-aut-mei=Tadahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TairaNaruto
en-aut-sei=Taira
en-aut-mei=Naruto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=DoiharaHiroyoshi
en-aut-sei=Doihara
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=breast cancer
kn-keyword=breast cancer
en-keyword=short-term hormone therapy
kn-keyword=short-term hormone therapy
en-keyword=gene expression profiling
kn-keyword=gene expression profiling
en-keyword=Ki-67
kn-keyword=Ki-67
en-keyword=targeted therapy
kn-keyword=targeted therapy
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=4
article-no=
start-page=359
end-page=371
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Systemic lupus erythematosus (SLE) is a potentially fatal systemic autoimmune disease, and its etiology involves both genetic and environmental factors such as sex hormone imbalance, genetic predisposition, epigenetic regulation, and immunological factors. Dysregulation of microRNA (miRNA) is suggested to be one of the epigenetic factors in SLE. miRNA is a 22-nucleotide single-stranded noncoding RNA that contributes to post-transcriptional modulation of gene expression. miRNA targeting therapy has been suggested to be useful for the treatment of cancers and other diseases. Gene knockout and miRNA targeting therapy have been demonstrated to improve SLE disease activity in mice. However, these approaches have not yet reached the level of clinical application. miRNA targeting therapy is limited by the fact that each miRNA has multiple targets. In addition, the expression of certain miRNAs may differ among cell tissues within a single SLE patient. This limitation can be overcome by targeted delivery and chemical modifications. In the future, further research into miRNA chemical modifications and delivery systems will help us develop novel therapeutic agents for SLE.
en-copyright=
kn-copyright=

en-aut-name=Hiramatsu-AsanoSumie
en-aut-sei=Hiramatsu-Asano
en-aut-mei=Sumie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=systemic lupus erythematosus
kn-keyword=systemic lupus erythematosus
en-keyword=miRNA
kn-keyword=miRNA
en-keyword=miRNA targeting therapy
kn-keyword=miRNA targeting therapy
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=
article-no=
start-page=891925
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220802
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Responses of regulatory and effector T-cells to low-dose interleukin-2 differ depending on the immune environment after allogeneic stem cell transplantation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=CD4(+)Foxp3(+) regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs promptly respond to low concentrations of IL-2 through the constitutive expression of high-affinity IL-2 receptors. It has been reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD. Clinical studies of IL-2 therapy so far have mainly targeted patients in the chronic phase of transplantation when acute immune responses has subsided. However, the biological and clinical effects of exogenous IL-2 in an acute immune environment have not been well investigated. In the current study, we investigated the impact of exogenous IL-2 therapy on the post-transplant homeostasis of T cell subsets which influence the balance between GVHD and GVL in the acute phase, by setting the various immune environments early after HSCT in murine model. We initially found that 5,000 IU of IL-2 was enough to induce the active proliferation of Treg without influencing other conventional T cells (Tcons) when administered to normal mice. However, activated Tcons showed the response to the same dose of IL-2 in recipients after allogeneic HSCT. In a mild inflammatory environment within a threshold, exogenous IL-2 could effectively modulate Treg homeostasis with just limited influence to activated T cells, which resulted in an efficient GVHD suppression. In contrast, in a severely inflammatory environment, exogenous IL-2 enhanced activated T cells rather than Tregs, which resulted in the exacerbation of GVHD. Of interest, in an immune-tolerant state after transplant, exogenous IL-2 triggered effector T-cells to exert an anti-tumor effect with maintaining GVHD suppression. These data suggested that the responses of Tregs and effector T cells to exogenous IL-2 differ depending on the immune environment in the host, and the mutual balance of the response to IL-2 between T-cell subsets modulates GVHD and GVL after HSCT. Our findings may provide useful information in the optimization of IL-2 therapy, which may be personalized for each patient having different immune status.
en-copyright=
kn-copyright=

en-aut-name=MeguriYusuke
en-aut-sei=Meguri
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AsanoTakeru
en-aut-sei=Asano
en-aut-mei=Takeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YoshiokaTakanori
en-aut-sei=Yoshioka
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IwamotoMiki
en-aut-sei=Iwamoto
en-aut-mei=Miki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=IkegawaShuntaro
en-aut-sei=Ikegawa
en-aut-mei=Shuntaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SugiuraHiroyuki
en-aut-sei=Sugiura
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KishiYuriko
en-aut-sei=Kishi
en-aut-mei=Yuriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NakamuraMakoto
en-aut-sei=Nakamura
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SandoYasuhisa
en-aut-sei=Sando
en-aut-mei=Yasuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KondoTakumi
en-aut-sei=Kondo
en-aut-mei=Takumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=SumiiYuichi
en-aut-sei=Sumii
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MatsuokaKen-Ichi
en-aut-sei=Matsuoka
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=regulatory T cell
kn-keyword=regulatory T cell
en-keyword=low-dose interleukin-2 therapy
kn-keyword=low-dose interleukin-2 therapy
en-keyword=graft-versus-host disease
kn-keyword=graft-versus-host disease
en-keyword=graft-versus-leukemia effect
kn-keyword=graft-versus-leukemia effect
en-keyword=transplantation tolerance
kn-keyword=transplantation tolerance
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=13540
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220808
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=RNA editing facilitates the enhanced production of neoantigens during the simultaneous administration of oxaliplatin and radiotherapy in colorectal cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Most cases of colorectal cancers (CRCs) are microsatellite stable (MSS), which frequently demonstrate lower response rates to immune checkpoint inhibitors (ICIs). RNA editing produces neoantigens by altering amino acid sequences. In this study, RNA editing was induced artificially by chemoradiation therapy (CRT) to generate neoantigens in MSS CRCs. Altogether, 543 CRC specimens were systematically analyzed, and the expression pattern of ADAR1 was investigated. In vitro and in vivo experiments were also performed. The RNA editing enzyme ADAR1 was upregulated in microsatellite instability-high CRCs, leading to their high affinity for ICIs. Although ADAR1 expression was low in MSS CRC, CRT including oxaliplatin (OX) treatment upregulated RNA editing levels by inducing ADAR1. Immunohistochemistry analyses showed the upregulation of ADAR1 in patients with CRC treated with CAPDX (capecitabine +OX) radiation therapy relative to ADAR1 expression in patients with CRC treated only by surgery (p <0.001). Compared with other regimens, CRT with OX effectively induced RNA editing in MSS CRC cell lines (HT29 and Caco2, p <0.001) via the induction of type 1 interferon-triggered ADAR1 expression. CRT with OX promoted the RNA editing of cyclin I, a neoantigen candidate. Neoantigens can be artificially induced by RNA editing via an OX-CRT regimen. CRT can promote proteomic diversity via RNA editing.
en-copyright=
kn-copyright=

en-aut-name=KomatsuYasuhiro
en-aut-sei=Komatsu
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakedaSho
en-aut-sei=Takeda
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakahashiKazutaka
en-aut-sei=Takahashi
en-aut-mei=Kazutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HataNanako
en-aut-sei=Hata
en-aut-mei=Nanako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=UmedaHibiki
en-aut-sei=Umeda
en-aut-mei=Hibiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YoshidaKazuhiro
en-aut-sei=Yoshida
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MoriYoshiko
en-aut-sei=Mori
en-aut-mei=Yoshiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=YasuiKazuya
en-aut-sei=Yasui
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KondoYoshitaka
en-aut-sei=Kondo
en-aut-mei=Yoshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KishimotoHiroyuki
en-aut-sei=Kishimoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=MichiueHiroyuki
en-aut-sei=Michiue
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=GoelAjay
en-aut-sei=Goel
en-aut-mei=Ajay
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Neutron Therapy  Research Center, Okayama University
kn-affil=

affil-num=18
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Department of Molecular  Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Biomedical Research  Center
kn-affil=

affil-num=20
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220718
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mechanisms of resistance to immune checkpoint inhibitors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors (ICIs) are effective for various types of cancer, and their application has led to paradigm shifts in cancer treatment. While many patients can obtain clinical benefits from ICI treatment, a large number of patients are primarily resistant to such treatment or acquire resistance after an initial response. Thus, elucidating the resistance mechanisms is warranted to improve the clinical outcomes of ICI treatment. ICIs exert their antitumor effects by activating T cells in the tumor microenvironment. There are various resistance mechanisms, such as insufficient antigen recognition by T cells, impaired T-cell migration and/or infiltration, and reduced T-cell cytotoxicity, most of which are related to the T-cell activation process. Thus, we classify them into three main mechanisms: resistance mechanisms related to antigen recognition, T-cell migration and/or infiltration, and effector functions of T cells. In this review, we summarize these mechanisms of resistance to ICIs related to the T-cell activation process and progress in the development of novel therapies that can overcome resistance.
en-copyright=
kn-copyright=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IshinoTakamasa
en-aut-sei=Ishino
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Tumor Microenvironment,  Faculty of Medicine, Dentistry and  Pharmaceutical Sciences, Okayama  University
kn-affil=

affil-num=2
en-affil=Department of Tumor Microenvironment,  Faculty of Medicine, Dentistry and  Pharmaceutical Sciences, Okayama  University
kn-affil=

affil-num=3
en-affil=Department of Tumor Microenvironment,  Faculty of Medicine, Dentistry and  Pharmaceutical Sciences, Okayama  University
kn-affil=
en-keyword=cancer immunology
kn-keyword=cancer immunology
en-keyword=exhaustion
kn-keyword=exhaustion
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=resistance
kn-keyword=resistance
en-keyword=T cell
kn-keyword=T cell
END

start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=1
article-no=
start-page=232
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220720
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Histidine-rich glycoprotein as a novel predictive biomarker of postoperative complications in intensive care unit patients: a prospective observational study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Decrease in histidine-rich glycoprotein (HRG) was reported as a cause of dysregulation of the coagulation-fibrinolysis and immune systems, leading to multi-organ failure, and it may be a biomarker for sepsis, ventilator-associated pneumonia, preeclampsia, and coronavirus disease 2019. However, the usefulness of HRG in perioperative management remains unclear. This study aimed to assess the usefulness of HRG as a biomarker for predicting postoperative complications. <br>
Methods This was a single-center, prospective, observational study of 150 adult patients who were admitted to the intensive care unit after surgery. Postoperative complications were defined as those having a grade II or higher in the Clavien-Dindo classification, occurring within 7 days after surgery. The primary outcome was HRG levels in the patients with and without postoperative complications. The secondary outcome was the ability of HRG, white blood cell, C-reactive protein, procalcitonin, and presepsin to predict postoperative complications. Data are presented as number and median (interquartile range). <br>
Results The incidence of postoperative complications was 40%. The HRG levels on postoperative day 1 were significantly lower in patients who developed postoperative complications (n = 60; 21.50 [18.12-25.74] mu g/mL) than in those who did not develop postoperative complications (n = 90; 25.46 [21.05-31.63] mu g/mL). The Harrell C-index scores for postoperative complications were HRG, 0.65; white blood cell, 0.50; C-reactive protein, 0.59; procalcitonin, 0.73; and presepsin, 0.73. HRG was independent predictor of postoperative complications when adjusted for age, the presence of preoperative cardiovascular comorbidities, American Society of Anesthesiologists Physical Status Classification, operative time, and the volume of intraoperative bleeding (adjusted hazard ratio = 0.94; 95% confidence interval, 0.90-0.99). <br>
Conclusions The HRG levels on postoperative day 1 could predict postoperative complications. Hence, HRG may be a useful biomarker for predicting postoperative complications.
en-copyright=
kn-copyright=

en-aut-name=OiwaMasahiko
en-aut-sei=Oiwa
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaKosuke
en-aut-sei=Kuroda
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KawanoueNaoya
en-aut-sei=Kawanoue
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MorimatsuHiroshi
en-aut-sei=Morimatsu
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Anesthesiology and Resuscitology, Okayama University  Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Anesthesiology and Resuscitology, Okayama University  Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Anesthesiology and Resuscitology, Okayama University  Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Anesthesiology and Resuscitology, Okayama University  Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Biomarker
kn-keyword=Biomarker
en-keyword=Clavien-Dindo classification
kn-keyword=Clavien-Dindo classification
en-keyword=Histidine-rich glycoprotein
kn-keyword=Histidine-rich glycoprotein
en-keyword=Intensive care unit
kn-keyword=Intensive care unit
en-keyword=Perioperative management
kn-keyword=Perioperative management
en-keyword=Postoperative complication
kn-keyword=Postoperative complication
en-keyword=Predictor
kn-keyword=Predictor
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=
article-no=
start-page=864225
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220629
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Nutrient Condition in the Microenvironment Determines Essential Metabolisms of CD8(+) T Cells for Enhanced IFN gamma Production by Metformin
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Metformin (Met), a first-line drug for type 2 diabetes, lowers blood glucose levels by suppressing gluconeogenesis in the liver, presumably through the liver kinase B1-dependent activation of AMP-activated protein kinase (AMPK) after inhibiting respiratory chain complex I. Met is also implicated as a drug to be repurposed for cancers; its mechanism is believed identical to that of gluconeogenesis inhibition. However, AMPK activation requires high Met concentrations at more than 1 mM, which are unachievable in vivo. The immune-mediated antitumor response might be the case in a low dose Met. Thus, we proposed activating or expanding tumor-infiltrating CD8(+) T cells (CD8TILs) in a mouse model by orally administering Met in free drinking water. Here we showed that Met, at around 10 mu M and a physiologically relevant concentration, enhanced production of IFN gamma,TNF alpha and expression of CD25 of CD8(+) T cells upon TCR stimulation. Under a glucose-rich condition, glycolysis was exclusively involved in enhancing IFN gamma production. Under a low-glucose condition, fatty acid oxidation or autophagy-dependent glutaminolysis, or both, was also involved. Moreover, phosphoenolpyruvate carboxykinase 1 (PCK1), converting oxaloacetate to phosphoenolpyruvate, became essential. Importantly, the enhanced IFN gamma production was blocked by a mitochondrial ROS scavenger and not by an inhibitor of AMPK. In addition, IFN gamma production by CD8TILs relied on pyruvate translocation to the mitochondria and PCK1. Our results revealed a direct effect of Met on IFN gamma production of CD8(+) T cells that was dependent on differential metabolic pathways and determined by nutrient conditions in the microenvironment.
en-copyright=
kn-copyright=

en-aut-name=ChaoRuoyu
en-aut-sei=Chao
en-aut-mei=Ruoyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishidaMikako
en-aut-sei=Nishida
en-aut-mei=Mikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YamashitaNahoko
en-aut-sei=Yamashita
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TokumasuMiho
en-aut-sei=Tokumasu
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ZhaoWeiyang
en-aut-sei=Zhao
en-aut-mei=Weiyang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KudoIkuru
en-aut-sei=Kudo
en-aut-mei=Ikuru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=CD8+T lymphocytes
kn-keyword=CD8+T lymphocytes
en-keyword=glycolysis
kn-keyword=glycolysis
en-keyword=FAO
kn-keyword=FAO
en-keyword=glutaminolysis
kn-keyword=glutaminolysis
en-keyword=IFNg
kn-keyword=IFNg
en-keyword=autophagy plus T
kn-keyword=autophagy plus T
en-keyword=metformin
kn-keyword=metformin
END

start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=1
article-no=
start-page=535
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220702
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Diffuse myometrium thinning and placenta accreta spectrum in a patient with systemic lupus erythematosus (SLE): a case report and review of the literature
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background : Cases of uterine wall thinning and placental abnormalities complicated with systemic lupus erythematosus (SLE) during pregnancy have been reported in Asian countries for ten years. Long-term steroid use can cause muscle degeneration, but the mechanism of myometrium thinning was not known. Through the review of published articles, this report is the first review of cases to discuss the pathogenesis and clinical features of thinned myometrium and placenta accreta spectrum (PAS) in pregnant patients with SLE. <br>
Case presentation : A twenty-nine-year-old primigravida with a history of lupus enteritis and paralytic ileus had a natural conception after less than two years of steroid treatment. An ultrasonographic study showed a thin uterine wall with a widespread thick placenta on the entire surface of the uterine cavity in the third trimester. At the 39th gestational week, she underwent a cesarean section due to the failure of the uterus to contract, even though the injection of oxytocin. There were several engorged vessels on the surface of the anterior uterine wall at the time of laparotomy. We decided to perform a hysterectomy because diffuse PAS replaced her uterus.<br>
Conclusion : A review of reported cases and our case shows an unusual complication of SLE that might be related to the particular condition of the estrogen-mediated immune system. Clinicians should always pay attention to the possibility of uterine wall thinning as uterine atony and the structural abnormality of the placenta for SLE patients with the unscarred uterus.
en-copyright=
kn-copyright=

en-aut-name=MitomaTomohiro
en-aut-sei=Mitoma
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HayataKei
en-aut-sei=Hayata
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YokohataSatomi
en-aut-sei=Yokohata
en-aut-mei=Satomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OhiraAkiko
en-aut-sei=Ohira
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KashinoChiaki
en-aut-sei=Kashino
en-aut-mei=Chiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KirinoSatoe
en-aut-sei=Kirino
en-aut-mei=Satoe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TaniKazumasa
en-aut-sei=Tani
en-aut-mei=Kazumasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MakiJota
en-aut-sei=Maki
en-aut-mei=Jota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=EtoEriko
en-aut-sei=Eto
en-aut-mei=Eriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MasuyamaHisashi
en-aut-sei=Masuyama
en-aut-mei=Hisashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine  Dentistry and Pharmaceutical Sciences, Department of Obstetrics  and Gynecology, Okayama University
kn-affil=
en-keyword=Lupus
kn-keyword=Lupus
en-keyword=Myometrium
kn-keyword=Myometrium
en-keyword=Placenta accreta spectrum
kn-keyword=Placenta accreta spectrum
en-keyword=Estrogen
kn-keyword=Estrogen
en-keyword=Uterine atony
kn-keyword=Uterine atony
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=12
article-no=
start-page=6847
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220620
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Control of STING Agonistic/Antagonistic Activity Using Amine-Skeleton-Based c-di-GMP Analogues
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Stimulator of Interferon Genes (STING) is a type of endoplasmic reticulum (ER)-membrane receptor. STING is activated by a ligand binding, which leads to an enhancement of the immune-system response. Therefore, a STING ligand can be used to regulate the immune system in therapeutic strategies. However, the natural (or native) STING ligand, cyclic-di-nucleotide (CDN), is unsuitable for pharmaceutical use because of its susceptibility to degradation by enzymes and its low cell-membrane permeability. In this study, we designed and synthesized CDN derivatives by replacing the sugar-phosphodiester moiety, which is responsible for various problems of natural CDNs, with an amine skeleton. As a result, we identified novel STING ligands that activate or inhibit STING. The cyclic ligand 7, with a cyclic amine structure containing two guanines, was found to have agonistic activity, whereas the linear ligand 12 showed antagonistic activity. In addition, these synthetic ligands were more chemically stable than the natural ligands.
en-copyright=
kn-copyright=

en-aut-name=YanaseYuta
en-aut-sei=Yanase
en-aut-mei=Yuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TsujiGenichiro
en-aut-sei=Tsuji
en-aut-mei=Genichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakamuraMiki
en-aut-sei=Nakamura
en-aut-mei=Miki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ShibataNorihito
en-aut-sei=Shibata
en-aut-mei=Norihito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=DemizuYosuke
en-aut-sei=Demizu
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=National Institute of Health Sciences
kn-affil=

affil-num=2
en-affil=National Institute of Health Sciences
kn-affil=

affil-num=3
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Division of Pharmaceutical Science of Okayama University
kn-affil=

affil-num=4
en-affil=National Institute of Health Sciences
kn-affil=

affil-num=5
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Division of Pharmaceutical Science of Okayama University
kn-affil=
en-keyword=STING
kn-keyword=STING
en-keyword=cyclic dinucleotide
kn-keyword=cyclic dinucleotide
en-keyword=amines
kn-keyword=amines
en-keyword=drug design
kn-keyword=drug design
en-keyword=agonist
kn-keyword=agonist
en-keyword=antagonist
kn-keyword=antagonist
END

start-ver=1.4
cd-journal=joma
no-vol=19
cd-vols=
no-issue=12
article-no=
start-page=7141
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220610
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Long-Term Kinetics of Serological Antibodies against Vibrio cholerae Following a Clinical Cholera Case: A Systematic Review and Meta-Analysis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Approximately 2.9 million people worldwide suffer from cholera each year, many of whom are destitute. However, understanding of immunity against cholera is still limited. Several studies have reported the duration of antibodies following cholera; however, systematic reviews including a quantitative synthesis are lacking. Objective: To meta-analyze cohort studies that have evaluated vibriocidal, cholera toxin B subunit (CTB), and lipopolysaccharide (LPS) antibody levels following a clinical cholera case. Methods: Design: Systematic review and meta-analysis. We searched PubMed and Web of science for studies assessing antibodies against Vibrio cholerae in cohorts of patients with clinical cholera. Two authors independently extracted data and assessed the quality of included studies. Random effects models were used to pool antibody titers in adults and older children (aged >= 6 years). In sensitivity analysis, studies reporting data on young children (2-5 years) were included. Results: Nine studies met our inclusion criteria for systematic review and seven for meta-analysis. The pooled mean of vibriocidal antibody titers in adults and older children (aged >= 6 years) was 123 on day 2 post-symptom onset, which sharply increased on day 7 (pooled mean = 6956) and gradually waned to 2247 on day 30, 578 on day 90, and 177 on day 360. Anti-CTB IgA antibodies also peaked on day 7 (pooled mean = 49), followed by a rapid decrease on day 30 (pooled mean = 21), and further declined on day 90 (pooled mean = 10), after which it plateaued from day 180 (pooled mean = 8) to 360 (pooled mean = 6). Similarly, anti-CTB IgG antibodies peaked in early convalescence between days 7 (pooled mean = 65) and 30 (pooled mean = 69), then gradually waned on days 90 (pooled mean = 42) and 180 (pooled mean = 30) and returned to baseline on day 360 (pooled mean = 24). Anti-LPS IgA antibodies peaked on day 7 (pooled mean = 124), gradually declined on day 30 (pooled mean = 44), which persisted until day 360 (pooled mean = 10). Anti LPS IgG antibodies peaked on day 7 (pooled mean = 94). Thereafter, they decreased on day 30 (pooled mean = 85), and dropped further on days 90 (pooled mean = 51) and 180 (pooled mean = 47), and returned to baseline on day 360 (pooled mean = 32). Sensitivity analysis including data from young children (aged 2-5 years) showed very similar findings as in the primary analysis. Conclusions: This study confirms that serological antibody (vibriocidal, CTB, and LPS) titers return to baseline levels within 1 year following clinical cholera, i.e., before the protective immunity against subsequent cholera wanes. However, this decay should not be interpreted as waning immunity because immunity conferred by cholera against subsequent disease lasts 3-10 years. Our study provides evidence for surveillance strategies and future research on vaccines and also demonstrates the need for further studies to improve our understanding of immunity against cholera.
en-copyright=
kn-copyright=

en-aut-name=MuzemboBasilua Andre
en-aut-sei=Muzembo
en-aut-mei=Basilua Andre
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KitaharaKei
en-aut-sei=Kitahara
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MitraDebmalya
en-aut-sei=Mitra
en-aut-mei=Debmalya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OhnoAyumu
en-aut-sei=Ohno
en-aut-mei=Ayumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MiyoshiShin-Ichi
en-aut-sei=Miyoshi
en-aut-mei=Shin-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India
kn-affil=

affil-num=4
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=cholera
kn-keyword=cholera
en-keyword=antibodies
kn-keyword=antibodies
en-keyword=vibriocidal
kn-keyword=vibriocidal
en-keyword=cholera toxin B
kn-keyword=cholera toxin B
en-keyword=lipopolysaccharide
kn-keyword=lipopolysaccharide
en-keyword=immunoglobulin
kn-keyword=immunoglobulin
en-keyword=immunity
kn-keyword=immunity
en-keyword=waning
kn-keyword=waning
END

start-ver=1.4
cd-journal=joma
no-vol=1866
cd-vols=
no-issue=8
article-no=
start-page=130171
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Metformin-ROS-Nrf2 connection in the host defense mechanism against oxidative stress, apoptosis, cancers, and ageing
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Reactive oxygen species (ROS) acts as a second messenger to trigger biological responses in low concentrations, while it is implicated to be toxic to biomolecules in high concentrations. Mild inhibition of respiratory chain Complex I by metformin at physiologically relevant concentrations stimulates production of low-level mitochondrial ROS. The ROS seems to induce anti-oxidative stress response via activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase (GPx), which results in not only elimination of ROS but also activation of cellular responses including resistance to apoptosis, metabolic changes, cell proliferation, senescence prevention, lifespan extension, and immune T cell activation against cancers, regardless of its effect controlling blood glucose level and T2DM. Although metformin's effect against T2DM, cancers, and ageing, are believed mostly attributed to the activation of AMP-activated protein kinase (AMPK), the cellular responses involving metformin-ROS-Nrf2 axis might be another natural asset to improve healthspan and lifespan.
en-copyright=
kn-copyright=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishidaMikako
en-aut-sei=Nishida
en-aut-mei=Mikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Mitochondrial ROS
kn-keyword=Mitochondrial ROS
en-keyword=Oxidative stress
kn-keyword=Oxidative stress
en-keyword=Apoptosis
kn-keyword=Apoptosis
en-keyword=Ageing
kn-keyword=Ageing
en-keyword=Nrf2
kn-keyword=Nrf2
END

start-ver=1.4
cd-journal=joma
no-vol=34
cd-vols=
no-issue=11
article-no=
start-page=563
end-page=570
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=2022423
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A variety of ‘exhausted’ T cells in the tumor microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=In T-cell biology, ‘exhaustion’ was initially described as a hyporesponsive state in CD8+ T cells during chronic infections. Recently, exhaustion has been recognized as a T-cell dysfunctional state in the tumor microenvironment (TME). The term ‘exhaustion’ is used mainly to refer to effector T cells with a reduced capacity to secrete cytokines and an increased expression of inhibitory receptors. The up-regulation of exhaustion-related inhibitory receptors, including programmed cell death protein 1 (PD-1), in such T cells has been associated with the development of tumors, prompting the development of immune checkpoint inhibitors. In addition to CD8+ T cells, CD4+ T cells, including the regulatory T (Treg) cell subset, perform a wide variety of functions within the adaptive immune system. Up-regulation of the same inhibitory receptors that are associated with CD8+ T-cell exhaustion has also been identified in CD4+ T cells in chronic infections and cancers, suggesting a similar CD4+ T-cell exhaustion phenotype. For instance, high expression of PD-1 has been observed in Treg cells in the TME, and such Treg cells can play an important role in the resistance to PD-1 blockade therapies. Furthermore, recent progress in single-cell RNA sequencing has shown that CD4+ T cells with cytotoxic activity are also vulnerable to exhaustion. In this review, we will discuss novel insights into various exhausted T-cell subsets, which could reveal novel therapeutic targets and strategies to induce a robust anti-tumor immune response.
en-copyright=
kn-copyright=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=CD4(+) T cell
kn-keyword=CD4(+) T cell
en-keyword=cytotoxic CD4(+ )T cell
kn-keyword=cytotoxic CD4(+ )T cell
en-keyword=regulatory T cell
kn-keyword=regulatory T cell
en-keyword=T-cell exhaustion
kn-keyword=T-cell exhaustion
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=3
article-no=
start-page=281
end-page=290
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202206
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Histone Demethylase Jmjd3 Regulates the Osteogenic Differentiation and Cytokine Expressions of Periodontal Ligament Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Periodontal ligament (PDL) cells are critical for the bone remodeling process in periapical lesions since they can differentiate into osteoblasts and secrete osteoclastogenesis-promoting cytokines. Post-translational histone modifications including alterations of the methylation status of H3K27 are involved in cell differentiation and inflammatory reaction. The histone demethylase Jumonji domain-containing 3 (Jmjd3) specifically removes methylation of H3K27. We investigated whether Jmjd3 is involved in the osteogenic differentiation and secretion of PDL cells’ inflammatory factors. Jmjd3 expression in periapical lesions was examined by immunostaining. Using siRNA specific for Jmjd3 or the specific Jmjd3 inhibitor GSK-J4, we determined Jmjd3’s roles in osteogenic differentiation and cytokine production by real-time RT-PCR. The locations of Jmjd3 and NF-κB were analyzed by immunocytochemistry. Compared to healthy PDLs, the periapical lesion samples showed higher Jmjd3 expression. Treatment with GSK-J4 or Jmjd3 siRNA suppressed PDL cells’ osteogenic differentiation by suppressing the expressions of bone-related genes (Runx2, Osterix, and osteocalcin) and mineralization. Jmjd3 knockdown decreased the expressions of cytokines (TNF-α, IL-1β, and IL-6) induced by lipopolysaccharide extracted from Porphyromonas endodontalis (Pe-LPS). Pe-LPS induced the nuclear translocations of Jmjd3 and NF-κB; the latter was inhibited by GSK-J4 treatment. Jmjd3 appears to regulate PDL cells’ osteogenic differentiation and proinflammatory cytokine expressions.
en-copyright=
kn-copyright=

en-aut-name=YuBo
en-aut-sei=Yu
en-aut-mei=Bo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WangRui
en-aut-sei=Wang
en-aut-mei=Rui
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LuoHuikun
en-aut-sei=Luo
en-aut-mei=Huikun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YangDi
en-aut-sei=Yang
en-aut-mei=Di
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WangSimo
en-aut-sei=Wang
en-aut-mei=Simo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YuYaqiong
en-aut-sei=Yu
en-aut-mei=Yaqiong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OkamuraHirohiko
en-aut-sei=Okamura
en-aut-mei=Hirohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=QiuLihong
en-aut-sei=Qiu
en-aut-mei=Lihong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease
kn-affil=

affil-num=2
en-affil=Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease
kn-affil=

affil-num=3
en-affil=Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease
kn-affil=

affil-num=4
en-affil=Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease
kn-affil=

affil-num=5
en-affil=Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease
kn-affil=

affil-num=6
en-affil=Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease
kn-affil=

affil-num=7
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease
kn-affil=
en-keyword=periapical lesions
kn-keyword=periapical lesions
en-keyword=histone demethylase Jmjd3
kn-keyword=histone demethylase Jmjd3
en-keyword=periodontal ligament cell
kn-keyword=periodontal ligament cell
en-keyword=osteogenic differentiation
kn-keyword=osteogenic differentiation
en-keyword=proinflammatory cytokines
kn-keyword=proinflammatory cytokines
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=3
article-no=
start-page=247
end-page=253
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202206
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Analysis of Immunity against Measles, Mumps, Rubella, and Varicella Zoster in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Vaccine-preventable disease (VPD) infections are more severe in immunocompromised hosts. Vaccination against measles, mumps, rubella, and varicella zoster (VZV) (MMRV) is therefore recommended for hematopoietic stem cell transplantation (HCT) recipients. However, studies on adult HCT recipients with VPD infections are limited. At our institution, we have systematically conducted serological MMRV tests as a part of check-up examinations during long-term follow-up (LTFU) after HCT since 2015. This retrospective study aimed to evaluate changes in the serostatus between before and 2 years after allogeneic HCT. Among 161 patients, the pre-transplant seropositivity was 82.7% for measles, 86.8% for mumps, 84.2% for rubella, and 94.3% for VZV. Among 56 patients who underwent LTFU including serological MMRV tests at 2 years after HCT, the percentages maintaining seroprotective antibody levels for measles, mumps, rubella and VZV were 71.5% (40/56), 51.8% (29/56), 48.2% (27/56), and 60.7% (34/56), respectively. Vaccination was recommended for 22 patients, and 12 were vaccinated. Among the 12 vaccinated patients, rates of seroconversion were examined in 2-6 patients for each of the four viruses. They were 100% (3/3) for measles, 33.3% (1/3) for mumps, 50% (3/6) for rubella, and 0% (0/2) for VZV. Further studies are warranted to clarify the effect of vaccination in adult HCT recipients.
en-copyright=
kn-copyright=

en-aut-name=YoshidaShohei
en-aut-sei=Yoshida
en-aut-mei=Shohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FujiiNobuharu
en-aut-sei=Fujii
en-aut-mei=Nobuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KamoiChihiro
en-aut-sei=Kamoi
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KitamuraWataru
en-aut-sei=Kitamura
en-aut-mei=Wataru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujiwaraHideaki
en-aut-sei=Fujiwara
en-aut-mei=Hideaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AsadaNoboru
en-aut-sei=Asada
en-aut-mei=Noboru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NishimoriHisakazu
en-aut-sei=Nishimori
en-aut-mei=Hisakazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=FujiiKeiko
en-aut-sei=Fujii
en-aut-mei=Keiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MatsuokaKen-ichi
en-aut-sei=Matsuoka
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=vaccine-preventable disease
kn-keyword=vaccine-preventable disease
en-keyword=vaccination
kn-keyword=vaccination
en-keyword=allogeneic hematopoietic stem cell transplantation
kn-keyword=allogeneic hematopoietic stem cell transplantation
en-keyword=adult
kn-keyword=adult
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=同種造血幹細胞移植の成人レシピエントにおける麻疹、おたふくかぜ、風疹、および水痘帯状疱疹に対する免疫反応の分析：単施設での経験
kn-title=Analysis of immunity against measles, mumps, rubella, and varicella zoster in adult recipients of allogeneic hematopoietic stem cell transplantation: A single-center experience
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=YoshidaShohei
en-aut-sei=Yoshida
en-aut-mei=Shohei
kn-aut-name=吉田将平
kn-aut-sei=吉田
kn-aut-mei=将平
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Humanities and Social Sciences, Okayama University
kn-affil=岡山大学大学院社会文化科学研究科
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=5
article-no=
start-page=1000
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220510
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Maternal Gut Microbiome Decelerates Fetal Endochondral Bone Formation by Inducing Inflammatory Reaction
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=To investigate the effect of the maternal gut microbiome on fetal endochondral bone formation, fetuses at embryonic day 18 were obtained from germ-free (GF) and specific-pathogen-free (SPF) pregnant mothers. Skeletal preparation of the fetuses' whole bodies did not show significant morphological alterations; however, micro-CT analysis of the tibiae showed a lower bone volume fraction in the SPF tibia. Primary cultured chondrocytes from fetal SPF rib cages showed a lower cell proliferation and lower accumulation of the extracellular matrix. RNA-sequencing analysis showed the induction of inflammation-associated genes such as the interleukin (IL) 17 receptor, IL 6, and immune-response genes in SPF chondrocytes. These data indicate that the maternal gut microbiome in SPF mice affects fetal embryonic endochondral ossification, possibly by changing the expression of genes related to inflammation and the immune response in fetal cartilage. The gut microbiome may modify endochondral ossification in the fetal chondrocytes passing through the placenta.
en-copyright=
kn-copyright=

en-aut-name=Uchida-FukuharaYoko
en-aut-sei=Uchida-Fukuhara
en-aut-mei=Yoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HattoriTakako
en-aut-sei=Hattori
en-aut-mei=Takako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FuShanqi
en-aut-sei=Fu
en-aut-mei=Shanqi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KondoSei
en-aut-sei=Kondo
en-aut-mei=Sei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KuwaharaMiho
en-aut-sei=Kuwahara
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FukuharaDaiki
en-aut-sei=Fukuhara
en-aut-mei=Daiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IslamMd Monirul
en-aut-sei=Islam
en-aut-mei=Md Monirul
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KataokaKota
en-aut-sei=Kataoka
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=EkuniDaisuke
en-aut-sei=Ekuni
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KubotaSatoshi
en-aut-sei=Kubota
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MoritaManabu
en-aut-sei=Morita
en-aut-mei=Manabu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=IikegameMika
en-aut-sei=Iikegame
en-aut-mei=Mika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OkamuraHirohiko
en-aut-sei=Okamura
en-aut-mei=Hirohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Oral Morphology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Preventive Dentistry, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=12
en-affil=Department of Oral Morphology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 
kn-affil=

affil-num=13
en-affil=Department of Oral Morphology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 
kn-affil=
en-keyword=maternal microbiome
kn-keyword=maternal microbiome
en-keyword=endochondral ossification
kn-keyword=endochondral ossification
en-keyword=fetal chondrocytes
kn-keyword=fetal chondrocytes
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=
article-no=
start-page=869393
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220504
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Engineering Cancer/Testis Antigens With Reversible S-Cationization to Evaluate Antigen Spreading
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Serum autoantibody to cancer/testis antigens (CTAs) is a critical biomarker that reflects the antitumor immune response. Quantitative and multiplexed anti-CTA detection arrays can assess the immune status in tumors and monitor therapy-induced antitumor immune reactions. Most full-length recombinant CTA proteins tend to aggregate. Cysteine residue-specific S-cationization techniques facilitate the preparation of water-soluble and full-length CTAs. Combined with Luminex technology, we designed a multiple S-cationized antigen-immobilized bead array (MUSCAT) assay system to evaluate multiple serum antibodies to CTAs. Reducible S-alkyl-disulfide-cationized antigens in cytosolic conditions were employed to develop rabbit polyclonal antibodies as positive controls. These control antibodies sensitively detected immobilized antigens on beads and endogenous antigens in human lung cancer-derived cell lines. Rabbit polyclonal antibodies successfully confirmed the dynamic ranges and quantitative MUSCAT assay results. An immune monitoring study was conducted using the serum samples on an adenovirus-mediated REIC/Dkk-3 gene therapy clinical trial that showed a successful clinical response in metastatic castration-resistant prostate cancer. Autoantibody responses were closely related to clinical outcomes. Notably, upregulation of anti-CTA responses was monitored before tumor regression. Thus, quantitative monitoring of anti-CTA antibody biomarkers can be used to evaluate the cancer-immunity cycle. A quality-certified serum autoantibody monitoring system is a powerful tool for developing and evaluating cancer immunotherapy.
en-copyright=
kn-copyright=

en-aut-name=MiyamotoAi
en-aut-sei=Miyamoto
en-aut-mei=Ai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HonjoTomoko
en-aut-sei=Honjo
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MasuiMirei
en-aut-sei=Masui
en-aut-mei=Mirei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KumonHiromi
en-aut-sei=Kumon
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KakimiKazuhiro
en-aut-sei=Kakimi
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Immunotherapeutics, The University of Tokyo Hospital
kn-affil=

affil-num=7
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=autoantibody
kn-keyword=autoantibody
en-keyword=biomarker
kn-keyword=biomarker
en-keyword=protein engineering
kn-keyword=protein engineering
en-keyword=cancer-immunity cycle
kn-keyword=cancer-immunity cycle
en-keyword=immune monitoring
kn-keyword=immune monitoring
en-keyword=cancer
kn-keyword=cancer
en-keyword=testis antigens
kn-keyword=testis antigens
END

start-ver=1.4
cd-journal=joma
no-vol=132
cd-vols=
no-issue=7
article-no=
start-page=e140869
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202241
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Tankyrase represses autoinflammation through the attenuation of TLR2 signaling
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Dysregulation of Toll-like receptor (TLR) signaling contributes to the pathogenesis of autoimmune diseases. Here, we provide genetic evidence that tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, negatively regulates TLR2 signaling. We show that mice lacking tankyrase in myeloid cells developed severe systemic inflammation with high serum inflammatory cytokine levels. We provide mechanistic evidence that tankyrase deficiency resulted in tyrosine phosphorylation and activation of TLR2 and show that phosphorylation of tyrosine 647 within the TIR domain by SRC and SYK kinases was critical for TLR2 stabilization and signaling. Last, we show that the elevated cytokine production and inflammation observed in mice lacking tankyrase in myeloid cells were dependent on the adaptor protein 3BP2, which is required for SRC and SYK activation. These data demonstrate that tankyrase provides a checkpoint on the TLR-mediated innate immune response.
en-copyright=
kn-copyright=

en-aut-name=MatsumotoYoshinori
en-aut-sei=Matsumoto
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=DimitriouIoannis D.
en-aut-sei=Dimitriou
en-aut-mei=Ioannis D.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=La RoseJose
en-aut-sei=La Rose
en-aut-mei=Jose
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=LimMelissa
en-aut-sei=Lim
en-aut-mei=Melissa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=CamilleriSusan
en-aut-sei=Camilleri
en-aut-mei=Susan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=LawNapoleon
en-aut-sei=Law
en-aut-mei=Napoleon
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AdissuHibret A.
en-aut-sei=Adissu
en-aut-mei=Hibret A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TongJiefei
en-aut-sei=Tong
en-aut-mei=Jiefei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MoranMichael F.
en-aut-sei=Moran
en-aut-mei=Michael F.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ChruscinskiAndrzej
en-aut-sei=Chruscinski
en-aut-mei=Andrzej
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=HeFang
en-aut-sei=He
en-aut-mei=Fang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=AsanoYosuke
en-aut-sei=Asano
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KatsuyamaTakayuki
en-aut-sei=Katsuyama
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=SadaKen-ei
en-aut-sei=Sada
en-aut-mei=Ken-ei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=RottapelRobert
en-aut-sei=Rottapel
en-aut-mei=Robert
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Princess Margaret Cancer Centre, University Health Network, University of Toronto
kn-affil=

affil-num=3
en-affil=Princess Margaret Cancer Centre, University Health Network, University of Toronto
kn-affil=

affil-num=4
en-affil=Princess Margaret Cancer Centre, University Health Network, University of Toronto
kn-affil=

affil-num=5
en-affil=Centre for Modeling Human Disease, Toronto Centre for Phenogenomics
kn-affil=

affil-num=6
en-affil=Centre for Modeling Human Disease, Toronto Centre for Phenogenomics
kn-affil=

affil-num=7
en-affil=Labcorp Early Development Laboratories Inc.
kn-affil=

affil-num=8
en-affil=Program in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics
kn-affil=

affil-num=9
en-affil=Program in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics
kn-affil=

affil-num=10
en-affil=Multi-Organ Transplant Program, University Health Network
kn-affil=

affil-num=11
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Princess Margaret Cancer Centre, University Health Network, University of Toronto
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=39
cd-vols=
no-issue=
article-no=
start-page=57
end-page=64
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202246
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Implications of immune cells in oncolytic herpes simplex virotherapy for glioma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Despite current progress in treatment, glioblastoma (GBM) remains a lethal primary malignant tumor of the central nervous system. Although immunotherapy has recently achieved remarkable survival effectiveness in multiple malignancies, none of the immune checkpoint inhibitors (ICIs) for GBM have shown anti-tumor efficacy in clinical trials. GBM has a characteristic immunosuppressive tumor microenvironment (TME) that results in the failure of ICIs. Oncolytic herpes simplex virotherapy (oHSV) is the most advanced United States Food and Drug Administration-approved virotherapy for advanced metastatic melanoma patients. Recently, another oHSV, Delytact®, was granted conditional approval in Japan against GBM, highlighting it as a promising treatment. Since oncolytic virotherapy can recruit abundant immune cells and modify the immune TME, oncolytic virotherapy for immunologically cold GBM will be an attractive therapeutic option for GBM. However, as these immune cells have roles in both anti-tumor and anti-viral immunity, fine-tuning of the TME using oncolytic virotherapy will be important to maximize the therapeutic efficacy. In this review, we discuss the current knowledge of oHSV, with a focus on the role of immune cells as friend or foe in oncolytic virotherapy.
en-copyright=
kn-copyright=

en-aut-name=OtaniYoshihiro
en-aut-sei=Otani
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YooJi Young
en-aut-sei=Yoo
en-aut-mei=Ji Young
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ShimizuToshihiko
en-aut-sei=Shimizu
en-aut-mei=Toshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KurozumiKazuhiko
en-aut-sei=Kurozumi
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=DateIsao
en-aut-sei=Date
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KaurBalveen
en-aut-sei=Kaur
en-aut-mei=Balveen
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston
kn-affil=

affil-num=3
en-affil=Department of Neurosurgery, Matsuyama Shimin Hospital
kn-affil=

affil-num=4
en-affil=Department of Neurosurgery, Hamamatsu University School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston
kn-affil=
en-keyword=Oncolytic virus
kn-keyword=Oncolytic virus
en-keyword=Immune cells
kn-keyword=Immune cells
en-keyword=Glioma
kn-keyword=Glioma
END

start-ver=1.4
cd-journal=joma
no-vol=45
cd-vols=
no-issue=
article-no=
start-page=1876
end-page=1890
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202247
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Three highly conserved hydrophobic residues in the predicted α2‐helix of rice NLR protein Pit contribute to its localization and immune induction
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Nucleotide-binding leucine-rich repeat (NLR) proteins work as crucial intracellular immune receptors. N-terminal domains of NLRs fall into two groups, coiled-coil (CC) and Toll-interleukin 1 receptor domains, which play critical roles in signal transduction and disease resistance. However, the activation mechanisms of NLRs, and how their N-termini function in immune induction, remain largely unknown. Here, we revealed that the CC domain of a rice NLR Pit contributes to self-association. The Pit CC domain possesses three conserved hydrophobic residues that are known to be involved in oligomer formation in two NLRs, barley MLA10 and Arabidopsis RPM1. Interestingly, the function of these residues in Pit differs from that in MLA10 and RPM1. Although three hydrophobic residues are important for Pit-induced disease resistance against rice blast fungus, they do not participate in self-association or binding to downstream signalling molecules. By homology modelling of Pit using the Arabidopsis ZAR1 structure, we tried to clarify the role of three conserved hydrophobic residues and found that they are located in the predicted α2-helix of the Pit CC domain and involved in the plasma membrane localization. Our findings provide novel insights for understanding the mechanisms of NLR activation as well as the relationship between subcellular localization and immune induction.
en-copyright=
kn-copyright=

en-aut-name=WangQiong
en-aut-sei=Wang
en-aut-mei=Qiong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=LiYuying
en-aut-sei=Li
en-aut-mei=Yuying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KosamiKen‐ichi
en-aut-sei=Kosami
en-aut-mei=Ken‐ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=LiuChaochao
en-aut-sei=Liu
en-aut-mei=Chaochao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=LiJing
en-aut-sei=Li
en-aut-mei=Jing
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ZhangDan
en-aut-sei=Zhang
en-aut-mei=Dan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MikiDaisuke
en-aut-sei=Miki
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KawanoYoji
en-aut-sei=Kawano
en-aut-mei=Yoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=School of Horticulture and Plant Protection Yangzhou University Yangzhou China
kn-affil=

affil-num=2
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology Chinese Academy of Sciences Shanghai China
kn-affil=

affil-num=3
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology Chinese Academy of Sciences Shanghai China
kn-affil=

affil-num=4
en-affil=School of Biotechnology Jiangsu University of Science and Technology Zhenjiang China
kn-affil=

affil-num=5
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology Chinese Academy of Sciences Shanghai China
kn-affil=

affil-num=6
en-affil=School of Horticulture and Plant Protection Yangzhou University Yangzhou China
kn-affil=

affil-num=7
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology Chinese Academy of Sciences Shanghai China
kn-affil=

affil-num=8
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=
en-keyword=NLR protein
kn-keyword=NLR protein
en-keyword=plasma membrane localization
kn-keyword=plasma membrane localization
en-keyword=self-association
kn-keyword=self-association
en-keyword=effector triggered immunity
kn-keyword=effector triggered immunity
en-keyword=rice
kn-keyword=rice
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=4
article-no=
start-page=e05725
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220418
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Analysis of subgingival microbiota in monozygotic twins with different severity and progression risk of periodontitis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The study aims to reveal the composition of subgingival bacteria in monozygotic twins with discordant in severity and progression risk of periodontitis. Microbiome analysis indicated that most bacteria were heritable but differed in their abundance and immune response. The dysbiotic bacteria can be considered as risk markers for periodontitis progression.
en-copyright=
kn-copyright=

en-aut-name=YamamotoTadashi
en-aut-sei=Yamamoto
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TaniguchiMakoto
en-aut-sei=Taniguchi
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MatsunagaKazuyuki
en-aut-sei=Matsunaga
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KawataYusuke
en-aut-sei=Kawata
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KawamuraMari
en-aut-sei=Kawamura
en-aut-mei=Mari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OkuboKeisuke
en-aut-sei=Okubo
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YamashiroKeisuke
en-aut-sei=Yamashiro
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OmoriKazuhiro
en-aut-sei=Omori
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TakashibaShogo
en-aut-sei=Takashiba
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Oral Microbiome Center, Taniguchi Dental Clinic, Takamatsu, Japan 3 Department of Neurology, Brain Attack Center Ota Memorial Hospital
kn-affil=

affil-num=3
en-affil=Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=disease progression
kn-keyword=disease progression
en-keyword=dysbiosis
kn-keyword=dysbiosis
en-keyword=environmental factors
kn-keyword=environmental factors
en-keyword=microbiome
kn-keyword=microbiome
en-keyword=monozygotic twins
kn-keyword=monozygotic twins
en-keyword=periodontitis
kn-keyword=periodontitis
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=2
article-no=
start-page=129
end-page=135
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202204
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Combination of D-dimer and Glasgow Prognostic Score Can Be Useful in Predicting VTE in Patients with Stage IIIC and IVA Ovarian Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer patients have increased risk of venous thromboembolism (VTE) that must be assessed before treatment. This study aimed to determine effective VTE biomarkers in gynecologic cancer (GC). We investigated the correlation between D-dimer levels, Khorana risk score (KRS), Glasgow prognostic score (GPS), and VTE in 1499 GC patients (583 cervical cancer (CC), 621 endometrial cancer (EC), and 295 ovarian cancer (OC) patients) treated at our institution between January 2008 and December 2019. χ2 and Mann–Whitney U-tests were used to determine statistical significance. We used receiver operating characteristic-curve analysis to evaluate the discriminatory ability of each parameter. D-dimer levels were significantly correlated with KRS and GPS in patients with GC. VTE was diagnosed in 11 CC (1.9%), 27 EC (4.3%), and 39 OC patients (13.2%). Optimal D-dimer cut-off values for VTE were 3.1, 3.2, and 3.9 μg/ml in CC, EC and OC patients, respectively. D-dimer could significantly predict VTE in all GC patients. Furthermore, D-dimer combined with GPS was more accurate in predicting VTE than other VTE biomarkers in stage IIIC and IVA OC (AUC: 0.846; p<0.001). This study demonstrates that combined D-dimer and GPS are useful in predicting VTE in patients with OC.
en-copyright=
kn-copyright=

en-aut-name=KuboKotaro
en-aut-sei=Kubo
en-aut-mei=Kotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NakamuraKeiichiro
en-aut-sei=Nakamura
en-aut-mei=Keiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OkamotoKazuhiro
en-aut-sei=Okamoto
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MatsuokaHirofumi
en-aut-sei=Matsuoka
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=IdaNaoyuki
en-aut-sei=Ida
en-aut-mei=Naoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HarumaTomoko
en-aut-sei=Haruma
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OgawaChikako
en-aut-sei=Ogawa
en-aut-mei=Chikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MasuyamaHisashi
en-aut-sei=Masuyama
en-aut-mei=Hisashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=D-dimer
kn-keyword=D-dimer
en-keyword=gynecologic cancer
kn-keyword=gynecologic cancer
en-keyword=venous thromboembolism
kn-keyword=venous thromboembolism
END

start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=2
article-no=
start-page=87
end-page=92
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=2022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Confirmation of efficacy, elucidation of mechanism, and new search for indications of radon therapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Indications of radon therapy include various diseases related to respiratory, painful, digestive, chronic degenerative, senile, etc. derived from reactive oxygen species, but most are based on empirical prescriptions. For this reason, we have evaluated the relation between the biological response caused by radon and the tissue/organ absorbed dose more quantitatively, and have promoted the elucidation of mechanisms related to the indication and searching newly. As a result, as a mechanism, a series of moderate physiological stimulative effects accompanying a small amount of oxidative stress by radon inhalation are being elucidated. That is, hyperfunction of anti-oxidation/immune regulation/damage repair, promotion of anti-inflammation/circulating metabolism/hormone secretion, induction of apoptosis/heat shock protein, etc. Also, new indications include inflammatory/neuropathic pain, hepatic/renal injury, colitis, type 1 diabetes, complication kidney injury, hyperuricemia, transient cerebral ischemia, and inflammatory edema. Furthermore, we examined the combined antioxidant effect of radon inhalation and antioxidants or therapeutic agents. As a result, it was clear that any combination treatment could enhance the suppression effect of disease. It can be expected that radon therapy can be used effectively by applying it in addition to usual treatment, since reduction in its dosage can also be expected by concomitant use for drugs with strong side effects.
en-copyright=
kn-copyright=

en-aut-name=YamaokaKiyonori
en-aut-sei=Yamaoka
en-aut-mei=Kiyonori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KataokaTakahiro
en-aut-sei=Kataoka
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Health Sciences, Institute of Academic and Research, Okayama University
kn-affil=

affil-num=2
en-affil=Health Sciences, Institute of Academic and Research, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=2
article-no=
start-page=154
end-page=159
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=2022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mechanisms of action of radon therapy on cytokine levels in normal mice and rheumatoid arthritis mouse model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The typical indication of radon therapy is rheumatoid arthritis. Although there are several reports that radon therapy has regulation effects on Th17 cells, there has been no study reporting that radon inhalation affects the immune balance among Th1, Th2, and Th17. The purpose of this study is to examine the cytokine changes after radon inhalation. BALB/c mice inhaled radon at 2,000 Bq/m3 for 2 or 4 weeks. SKG/Jcl mice inhaled radon at 2,000 Bq/m3 for 4 weeks after zymosan administration. The results showed that radon inhalation for 4 weeks activated the immune response of Th1, Th2, and Th17. Moreover, the balance among them was not lost by radon inhalation. Radon inhalation for 4 weeks decreased superoxide dismutase activity and increased catalase activity in spleen. These findings suggest that an imbalance of oxidative stress may contribute to activate the immune response. Although zymosan administration activated Th17 immune response and decreased Th1 and Th2 immune response in SKG/Jcl mice, most cytokines related to Th1, Th2, and Th17 approached the normal level by radon inhalation. These findings suggested that radon inhalation has a different action between SKG/Jcl mice and normal BABL/c mice. This may indicate that radon inhalation has an immunomodulation function.
en-copyright=
kn-copyright=

en-aut-name=KataokaTakahiro
en-aut-sei=Kataoka
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NaoeShota
en-aut-sei=Naoe
en-aut-mei=Shota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MurakamiKaito
en-aut-sei=Murakami
en-aut-mei=Kaito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YukimineRyohei
en-aut-sei=Yukimine
en-aut-mei=Ryohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujimotoYuki
en-aut-sei=Fujimoto
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KanzakiNorie
en-aut-sei=Kanzaki
en-aut-mei=Norie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SakodaAkihiro
en-aut-sei=Sakoda
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MitsunobuFumihiro
en-aut-sei=Mitsunobu
en-aut-mei=Fumihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YamaokaKiyonori
en-aut-sei=Yamaoka
en-aut-mei=Kiyonori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency
kn-affil=

affil-num=7
en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency
kn-affil=

affil-num=8
en-affil=Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Graduate School of Health Sciences, Okayama University
kn-affil=
en-keyword=radon
kn-keyword=radon
en-keyword=cytokine
kn-keyword=cytokine
en-keyword=oxidative stress
kn-keyword=oxidative stress
en-keyword=rheumatoid arthritis
kn-keyword=rheumatoid arthritis
en-keyword=immunomodulation function
kn-keyword=immunomodulation function
END

start-ver=1.4
cd-journal=joma
no-vol=19
cd-vols=
no-issue=2
article-no=
start-page=377
end-page=392
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220124
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Novel Prognostic Predictor of Immune Micro-environment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Necroptosis, a cell death of caspase-independence, plays a pivotal role in cancer biological regulation. Although necroptosis is closely associated with oncogenesis, cancer metastasis, and immunity, there remains a lack of studies determining the role of necroptosis-related genes (NRGs) in the highly immunogenic cancer type, kidney renal clear cell carcinoma (KIRC). Methods: The information of clinicopathology and transcriptome was extracted from TCGA database. Following the division into the train and test cohorts, a three-NRGs (TLR3, FASLG, ZBP1) risk model was identified in train cohort by LASSO regression. The overall survival (OS) comparison was conducted between different risk groups through Kaplan-Meier analysis, which was further validated in test cohort. The Cox proportional hazards regression model was introduced to assess its impact of clinicopathological factors and risk score on survival. ESTIMATE and CIBERSORT algorithms were introduced to evaluate immune microenvironment, while enrichment analysis was conducted to explore the biological significance. Correlation analysis was applied for the correlation assessment between checkpoint gene expression and risk score, between gene expression and therapeutic response. Gene expressions from TCGA were verified by GEO datasets and immunohistochemistry (IHC) analysis. Results: This NRGs-related signature predicted poorer OS in high-risk group, which was also verified in test cohort. Risk score could also independently predict survival outcome of KIRC. Significant changes were also found in immune microenvironment and checkpoint gene expressions between different risk groups, with immune functional enrichment in high-risk group. Interestingly, therapeutic response was correlated with the expressions of NRGs. The expressions of NRGs from TCGA were consistent with those from GEO datasets and IHC analysis. Conclusion: The NRGs-related signature functions as a novel prognostic predictor of immune microenvironment and therapeutic response in KIRC.
en-copyright=
kn-copyright=

en-aut-name=ChenWenwei
en-aut-sei=Chen
en-aut-mei=Wenwei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=LinWenfeng
en-aut-sei=Lin
en-aut-mei=Wenfeng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WuLiang
en-aut-sei=Wu
en-aut-mei=Liang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=XuAbai
en-aut-sei=Xu
en-aut-mei=Abai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=LiuChunxiao
en-aut-sei=Liu
en-aut-mei=Chunxiao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HuangPeng
en-aut-sei=Huang
en-aut-mei=Peng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University
kn-affil=

affil-num=2
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Pathology, The First Affiliated Hospital, Wenzhou Medical University
kn-affil=

affil-num=4
en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University
kn-affil=

affil-num=5
en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University
kn-affil=

affil-num=6
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=prognosis
kn-keyword=prognosis
en-keyword=immune microenvironment
kn-keyword=immune microenvironment
en-keyword=therapeutic response
kn-keyword=therapeutic response
en-keyword=kidney renal clear cell carcinoma
kn-keyword=kidney renal clear cell carcinoma
en-keyword=necroptosis
kn-keyword=necroptosis
en-keyword=gene signature
kn-keyword=gene signature
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=6
article-no=
start-page=885
end-page=894
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220301
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=HopAZ1, a type III effector of Pseudomonas amygdali pv. tabaci, induces a hypersensitive response in tobacco wildfire-resistant Nicotiana tabacum 'N509'
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pseudomonas amygdali pv. tabaci (formerly Pseudomonas syringae pv. tabaci; Pta) is a gram-negative bacterium that causes bacterial wildfire disease in Nicotiana tabacum. The pathogen establishes infections by using a type III secretion system to inject type III effector proteins (T3Es) into cells, thereby interfering with the host & apos;s immune system. To counteract the effectors, plants have evolved disease-resistance genes and mechanisms to induce strong resistance on effector recognition. By screening a series of Pta T3E-deficient mutants, we have identified HopAZ1 as the T3E that induces disease resistance in N. tabacum 'N509'. Inoculation with the Pta increment hopAZ1 mutant did not induce resistance to Pta in N509. We also found that the Pta increment hopAZ1 mutant did not induce a hypersensitive response and promoted severe disease symptoms in N509. Furthermore, a C-terminal truncated HopAZ1 abolished HopAZ1-dependent cell death in N509. These results indicate that HopAZ1 is the avirulence factor that induces resistance to Pta by N509.
en-copyright=
kn-copyright=

en-aut-name=KashiharaSachi
en-aut-sei=Kashihara
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishimuraTakafumi
en-aut-sei=Nishimura
en-aut-mei=Takafumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NoutoshiYoshiteru
en-aut-sei=Noutoshi
en-aut-mei=Yoshiteru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YamamotoMikihiro
en-aut-sei=Yamamoto
en-aut-mei=Mikihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ToyodaKazuhiro
en-aut-sei=Toyoda
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IchinoseYuki
en-aut-sei=Ichinose
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MatsuiHidenori
en-aut-sei=Matsui
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=6
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=

affil-num=7
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=
en-keyword=effector
kn-keyword=effector
en-keyword=hypersensitive responses
kn-keyword=hypersensitive responses
en-keyword=Pseudomonas syringae pv
kn-keyword=Pseudomonas syringae pv
en-keyword=tabaci
kn-keyword=tabaci
en-keyword=type III secretion system
kn-keyword=type III secretion system
END

start-ver=1.4
cd-journal=joma
no-vol=44
cd-vols=
no-issue=4
article-no=
start-page=716
end-page=726
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2003
dt-pub=200304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Circulating oxidized LDL forms complexes with β(2)-glycoprotein I: implication as an atherogenic autoantigen
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=beta(2)-glycoprotein I (beta(2)-GPI) is a major antigen for antiphospholipid antibodies (Abs, aPL) present in patients with antiphospholipid syndrome (APS). We recently reported (I. Lipid Res., 42: 697, 200 1; J Lipid Res., 43: 1486, 2002) that beta(2)-GPI specifically binds to Cu2+-oxidized LDL (oxLDL) and that the beta(2)-GPI ligands are omega-carboxylated 7-ketocholesteryl esters. In the present study, we demonstrate that oxLDL forms stable and nondissociable complexes with beta(2)-GPI in serum, and that high serum levels of the complexes are associated with arterial thrombosis in APS. A conjugated ketone function at the 7-position of cholesterol as well as the omega-carboxyl function of the beta(2)-GPI ligands was necessary for beta(2)-GPI binding. The ligand-mediated noncovalent interaction of beta(2)-GPI and oxLDL undergoes a temperature- and time-dependent conversion to much more stable but readily dissociable complexes in vitro at neutral pH. In contrast, stable and nondissociable beta(2)-GPI-oxLDL complexes were frequently detected in sera from patients with APS and/or systemic lupus erythematodes. Both the presence Of beta(2)-GPI-oxLDL complexes and IgG Abs recognizing these complexes were strongly associated with arterial thrombosis. Further, these same Abs correlated with IgG immune complexes containing beta(2)-GPI or LDL.jlr Thus, the beta(2)-GPI-oxLDL complexes acting as an autoantigen are closely associated with autoimmune-mediated atherogenesis.
en-copyright=
kn-copyright=

en-aut-name=KobayashiKazuko
en-aut-sei=Kobayashi
en-aut-mei=Kazuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KishiMakoto
en-aut-sei=Kishi
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AtsumiTatsuya
en-aut-sei=Atsumi
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=BertolacciniMaria L.
en-aut-sei=Bertolaccini
en-aut-mei=Maria L.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SakairiNobuo
en-aut-sei=Sakairi
en-aut-mei=Nobuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YamamotoItaru
en-aut-sei=Yamamoto
en-aut-mei=Itaru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YasudaTatsuji
en-aut-sei=Yasuda
en-aut-mei=Tatsuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KhamashtaMunther A.
en-aut-sei=Khamashta
en-aut-mei=Munther A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HughesGraham R. V.
en-aut-sei=Hughes
en-aut-mei=Graham R. V.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KoikeTakao
en-aut-sei=Koike
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=VoelkerDennis R.
en-aut-sei=Voelker
en-aut-mei=Dennis R.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MatsuuraEiji
en-aut-sei=Matsuura
en-aut-mei=Eiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry
kn-affil=

affil-num=2
en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry
kn-affil=

affil-num=3
en-affil=Department of Medicine II, Hokkaido University Graduate School of Medicine
kn-affil=

affil-num=4
en-affil=Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital London
kn-affil=

affil-num=5
en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry
kn-affil=

affil-num=6
en-affil=Division of Bioscience, Graduate School of Environment Earth Science, Hokkaido University
kn-affil=

affil-num=7
en-affil=Department of Immunochemistry, Faculty of Pharmaceutical Science, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry
kn-affil=

affil-num=9
en-affil=Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital London
kn-affil=

affil-num=10
en-affil=Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital London
kn-affil=

affil-num=11
en-affil=Department of Medicine II, Hokkaido University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Program in Cell Biology, Department of Medicine, National Jewish Medical and Research Center
kn-affil=

affil-num=13
en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry
kn-affil=
en-keyword=antiphospholipid syndrome
kn-keyword=antiphospholipid syndrome
en-keyword=arterial thrombosis
kn-keyword=arterial thrombosis
en-keyword=autoantibody
kn-keyword=autoantibody
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=3
article-no=
start-page=1214
end-page=1228
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220116
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Identification of MICALL2 as a Novel Prognostic Biomarker Correlating with Inflammation and T Cell Exhaustion of Kidney Renal Clear Cell Carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose: The interplay of inflammation and immunity affects all stages from tumorigenesis to progression, and even tumor response to therapy. A growing interest has been attracted from the biological function of MICALL2 to its effects on tumor progression. This study was designed to verify whether MICALL2 could be a prognostic biomarker to predict kidney renal clear cell carcinoma (KIRC) progression, inflammation, and immune infiltration within tumor microenvironment (TME). <br>
<br>
Methods: We firstly analyzed MICALL2 expressions across 33 cancer types from the UCSC Xena database and verified its expression in KIRC through GEPIA platform and GEO datasets. The clinicopathological characteristics were further analyzed based on the median expression. Kaplan-Meier method, univariate and multivariate analyses were applied to compare survival outcomes. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration, and a co-expression analysis was conducted to evaluate the correlation between MICALL2 and immunoregulatory genes. Enrichment analysis was finally performed to explore the biological significance of MICALL2. <br>
<br>
Results: MICALL2 was highly expressed in 16 types of cancers compared with normal tissues. MICALL2 expression increased with advanced clinicopathological parameters and was an independent predictor for poor prognosis in KIRC. Moreover, MICALL2 closely correlated with inflammation-promoting signatures and immune infiltration including T cell exhaustion markers. Consistently, MICALL2 involved in the regulation of signaling pathways associated with tumor immunity, tumor progression, and impaired metabolic activities. <br>
<br>
Conclusion: MICALL2 can function as a prognostic biomarker mediating inflammation, immune infiltration, and T cell exhaustion within the microenvironment of KIRC.
en-copyright=
kn-copyright=

en-aut-name=LinWenfeng
en-aut-sei=Lin
en-aut-mei=Wenfeng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ChenWenwei
en-aut-sei=Chen
en-aut-mei=Wenwei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ZhongJisheng
en-aut-sei=Zhong
en-aut-mei=Jisheng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=UekiHideo
en-aut-sei=Ueki
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=XuAbai
en-aut-sei=Xu
en-aut-mei=Abai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=WatanabeMasami
en-aut-sei=Watanabe
en-aut-mei=Masami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ArakiMotoo
en-aut-sei=Araki
en-aut-mei=Motoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LiuChunxiao
en-aut-sei=Liu
en-aut-mei=Chunxiao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NasuYasutomo
en-aut-sei=Nasu
en-aut-mei=Yasutomo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HuangPeng
en-aut-sei=Huang
en-aut-mei=Peng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University
kn-affil=

affil-num=3
en-affil=School of Medicine, Xiamen University
kn-affil=

affil-num=4
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University
kn-affil=

affil-num=6
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University
kn-affil=

affil-num=9
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=MICALL2
kn-keyword=MICALL2
en-keyword=biomarker
kn-keyword=biomarker
en-keyword=inflammation
kn-keyword=inflammation
en-keyword=T cell exhaustion
kn-keyword=T cell exhaustion
en-keyword=kidney renal clear cell carcinoma
kn-keyword=kidney renal clear cell carcinoma
END

start-ver=1.4
cd-journal=joma
no-vol=67
cd-vols=
no-issue=1
article-no=
start-page=26
end-page=30
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210120
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=HIV infection diagnosed from delayed wound healing after tonsillectomy : A case report
kn-title=口蓋扁桃摘出術後の創傷治癒遅延を契機に判明した HIV 感染症の1例
en-subtitle=
kn-subtitle=
en-abstract=HIV (human immunodeficiency virus) lowers the immune capacity of the host and causes AIDS (acquired immunodeficiency syndrome) when it progresses. HIV infection is known to have a variety of symptoms, and it is often diagnosed based on the occurrence of various otorhinolaryngological conditions. We experienced a case in which an HIV infection was diagnosed based on delayed wound healing after tonsillectomy. The early initiation of treatment for HIV infection is known to be effective for controlling progression, so it is important to detect HIV infection as early as possible. Preoperative HIV screening tests may lead to the early detection of HIV, and such tests are also important to prevent delayed wound healing. In Japan, it remains a problem that preoperative HIV screening is sometimes not allowed under by the Japanese National health insurance system.
kn-abstract=HIV（human immunodeficiency virus）は感染すると宿主の免疫能を低下させ、進行すると AIDS（acquired immunodeficiency syndrome）を引き起こす。HIV 感染症は多彩な症状を呈することが知られており、創傷治癒遅延もその一つである。今回われわれは口蓋扁桃摘出術後の創傷治癒遅延から HIV 感染症と判明した症例を経験した。HIV 感染症は早期の治療開始が予後改善のために推奨されており、早期発見が重要である。手術前 HIV スクリーニング検査は創傷治癒遅延を防ぐ意味でも重要と考えられるが、現行の保険制度上は認められない場合があり、保険適用範囲の拡大が望まれる。
en-copyright=
kn-copyright=

en-aut-name=KariyaAkifumi
en-aut-sei=Kariya
en-aut-mei=Akifumi
kn-aut-name=假谷彰文
kn-aut-sei=假谷
kn-aut-mei=彰文
aut-affil-num=1
ORCID=

en-aut-name=IshiharaHisashi
en-aut-sei=Ishihara
en-aut-mei=Hisashi
kn-aut-name=石原久司
kn-aut-sei=石原
kn-aut-mei=久司
aut-affil-num=2
ORCID=

en-aut-name=AkisadaNaoki
en-aut-sei=Akisada
en-aut-mei=Naoki
kn-aut-name=秋定直樹
kn-aut-sei=秋定
kn-aut-mei=直樹
aut-affil-num=3
ORCID=

en-aut-name=FujisawaIku
en-aut-sei=Fujisawa
en-aut-mei=Iku
kn-aut-name=藤澤郁
kn-aut-sei=藤澤
kn-aut-mei=郁
aut-affil-num=4
ORCID=

en-aut-name=FujiSayaka
en-aut-sei=Fuji
en-aut-mei=Sayaka
kn-aut-name=藤さやか
kn-aut-sei=藤
kn-aut-mei=さやか
aut-affil-num=5
ORCID=

en-aut-name=AkagiSeiko
en-aut-sei=Akagi
en-aut-mei=Seiko
kn-aut-name=赤木成子
kn-aut-sei=赤木
kn-aut-mei=成子
aut-affil-num=6
ORCID=

en-aut-name=TakeuchiAyako
en-aut-sei=Takeuchi
en-aut-mei=Ayako
kn-aut-name=竹内彩子
kn-aut-sei=竹内
kn-aut-mei=彩子
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital
kn-affil=岡山赤十字病院耳鼻咽喉科

affil-num=2
en-affil=Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital
kn-affil=岡山赤十字病院耳鼻咽喉科

affil-num=3
en-affil=Department of Head and Neck Surgery, Shikoku Cancer Center
kn-affil=国立病院機構四国がんセンター頭頸科

affil-num=4
en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科耳鼻咽喉・頭頸部外科学

affil-num=5
en-affil=Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital
kn-affil=岡山赤十字病院耳鼻咽喉科

affil-num=6
en-affil=Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital
kn-affil=岡山赤十字病院耳鼻咽喉科

affil-num=7
en-affil=Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital
kn-affil=岡山赤十字病院耳鼻咽喉科
en-keyword=HIV（human immunodeficiency virus）
kn-keyword=HIV（human immunodeficiency virus）
en-keyword=創傷治癒遅延
kn-keyword=創傷治癒遅延
en-keyword=口蓋扁桃摘出術
kn-keyword=口蓋扁桃摘出術
en-keyword=手術合併症
kn-keyword=手術合併症
en-keyword=性感染症
kn-keyword=性感染症
END

start-ver=1.4
cd-journal=joma
no-vol=62
cd-vols=
no-issue=11
article-no=
start-page=1662
end-page=1675
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=2021827
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Small GTPase OsRac1 Forms Two Distinct Immune Receptor Complexes Containing the PRR OsCERK1 and the NLR Pit
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors. In this study, using biochemical and bioimaging approaches, we revealed that OsRac1 formed two distinct receptor complexes with OsCERK1 and with Pit. Supporting this result, OsCERK1 and Pit utilized different transport systems for anchorage to the plasma membrane (PM). Activation of OsCERK1 and Pit led to OsRac1 activation and, concomitantly, OsRac1 shifted from a small to a large protein complex fraction. We also found that the chaperone Hsp90 contributed to the proper transport of Pit to the PM and the immune induction of Pit. These findings illuminate how the PRR OsCERK1 and the NLR Pit orchestrate rice immunity through the small GTPase OsRac1.
en-copyright=
kn-copyright=

en-aut-name=AkamatsuAkira
en-aut-sei=Akamatsu
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FujiwaraMasayuki
en-aut-sei=Fujiwara
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HamadaSatoshi
en-aut-sei=Hamada
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WakabayashiMegumi
en-aut-sei=Wakabayashi
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YaoAi
en-aut-sei=Yao
en-aut-mei=Ai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=WangQiong
en-aut-sei=Wang
en-aut-mei=Qiong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KosamiKen-ichi
en-aut-sei=Kosami
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=DangThu Thi
en-aut-sei=Dang
en-aut-mei=Thu Thi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=Kaneko-KawanoTakako
en-aut-sei=Kaneko-Kawano
en-aut-mei=Takako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FukadaFumi
en-aut-sei=Fukada
en-aut-mei=Fumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ShimamotoKo
en-aut-sei=Shimamoto
en-aut-mei=Ko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KawanoYoji
en-aut-sei=Kawano
en-aut-mei=Yoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Biosciences, Kwansei Gakuin University
kn-affil=

affil-num=2
en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology
kn-affil=

affil-num=3
en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology
kn-affil=

affil-num=4
en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology
kn-affil=

affil-num=5
en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology
kn-affil=

affil-num=6
en-affil=Department of Horticulture and Plant Protection
kn-affil=

affil-num=7
en-affil=CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology, Chinese Academy of Sciences
kn-affil=

affil-num=8
en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology
kn-affil=

affil-num=9
en-affil=College of Pharmaceutical Sciences, Ritsumeikan University
kn-affil=

affil-num=10
en-affil=Institute of Plant Science and Resources
kn-affil=

affil-num=11
en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology
kn-affil=

affil-num=12
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=10
article-no=
start-page=e0258977
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentially regulated with greater than a twofold change in 12-month-old cochleae with ARHL relative to young control mice, 33 (39.3%) of which were upregulated. These differentially regulated genes (DEGs) were involved in functional pathways for cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-kappa B subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-kappa B would interact with the genomic regulatory regions of eight upregulated DEGs, including Tnf and Ptgs2. In aging cochleae, major proinflammatory molecules, IL1B and IL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1, IL18r1, IL1B, Card9, Clec4e, Ifit1, and Tlr9) occurred at an advanced stage (between 9 and 12 months of age) of ARHL. Immunohistochemistry analysis of cochlear sections from the 12-month-old mice indicated that IL-18r1 and IL-1B were localized to the spiral ligament, spiral limbus, and organ of Corti. The two NF-kappa B-interacting inflammatory molecules, TNF alpha and PTGS2, immunolocalized ubiquitously in cochlear structures, including the lateral wall (the stria vascularis and spiral ligament), in the histological sections of aged cochleae. IBA1-positive macrophages were observed in the stria vascularis and spiral ligament in aged mice. Therefore, inflammatory and immune reactions are modulated in aged cochlear tissues with ARHL.
en-copyright=
kn-copyright=

en-aut-name=UraguchiKensuke
en-aut-sei=Uraguchi
en-aut-mei=Kensuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakaharaJunko
en-aut-sei=Takahara
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OmichiRyotaro
en-aut-sei=Omichi
en-aut-mei=Ryotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujimotoShohei
en-aut-sei=Fujimoto
en-aut-mei=Shohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KariyaShin
en-aut-sei=Kariya
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NishizakiKazunori
en-aut-sei=Nishizaki
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AndoMizuo
en-aut-sei=Ando
en-aut-mei=Mizuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=
article-no=
start-page=703298
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210827
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Crosstalk Between Intestinal Microbiota Derived Metabolites and Tissues in Allogeneic Hematopoietic Cell Transplantation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an evidence based- cellular immunotherapy for hematological malignancies. Immune reactions not only promote graft-versus-tumor effects that kill hematological malignant cells but also graft-versus-host disease (GVHD) that is the primary complication characterized by systemic organ damages consisting of T-cells and antigen presenting cells (APCs) activation. GVHD has long been recognized as an immunological reaction that requires an immunosuppressive treatment targeting immune cells. However immune suppression cannot always prevent GVHD or effectively treat it once it has developed. Recent studies using high-throughput sequencing technology investigated the impact of microbial flora on GVHD and provided profound insights of the mechanism of GVHD other than immune cells. Allo-HSCT affects the intestinal microbiota and microbiome-metabolome axis that can alter intestinal homeostasis and the severity of experimental GVHD. This axis can potentially be manipulated via dietary intervention or metabolites produced by intestinal bacteria affected post-allo-HSCT. In this review, we discuss the mechanism of experimental GVHD regulation by the complex microbial community-metabolites-host tissue axis. Furthermore, we summarize the major findings of microbiome-based immunotherapeutic approaches that protect tissues from experimental GVHD. Understanding the complex relationships between gut microbiota-metabolites-host tissues axis provides crucial insight into the pathogenesis of GVHD and advances the development of new therapeutic approaches.
en-copyright=
kn-copyright=

en-aut-name=FujiwaraHideaki
en-aut-sei=Fujiwara
en-aut-mei=Hideaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
en-keyword=graft-versus-host disease
kn-keyword=graft-versus-host disease
en-keyword=microbial metabolite
kn-keyword=microbial metabolite
en-keyword=dysbiosis
kn-keyword=dysbiosis
en-keyword=microbiota
kn-keyword=microbiota
en-keyword=allogeneic stem cell transplantation
kn-keyword=allogeneic stem cell transplantation
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=1
article-no=
start-page=12
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211118
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Proton beam therapy followed by pembrolizumab for giant ocular surface conjunctival malignant melanoma: A case report
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The present study describes proton beam therapy as a clinical option to achieve local control of giant conjunctival melanoma in an aged person, instead of orbital exenteration. An 80‑year‑old woman with one‑year history of left‑eye injection and hemorrhage experienced rapid growth of the ocular surface black mass. At the initial visit, a black, elastic hard, hemorrhage‑prone, thickened mass in the size of 30x40 mm with a presumed wide stalk covered the total area of the lid fissure on the left side. Biopsy of the mass demonstrated anomalous melanin‑containing cells in fibrin and hemorrhage, which were positive for cocktail‑mix antibodies against tyrosinase, melanoma antigen recognized by T cells‑1 and human melanoma black‑45, indicative of malignant melanoma. One month after the initial visit, the patient underwent proton beam therapy at the total dose of 70.4 Gy (relative biological effectiveness) in 32 fractions (~10 min each) in one and a half months. One month after the end of proton beam therapy, 3.5 months from the initial visit, the patient was found by computed tomographic scan to have multiple metastatic lesions in bilateral lung fields. With the evidence of absent BRAF mutation, the patient underwent intravenous administration of pembrolizumab 77.2 mg every three weeks five times in total. Then, three months after proton beam therapy, ocular surface melanoma almost subsided and the clear cornea allowed visualization of the intraocular lens inside the eye. In three weeks, spontaneous corneal perforation was plugged with iris incarceration. The patient died suddenly of unknown cause 7.5 months from the initial visit. The local control of giant conjunctival melanoma was achieved by proton beam therapy, leading to patient's satisfaction and better quality of life. Proton beam therapy, followed by immune checkpoint inhibitors, would become the future standard of care for unresectable giant conjunctival melanoma.
en-copyright=
kn-copyright=

en-aut-name=MatsuoToshihiko
en-aut-sei=Matsuo
en-aut-mei=Toshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YamasakiOsamu
en-aut-sei=Yamasaki
en-aut-mei=Osamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KatsuiKuniaki
en-aut-sei=Katsui
en-aut-mei=Kuniaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WakiTakahiro
en-aut-sei=Waki
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Regenerative and Reconstructive Medicine (Ophthalmology), Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems
kn-affil=

affil-num=2
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Division of Radiation Oncology, Department of Radiology, Kawasaki Medical School
kn-affil=

affil-num=5
en-affil=Department of Radiology, Tsuyama Chuo Hospital
kn-affil=
en-keyword=ocular surface
kn-keyword=ocular surface
en-keyword=conjunctiva
kn-keyword=conjunctiva
en-keyword=malignant melanoma
kn-keyword=malignant melanoma
en-keyword=proton beam therapy
kn-keyword=proton beam therapy
en-keyword=pembrolizumab
kn-keyword=pembrolizumab
en-keyword=PD‑1 inhibitor
kn-keyword=PD‑1 inhibitor
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=corneal perforation
kn-keyword=corneal perforation
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=11
article-no=
start-page=e003134
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202111
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background<br>
Patients with cancer benefit from treatment with immune checkpoint inhibitors (ICIs), and those with an inflamed tumor microenvironment (TME) and/or high tumor mutation burden (TMB), particularly, tend to respond to ICIs; however, some patients fail, whereas others acquire resistance after initial response despite the inflamed TME and/or high TMB. We assessed the detailed biological mechanisms of resistance to ICIs such as programmed death 1 and/or cytotoxic T-lymphocyte-associated protein 4 blockade therapies using clinical samples.<br>
<br>
Methods<br>
We established four pairs of autologous tumor cell lines and tumor-infiltrating lymphocytes (TILs) from patients with melanoma treated with ICIs. These tumor cell lines and TILs were subjected to comprehensive analyses and in vitro functional assays. We assessed tumor volume and TILs in vivo mouse models to validate identified mechanism. Furthermore, we analyzed additional clinical samples from another large melanoma cohort.<br>
<br>
Results<br>
Two patients were super-responders, and the others acquired resistance: the first patient had a non-inflamed TME and acquired resistance due to the loss of the beta-2 microglobulin gene, and the other acquired resistance despite having inflamed TME and extremely high TMB which are reportedly predictive biomarkers. Tumor cell line and paired TIL analyses showed high CD155, TIGIT ligand, and TIGIT expression in the tumor cell line and tumor-infiltrating T cells, respectively. TIGIT blockade or CD155-deletion activated T cells in a functional assay using an autologous cell line and paired TILs from this patient. CD155 expression increased in surviving tumor cells after coculturing with TILs from a responder, which suppressed TIGIT+ T-cell activation. Consistently, TIGIT blockade or CD155-deletion could aid in overcoming resistance to ICIs in vivo mouse models. In clinical samples, CD155 was related to resistance to ICIs in patients with melanoma with an inflamed TME, including both primary and acquired resistance.<br>
<br>
Conclusions<br>
The TIGIT/CD155 axis mediates resistance to ICIs in patients with melanoma with an inflamed TME, promoting the development of TIGIT blockade therapies in such patients with cancer.
en-copyright=
kn-copyright=

en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=InozumeTakashi
en-aut-sei=Inozume
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=UenoToshihide
en-aut-sei=Ueno
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TanjiEtsuko
en-aut-sei=Tanji
en-aut-mei=Etsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HonobeAkiko
en-aut-sei=Honobe
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OhnumaTakehiro
en-aut-sei=Ohnuma
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KawamuraTatsuyoshi
en-aut-sei=Kawamura
en-aut-mei=Tatsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UmedaYoshiyasu
en-aut-sei=Umeda
en-aut-mei=Yoshiyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NakamuraYasuhiro
en-aut-sei=Nakamura
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KawasakiTomonori
en-aut-sei=Kawasaki
en-aut-mei=Tomonori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KiniwaYukiko
en-aut-sei=Kiniwa
en-aut-mei=Yukiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=YamasakiOsamu
en-aut-sei=Yamasaki
en-aut-mei=Osamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=FukushimaSatoshi
en-aut-sei=Fukushima
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=IkeharaYuzuru
en-aut-sei=Ikehara
en-aut-mei=Yuzuru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=ManoHiroyuki
en-aut-sei=Mano
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=SuzukiYutaka
en-aut-sei=Suzuki
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=NishikawaHiroyoshi
en-aut-sei=Nishikawa
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=MatsueHiroyuki
en-aut-sei=Matsue
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

affil-num=1
en-affil=Research Institute, Chiba Cancer Center
kn-affil=

affil-num=2
en-affil=Research Institute, Chiba Cancer Center
kn-affil=

affil-num=3
en-affil=Research Institute, Chiba Cancer Center
kn-affil=

affil-num=4
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=

affil-num=5
en-affil=Research Institute, Chiba Cancer Center
kn-affil=

affil-num=6
en-affil=Research Institute, Chiba Cancer Center
kn-affil=

affil-num=7
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=8
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=9
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=10
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=

affil-num=11
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=

affil-num=12
en-affil=Department of Pathology, Saitama Medical University International Medical Center
kn-affil=

affil-num=13
en-affil=Department of Dermatology, Shinshu University School of Medicine
kn-affil=

affil-num=14
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University
kn-affil=

affil-num=16
en-affil=Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine
kn-affil=

affil-num=17
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=

affil-num=18
en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
kn-affil=

affil-num=19
en-affil=Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center
kn-affil=

affil-num=20
en-affil=Department of Dermatology, Chiba University Graduate School of Medicine
kn-affil=

affil-num=21
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210924
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=リポソーム化α-ガラクトシルセラミドはドナー制御性T細胞を増加させ、濾胞ヘルパーT細胞に作用し、強皮症型慢性移植片対宿主病の発症を予防する
kn-title=Donor Treg expansion by liposomal α‐galactosylceramide modulates Tfh cells and prevents sclerodermatous chronic graft‐versus‐host disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=SugiuraHiroyuki
en-aut-sei=Sugiura
en-aut-mei=Hiroyuki
kn-aut-name=杉浦弘幸
kn-aut-sei=杉浦
kn-aut-mei=弘幸
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=1
article-no=
start-page=592
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211104
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Increased expression of TAZ and associated upregulation of PD-L1 in cervical cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background As an important component of the Hippo pathway, WW domain-containing transcription regulator 1 (TAZ), is a transcriptional coactivator that is responsible for the progression of various types of cancers. Programmed cell death protein 1 (PD-1) receptors in activated T cells and their ligand programming death force 1 (PD-L1) are the main checkpoint signals that control T cell activity. Studies have shown high levels of PD-L1 in various cancers and that PD-L1/PD-1 signals to evade T-cell immunity. Recent data have demonstrated that TAZ can regulate the characteristics of cancer cells via PD-L1. Cervical cancer is a common gynecological disease worldwide. In this study, we attempted to evaluate the effects of TAZ and PD-L1 on cervical cancer. <br>
Methods Hela cervical cancer cells were transfected with TAZ plasmid or TAZ siRNA or PD-L1 siRNA by using Lipofectamine 2000. The relationship between TAZ and PD-L1 in cervical cancer cells was determined by qRT-PCR and western blotting. The functional roles of TAZ were confirmed via CCK-8, Transwell and flow cytometry assays. Western blotting was utilized to observe the expression of BCL-2 and Caspase-3. The clinicopathological correlation of TAZ and PD-L1 was evaluated via relevant databases. <br>
Result TAZ is upregulated in cervical cancer and induces the growth and metastasis of cervical cancer cells by targeting PD-L1and inhibiting the ratio of apoptotic of cancer cells. High TAZ and PD-L1 expression was observed in different stage, grade, histological patterns, and ages of cervical cancer groups compared with normal cervix groups. Furthermore, high TAZ expression was positively correlated with the infiltration levels of immune cells and the expression of PD-L1.
en-copyright=
kn-copyright=

en-aut-name=HanYanyan
en-aut-sei=Han
en-aut-mei=Yanyan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=LiuDandan
en-aut-sei=Liu
en-aut-mei=Dandan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LiLianhong
en-aut-sei=Li
en-aut-mei=Lianhong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=The Fourth Medical Center of The General Hospital of the Chinese People’s Liberation Army
kn-affil=

affil-num=3
en-affil=Pathology Department of Dalian Medical University
kn-affil=
en-keyword=TAZ
kn-keyword=TAZ
en-keyword=PD-L1
kn-keyword=PD-L1
en-keyword=Cervical cancer
kn-keyword=Cervical cancer
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=
article-no=
start-page=740610
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211006
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Comprehensive Comparative Genomics and Phenotyping of Methylobacterium Species
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The pink-pigmented facultative methylotrophs (PPFMs), a major bacterial group found in the plant phyllosphere, comprise two genera: Methylobacterium and Methylorubrum. They have been separated into three major clades: A, B (Methylorubrum), and C. Within these genera, however, some species lack either pigmentation or methylotrophy, which raises the question of what actually defines the PPFMs. The present study employed a comprehensive comparative genomics approach to reveal the phylogenetic relationship among the PPFMs and to explain the genotypic differences that confer their different phenotypes. We newly sequenced the genomes of 29 relevant-type strains to complete a dataset for almost all validly published species in the genera. Through comparative analysis, we revealed that methylotrophy, nitrate utilization, and anoxygenic photosynthesis are hallmarks differentiating the PPFMs from the other Methylobacteriaceae. The Methylobacterium species in clade A, including the type species Methylobacterium organophilum, were phylogenetically classified into six subclades, each possessing relatively high genomic homology and shared phenotypic characteristics. One of these subclades is phylogenetically close to Methylorubrum species; this finding led us to reunite the two genera into a single genus Methylobacterium. Clade C, meanwhile, is composed of phylogenetically distinct species that share relatively higher percent G+C content and larger genome sizes, including larger numbers of secondary metabolite clusters. Most species of clade C and some of clade A have the glutathione-dependent pathway for formaldehyde oxidation in addition to the H4MPT pathway. Some species cannot utilize methanol due to their lack of MxaF-type methanol dehydrogenase (MDH), but most harbor an XoxF-type MDH that enables growth on methanol in the presence of lanthanum. The genomes of PPFMs encode between two and seven (average 3.7) genes for pyrroloquinoline quinone-dependent alcohol dehydrogenases, and their phylogeny is distinctly correlated with their genomic phylogeny. All PPFMs were capable of synthesizing auxin and did not induce any immune response in rice cells. Other phenotypes including sugar utilization, antibiotic resistance, and antifungal activity correlated with their phylogenetic relationship. This study provides the first inclusive genotypic insight into the phylogeny and phenotypes of PPFMs.
en-copyright=
kn-copyright=

en-aut-name=AlessaOla
en-aut-sei=Alessa
en-aut-mei=Ola
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OguraYoshitoshi
en-aut-sei=Ogura
en-aut-mei=Yoshitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FujitaniYoshiko
en-aut-sei=Fujitani
en-aut-mei=Yoshiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakamiHideto
en-aut-sei=Takami
en-aut-mei=Hideto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HayashiTetsuya
en-aut-sei=Hayashi
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SahinNurettin
en-aut-sei=Sahin
en-aut-mei=Nurettin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TaniAkio
en-aut-sei=Tani
en-aut-mei=Akio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=2
en-affil=Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine
kn-affil=

affil-num=3
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=4
en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo
kn-affil=

affil-num=5
en-affil=Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University
kn-affil=

affil-num=6
en-affil=Egitim Fakultesi, Mugla Sitki Kocman University
kn-affil=

affil-num=7
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=
en-keyword=Methylobacterium
kn-keyword=Methylobacterium
en-keyword=comparative genomics
kn-keyword=comparative genomics
en-keyword=methylotroph
kn-keyword=methylotroph
en-keyword=methanol dehydrogenase
kn-keyword=methanol dehydrogenase
en-keyword=Methylorubrum
kn-keyword=Methylorubrum
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210920
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=This prespecified subanalysis of the global, randomized controlled phase Ill KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or greater evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). The hazard ratio (HR) for progression-free survival by independent central review (data cut-off date, 10 July 2017) was 0.25 (95% confidence interval [CI], 0.10-0.64; one-sided, nominal P = .001). The HR for overall survival (data cut-off date, 15 February 2019) was 0.39 (95% CI, 0.17-0.91; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 patients (52%) and four patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFRIALK alterations and a PD-L1 tumor proportion score of 50% or greater.
en-copyright=
kn-copyright=

en-aut-name=SatouchiMiyako
en-aut-sei=Satouchi
en-aut-mei=Miyako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NosakiKaname
en-aut-sei=Nosaki
en-aut-mei=Kaname
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakahashiToshiaki
en-aut-sei=Takahashi
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NakagawaKazuhiko
en-aut-sei=Nakagawa
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AoeKeisuke
en-aut-sei=Aoe
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KurataTakayasu
en-aut-sei=Kurata
en-aut-mei=Takayasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SekineAkimasa
en-aut-sei=Sekine
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HoriikeAtsushi
en-aut-sei=Horiike
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FukuharaTatsuro
en-aut-sei=Fukuhara
en-aut-mei=Tatsuro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SugawaraShunichi
en-aut-sei=Sugawara
en-aut-mei=Shunichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UmemuraShigeki
en-aut-sei=Umemura
en-aut-mei=Shigeki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SakaHideo
en-aut-sei=Saka
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OkamotoIsamu
en-aut-sei=Okamoto
en-aut-mei=Isamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=YamamotoNobuyuki
en-aut-sei=Yamamoto
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=SakaiHiroshi
en-aut-sei=Sakai
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KishiKazuma
en-aut-sei=Kishi
en-aut-mei=Kazuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KatakamiNobuyuki
en-aut-sei=Katakami
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=HorinouchiHidehito
en-aut-sei=Horinouchi
en-aut-mei=Hidehito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=HidaToyoaki
en-aut-sei=Hida
en-aut-mei=Toyoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=OkamotoHiroaki
en-aut-sei=Okamoto
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=AtagiShinji
en-aut-sei=Atagi
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=OhiraTatsuo
en-aut-sei=Ohira
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=HanShi Rong
en-aut-sei=Han
en-aut-mei=Shi Rong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=NoguchiKazuo
en-aut-sei=Noguchi
en-aut-mei=Kazuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=EbianaVictoria
en-aut-sei=Ebiana
en-aut-mei=Victoria
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=

affil-num=1
en-affil=Department of Thoracic Oncology, Hyogo Cancer Center
kn-affil=

affil-num=2
en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center
kn-affil=

affil-num=3
en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center
kn-affil=

affil-num=4
en-affil=Department of Medical Oncology, Faculty of Medicine, Kindai University
kn-affil=

affil-num=5
en-affil=Department of Medical Oncology, National Hospital Organization Yamaguchi Ube Medical Center
kn-affil=

affil-num=6
en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital
kn-affil=

affil-num=7
en-affil=Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center
kn-affil=

affil-num=8
en-affil=Department of Thoracic Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research
kn-affil=

affil-num=9
en-affil=Miyagi Cancer Center
kn-affil=

affil-num=10
en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital
kn-affil=

affil-num=11
en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East
kn-affil=

affil-num=12
en-affil=Department of Respiratory Medicine and Medical Oncology, National Hospital Organization Nagoya Medical Center
kn-affil=

affil-num=13
en-affil=Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University
kn-affil=

affil-num=14
en-affil=Internal Medicine III, Wakayama Medical University
kn-affil=

affil-num=15
en-affil=Department of Thoracic Oncology, Saitama Cancer Center
kn-affil=

affil-num=16
en-affil=Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital
kn-affil=

affil-num=17
en-affil=Division of Integrated Oncology, Institute of Biomedical Research and Innovation Hospital
kn-affil=

affil-num=18
en-affil=Department of Thoracic Oncology, National Cancer Center Hospital
kn-affil=

affil-num=19
en-affil=Department of Thoracic Oncology, Aichi Cancer Center
kn-affil=

affil-num=20
en-affil=Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital
kn-affil=

affil-num=21
en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center
kn-affil=

affil-num=22
en-affil=Department of Surgery, Tokyo Medical University
kn-affil=

affil-num=23
en-affil=MSD K.K.
kn-affil=

affil-num=24
en-affil=MSD K.K.
kn-affil=

affil-num=25
en-affil=Merck & Co., Inc.
kn-affil=

affil-num=26
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
en-keyword=Japan
kn-keyword=Japan
en-keyword=non-small-cell lung carcinoma
kn-keyword=non-small-cell lung carcinoma
en-keyword=PD-L1 protein
kn-keyword=PD-L1 protein
en-keyword=pembrolizumab
kn-keyword=pembrolizumab
en-keyword=treatment outcome
kn-keyword=treatment outcome
END

start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=6
article-no=
start-page=671
end-page=675
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202112
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Multiple Roles of Histidine-Rich Glycoprotein in Vascular Homeostasis and Angiogenesis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Histidine-rich glycoprotein (HRG) is a 75 kDa plasma protein that is synthesized in the liver of many verte-brates and present in their plasma at relatively high concentrations of 100-150 μg/mL. HRG is an abundant and well-characterized protein having a multidomain structure that enable it to interact with many ligands, func-tion as an adaptor molecule, and participate in numerous physiological and pathological processes. As a plasma protein, HRG has been reported to regulate vascular biology, including coagulation, fibrinolysis and angiogenesis, through its binding with several ligands (heparin, FXII, fibrinogen, thrombospondin, and plas-minogen) and interaction with many types of cells (endothelial cells, erythrocytes, neutrophils and platelets). This review aims to summarize the roles of HRG in maintaining vascular homeostasis and regulating angiogen-esis in various pathological conditions.
en-copyright=
kn-copyright=

en-aut-name=GaoShangze
en-aut-sei=Gao
en-aut-mei=Shangze
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=histidine-rich glycoprotein
kn-keyword=histidine-rich glycoprotein
en-keyword=vascular biology
kn-keyword=vascular biology
en-keyword=coagulation
kn-keyword=coagulation
en-keyword=angiogenesis
kn-keyword=angiogenesis
END

start-ver=1.4
cd-journal=joma
no-vol=57
cd-vols=
no-issue=
article-no=
start-page=138
end-page=146
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202111
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Outer membrane vesicles of Porphyromonas gingivalis: Novel communication tool and strategy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Extracellular vesicles (EVs) have been recognized as a universal method of cellular communications and are reportedly produced in bacteria, archaea, and eukaryotes. Bacterial EVs are often called "Outer Membrane Vesicles" (OMVs) as they were the result of a controlled blebbing of the outer membrane of gram-negative bacteria such as Porphyromonas gingivalis (P. gingivalis). Bacterial EVs are natural messengers, implicated in intra-and inter-species cell-to-cell communication among microorganism populations present in microbiota. Bacteria can incorporate their pathogens into OMVs; the content of OMVs differs, depending on the type of bacteria. The production of distinct types of OMVs can be mediated by different factors and routes. A recent study highlighted OMVs ability to carry crucial molecules implicated in immune modulation, and, nowadays, they are considered as a way to communicate and transfer messages from the bacteria to the host and vice versa. This review article focuses on the current understanding of OMVs produced from major oral bacteria, P. gingivalis: generation, characteristics, and contents as well as the involvement in signal transduction of host cells and systemic diseases. Our recent study regarding the action of P. gingivalis OMVs in the living body is also summarized. 
en-copyright=
kn-copyright=

en-aut-name=OkamuraHirohiko
en-aut-sei=Okamura
en-aut-mei=Hirohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HirotaKatsuhiko
en-aut-sei=Hirota
en-aut-mei=Katsuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YoshidaKaya
en-aut-sei=Yoshida
en-aut-mei=Kaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WengYao
en-aut-sei=Weng
en-aut-mei=Yao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HeYuhan
en-aut-sei=He
en-aut-mei=Yuhan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShiotsuNoriko
en-aut-sei=Shiotsu
en-aut-mei=Noriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IkegameMika
en-aut-sei=Ikegame
en-aut-mei=Mika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=Uchida-FukuharaYoko
en-aut-sei=Uchida-Fukuhara
en-aut-mei=Yoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TanaiAiri
en-aut-sei=Tanai
en-aut-mei=Airi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=GuoJiajie
en-aut-sei=Guo
en-aut-mei=Jiajie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Medical Hygiene, Dental Hygiene Course, Kochi Gakuen College
kn-affil=

affil-num=3
en-affil=Department of Oral Healthcare Education, Institute of Biomedical Sciences, Tokushima University Graduate School
kn-affil=

affil-num=4
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Comprehensive Dental Clinic, Okayama University Hospital, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Extracellular vesicles
kn-keyword=Extracellular vesicles
en-keyword=Outer membrane vesicles
kn-keyword=Outer membrane vesicles
en-keyword=Porphyromonas gingivalis
kn-keyword=Porphyromonas gingivalis
en-keyword=Host cell interaction
kn-keyword=Host cell interaction
en-keyword=In vivo imaging
kn-keyword=In vivo imaging
END

start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=5
article-no=
start-page=567
end-page=574
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Clinical Manifestations of Patients with Influenza Differ by Age : A Prospective, Multi-centered Study in the Setouchi Marine Area
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Influenza potentially has a high mortality rate when it affects the elderly. We aimed to examine the differences in clinical manifestations in patients with influenza according to their age. This multicenter prospective study was performed in six medical institutions in Okayama and Kagawa prefectures (Japan). Between December 1, 2019 and March 31, 2020, we collected data on adult patients diagnosed with influenza type A, who were strat-ified into younger (20-49 years), middle-aged (50-64 years), and older groups (≥ 65 years). We compared the presence or absence of fever, respiratory symptoms, and extrapulmonary symptoms according to age group. In total, 203 patients (113, younger; 51, middle-aged; and 39, older) were eligible for the analysis. The maxi-mum body temperature and temperature at first physician visit in the older group were significantly lower than those in the younger group. The incidence of respiratory symptoms was not different among the three groups. Chills, muscle pain, and arthralgia as systemic symptoms were noted significantly more frequently in the younger (80.9%) and middle-aged (75.5%) groups than in the older group (51.3%) (p = 0.002). Fever and sys-temic symptoms were less likely to appear in older patients, possibly resulting in the delaying of hospital visits among older adults.
en-copyright=
kn-copyright=

en-aut-name=TakaseRyosuke
en-aut-sei=Takase
en-aut-mei=Ryosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HagiyaHideharu
en-aut-sei=Hagiya
en-aut-mei=Hideharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HondaHiroyuki
en-aut-sei=Honda
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NakanoYasuhiro
en-aut-sei=Nakano
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OgawaHiroko
en-aut-sei=Ogawa
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ObikaMikako
en-aut-sei=Obika
en-aut-mei=Mikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=UedaKeigo
en-aut-sei=Ueda
en-aut-mei=Keigo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KataokaHitomi
en-aut-sei=Kataoka
en-aut-mei=Hitomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HanayamaYoshihisa
en-aut-sei=Hanayama
en-aut-mei=Yoshihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OtsukaFumio
en-aut-sei=Otsuka
en-aut-mei=Fumio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=influenza,
kn-keyword=influenza,
en-keyword=elderly
kn-keyword=elderly
en-keyword= fever
kn-keyword= fever
en-keyword=respiratory symptom
kn-keyword=respiratory symptom
END

start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=5
article-no=
start-page=549
end-page=556
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Glial Cells as Possible Targets of Neuroprotection through Neurotrophic and Antioxidative Molecules in the Central and Enteric Nervous Systems in Parkinson’s Disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. The loss of nigrostriatal dopaminergic neurons produces its characteristic motor symptoms, but PD patients also have non-motor symptoms such as constipation and orthostatic hypotension. The pathological hallmark of PD is the presence of α-synuclein-containing Lewy bodies and neurites in the brain. However, the PD pathology is observed in not only the central nervous system (CNS) but also in parts of the peripheral nervous system such as the enteric nervous system (ENS). Since constipation is a typical prodromal non-motor symptom in PD, often preceding motor symptoms by 10-20 years, it has been hypothesized that PD pathology propagates from the ENS to the CNS via the vagal nerve. Discovery of pharmacological and other methods to halt this progression of neurodegeneration in PD has the potential to improve millions of lives. Astrocytes protect neurons in the CNS by secretion of neurotrophic and antioxidative factors. Similarly, astrocyte-like enteric glial cells (EGCs) are known to secrete neuroprotective factors in the ENS. In this article, we summarize the neuroprotective function of astrocytes and EGCs and discuss therapeutic strategies for the prevention of neurodegeneration in PD targeting neurotrophic and antioxidative molecules in glial cells.
en-copyright=
kn-copyright=

en-aut-name=IsookaNami
en-aut-sei=Isooka
en-aut-mei=Nami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MiyazakiIkuko
en-aut-sei=Miyazaki
en-aut-mei=Ikuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AsanumaMasato
en-aut-sei=Asanuma
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Parkinson’s disease
kn-keyword=Parkinson’s disease
en-keyword=astrocyte
kn-keyword=astrocyte
en-keyword=enteric glial cell
kn-keyword=enteric glial cell
en-keyword=neurotrophic factor
kn-keyword=neurotrophic factor
en-keyword=antioxidative molecule
kn-keyword=antioxidative molecule
END

start-ver=1.4
cd-journal=joma
no-vol=133
cd-vols=
no-issue=2
article-no=
start-page=90
end-page=92
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210802
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 2020 Incentive Award of the Okayama Medical Association in Cancer Research (2020 Hayashibara Prize and Yamada Prize)
kn-title=令和２年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞）
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=金谷信彦
kn-aut-sei=金谷
kn-aut-mei=信彦
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=9
article-no=
start-page=e04574
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes mellitus: A report of two cases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitor-induced diabetes mellitus is a rare immune-related adverse event. This report illustrates clinical data and insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes.
en-copyright=
kn-copyright=

en-aut-name=FujiwaraNoriko
en-aut-sei=Fujiwara
en-aut-mei=Noriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NodaYohei
en-aut-sei=Noda
en-aut-mei=Yohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KataokaHitomi
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en-aut-mei=Hitomi
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
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kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Primary Care and Medical Education, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Diabetes Center, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Primary Care and Medical Education, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Minimally Invasive Therapy Center, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
en-keyword=C-peptide
kn-keyword=C-peptide
en-keyword=diabetes mellitus
kn-keyword=diabetes mellitus
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=insulin secretion
kn-keyword=insulin secretion
END

start-ver=1.4
cd-journal=joma
no-vol=29
cd-vols=
no-issue=10
article-no=
start-page=2920
end-page=2930
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210521
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.
en-copyright=
kn-copyright=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayaNobuhiko
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en-aut-mei=Nobuhiko
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KumonKento
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en-aut-mei=Kento
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TsumuraTomoko
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en-aut-mei=Tomoko
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HashimotoMasashi
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en-aut-mei=Masashi
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YagiChiaki
en-aut-sei=Yagi
en-aut-mei=Chiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SugimotoRyoma
en-aut-sei=Sugimoto
en-aut-mei=Ryoma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HamadaYuki
en-aut-sei=Hamada
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

affil-num=1
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Oncolys BioPharma, Inc
kn-affil=

affil-num=15
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Extracellular vesicles
kn-keyword=Extracellular vesicles
en-keyword=Exosome
kn-keyword=Exosome
en-keyword=Abscopal effect
kn-keyword=Abscopal effect
en-keyword=Oncolytic adenovirus
kn-keyword=Oncolytic adenovirus
en-keyword=Local treatment
kn-keyword=Local treatment
en-keyword=Systemic delivery
kn-keyword=Systemic delivery
en-keyword=Drug delivery system
kn-keyword=Drug delivery system
END