start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=4
article-no=
start-page=760
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2026
dt-pub=20260327
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Role of Nitrate-Reducing Bacteria Isolated from Helicobacter pylori-Infected Individuals in Gastric Cancer Development
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric mucosa, with a global prevalence in humans of approximately 40%. It is likely the cause of 90% of gastric cancer (GC) cases and thus considered the most prominent driver of GC development. However, during gastric mucosal atrophy, other bacteria such as nitrate-reducing bacteria (NRB) also proliferate. In this study, we isolated NRB from patients with gastritis and GC to examine their effects on the epithelial cell cycle and production of various cytokines in monocytic cell lines. Bacterial counts (excluding H. pylori and NRB) increased with the progression of gastric mucosal atrophy and were significantly higher in patients with GC. Gastric epithelial cell lines were stimulated with isolated NRB, and the proportion of cells in each cell cycle was measured. Strains from patients with open-type gastritis progressed more rapidly through cell cycles than those from patients with GC. NRB isolated from gastric cancer had high nitrate-reducing activity. Thus, NRB may contribute to GC progression during H. pylori-induced carcinogenesis. Therefore, evaluating gastric atrophy and microbiota may be important for managing the risk of GC.
en-copyright=
kn-copyright=

en-aut-name=KuwagiSerika
en-aut-sei=Kuwagi
en-aut-mei=Serika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=GotohKazuyoshi
en-aut-sei=Gotoh
en-aut-mei=Kazuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KomatsubaraMarina
en-aut-sei=Komatsubara
en-aut-mei=Marina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TsujiShuma
en-aut-sei=Tsuji
en-aut-mei=Shuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OkanoueShyoutarou
en-aut-sei=Okanoue
en-aut-mei=Shyoutarou
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=UchiyamaJumpei
en-aut-sei=Uchiyama
en-aut-mei=Jumpei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=WatanabeAkari
en-aut-sei=Watanabe
en-aut-mei=Akari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YokotaKenji
en-aut-sei=Yokota
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Gastroenterology and Hepatology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Himeji Red Cross Hospital
kn-affil=

affil-num=7
en-affil=Department of Bacteriology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Oral Health Care and Rehabilitation, Institute of Biomedical Sciences, Graduate School, Tokushima University
kn-affil=

affil-num=9
en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University
kn-affil=
en-keyword=Helicobacter pylori infection
kn-keyword=Helicobacter pylori infection
en-keyword=gastric cancer
kn-keyword=gastric cancer
en-keyword=nitrate-reducing bacteria
kn-keyword=nitrate-reducing bacteria
en-keyword=gastritis
kn-keyword=gastritis
END

start-ver=1.4
cd-journal=joma
no-vol=19
cd-vols=
no-issue=2
article-no=
start-page=dmm052605
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2026
dt-pub=20260201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Congenital intestinal atresia (IA) is a birth defect characterised by the absence or closure of part of the intestine. Although genetic factors are implicated, mechanistic understanding has been hindered by the lack of suitable animal models. Here, we describe a medaka (Oryzias latipes) mutant, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, that develops IA during embryogenesis. Positional cloning identified a nonsense mutation in mypt1, encoding myosin phosphatase target subunit 1. Mutant embryos exhibited ectopic accumulation of F-actin and phosphorylated myosin regulatory light chain (Mrlc) in the intestinal epithelium, consistent with disrupted actomyosin regulation. These cytoskeletal abnormalities were accompanied by epithelial disorganisation, without notable alterations in cell proliferation, motility or apoptosis. Inhibition of myh11a, encoding smooth muscle (SM) myosin heavy chain, ameliorated the IA phenotype, whereas blebbistatin treatment completely rescued the defect, suggesting a non-contractile role prior to SM maturation. Together, these findings demonstrate that mypt1 loss disrupts intestinal morphogenesis through actomyosin dysregulation. Given the recent clinical identification of IA associated with MYPT1 variants, this medaka model offers a valuable platform to investigate the developmental and molecular basis of MYPT1-associated IA in humans.
en-copyright=
kn-copyright=

en-aut-name=KobayashiDaisuke
en-aut-sei=Kobayashi
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=UrasakiAkihiro
en-aut-sei=Urasaki
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KimuraTetsuaki
en-aut-sei=Kimura
en-aut-mei=Tetsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AnsaiSatoshi
en-aut-sei=Ansai
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MatsuoKazuhiko
en-aut-sei=Matsuo
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YokoiHayato
en-aut-sei=Yokoi
en-aut-mei=Hayato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakashimaShigeo
en-aut-sei=Takashima
en-aut-mei=Shigeo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KitagawaTadao
en-aut-sei=Kitagawa
en-aut-mei=Tadao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KageTakahiro
en-aut-sei=Kage
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NaritaTakanori
en-aut-sei=Narita
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=JindoTomoko
en-aut-sei=Jindo
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KinoshitaMasato
en-aut-sei=Kinoshita
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=NaruseKiyoshi
en-aut-sei=Naruse
en-aut-mei=Kiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=NakajimaYoshiro
en-aut-sei=Nakajima
en-aut-mei=Yoshiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ShigetaMasaki
en-aut-sei=Shigeta
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=SakakiShinichiro
en-aut-sei=Sakaki
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=InoueSatoshi
en-aut-sei=Inoue
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=SabaRie
en-aut-sei=Saba
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=YamadaKei
en-aut-sei=Yamada
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=YokoyamaTakahiko
en-aut-sei=Yokoyama
en-aut-mei=Takahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=IshikawaYuji
en-aut-sei=Ishikawa
en-aut-mei=Yuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=ArakiKazuo
en-aut-sei=Araki
en-aut-mei=Kazuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=SagaYumiko
en-aut-sei=Saga
en-aut-mei=Yumiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=TakedaHiroyuki
en-aut-sei=Takeda
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=YashiroKenta
en-aut-sei=Yashiro
en-aut-mei=Kenta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

affil-num=1
en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=2
en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=3
en-affil=Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology
kn-affil=

affil-num=4
en-affil=Ushimado Marine Institute, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=6
en-affil=Graduate School of Agricultural Science, Tohoku University
kn-affil=

affil-num=7
en-affil=Institute for Glyco-core Research (iGCORE)/Life Science Research Centre, Gifu University
kn-affil=

affil-num=8
en-affil=Program in Environmental Management, Graduate School of Agriculture, Kindai University
kn-affil=

affil-num=9
en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo
kn-affil=

affil-num=10
en-affil=Laboratory of Molecular Biology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University
kn-affil=

affil-num=11
en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo
kn-affil=

affil-num=12
en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University
kn-affil=

affil-num=13
en-affil=Laboratory of Bioresources, National Institute for Basic Biology
kn-affil=

affil-num=14
en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=15
en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=16
en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=17
en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=18
en-affil=Department of Radiology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=19
en-affil=Department of Radiology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=20
en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
kn-affil=

affil-num=21
en-affil=Research Centre for Radiation Protection, National Institute of Radiological Sciences
kn-affil=

affil-num=22
en-affil=Research Center for Aquatic Breeding, National Research Institute of Aquaculture, Fisheries Research Agency
kn-affil=

affil-num=23
en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo
kn-affil=

affil-num=24
en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo
kn-affil=

affil-num=25
en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
kn-affil=
en-keyword=Intestinal atresia
kn-keyword=Intestinal atresia
en-keyword=Mypt1
kn-keyword=Mypt1
en-keyword=Disease model
kn-keyword=Disease model
en-keyword=Actomyosin regulation
kn-keyword=Actomyosin regulation
en-keyword=Intestinal development
kn-keyword=Intestinal development
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=1
article-no=
start-page=888
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20251215
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Skeletal muscle remodelling relies on muscle stem cells (MuSCs) for regeneration after injury and hypertrophy in response to mechanical loading. However, the mechanisms that trigger MuSC activation and proliferation remain unclear. Transient receptor potential vanilloid 2 (TRPV2) ion channels respond to insulin-like growth factor-1 and mechanical stimuli to regulate the biological characteristics of various cells. Using a temporally inducible MuSC-specific conditional knockout (cKO) mouse, we show that TRPV2 regulates MuSC function and is essential for muscle remodelling. In cultured myofibre, MuSCs express TRPV2 and exhibit Ca2+ responses to the TRPV2 agonists 2-aminoethoxydiphenyl borate and probenecid, which are abolished upon TRPV2 deletion. TRPV2-deficient MuSCs exhibit reduced paired box 7 (Pax7) expression and impaired proliferation, suggesting TRPV2 is a factor that regulates the early stage of MuSC function. Myotube formation in MuSCs was enhanced by overexpression of TRPV2 and suppressed by TRPV2 deficiency, suggesting that TRPV2 is a factor that promotes myogenesis. Muscle-administered cardiotoxin promoted muscle regeneration and resulted in the appearance of numerous Pax7-positive MuSCs between myofibres. MuSC-specific TRPV2 cKO mice exhibit substantially impaired muscle regeneration after cardiotoxin-induced injury, drastically reducing Pax7-positive MuSCs between myofibres. In floxed mice, mechanical loading via synergist ablation induces hypertrophy and greatly increases the number of myonuclei per myofibre. In contrast, MuSC-specific TRPV2 cKO mice show no changes in myofibre thickness or nuclear number, either at baseline or after mechanical loading. Mechanical loading of floxed mice increased TRPV2+/Pax7+ double-positive MuSCs, but MuSC-specific TRPV2 cKO mice showed no change. Additionally, MuSCs exhibit Ca2+ responses to hypo-osmotic stimuli, which are suppressed by TRPV2 inhibitors and TRPV2 deletion, suggesting that MuSCs exhibit TRPV2-dependent mechanical responses. These results establish TRPV2 as a critical regulator of MuSC-mediated muscle remodelling, an important finding that may lead to therapeutic strategies for muscle repair and adaptation.
en-copyright=
kn-copyright=

en-aut-name=ChenYanzhu
en-aut-sei=Chen
en-aut-mei=Yanzhu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KatanosakaKimiaki
en-aut-sei=Katanosaka
en-aut-mei=Kimiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ShibuyaMakoto
en-aut-sei=Shibuya
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=DongYubing
en-aut-sei=Dong
en-aut-mei=Yubing
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ZhangLidan
en-aut-sei=Zhang
en-aut-mei=Lidan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KanagawaMotoi
en-aut-sei=Kanagawa
en-aut-mei=Motoi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FukadaSo-ichiro
en-aut-sei=Fukada
en-aut-mei=So-ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NaruseKeiji
en-aut-sei=Naruse
en-aut-mei=Keiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KatanosakaYuki
en-aut-sei=Katanosaka
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

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

affil-num=2
en-affil=Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University
kn-affil=

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

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

affil-num=5
en-affil=Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka
kn-affil=

affil-num=6
en-affil=Department of Cell Biology and Molecular Medicine, Ehime University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka
kn-affil=

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

affil-num=9
en-affil=Department of Cardiovascular Physiology, 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=2026
dt-pub=20260219
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Induction of IL-9-producing CD8+ T cells by ascochlorin derivatives
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background and Purpose: Ascochlorin (ASC) is an antiviral antibiotic from the fermented broth of Ascochyta viciae which exerts an inhibitory effect to cancers. Its impact on immune cells has not been examined. In this study, we obtained ASC derivatives with less cytotoxicity and determined whether they affected T cells, indicating possible immune-mediated antitumour effects.<br>
Experimental Approach: Newly synthesised ASC derivatives were screened for inhibitory effects on T-cell antigen receptor (TCR)-stimulated proliferative responses using murine CD4+ and CD8+ T cells. Two compounds were identified that exhibited >10-fold less toxicity compared with ASC. N184, the less toxic of the two, was analysed for its in vivo antitumour effects, and in vitro effects on CD8+ T-cell proliferation, survival, cytokine production and exhaustion, using microscopy, qPCR and flow cytometry.<br>
Key Results: N184 induced limited IL-9 production in CD8+ T cells following TCR stimulation, thereby improving cell survival. It also enhanced cytokine production in the late phase of proliferation and suppressed the induction of exhaustion. N184 suppressed tumour growth in mice in a CD8+ T cell-dependent manner. The effect was partially prevented by an IL-9-neutralising antibody.<br>
Conclusion and Implications: N184 induces differentiation of IL-9-producing CD8+ T cells in vitro and elicits antitumour immunity in an IL-9-dependent manner.
en-copyright=
kn-copyright=

en-aut-name=ImanoNatsumi
en-aut-sei=Imano
en-aut-mei=Natsumi
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=TokumasuMiho
en-aut-sei=Tokumasu
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
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=6
ORCID=

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

affil-num=2
en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

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

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

affil-num=5
en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=ascochlorin derivative
kn-keyword=ascochlorin derivative
en-keyword=CD8 positive T lymphocytes
kn-keyword=CD8 positive T lymphocytes
en-keyword=cell survival
kn-keyword=cell survival
en-keyword=IFN-γ
kn-keyword=IFN-γ
en-keyword=interleukin-9
kn-keyword=interleukin-9
en-keyword=Tc9
kn-keyword=Tc9
en-keyword=tumour immunity
kn-keyword=tumour immunity
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=1
article-no=
start-page=9
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2026
dt-pub=20260212
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Influence of Fluidic Flow Stress on the Development of the Secondary Palate
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and β-catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/β-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate.
en-copyright=
kn-copyright=

en-aut-name=NagataMasayo
en-aut-sei=Nagata
en-aut-mei=Masayo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HayanoSatoru
en-aut-sei=Hayano
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=KosamiTakahiro
en-aut-sei=Kosami
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KamiokaHiroshi
en-aut-sei=Kamioka
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

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

affil-num=2
en-affil=Department of Orthodontics, Okayama University Hospital
kn-affil=

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

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

affil-num=5
en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=mechanical stress
kn-keyword=mechanical stress
en-keyword=palatal development
kn-keyword=palatal development
en-keyword=β-catenin
kn-keyword=β-catenin
en-keyword=YAP
kn-keyword=YAP
END

start-ver=1.4
cd-journal=joma
no-vol=5
cd-vols=
no-issue=1
article-no=
start-page=ycaf192
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=Proliferation of a bloom-forming phytoplankton via uptake of polyphosphate-accumulating bacteria under phosphate-limiting conditions
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Harmful algal blooms negatively impact the ecosystem and fisheries in affected areas. Eutrophication is a major factor contributing to bloom occurrence, and phosphorus is particularly important in limiting the growth of bloom-forming algae. Although algae efficiently utilize orthophosphate (Pi) as a phosphorous source over other molecular forms, Pi is often limited in the marine environment. While uptake and utilization of soluble inorganic and organic phosphorous by bloom-forming algae has been extensively studied, the details of geochemical and biological phosphorous cycling remain to be elucidated. Here, we report for the first time that the bloom-forming alga Heterosigma akashiwo can phagocytose bacteria and grow under phosphate-depleted conditions. The addition of Vibrio comitans to Pi-depleted H. akashiwo enabled the alga propagate to high cell densities, whereas other bacterial strains had only a minor effect. Importantly, V. comitans accumulates polyphosphate—a linear polymer of Pi—at high levels. The extent of algal proliferation induced by the addition of Vibrio species and polyphosphate-accumulating Escherichia coli correlated strongly with their polyphosphate content, indicating that bacterial polyphosphate served as an alternative PO43− source for H. akashiwo. The direct uptake of polyphosphate-accumulating bacteria through algal phagocytosis may represent a novel biological phosphorous-cycling pathway in marine ecosystems. The role of polyphosphate-accumulating marine bacteria as a hidden phosphorous source required for bloom formation warrants further investigation.
en-copyright=
kn-copyright=

en-aut-name=FukuyamaSeiya
en-aut-sei=Fukuyama
en-aut-mei=Seiya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=UsamiFumiko
en-aut-sei=Usami
en-aut-mei=Fumiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HirotaRyuichi
en-aut-sei=Hirota
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

en-aut-name=OharaShizuka
en-aut-sei=Ohara
en-aut-mei=Shizuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KondoKen
en-aut-sei=Kondo
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=GomibuchiYuki
en-aut-sei=Gomibuchi
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YasunagaTakuo
en-aut-sei=Yasunaga
en-aut-mei=Takuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OndukaToshimitsu
en-aut-sei=Onduka
en-aut-mei=Toshimitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KurodaAkio
en-aut-sei=Kuroda
en-aut-mei=Akio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KoikeKazuhiko
en-aut-sei=Koike
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=UekiShoko
en-aut-sei=Ueki
en-aut-mei=Shoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=2
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Integrated Sciences for Life, Hiroshima 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=Graduate School of Integrated Sciences for Life, Hiroshima University
kn-affil=

affil-num=6
en-affil=Research Institute of Environment, Agriculture and Fisheries , Osaka Prefecture
kn-affil=

affil-num=7
en-affil=Department of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology
kn-affil=

affil-num=8
en-affil=Department of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology
kn-affil=

affil-num=9
en-affil=Hatsukaichi Branch, Fisheries Technology Institute , Fisheries Research and Education Agency
kn-affil=

affil-num=10
en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University
kn-affil=

affil-num=11
en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University
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=26
cd-vols=
no-issue=19
article-no=
start-page=9630
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20251002
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Critical Requirement of Senescence-Associated CCN3 Expression in CD44-Positive Stem Cells for Osteoarthritis Progression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and subchondral bone remodeling. Previous studies have shown that cellular communication network factor 3 (CCN3) expression increases with age in cartilage, and its overexpression promotes OA-like changes by inducing senescence-associated secretory phenotypes. This study aimed to investigate the effect of Ccn3 knockout (KO) on OA development using a murine OA model. Destabilization of the medial meniscus (DMM) surgery was performed in wild-type (WT) and Ccn3-KO mice. Histological scoring and staining were used to assess cartilage degeneration and proteoglycan loss. Gene and protein expressions of catabolic enzyme (Mmp9), hypertrophic chondrocyte marker (Col10a1), senescence marker, and cyclin-dependent kinase inhibitor 1A (Cdkn1a) were evaluated. Single-cell RNA sequencing (scRNA-seq) data from WT and Sox9-deficient cartilage were reanalyzed to identify Ccn3+ progenitor populations. Immunofluorescence staining assessed CD44 and Ki67 expression in articular cartilage. The effects of Ccn3 knockdown on IL-1β-induced Mmp13 and Adamts5 expression in chondrocytes were examined in vitro. Ccn3 KO mice exhibited reduced cartilage degradation and catabolic gene expression compared with WT mice post-DMM. scRNA-seq revealed enriched Ccn3-Cd44 double-positive cells in osteoblast progenitor, synovial mesenchymal stem cell, and mesenchymal stem cell clusters. Immunofluorescence showed increased CCN3+/CD44+ cells in femoral and tibial cartilage and meniscus. Ki67+ cells were significantly increased in DMM-treated Ccn3 KO cartilage, mostly CD44+. In vitro Ccn3 knockdown attenuated IL-1β-induced Mmp13 and Adamts5 expressions in chondrocytes. Ccn3 contributes to OA pathogenesis by promoting matrix degradation, inducing hypertrophic changes, and restricting progenitor cell proliferation, highlighting Ccn3 as a potential therapeutic target for OA.
en-copyright=
kn-copyright=

en-aut-name=HabumugishaJanvier
en-aut-sei=Habumugisha
en-aut-mei=Janvier
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OkudaRyuichiro
en-aut-sei=Okuda
en-aut-mei=Ryuichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HiroseKazuki
en-aut-sei=Hirose
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
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=6
ORCID=

en-aut-name=KamiokaHiroshi
en-aut-sei=Kamioka
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=9
ORCID=

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

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

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

affil-num=4
en-affil=Department of Biochemistry and Molecular Dentistry, 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=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

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

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

affil-num=9
en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=articular
kn-keyword=articular
en-keyword=cartilage
kn-keyword=cartilage
en-keyword=mesenchymal stem cells
kn-keyword=mesenchymal stem cells
en-keyword=nephroblastoma overexpressed protein
kn-keyword=nephroblastoma overexpressed protein
en-keyword=osteoarthritis
kn-keyword=osteoarthritis
END

start-ver=1.4
cd-journal=joma
no-vol=30
cd-vols=
no-issue=5
article-no=
start-page=e70057
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202505
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Features Miyu Kanazawa, 
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18 years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7 g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5 months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features.
en-copyright=
kn-copyright=

en-aut-name=KanazawaMiyu
en-aut-sei=Kanazawa
en-aut-mei=Miyu
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=AokiRyoya
en-aut-sei=Aoki
en-aut-mei=Ryoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SueMihiro
en-aut-sei=Sue
en-aut-mei=Mihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MiyakeHiromasa
en-aut-sei=Miyake
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
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=7
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=8
ORCID=

en-aut-name=UchidaHaruhito A.
en-aut-sei=Uchida
en-aut-mei=Haruhito A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=

affil-num=1
en-affil=Okayama University Medical School
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=Okayama University Medical School
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 Chronic Kidney Disease and Cardiovascular Disease, 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=
en-keyword=Gd-IgA1
kn-keyword=Gd-IgA1
en-keyword=IgA nephropathy
kn-keyword=IgA nephropathy
en-keyword=membranoproliferative glomerulonephritis
kn-keyword=membranoproliferative glomerulonephritis
en-keyword=nephrotic syndrome
kn-keyword=nephrotic syndrome
en-keyword=rheumatoid arthritis
kn-keyword=rheumatoid arthritis
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=14
article-no=
start-page=4055
end-page=4070
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250922
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=CXCR4 Inhibition Induces Tumor Necrosis by Selectively Targeting the Proliferating Blood Vessels in Oral Squamous Cell Carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The C-X-C chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor that contributes to tumor growth and angiogenesis. While prior studies have primarily focused on CXCR4 expression in cancer cells and its role in metastasis, a few have examined its involvement in tumor-associated vasculature. In this study, we reported for the first time that CXCR4 expression within the tumor vasculature is significantly associated with higher pathological grades of human oral squamous cell carcinoma (OSCC) (p<0.03). A previous study reported that inhibiting CXCR4 with AMD3100 induces tumor cell death and enhances the efficacy of the chemotherapeutic agent cisplatin. These findings suggest that CXCR4 is an important target for cancer treatment. However, the tumor vascular system is known to be heterogeneous within the tumor microenvironment (TME), which may influence the treatment outcomes. Therefore, this study aimed to explore the effect of CXCR4 antagonism on various blood vessels present within the oral squamous cell carcinoma (OSCC) tumor stroma. Although the efficiency of AMD3100 was not significant in MOC cancer cells, necrosis was induced in the TME when applied to a poorly differentiated OSCC model, highlighting the role of the TME. Notably, CXCR4 is found to be highly overlapped with CD105+ angiogenic tumor vessels among various vascular markers. Treatment with AMD3100 leads to a marked reduction in the CD105+ vessels and impairs the maturation of tumor micro-vessels, explaining the cause of observed necrosis. Thus, CXCR4 serves as a promising biomarker in OSCC, and its inhibition with AMD3100 offers the therapeutic potential, particularly in cases with advanced pathological grades.
en-copyright=
kn-copyright=

en-aut-name=SoeYamin
en-aut-sei=Soe
en-aut-mei=Yamin
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=EainHtoo Shwe
en-aut-sei=Eain
en-aut-mei=Htoo Shwe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YoshidaSaori
en-aut-sei=Yoshida
en-aut-mei=Saori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=MinZin Zin
en-aut-sei=Min
en-aut-mei=Zin Zin
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=NakanoKeisuke
en-aut-sei=Nakano
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=

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

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

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

affil-num=4
en-affil=Preliminary Examination Room, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=

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

affil-num=9
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=
en-keyword=CXCR4
kn-keyword=CXCR4
en-keyword=tumor angiogenesis
kn-keyword=tumor angiogenesis
en-keyword=chemokine receptors
kn-keyword=chemokine receptors
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
en-keyword=oral squamous cell carcinoma (OSCC)
kn-keyword=oral squamous cell carcinoma (OSCC)
en-keyword=AMD3100
kn-keyword=AMD3100
END

start-ver=1.4
cd-journal=joma
no-vol=81
cd-vols=
no-issue=
article-no=
start-page=152587
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2026
dt-pub=202604
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The diagnostic utility and frequency of CD56 expression in plasma cell myeloma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Plasma cell myeloma (PCM) is a hematological malignancy characterized by systemic proliferation of neoplastic plasma cells within the bone marrow. Diagnosis requires clinical findings and immunohistochemical staining, including CD138, CD79a, cyclin D1, immunoglobulin κ (Igκ), and λ (Igλ). However, CD79a and cyclin D1 have limited sensitivity and specificity, and Igκ/Igλ assessment is often difficult due to overstaining. Therefore, more reliable antibodies are needed to accurately diagnose PCM. In this study, we examined the diagnostic utility of CD56 expression in PCM. We retrospectively performed immunostaining for CD138, CD56, CD79a, cyclin D1, Igκ, and Igλ in bone marrow samples from 116 patients with PCM.<br>
CD56 expression was observed in 85/116 cases (73.3 %), CD79a was downregulated in 46/116 cases (39.7 %), and cyclin D1 expression was observed in 42/116 cases (36.2 %). The expression of CD56 was significantly higher than that of CD79a and cyclin D1 (both p < 0.001). The combination of two antibodies resulted in the highest detection rate when combining CD56 and CD79a (105/116, 90.5 %), which was significantly higher than the detection rates of CD56 and cyclin D1 (93/116, 80.2 %) and CD79a and cyclin D1 (75/116, 64.7 %) (both p < 0.001). In contrast, lymphoplasmacytic lymphoma and marginal zone lymphoma lacked CD56 and cyclin D1 expression. Furthermore, in cases where light chain restriction was undetectable (11/116, 9.5 %), all could be diagnosed as PCM based on CD56, CD79a, and cyclin D1. Among these, CD56 showed the highest detection rate (8/11, 72.7 %).<br>
These findings highlight CD56 as a helpful marker for PCM diagnosis and support further clinical research.<br>
en-copyright=
kn-copyright=

en-aut-name=ImaiMidori
en-aut-sei=Imai
en-aut-mei=Midori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=HaratakeTomoka
en-aut-sei=Haratake
en-aut-mei=Tomoka
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=YamadaRio
en-aut-sei=Yamada
en-aut-mei=Rio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KatoSyoma
en-aut-sei=Kato
en-aut-mei=Syoma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TabeMizuha
en-aut-sei=Tabe
en-aut-mei=Mizuha
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=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 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 Molecular Hematopathology, Okayama University Graduate School of Health 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 Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=8
en-affil=Department of Diagnostic Pathology, Okayama University Hospital
kn-affil=

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

affil-num=10
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=
en-keyword=Plasma cell myeloma
kn-keyword=Plasma cell myeloma
en-keyword=Immunohistochemical staining
kn-keyword=Immunohistochemical staining
en-keyword=CD56
kn-keyword=CD56
END

start-ver=1.4
cd-journal=joma
no-vol=152
cd-vols=
no-issue=22
article-no=
start-page=dev204763
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20251115
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=ROS produced by Dual oxidase regulate cell proliferation and haemocyte migration during leg regeneration in the cricket
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Many animals regenerate lost body parts through several signalling pathways; however, the triggers that initiate regeneration remain unclear. In the present study, we focused on the role of reactive oxygen species (ROS) produced by the NADPH oxidase Dual oxidase (Duox) during cricket leg regeneration. The results showed that ROS levels were upregulated during leg regeneration and decreased by DuoxRNAi. In DuoxRNAi nymphs, wound closure and scab formation were incomplete 2 days after amputation, and hypertrophy occurred in the distal region of the regenerating legs at 5 days after amputation. In addition, the hypertrophic phenotype was induced by DuoxARNAi and NADPH oxidase inhibitor treatment. During hypertrophy, haemocytes, including plasmatocytes, oenocytoids and granulocytes, accumulated. Proliferation of haemocytes in regenerating legs was not increased by DuoxRNAi; however, haemocyte accumulation was regulated by the Spatzle (Spz) family molecules, which are Toll receptor ligands. As the exoskeleton of DuoxRNAi nymphs was thinner than that of the control, excessive haemocyte accumulation can cause hypertrophy in DuoxRNAi nymphs. Thus, Duox-derived ROS are involved in wound healing and haemocyte accumulation through the Spz/Toll signalling pathway during leg regeneration in crickets.
en-copyright=
kn-copyright=

en-aut-name=Okumura-HironoMisa
en-aut-sei=Okumura-Hirono
en-aut-mei=Misa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=BandoTetsuya
en-aut-sei=Bando
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HamadaYoshimasa
en-aut-sei=Hamada
en-aut-mei=Yoshimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
ORCID=

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

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

affil-num=3
en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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 Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Regeneration
kn-keyword=Regeneration
en-keyword=Reactive oxygen species (ROS)
kn-keyword=Reactive oxygen species (ROS)
en-keyword=NADPH oxidase (Nox)
kn-keyword=NADPH oxidase (Nox)
en-keyword=Dual oxidase (Duox)
kn-keyword=Dual oxidase (Duox)
en-keyword=Inflammation
kn-keyword=Inflammation
en-keyword=Gryllus bimaculatus
kn-keyword=Gryllus bimaculatus
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=1
article-no=
start-page=234
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20251114
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Exposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkinson's disease (PD). Rotenone induces PD-like pathology and is therefore used to develop parkinsonian animal models. Dopaminergic neurotoxicity caused by rotenone has been attributed to the inhibition of mitochondrial complex I, oxidative stress and neuroinflammation; however, the mechanisms underlying selective dopaminergic neurodegeneration by rotenone remain unclear. To resolve this, we focused on glial diversity and examined whether the brain region-specific glial response to rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astrocyte and microglia or conditioned media from rotenone-treated midbrain glial cultures containing astrocytes and microglia produced dopaminergic neurotoxicity, but striatal glia did not. Surprisingly, conditioned media from rotenone-treated midbrain astrocytes or microglia monocultures did not affect neuronal survival. We also demonstrated that rotenone targeted midbrain astrocytes prior to microglia to induce dopaminergic neurotoxicity. Rotenone-treated astrocytes produced secreted protein acidic and rich in cysteine (SPARC) extracellularly, which induced microglial proliferation, increase in IL-1β and TNF-α, and NF-κB (p65) nuclear translocation in microglia, resulting in dopaminergic neurodegeneration. In addition, rotenone exposure caused the secretion of NFAT-related inflammatory cytokines and a reduction in the level of an antioxidant metallothionein (MT)-1 from midbrain glia. Furthermore, we observed microglial proliferation and a decrease in the number of MT-positive astrocytes in the substantia nigra, but not the striatum, of low-dose rotenone-injected PD model mice. Our data highlight that rotenone targets midbrain astrocytes, leading to SPARC secretion, which promotes the neurotoxic conversion of microglia and leads to glial dysfunction-mediated dopaminergic neurodegeneration.
en-copyright=
kn-copyright=

en-aut-name=MiyazakiIkuko
en-aut-sei=Miyazaki
en-aut-mei=Ikuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IsookaNami
en-aut-sei=Isooka
en-aut-mei=Nami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KikuokaRyo
en-aut-sei=Kikuoka
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ImafukuFuminori
en-aut-sei=Imafuku
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MasaiKaori
en-aut-sei=Masai
en-aut-mei=Kaori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TomimotoKana
en-aut-sei=Tomimoto
en-aut-mei=Kana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=SogawaChiharu
en-aut-sei=Sogawa
en-aut-mei=Chiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SogawaNorio
en-aut-sei=Sogawa
en-aut-mei=Norio
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=AsanumaMasato
en-aut-sei=Asanuma
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=

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

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

affil-num=6
en-affil=Department of Medical Neurobiology, 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 Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology
kn-affil=

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

affil-num=10
en-affil=Department of Pharmacotherapy, School of Pharmacy, Shujitsu University
kn-affil=

affil-num=11
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Rotenone
kn-keyword=Rotenone
en-keyword=Astrocyte
kn-keyword=Astrocyte
en-keyword=Microglia
kn-keyword=Microglia
en-keyword=SPARC
kn-keyword=SPARC
en-keyword=Parkinson's disease
kn-keyword=Parkinson's disease
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=20251104
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Optogenetic Cancer Therapy Using the Light-Driven Outward Proton Pump Rhodopsin Archaerhodopsin-3 (AR3)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Medicines used for cancer treatment often cause serious side effects by damaging normal cells due to nonspecific diffusion. To address this issue, we previously developed an optical method to induce apoptotic cell death via intracellular pH alkalinization using the outward proton pump rhodopsin, Archaerhodopsin-3 (AR3) in various noncancer model cells in vitro and in vivo. In this study, we applied this method to cancer cells and tumors to evaluate its potential as an anticancer therapeutic strategy. First, we confirmed that AR3-expressing murine cancer cell lines (MC38, B16F10) showed apoptotic cell death upon green light irradiation, as indicated by increased levels of cell death and apoptosis-related markers. Next, we established stable AR3-expressing MC38 and B16F10 cells by using viral vectors. When these AR3-expressing cells were subcutaneously transplanted into C57BL/6 mice, the resulting tumors initially grew at a rate comparable to that of control tumors lacking AR3 expression or light stimulation. However, upon green light irradiation, AR3-expressing tumors exhibited either a marked reduction in size or significantly suppressed growth, accompanied by the induction of apoptosis signals and decreased proliferation signals. These results demonstrate that AR3-mediated cell death has potent antitumor effects both in vitro and in vivo. This optical method thus holds promise as a novel cancer therapy with potentially reduced side effects.
en-copyright=
kn-copyright=

en-aut-name=NakaoShin
en-aut-sei=Nakao
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KojimaKeiichi
en-aut-sei=Kojima
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SatoKeita
en-aut-sei=Sato
en-aut-mei=Keita
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
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=6
ORCID=

en-aut-name=SudoYuki
en-aut-sei=Sudo
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=

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

affil-num=7
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=2025
dt-pub=20251014
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Comparative analysis of interactions between five strains of Pseudomonas syringae pv. tabaci and Nicotiana benthamiana
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pseudomonas syringae pv. tabaci 6605 (Pta 6605), the agent of wildfire disease in tobacco, has been used as a model strain for elucidating the virulence mechanisms of Pta. However, the host genes involved in resistance or susceptibility to Pta remain largely unknown. Nicotiana benthamiana is a model plant species in the Solanaceae family and is useful in functional analyses of genes. We herein compared five Pta strains (6605, 6823, 7372, 7375, and 7380) in terms of their phenotypes on medium and interactions with N. benthamiana. Pta 6605 and Pta 6823 showed more active proliferation than the other strains in a high cell density culture. Moreover, Pta 6605 exhibited markedly higher swarming motility than the other strains. In inoculated leaves of N. benthamiana, Pta 6605 and Pta 6823 caused more severe disease symptoms and proliferated to a higher cell density than the other strains. However, Pta 6823 as well as Pta 7372 and Pta 7380 induced the high accumulation of salicylic acid (SA). Moreover, the inoculations of Pta 6823 and Pta 7372 resulted in the upregulation of ethylene biosynthesis genes. On the other hand, Pta 6605 induced neither SA accumulation nor the expression of ethylene biosynthesis genes, and suppressed the expression of jasmonate biosynthesis genes. Moreover, chlorosis was clearly induced in the upper uninoculated leaves of Pta 6605-infected plants. These results suggest that Pta 6605 escapes from or suppresses plant immune systems and, thus, is the most virulent on N. benthamiana among the five strains tested.
en-copyright=
kn-copyright=

en-aut-name=NakaoYuna
en-aut-sei=Nakao
en-aut-mei=Yuna
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AsaiShuta
en-aut-sei=Asai
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
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=4
ORCID=

en-aut-name=KatouShinpei
en-aut-sei=Katou
en-aut-mei=Shinpei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Science and Technology, Shinshu University
kn-affil=

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

affil-num=3
en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University
kn-affil=

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

affil-num=5
en-affil=Graduate School of Medicine, Science and Technology, Shinshu University
kn-affil=
en-keyword=Chlorosis
kn-keyword=Chlorosis
en-keyword=Nicotiana benthamiana
kn-keyword=Nicotiana benthamiana
en-keyword=Phytohormones
kn-keyword=Phytohormones
en-keyword=Pseudomonas syringae pv. tabaci
kn-keyword=Pseudomonas syringae pv. tabaci
END

start-ver=1.4
cd-journal=joma
no-vol=26
cd-vols=
no-issue=20
article-no=
start-page=10072
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20251016
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Neurofibromin (NF) inhibits the RAS/RAF/ERK pathway through its interaction with SPRED1 (Sprouty-related EVH1 domain-containing protein 1). Here, we investigated the functional relationship between NF and SPRED2 in breast cancer (BC). Human BC cell lines were transfected to downregulate or overexpress NF and SPRED2 and subsequently subjected to functional assays. Protein and mRNA levels were analyzed by Western blotting and RT-qPCR, respectively. Protein–protein interactions were examined by immunoprecipitation. Database analyses and immunohistochemistry (IHC) of BC tissues were performed to validate the in vitro findings. Downregulating NF or SPRED2 expression in BC cells enhanced cell proliferation, migration and invasion accompanied by RAF/ERK activation, whereas overexpression produced opposite effects. NF formed a protein complex with SPRED2 and facilitated its translocation to the plasma membrane. By IHC, SPRED2 membrane localization was absent in NF-negative luminal A and triple-negative BC (TNBC) but present in a subset of luminal A BC. By database analyses, both NF1 and SPRED2 mRNA levels were reduced in BC tissues, and luminal A BC patients with high expression of both NF1 and SPRED2 mRNA exhibited improved relapse-free survival. These results suggest a critical role for the NF–SPRED2 axis in BC progression and highlight it as a potential therapeutic target.
en-copyright=
kn-copyright=

en-aut-name=Su PwintNang Thee
en-aut-sei=Su Pwint
en-aut-mei=Nang Thee
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=LiChunning
en-aut-sei=Li
en-aut-mei=Chunning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=GaoTong
en-aut-sei=Gao
en-aut-mei=Tong
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=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
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=7
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=8
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=9
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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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=
en-keyword=breast cancer
kn-keyword=breast cancer
en-keyword=SPRED2
kn-keyword=SPRED2
en-keyword=neurofibromatosis type 1
kn-keyword=neurofibromatosis type 1
en-keyword=neurofibromin
kn-keyword=neurofibromin
en-keyword=RAS/RAF/ERK
kn-keyword=RAS/RAF/ERK
END

start-ver=1.4
cd-journal=joma
no-vol=28
cd-vols=
no-issue=4
article-no=
start-page=51
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250930
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target.
en-copyright=
kn-copyright=

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=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=MashimaTomoha
en-aut-sei=Mashima
en-aut-mei=Tomoha
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TorigataKosuke
en-aut-sei=Torigata
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ThuYin Min
en-aut-sei=Thu
en-aut-mei=Yin Min
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HabuTomohiro
en-aut-sei=Habu
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=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=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=ItoSachio
en-aut-sei=Ito
en-aut-mei=Sachio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
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=12
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=13
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=14
ORCID=

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

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

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

affil-num=4
en-affil=School of Medicine, Kobe University
kn-affil=

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

affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, 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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

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

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

affil-num=12
en-affil=Department of Thoracic Surgery, National Hospital Organization, Shikoku Cancer Center
kn-affil=

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

affil-num=14
en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Cancer-associated fibroblast
kn-keyword=Cancer-associated fibroblast
en-keyword=Superoxide dismutase 3
kn-keyword=Superoxide dismutase 3
en-keyword=Lymphangiogenesis
kn-keyword=Lymphangiogenesis
en-keyword=Angiogenesis
kn-keyword=Angiogenesis
en-keyword=Metastasis
kn-keyword=Metastasis
en-keyword=Lung adenocarcinoma
kn-keyword=Lung adenocarcinoma
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=20250909
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=S100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis. However, the exact mechanisms by which S100A8/A9 contributes to GC pathogenesis remain unclear. This study investigates the role of S100A8/A9 and its receptor in GC. Immunohistochemical analysis was performed on GC tissue samples to assess the expression of the S100A8/A9 receptor melanoma cell adhesion molecule (MCAM). In vitro transwell migration and invasion assays were used to evaluate the motility and invasiveness of GC cells. Cell proliferation was assessed using a growth assay, and Western blotting (WB) was employed to examine downstream signaling pathways, including ERK and the transcription factor c-Jun, in response to S100A8/A9–MCAM interaction. S100A8/A9 stimulation enhanced both proliferation and migration through MCAM binding in GC cell lines. These cellular events were accompanied by ERK activation and c-Jun induction. Downregulation of MCAM suppressed both ERK phosphorylation and c-Jun expression, highlighting the importance of the S100A8/A9‒MCAM‒ERK‒c-Jun axis in promoting GC progression. These findings indicate that S100A8/A9 contributes to GC progression via MCAM, which activates the ERK‒c-Jun pathway. The S100A8/A9‒signaling axis may represent a novel therapeutic target in GC.
en-copyright=
kn-copyright=

en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YangXu
en-aut-sei=Yang
en-aut-mei=Xu
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=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=PanBo
en-aut-sei=Pan
en-aut-mei=Bo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=WuFangping
en-aut-sei=Wu
en-aut-mei=Fangping
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ZhangXu
en-aut-sei=Zhang
en-aut-mei=Xu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SagayamaKazumi
en-aut-sei=Sagayama
en-aut-mei=Kazumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SunBei
en-aut-sei=Sun
en-aut-mei=Bei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=

affil-num=1
en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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=The First Affiliated Hospital, Zhejiang University School of Medicine
kn-affil=

affil-num=6
en-affil=School of Pharmaceutical Sciences, Zhejiang Chinese Medical University
kn-affil=

affil-num=7
en-affil=Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine
kn-affil=

affil-num=8
en-affil=Faculties of Educational and Research Management Field, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University
kn-affil=

affil-num=10
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Gastric cancer
kn-keyword=Gastric cancer
en-keyword=S100 protein
kn-keyword=S100 protein
en-keyword=MCAM
kn-keyword=MCAM
en-keyword=Inflammation
kn-keyword=Inflammation
en-keyword=Metastasis
kn-keyword=Metastasis
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=20250830
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Pseudohypoxia induced by iron chelator activates tumor immune response in lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hypoxia-inducible factor (HIF) signaling plays a critical role in immune cell function. Pseudohypoxia is characterized as iron-mediated stabilization of HIF-1α under normoxic conditions, which can be induced by iron chelators. This study explored whether iron chelators exert antitumor effects by enhancing tumor immune responses and elucidating the underlying mechanisms. The iron chelators Super–polyphenol 10 (SP10) and Deferoxamine (DFO) were used to create iron-deficient and pseudohypoxia conditions. Pseudohypoxia induced by iron chelators stimulates IL-2 secretion from T cells and from both human and murine nonsmall cell lung cancer (NSCLC) cell lines (A549, PC-3, and LLC). Administration of SP10 reduced tumor growth when LLC tumors were implanted in C57BL/6 mice; however, this was not observed in immunodeficient RAG1-deficient C57BL/6 mice. SP10 itself did not directly inhibit LLC cells proliferation in vitro, suggesting an activation of the tumor immune response. SP10 synergistically enhanced the efficacy of PD-1 antibody therapy in lung cancer by increasing the number of tumor-infiltrating lymphocytes (TILs). In conclusion, iron chelation-induced pseudohypoxia activates tumor immune responses by directly upregulating HIF-1α, augmenting T cell function, and inducing IL-2 secretion from T cells, and cancer cells, thereby amplifying the immune efficacy of the PD-1 antibody in lung cancer treatment.
en-copyright=
kn-copyright=

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

en-aut-name=TeradaManato
en-aut-sei=Terada
en-aut-mei=Manato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
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=6
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=7
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=8
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=9
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 Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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=
en-keyword=Lung cancer
kn-keyword=Lung cancer
en-keyword=iron
kn-keyword=iron
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=26
cd-vols=
no-issue=9
article-no=
start-page=4310
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=The Possibility of Plasma Membrane Transporters as Drug Targets in Oral Cancers
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Plasma membrane transporters are increasingly recognized as potential drug targets for oral cancer, particularly oral squamous cell carcinoma (OSCC). These transporters play crucial roles in cancer cell metabolism, drug resistance, and the tumor microenvironment, making them attractive targets for therapeutic intervention. Among the two main families of plasma membrane transporters, ATP-binding cassette (ABC) transporters have long been known to be involved in drug efflux and contribute to chemoresistance in cancer cells. On the other hand, solute carriers (SLCs) are also a family of transporters that facilitate the transport of various substrates, including nutrients and drugs, and have recently been shown to contribute to cancer chemosensitivity, metabolism, and proliferation. SLC transporters have been identified as potential cancer biomarkers and therapeutic targets, and their expression profiles suggest that they could be utilized in precision oncology approaches. We summarize previous reports on the expression and role of ABC and SLC transporters in oral cancer and discuss their potential as therapeutic targets.
en-copyright=
kn-copyright=

en-aut-name=SogawaChiharu
en-aut-sei=Sogawa
en-aut-mei=Chiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShimadaKatsumitsu
en-aut-sei=Shimada
en-aut-mei=Katsumitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

affil-num=1
en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology
kn-affil=

affil-num=2
en-affil=Department of Clinical Phathophysiology, Matsumoto Dental University
kn-affil=

affil-num=3
en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=SLC transporter
kn-keyword=SLC transporter
en-keyword=ABC transporter
kn-keyword=ABC transporter
en-keyword=oral cancer
kn-keyword=oral cancer
en-keyword=oral squamous cell carcinoma
kn-keyword=oral squamous cell carcinoma
END

start-ver=1.4
cd-journal=joma
no-vol=329
cd-vols=
no-issue=1
article-no=
start-page=L183
end-page=L196
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250701
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Activated factor X inhibition ameliorates NF-κB-IL-6-mediated perivascular inflammation and pulmonary hypertension
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Activated factor X (FXa) induces inflammatory response and cell proliferation in various cell types via activation of proteinase-activated receptor-1 (PAR1) and/or PAR2. We thus aimed to investigate the impact of FXa on the development of pulmonary arterial hypertension (PAH) and the mechanisms involved. The effects of edoxaban, a selective FXa inhibitor, on hemodynamic, right ventricular (RV) hypertrophy, and vascular remodeling were evaluated in a monocrotaline (MCT)-exposed pulmonary hypertension (PH) rat model. At 21 days after a single subcutaneous injection of MCT of 60 mg/kg, right ventricular systolic pressure (RVSP) and total pulmonary vascular resistance index (TPRI) were elevated concomitant with the increased plasma FXa and lung interleukin-6 (IL-6) mRNA. Daily administration of edoxaban (10 mg/kg/day, by gavage) starting from the day of MCT injection for 21 days ameliorated RVSP, TPRI, RV hypertrophy, pulmonary vascular remodeling, and macrophage accumulation. Edoxaban reduced nuclear factor-kappa B (NF-κB) activity and IL-6 mRNA level in the lungs of MCT-exposed rats. mRNA levels of FXa, PAR1, and PAR2 in cultured pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with PAH were higher than those seen in normal PASMCs. FXa stimulation increased cell proliferation and mRNA level of IL-6 in normal PASMCs, both of which were blunted by edoxaban and PAR1 antagonist. Moreover, FXa stimulation activated extracellularly regulated kinases 1/2 in a PAR1-dependent manner. Inhibition of FXa ameliorates NF-κB-IL-6-mediated perivascular inflammation, pulmonary vascular remodeling, and the development of PH in MCT-exposed rats, suggesting that FXa may be a potential target for the treatment of PAH.<br>
NEW & NOTEWORTHY This study demonstrated that chronic treatment with activated factor X (FXa) inhibitor ameliorated NF-κB-IL-6-mediated perivascular inflammation in a rat model with pulmonary arterial hypertension, which is associated with elevated FXa activity. FXa may act on pulmonary arterial smooth muscle cells, inducing cell proliferation and inflammatory response via upregulated PAR1, thereby contributing to pulmonary vascular remodeling. Understanding the patient-specific pathophysiology is a prerequisite for applying FXa-targeted therapy to the treatment of pulmonary arterial hypertension.
en-copyright=
kn-copyright=

en-aut-name=ImakiireSatomi
en-aut-sei=Imakiire
en-aut-mei=Satomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KimuroKeiji
en-aut-sei=Kimuro
en-aut-mei=Keiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YoshidaKeimei
en-aut-sei=Yoshida
en-aut-mei=Keimei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MasakiKohei
en-aut-sei=Masaki
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=IzumiRyo
en-aut-sei=Izumi
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ImabayashiMisaki
en-aut-sei=Imabayashi
en-aut-mei=Misaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=WatanabeTakanori
en-aut-sei=Watanabe
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=IshikawaTomohito
en-aut-sei=Ishikawa
en-aut-mei=Tomohito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HosokawaKazuya
en-aut-sei=Hosokawa
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MatsushimaShouji
en-aut-sei=Matsushima
en-aut-mei=Shouji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=HashimotoToru
en-aut-sei=Hashimoto
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ShinoharaKeisuke
en-aut-sei=Shinohara
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KatsukiShunsuke
en-aut-sei=Katsuki
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=MatobaTetsuya
en-aut-sei=Matoba
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
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=15
ORCID=

en-aut-name=HiranoKatsuya
en-aut-sei=Hirano
en-aut-mei=Katsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=TsutsuiHiroyuki
en-aut-sei=Tsutsui
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=AbeKohtaro
en-aut-sei=Abe
en-aut-mei=Kohtaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

affil-num=1
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=2
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=4
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=5
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=6
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=7
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=8
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=9
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=10
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=11
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=12
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=13
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=14
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=15
en-affil=Department of Cardiovascular Medicine, Okayama University
kn-affil=

affil-num=16
en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University
kn-affil=

affil-num=17
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=

affil-num=18
en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
kn-affil=
en-keyword=factor Xa
kn-keyword=factor Xa
en-keyword=IL-6
kn-keyword=IL-6
en-keyword=proteinase-activated receptor
kn-keyword=proteinase-activated receptor
en-keyword=pulmonary arterial hypertension
kn-keyword=pulmonary arterial hypertension
en-keyword=pulmonary hypertension
kn-keyword=pulmonary hypertension
END

start-ver=1.4
cd-journal=joma
no-vol=60
cd-vols=
no-issue=10
article-no=
start-page=1151
end-page=1159
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202412
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=NCF-1 plays a pivotal role in the survival of adenocarcinoma cells of pancreatic and gastric origins
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Reactive oxygen species (ROS) play a pivotal biological role in cells, with ROS function differing depending on cellular conditions and the extracellular environment. Notably, ROS act as cytotoxic factors to eliminate infectious pathogens or promote cell death under cellular stress, while also facilitating cell growth (via ROS-sensing pathways) by modifying gene expression. Among ROS-related genes, neutrophil cytosolic factor-1 (NCF-1; p47phox) was identified as a ROS generator in neutrophils. This product is a subunit of a cytosolic NADPH oxidase complex activated in response to pathogens such as bacteria and viruses. NCF-1 has been examined primarily in terms of ROS-production pathways in macrophages and neutrophils; however, the expression of this protein and its biological role in cancer cells remain unclear. Here, we report expression of NCF-1 in pancreatic and gastric cancers, and demonstrate its biological significance in these tumor cells. Abundant expression of NCF-1 was observed in pancreatic adenocarcinoma (PDAC) lines and in patient tissues, as well as in gastric adenocarcinomas. Accumulation of the protein was also detected in the invasive/metastatic foci of these tumors. Unexpectedly, BxPC-3 underwent apoptotic cell death when transfected with a small interfering RNA (siRNA) specific to NCF-1, whereas the cells treated with a control siRNA proliferated in a time-dependent manner. A similar phenomenon was observed in HSC-58, a poorly differentiated gastric adenocarcinoma line. Consequently, the tumor cells highly expressing NCF-1 obtained coincident accumulation of ROS and reduced glutathione (GSH) with expression of glutathione peroxidase 4 (GPX4), a quencher involved in ferroptosis. Unlike the conventional role of ROS as a representative cytotoxic factor, these findings suggest that NCF-1-mediated ROS generation may be required for expansive growth of PDAC and gastric cancers.
en-copyright=
kn-copyright=

en-aut-name=Furuya-IkudeChiemi
en-aut-sei=Furuya-Ikude
en-aut-mei=Chiemi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KittaAkane
en-aut-sei=Kitta
en-aut-mei=Akane
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TomonobuNaoko
en-aut-sei=Tomonobu
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KawasakiYoshihiro
en-aut-sei=Kawasaki
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
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=6
ORCID=

affil-num=1
en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University
kn-affil=

affil-num=2
en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University
kn-affil=

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

affil-num=4
en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University
kn-affil=

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

affil-num=6
en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University
kn-affil=
en-keyword=NCF-1 (p47phox)
kn-keyword=NCF-1 (p47phox)
en-keyword=ROS
kn-keyword=ROS
en-keyword=Cancer
kn-keyword=Cancer
en-keyword=Tumor growth
kn-keyword=Tumor growth
en-keyword=Apoptosis
kn-keyword=Apoptosis
END

start-ver=1.4
cd-journal=joma
no-vol=4
cd-vols=
no-issue=4
article-no=
start-page=263
end-page=272
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240607
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Light-Responsive and Antibacterial Graphenic Materials as a Holistic Approach to Tissue Engineering
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=While the continuous development of advanced bioprinting technologies is under fervent study, enhancing the regenerative potential of hydrogel-based constructs using external stimuli for wound dressing has yet to be tackled. Fibroblasts play a significant role in wound healing and tissue implants at different stages, including extracellular matrix production, collagen synthesis, and wound and tissue remodeling. This study explores the synergistic interplay between photothermal activity and nanomaterial-mediated cell proliferation. The use of different graphene-based materials (GBM) in the development of photoactive bioinks is investigated. In particular, we report the creation of a skin-inspired dressing for wound healing and regenerative medicine. Three distinct GBM, namely, graphene oxide (GO), reduced graphene oxide (rGO), and graphene platelets (GP), were rigorously characterized, and their photothermal capabilities were elucidated. Our investigations revealed that rGO exhibited the highest photothermal efficiency and antibacterial properties when irradiated, even at a concentration as low as 0.05 mg/mL, without compromising human fibroblast viability. Alginate-based bioinks alongside human fibroblasts were employed for the bioprinting with rGO. The scaffold did not affect the survival of fibroblasts for 3 days after bioprinting, as cell viability was not affected. Remarkably, the inclusion of rGO did not compromise the printability of the hydrogel, ensuring the successful fabrication of complex constructs. Furthermore, the presence of rGO in the final scaffold continued to provide the benefits of photothermal antimicrobial therapy without detrimentally affecting fibroblast growth. This outcome underscores the potential of rGO-enhanced hydrogels in tissue engineering and regenerative medicine applications. Our findings hold promise for developing game-changer strategies in 4D bioprinting to create smart and functional tissue constructs with high fibroblast proliferation and promising therapeutic capabilities in drug delivery and bactericidal skin-inspired dressings.
en-copyright=
kn-copyright=

en-aut-name=FerrerasAndrea
en-aut-sei=Ferreras
en-aut-mei=Andrea
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MatesanzAna
en-aut-sei=Matesanz
en-aut-mei=Ana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MendizabalJabier
en-aut-sei=Mendizabal
en-aut-mei=Jabier
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ArtolaKoldo
en-aut-sei=Artola
en-aut-mei=Koldo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=AcedoPablo
en-aut-sei=Acedo
en-aut-mei=Pablo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=JorcanoJosé L.
en-aut-sei=Jorcano
en-aut-mei=José L.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=RuizAmalia
en-aut-sei=Ruiz
en-aut-mei=Amalia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ReinaGiacomo
en-aut-sei=Reina
en-aut-mei=Giacomo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MartínCristina
en-aut-sei=Martín
en-aut-mei=Cristina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Bioengineering, Universidad Carlos III de Madrid
kn-affil=

affil-num=2
en-affil=Department of Electronic Technology, Universidad Carlos III de Madrid
kn-affil=

affil-num=3
en-affil=Domotek ingeniería prototipado y formación S.L.
kn-affil=

affil-num=4
en-affil=Domotek ingeniería prototipado y formación S.L.
kn-affil=

affil-num=5
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Electronic Technology, Universidad Carlos III de Madrid
kn-affil=

affil-num=7
en-affil=Department of Bioengineering, Universidad Carlos III de Madrid
kn-affil=

affil-num=8
en-affil=Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford
kn-affil=

affil-num=9
en-affil=Empa Swiss Federal Laboratories for Materials Science and Technology
kn-affil=

affil-num=10
en-affil=Department of Bioengineering, Universidad Carlos III de Madrid
kn-affil=
en-keyword=photothermal therapy
kn-keyword=photothermal therapy
en-keyword=graphene derivatives
kn-keyword=graphene derivatives
en-keyword=4D bioprinting
kn-keyword=4D bioprinting
en-keyword=alginate
kn-keyword=alginate
en-keyword=tissue engineering
kn-keyword=tissue engineering
END

start-ver=1.4
cd-journal=joma
no-vol=26
cd-vols=
no-issue=14
article-no=
start-page=6927
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250718
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Gain-of-function gene alterations in rearranged during transfection (RET), a receptor tyrosine kinase, are observed in both sporadic and hereditary medullary thyroid cancers (MTCs) and pheochromocytomas and paragangliomas (PPGLs). Several tyrosine kinase inhibitors (TKIs) that target RET have been proven to be effective on MTCs and PCCs. Recently, TKIs, namely, sunitinib and selpercatinib, which were clinically used to target PPGLs, have been reported to decrease catecholamine levels without reducing tumor size. Our clinical case of metastatic medullary thyroid cancer, which is associated with RET mutations undergoing treatment with vandetanib, also suggests that vandetanib can decrease catecholamine levels. Therefore, we investigated the effect of vandetanib, a representative multi-targeted TKI for RET-related MTC, on cell proliferation and catecholamine synthesis in rat pheochromocytoma PC12 cells. Vandetanib reduced viable cells in a concentration-dependent manner. The dopamine and noradrenaline levels of the cell lysate were reduced in a concentration-dependent manner. They also decreased more prominently at lower concentrations of vandetanib compared to the inhibition of cell proliferation. The RNA knockdown study of Ret revealed that this inhibitory effect on catecholamine synthesis is mainly mediated by the suppression of RET signaling. Next, we focused on two signaling pathways downstream of RET, namely, ERK and AKT signaling. Treatment with vandetanib reduced both ERK and AKT phosphorylation in PC12 cells. Moreover, both an MEK inhibitor U0126 and a PI3K/AKT inhibitor LY294002 suppressed catecholamine synthesis without decreasing viable cells. This study in rat pheochromocytoma PC12 cells reveals the direct inhibitory effects of vandetanib on catecholamine synthesis via the suppression of RET-ERK and RET-AKT signaling.
en-copyright=
kn-copyright=

en-aut-name=ItohYoshihiko
en-aut-sei=Itoh
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=InagakiKenichi
en-aut-sei=Inagaki
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TerasakaTomohiro
en-aut-sei=Terasaka
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MorimotoEisaku
en-aut-sei=Morimoto
en-aut-mei=Eisaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=IshiiTakahiro
en-aut-sei=Ishii
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YamaokaKimitomo
en-aut-sei=Yamaoka
en-aut-mei=Kimitomo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FujisawaSatoshi
en-aut-sei=Fujisawa
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=

affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=tyrosine kinase inhibitor
kn-keyword=tyrosine kinase inhibitor
en-keyword=multiple endocrine neoplasia type 2
kn-keyword=multiple endocrine neoplasia type 2
en-keyword=paraganglioma
kn-keyword=paraganglioma
en-keyword=RET
kn-keyword=RET
en-keyword=ERK
kn-keyword=ERK
en-keyword=AKT
kn-keyword=AKT
END

start-ver=1.4
cd-journal=joma
no-vol=186
cd-vols=
no-issue=
article-no=
start-page=118030
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202505
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=(+)-Terrein exerts anti-obesity and anti-diabetic effects by regulating the differentiation and thermogenesis of brown adipocytes in mice fed a high-fat diet
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objective: (+)-Terrein, a low-molecular-weight secondary metabolite from Aspergillus terreus, inhibits adipocyte differentiation in vitro. However, the precise mechanisms underlying the effects of (+)-terrein on adipocytes remain unclear. We hypothesized that (+)-terrein modulates adipogenesis and glucose homeostasis in obesity and diabetes via anti-inflammatory action and regulation of adipocyte differentiation. Hence, in this study, we aimed to investigate the in vivo anti-diabetic and anti-obesity effects of (+)-terrein.<br>
Methods: Male C57BL/6 J mice were fed normal chow or high-fat (HF) diet and administered (+)-terrein (180 mg/kg) via intraperitoneal injection. Glucose and insulin tolerance tests, serum biochemical assays, and histological analyses were also performed. Rat brown preadipocytes, mouse brown preadipocytes (T37i cells), and inguinal white adipose tissue (ingWAT) preadipocytes were exposed to (+)-terrein during in vitro adipocyte differentiation. Molecular markers associated with thermogenesis and differentiation were quantified using real-time polymerase chain reaction and western blotting.<br>
Results: (+)-Terrein-treated mice exhibited improved insulin sensitivity and reduced serum lipid and glucose levels, irrespective of the diet. Furthermore, (+)-terrein suppressed body weight gain and mitigated fat accumulation by activating brown adipose tissue in HF-fed mice. (+)-Terrein facilitated the in vitro differentiation of rat brown preadipocytes, T37i cells, and ingWAT preadipocytes by upregulating peroxisome proliferator-activated receptor-γ (PPARγ). This effect was synergistic with that of a PPARγ agonist.<br>
Conclusion: This study demonstrated that (+)-terrein effectively induces PPARγ expression and brown adipocyte differentiation, leading to reduced weight gain and improved glucose and lipid profiles in HF-fed mice. Thus, (+)-terrein is a potent novel agent with potential anti-obesity and anti-diabetic properties.
en-copyright=
kn-copyright=

en-aut-name=Aoki-SaitoHaruka
en-aut-sei=Aoki-Saito
en-aut-mei=Haruka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MandaiHiroki
en-aut-sei=Mandai
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakakuraTakashi
en-aut-sei=Nakakura
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SasakiTsutomu
en-aut-sei=Sasaki
en-aut-mei=Tsutomu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KitamuraTadahiro
en-aut-sei=Kitamura
en-aut-mei=Tadahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=HisadaTakeshi
en-aut-sei=Hisada
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OkadaShuichi
en-aut-sei=Okada
en-aut-mei=Shuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SugaSeiji
en-aut-sei=Suga
en-aut-mei=Seiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=YamadaMasanobu
en-aut-sei=Yamada
en-aut-mei=Masanobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=SaitoTsugumichi
en-aut-sei=Saito
en-aut-mei=Tsugumichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science
kn-affil=

affil-num=3
en-affil=Department of Anatomy, Teikyo University School of Medicine
kn-affil=

affil-num=4
en-affil=Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University
kn-affil=

affil-num=5
en-affil=Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University
kn-affil=

affil-num=6
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Gunma University Graduate School of Health Sciences
kn-affil=

affil-num=8
en-affil=Department of Diabetes, Soleiyu Asahi Clinic
kn-affil=

affil-num=9
en-affil=Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University
kn-affil=
en-keyword=(+)-Terrein
kn-keyword=(+)-Terrein
en-keyword=Brown adipose tissue
kn-keyword=Brown adipose tissue
en-keyword=Thermogenesis
kn-keyword=Thermogenesis
en-keyword=Obesity
kn-keyword=Obesity
en-keyword=PPARγ
kn-keyword=PPARγ
END

start-ver=1.4
cd-journal=joma
no-vol=66
cd-vols=
no-issue=5
article-no=
start-page=705
end-page=721
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241220
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=SHORT AND CROOKED AWN, encoding the epigenetic regulator EMF1, promotes barley awn development
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The awn is a bristle-like extension from the tip of the lemma in grasses. In barley, the predominant cultivars possess long awns that contribute to grain yield and quality through photosynthesis. In addition, various awn morphological mutants are available in barley, rendering it a useful cereal crop to investigate the mechanims of awn development. Here, we identified the gene causative of the short and crooked awn (sca) mutant, which exhibits a short and curved awn phenotype. Intercrossing experiments revealed that the sca mutant induced in the Japanese cultivar (cv.) “Akashinriki” is allelic to the independently isolated moderately short-awn mutant breviaristatum-a (ari-a). Map-based cloning and sequencing revealed that SCA encodes the Polycomb group–associated protein EMBRYONIC FLOWER 1. We found that SCA affects awn development through the promotion of cell proliferation, elongation, and cell wall synthesis. RNA sequencing of cv. Bowman backcross-derived near-isogenic lines of sca and ari-a6 alleles showed that SCA is directly or indirectly involved in promoting the expression of genes related to awn development. Additionally, SCA represses various transcription factors essential for floral organ development and plant architecture, such as MADS-box and Knotted1-like homeobox genes. Notably, the repression of the C-class MADS-box gene HvMADS58 by SCA in awns is associated with the accumulation of the repressive histone modification H3K27me3. These findings highlight the potential role of SCA-mediated gene regulation, including histone modification, as a novel pathway in barley awn development.
en-copyright=
kn-copyright=

en-aut-name=NakamuraKoki
en-aut-sei=Nakamura
en-aut-mei=Koki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KikuchiYuichi
en-aut-sei=Kikuchi
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ShiragaMizuho
en-aut-sei=Shiraga
en-aut-mei=Mizuho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KotakeToshihisa
en-aut-sei=Kotake
en-aut-mei=Toshihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HyodoKiwamu
en-aut-sei=Hyodo
en-aut-mei=Kiwamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TaketaShin
en-aut-sei=Taketa
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IkedaYoko
en-aut-sei=Ikeda
en-aut-mei=Yoko
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=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=3
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Science and Engineering, Saitama University
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=Institute of Plant Science and Resources, Okayama University
kn-affil=
en-keyword=barley
kn-keyword=barley
en-keyword=awn development
kn-keyword=awn development
en-keyword=EMBRYONIC FLOWER 1 (EMF1)
kn-keyword=EMBRYONIC FLOWER 1 (EMF1)
en-keyword=homeotic genes
kn-keyword=homeotic genes
en-keyword=H3K27 trimethylation
kn-keyword=H3K27 trimethylation
en-keyword=epigenetic regulation
kn-keyword=epigenetic regulation
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=18981
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250530
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Role of galectin-9 in the development of gestational diabetes mellitus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Galectin-9 (Gal-9) is highly expressed in trophoblasts in placenta. Interaction between Gal-9 and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is important for the differentiation of tissue resident natural killer (trNK) cells in placenta and maintenance of normal pregnancy. Furthermore, the enhanced maternal systemic inflammation associated with increased proinflammatory cytokines in preeclampsia is mediated by enhanced interaction between Gal-9 and Tim-3. However, the role of Gal-9 in gestational diabetes (GDM) remains unexplored. Plasma Gal-9 levels were elevated at 3rd trimester in pregnant women with GDM and positively correlated with placenta and newborn weight. Lgals9 knockout pregnant mice fed with high fat diet (HFD KO) demonstrated maternal glucose intolerance and fetus macrosomia compared with controls (HFD WT). In HFD KO, increased proliferating cells, reduced apoptosis, and autophagy impairment were observed in junctional zones. The number of trNK cells and percentage of Tim-3 + trNK increased, while early apoptosis percentage in Tim-3 + trNK was reduced in placenta of HFD KO. The elevation of plasma Gal-9 may be a biomarker for prediction of maternal glucose intolerance and fetal macrosomia in pregnant women with GDM and Gal-9 functions as a compensation factor for GDM by inducing apoptosis in Tim-3 + trNK cells.
en-copyright=
kn-copyright=

en-aut-name=AlbuayjanHaya Hamed Hassan
en-aut-sei=Albuayjan
en-aut-mei=Haya Hamed Hassan
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=SugawaraRyosuke
en-aut-sei=Sugawara
en-aut-mei=Ryosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

en-aut-name=MiseKoki
en-aut-sei=Mise
en-aut-mei=Koki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OiYukiko
en-aut-sei=Oi
en-aut-mei=Yukiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KannoAyaka
en-aut-sei=Kanno
en-aut-mei=Ayaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YangBoXuan
en-aut-sei=Yang
en-aut-mei=BoXuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TaharaToshihisa
en-aut-sei=Tahara
en-aut-mei=Toshihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NojimaIchiro
en-aut-sei=Nojima
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
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=13
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=14
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=15
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=16
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=17
ORCID=

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

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

affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 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, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=12
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

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

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

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

affil-num=16
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=17
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
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=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=79
cd-vols=
no-issue=2
article-no=
start-page=129
end-page=134
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202504
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Case of Retinitis Pigmentosa Diagnosed with Severe Anterior Capsule Contraction after Cataract Surgery
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 66-year-old woman presented with significant anterior capsule contraction and intraocular lens dislocation in both eyes 4 months after cataract surgery. Postoperative examinations such as fluorescein angiography, Goldmann perimetry, and electroretinography revealed retinitis pigmentosa (RP). Patients with significant anterior capsule contraction after cataract surgery should be closely examined because RP may be a contributing factor.
en-copyright=
kn-copyright=

en-aut-name=TsujiAkihiro
en-aut-sei=Tsuji
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShiodeYusuke
en-aut-sei=Shiode
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KimuraShuhei
en-aut-sei=Kimura
en-aut-mei=Shuhei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HosokawaMio
en-aut-sei=Hosokawa
en-aut-mei=Mio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MatobaRyo
en-aut-sei=Matoba
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MoritaTetsuro
en-aut-sei=Morita
en-aut-mei=Tetsuro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakahashiKosuke
en-aut-sei=Takahashi
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MorizaneYuki
en-aut-sei=Morizane
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

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

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

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

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

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

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

affil-num=7
en-affil=Fukuyama City Hospital, Fukuyama City
kn-affil=

affil-num=8
en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=retinitis pigmentosa
kn-keyword=retinitis pigmentosa
en-keyword=intraocular lens
kn-keyword=intraocular lens
en-keyword=anterior capsule contraction
kn-keyword=anterior capsule contraction
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=197
cd-vols=
no-issue=
article-no=
start-page=115301
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=Fraglide-1 from traditional Chinese aromatic vinegar: A natural AhR antagonist for atopic dermatitis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Traditional Chinese Zhenjiang aromatic vinegar (Kozu) contains Fraglide-1 (FG1), a bioactive lactone with demonstrated peroxisome proliferator-activated receptor gamma (PPARγ) agonist and antioxidant activities. This study explored FG1's novel ability to antagonize the aryl hydrocarbon receptor (AhR) signaling pathway, which regulates artemin expression and contributes to itching and inflammation in atopic dermatitis. Through molecular docking simulations and cell-based assays in human keratinocytes, we demonstrated FG1's potent antagonistic activity against AhR signaling. FG1 effectively suppressed FICZ-induced inflammatory responses, including artemin expression, with potency (half maximal inhibitory concentration, IC50 = 5.1 μM) comparable to the synthetic antagonist StemRegenin 1 (SR1) while demonstrating a superior safety profile (median lethal concentration, LC50 > 100 μM vs. 27.5 μM for SR1). These findings expand our understanding of bioactive compounds from traditional fermented foods and their regulatory effects on AhR signaling, providing a foundation for future studies on FG1's role in modulating skin inflammation.
en-copyright=
kn-copyright=

en-aut-name=KatoKosuke
en-aut-sei=Kato
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AkamatsuMiki
en-aut-sei=Akamatsu
en-aut-mei=Miki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KakimaruSaya
en-aut-sei=Kakimaru
en-aut-mei=Saya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KoreishiMayuko
en-aut-sei=Koreishi
en-aut-mei=Mayuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakagiMasahiro
en-aut-sei=Takagi
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MiyashitaMasahiro
en-aut-sei=Miyashita
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=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=SatohAyano
en-aut-sei=Satoh
en-aut-mei=Ayano
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TsujinoYoshio
en-aut-sei=Tsujino
en-aut-mei=Yoshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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 Environmental and Life Science, 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 Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=School of Materials Science, Japan Advanced Institute of Science and Technology
kn-affil=

affil-num=6
en-affil=Graduate School of Agriculture, Kyoto University
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 Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=10
en-affil=Graduate School of Science, Technology and Innovation, Kobe University
kn-affil=
en-keyword=AhR
kn-keyword=AhR
en-keyword=Xenobiotic responsive element
kn-keyword=Xenobiotic responsive element
en-keyword=StemRegenin 1
kn-keyword=StemRegenin 1
en-keyword=ARNT
kn-keyword=ARNT
en-keyword=Atopic dermatitis
kn-keyword=Atopic dermatitis
en-keyword=Artemin
kn-keyword=Artemin
END

start-ver=1.4
cd-journal=joma
no-vol=64
cd-vols=
no-issue=2
article-no=
start-page=97
end-page=106
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=Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including “atypical lymphoplasmacytic and immunoblastic lymphadenopathy” from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial.
en-copyright=
kn-copyright=

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=1
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=2
ORCID=

en-aut-name=TakaokaKensuke
en-aut-sei=Takaoka
en-aut-mei=Kensuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MacapagalSharina
en-aut-sei=Macapagal
en-aut-mei=Sharina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WannaphutChalothorn
en-aut-sei=Wannaphut
en-aut-mei=Chalothorn
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=TodaHiroko
en-aut-sei=Toda
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=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 Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=2
en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i
kn-affil=

affil-num=3
en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i
kn-affil=

affil-num=4
en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i
kn-affil=

affil-num=5
en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i
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, Chugoku Central Hospital
kn-affil=

affil-num=8
en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i
kn-affil=

affil-num=9
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=
en-keyword=systematic review
kn-keyword=systematic review
en-keyword=atypical lymphoplasmacytic and immunoblastic proliferation
kn-keyword=atypical lymphoplasmacytic and immunoblastic proliferation
en-keyword=IgG4-related disease
kn-keyword=IgG4-related disease
en-keyword=angioimmunoblastic T-cell lymphoma
kn-keyword=angioimmunoblastic T-cell lymphoma
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=361
cd-vols=
no-issue=
article-no=
start-page=114657
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=Crosstalk between prolactin, insulin-like growth factors, and thyroid hormones in feather growth regulation in neonatal chick wings
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The elongation of primary feathers in neonatal chicks is delayed by the late-feathering K gene located on the Z chromosome. We recently found that the K gene slows feather growth by reducing the number of functional prolactin (PRL) receptor (PRLR) dimers. In this study, we investigated the molecular mechanisms by which PRL promotes feather elongation. RT-qPCR and immunohistochemistry analyses revealed that PRLRs are predominantly localized in the pulp rather than in the epidermal layer of the feather follicle. Treatment of primary cultured feather pulp cells with PRL increased the expression of mRNAs for insulin-like growth factors (IGFs; IGF-1 and IGF-2) and type 2 deiodinase (DIO2). Furthermore, treatments with IGF-1 and triiodothyronine (T3) reciprocally enhanced the expression of mRNAs for DIO2 and IGFs. Additionally, BrdU staining in neonatal chicks showed that T3 promoted cell proliferation in both the epidermal layer and pulp cells, while this effect was suppressed by an IGF-1 receptor (IGF1R) inhibitor. These findings suggest a novel model in which PRL upregulates IGFs and DIO2 in feather pulp cells, creating a positive feedback loop between IGFs and T3, ultimately leading to the promotion of cell proliferation in both the epidermal layer and the pulp cells by IGFs. This is the first report proposing crosstalk between PRL, thyroid hormone (TH), and IGFs in feather follicles.
en-copyright=
kn-copyright=

en-aut-name=NozawaYuri
en-aut-sei=Nozawa
en-aut-mei=Yuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OkamuraAyako
en-aut-sei=Okamura
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FukuchiHibiki
en-aut-sei=Fukuchi
en-aut-mei=Hibiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ShinoharaMasamichi
en-aut-sei=Shinohara
en-aut-mei=Masamichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AizawaSayaka
en-aut-sei=Aizawa
en-aut-mei=Sayaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakeuchiSakae
en-aut-sei=Takeuchi
en-aut-mei=Sakae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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 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=
en-keyword=Prolactin
kn-keyword=Prolactin
en-keyword=Thyroid hormone
kn-keyword=Thyroid hormone
en-keyword=IGF
kn-keyword=IGF
en-keyword=Iodothyronine deiodinase
kn-keyword=Iodothyronine deiodinase
en-keyword=Feather growth
kn-keyword=Feather growth
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=45
cd-vols=
no-issue=1
article-no=
start-page=11
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230323
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mutation and apoptosis are well-coordinated for protecting against DNA damage-inducing toxicity in Drosophila
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Apoptotic cell death is an important survival system for multicellular organisms because it removes damaged cells. Mutation is also a survival method for dealing with damaged cells in multicellular and also unicellular organisms, when DNA lesions are not removed. However, to the best of our knowledge, no reports have comprehensively explored the direct relationship between apoptosis and somatic cell mutations induced by various mutagenic factors.<br>
Results Mutation was examined by the wing-spot test, which is used to detect somatic cell mutations, including chromosomal recombination. Apoptosis was observed in the wing discs by acridine orange staining in situ. After treatment with chemical mutagens, ultraviolet light (UV), and X-ray, both the apoptotic frequency and mutagenic activity increased in a dose-dependent manner at non-toxic doses. When we used DNA repair-deficient Drosophila strains, the correlation coefficient of the relationship between apoptosis and mutagenicity, differed from that of the wild-type. To explore how apoptosis affects the behavior of mutated cells, we determined the spot size, i.e., the number of mutated cells in a spot. In parallel with an increase in apoptosis, the spot size increased with MNU or X-ray treatment dose-dependently; however, this increase was not seen with UV irradiation. In addition, BrdU incorporation, an indicator of cell proliferation, in the wing discs was suppressed at 6 h, with peak at 12 h post-treatment with X-ray, and that it started to increase again at 24 h; however, this was not seen with UV irradiation.<br>
Conclusion Damage-induced apoptosis and mutation might be coordinated with each other, and the frequency of apoptosis and mutagenicity are balanced depending on the type of DNA damage. From the data of the spot size and BrdU incorporation, it is possible that mutated cells replace apoptotic cells due to their high frequency of cell division, resulting in enlargement of the spot size after MNU or X-ray treatment. We consider that the induction of mutation, apoptosis, and/or cell growth varies in multi-cellular organisms depending on the type of the mutagens, and that their balance and coordination have an important function to counter DNA damage for the survival of the organism.
en-copyright=
kn-copyright=

en-aut-name=Toyoshima-SasataniMegumi
en-aut-sei=Toyoshima-Sasatani
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ImuraFumika
en-aut-sei=Imura
en-aut-mei=Fumika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HamatakeYuko
en-aut-sei=Hamatake
en-aut-mei=Yuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FukunagaAkihiro
en-aut-sei=Fukunaga
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NegishiTomoe
en-aut-sei=Negishi
en-aut-mei=Tomoe
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=School of Nursing, Osaka City University
kn-affil=

affil-num=5
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Drosophila
kn-keyword=Drosophila
en-keyword=Apoptosis
kn-keyword=Apoptosis
en-keyword=Mutation
kn-keyword=Mutation
en-keyword=Larval wing disc
kn-keyword=Larval wing disc
en-keyword=X-ray
kn-keyword=X-ray
en-keyword=Ultraviolet
kn-keyword=Ultraviolet
en-keyword=Alkylating agents
kn-keyword=Alkylating agents
en-keyword=Tobacco smoke
kn-keyword=Tobacco smoke
en-keyword=Acridine orange
kn-keyword=Acridine orange
en-keyword=BrdU
kn-keyword=BrdU
END

start-ver=1.4
cd-journal=joma
no-vol=25
cd-vols=
no-issue=21
article-no=
start-page=11592
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241029
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Epigenetic Regulation of CXC Chemokine Expression by Environmental Electrophiles Through DNA Methyltransferase Inhibition
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Ubiquitously distributed environmental electrophiles covalently modify DNA and proteins, potentially leading to adverse health effects. However, the impacts of specific electrophiles on target proteins and their physiological roles remain largely unknown. In the present study, we focused on DNA methylation, which regulates gene expression and physiological responses. A total of 45 environmental electrophiles were screened for inhibitory effects on the activity of DNA methyltransferase 3B (DNMT3B), a key enzyme in DNA methylation, and four compounds were identified. We focused on 1,2-naphthoquinone (1,2-NQ), an air pollutant whose toxicity has been reported previously. Interestingly, we found that 1,2-NQ modified multiple lysine and histidine residues in DNMT3B, one of which was near the active site in DNMT3B. It was found that 1,2-NQ altered gene expression and evoked inflammatory responses in lung adenocarcinoma cell lines. Furthermore, we found that 1,2-NQ upregulated CXCL8 expression through DNA demethylation of the distal enhancer and promoted cancer cell growth. Our study reveals novel mechanisms of epigenetic regulation by environmental electrophiles through the inhibition of DNMT3B activity and suggests their physiological impact.
en-copyright=
kn-copyright=

en-aut-name=TsuchidaTomoki
en-aut-sei=Tsuchida
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KubotaSho
en-aut-sei=Kubota
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KamiuezonoShizuki
en-aut-sei=Kamiuezono
en-aut-mei=Shizuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakasugiNobumasa
en-aut-sei=Takasugi
en-aut-mei=Nobumasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ItoAkihiro
en-aut-sei=Ito
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KumagaiYoshito
en-aut-sei=Kumagai
en-aut-mei=Yoshito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=UeharaTakashi
en-aut-sei=Uehara
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 Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

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

affil-num=3
en-affil=Department of Medicinal Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University
kn-affil=

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

affil-num=5
en-affil=School of Life Sciences, Tokyo University of Pharmacy and Life Sciences
kn-affil=

affil-num=6
en-affil=Graduate School of Pharmaceutical Sciences, Kyushu University
kn-affil=

affil-num=7
en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=DNA methylation
kn-keyword=DNA methylation
en-keyword=DNA methyltransferase
kn-keyword=DNA methyltransferase
en-keyword=chemical modification
kn-keyword=chemical modification
en-keyword=chemokine
kn-keyword=chemokine
en-keyword=cell proliferation
kn-keyword=cell proliferation
en-keyword=toxicology
kn-keyword=toxicology
en-keyword=exposome
kn-keyword=exposome
en-keyword=environmental electrophiles
kn-keyword=environmental electrophiles
END

start-ver=1.4
cd-journal=joma
no-vol=300
cd-vols=
no-issue=3
article-no=
start-page=105679
end-page=
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=Methyl vinyl ketone and its analogs covalently modify PI3K and alter physiological functions by inhibiting PI3K signaling
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Reactive carbonyl species (RCS), which are abundant in the environment and are produced in vivo under stress, covalently bind to nucleophilic residues such as Cys in proteins. Disruption of protein function by RCS exposure is predicted to play a role in the development of various diseases such as cancer and metabolic disorders, but most studies on RCS have been limited to simple cytotoxicity validation, leaving their target proteins and resulting physiological changes unknown. In this study, we focused on methyl vinyl ketone (MVK), which is one of the main RCS found in cigarette smoke and exhaust gas. We found that MVK suppressed PI3K-Akt signaling, which regulates processes involved in cellular homeostasis, including cell proliferation, autophagy, and glucose metabolism. Interestingly, MVK inhibits the interaction between the epidermal growth factor receptor and PI3K. Cys656 in the SH2 domain of the PI3K p85 subunit, which is the covalently binding site of MVK, is important for this interaction. Suppression of PI3K- Akt signaling by MVK reversed epidermal growth factor- induced negative regulation of autophagy and attenuated glucose uptake. Furthermore, we analyzed the effects of the 23 RCS compounds with structures similar to MVK and showed that their analogs also suppressed PI3K-Akt signaling in a manner that correlated with their similarities to MVK. Our study demonstrates the mechanism of MVK and its analogs in suppressing PI3K-Akt signaling and modulating physiological functions, providing a model for future studies analyzing environmental reactive species.
en-copyright=
kn-copyright=

en-aut-name=MorimotoAtsushi
en-aut-sei=Morimoto
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakasugiNobumasa
en-aut-sei=Takasugi
en-aut-mei=Nobumasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=PanYuexuan
en-aut-sei=Pan
en-aut-mei=Yuexuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KubotaSho
en-aut-sei=Kubota
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=DohmaeNaoshi
en-aut-sei=Dohmae
en-aut-mei=Naoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AbikoYumi
en-aut-sei=Abiko
en-aut-mei=Yumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=UchidaKoji
en-aut-sei=Uchida
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KumagaiYoshito
en-aut-sei=Kumagai
en-aut-mei=Yoshito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UeharaTakashi
en-aut-sei=Uehara
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

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

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

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

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

affil-num=5
en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=6
en-affil=Graduate School of Biomedical Science, Nagasaki University
kn-affil=

affil-num=7
en-affil=Laboratory of Food Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo
kn-affil=

affil-num=8
en-affil=Graduate School of Pharmaceutical Sciences, Kyushu University
kn-affil=

affil-num=9
en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=phosphatidylinositol 3-kinase (PI 3-kinase)
kn-keyword=phosphatidylinositol 3-kinase (PI 3-kinase)
en-keyword=cell signaling
kn-keyword=cell signaling
en-keyword=chemical modification
kn-keyword=chemical modification
en-keyword=autophagy
kn-keyword=autophagy
en-keyword=glucose uptake
kn-keyword=glucose uptake
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=1
article-no=
start-page=24968
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241023
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Apolipoprotein-B mRNA-editing complex 3B could be a new potential therapeutic target in endometriosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p < 0.001, p < 0.001, p = 0.029, p = 0.001). Knockdown of APOBEC3B increased apoptosis, which was 28.03% and 22.27% higher than in mock and control siRNA samples, respectively. APOBEC3B knockdown also decreased PIK3CA expression and increased Caspase 8 expression, suggesting a potential role in the regulation of apoptosis. Furthermore, knockdown of APOBEC3B significantly inhibited cell proliferation, invasion, and migration compared to mock and control siRNA. (Cell proliferation: mock: p < 0.001 and control siRNA: p = 0.049. Cell invasion: mock: p < 0.001 and control siRNA: p = 0.029. Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis.
en-copyright=
kn-copyright=

en-aut-name=VuThuy Ha
en-aut-sei=Vu
en-aut-mei=Thuy Ha
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=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
ORCID=

en-aut-name=KuboKotaro
en-aut-sei=Kubo
en-aut-mei=Kotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KamadaYasuhiko
en-aut-sei=Kamada
en-aut-mei=Yasuhiko
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, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

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

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

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

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

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

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

affil-num=8
en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
en-keyword=Apolipoprotein-B mRNA-editing complex 3B
kn-keyword=Apolipoprotein-B mRNA-editing complex 3B
en-keyword=Endometriosis
kn-keyword=Endometriosis
en-keyword=Apoptosis
kn-keyword=Apoptosis
en-keyword=Potential therapeutic target
kn-keyword=Potential therapeutic target
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=21
cd-vols=
no-issue=5
article-no=
start-page=464
end-page=473
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240827
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background/Aim: Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms. Materials and methods: Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically. Results: Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models. Conclusion: This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate.
en-copyright=
kn-copyright=

en-aut-name=HIROSETAIRA
en-aut-sei=HIROSE
en-aut-mei=TAIRA
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KUNISADAYUKI
en-aut-sei=KUNISADA
en-aut-mei=YUKI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KADOYAKOICHI
en-aut-sei=KADOYA
en-aut-mei=KOICHI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MANDAIHIROKI
en-aut-sei=MANDAI
en-aut-mei=HIROKI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SAKAMOTOYUMI
en-aut-sei=SAKAMOTO
en-aut-mei=YUMI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OBATAKYOICHI
en-aut-sei=OBATA
en-aut-mei=KYOICHI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=TAKAKURAHIROAKI
en-aut-sei=TAKAKURA
en-aut-mei=HIROAKI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
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=10
ORCID=

en-aut-name=SUGASEIJI
en-aut-sei=SUGA
en-aut-mei=SEIJI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=

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

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

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

affil-num=4
en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science
kn-affil=

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

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

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

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

affil-num=9
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University
kn-affil=

affil-num=12
en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Head and neck cancer
kn-keyword=Head and neck cancer
en-keyword=oral cancer
kn-keyword=oral cancer
en-keyword=malignant melanoma
kn-keyword=malignant melanoma
en-keyword=angiogenin
kn-keyword=angiogenin
en-keyword=terrein
kn-keyword=terrein
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=13
article-no=
start-page=e34206
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240715
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Resolvin D2-induced reparative dentin and pulp stem cells after pulpotomy in a rat model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction: Vital pulp therapy (VPT) is performed to preserve dental pulp. However, the biocompatibility of the existing materials is of concern. Therefore, novel materials that can induce pulp healing without adverse effects need to be developed. Resolvin D2 (RvD2), one of specialized pro-resolving mediators, can resolve inflammation and promote the healing of periapical lesions. Therefore, RvD2 may be suitable for use in VPT. In the present study, we evaluated the efficacy of RvD2 against VPT using in vivo and in vitro models.<br>
Methods: First molars of eight-week-old male Sprague–Dawley rats were used for pulpotomy. They were then divided into three treatment groups: RvD2, phosphate-buffered saline, and calcium hydroxide groups. Treatment results were assessed using radiological, histological, and immunohistochemical (GPR18, TNF-α, Ki67, VEGF, TGF-β, CD44, CD90, and TRPA1) analyses. Dental pulp-derived cells were treated with RvD2 in vitro and analyzed using cell-proliferation and cell-migration assays, real-time PCR (Gpr18, Tnf-α, Il-1β, Tgf-β, Vegf, Nanog, and Trpa1), ELISA (VEGF and TGF-β), immunocytochemistry (TRPA1), and flow cytometry (dental pulp stem cells: DPSCs).<br>
Results: The formation of calcified tissue in the pulp was observed in the RvD2 and calcium hydroxide groups. RvD2 inhibited inflammation in dental pulp cells. RvD2 promoted cell proliferation and migration and the expression of TGF-β and VEGF in vitro and in vivo. RvD2 increased the number of DPSCs. In addition, RvD2 suppressed TRPA1 expression as a pain receptor.<br>
Conclusion: RvD2 induced the formation of reparative dentin, anti-inflammatory effects, and decreased pain, along with the proliferation of DPSCs via the expression of VEGF and TGF-β, on the pulp surface in pulpotomy models.
en-copyright=
kn-copyright=

en-aut-name=YonedaMitsuhiro
en-aut-sei=Yoneda
en-aut-mei=Mitsuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IdeguchiHidetaka
en-aut-sei=Ideguchi
en-aut-mei=Hidetaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakamuraShin
en-aut-sei=Nakamura
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
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=6
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=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 Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University
kn-affil=

affil-num=4
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Dental pulp
kn-keyword=Dental pulp
en-keyword=Regeneration
kn-keyword=Regeneration
en-keyword=Pulp-capping agents
kn-keyword=Pulp-capping agents
en-keyword=Specialized pro-resolving mediators
kn-keyword=Specialized pro-resolving mediators
en-keyword=Resolvin D2
kn-keyword=Resolvin D2
en-keyword=Calcification
kn-keyword=Calcification
en-keyword=Cytokine
kn-keyword=Cytokine
en-keyword=TRPA1
kn-keyword=TRPA1
en-keyword=Animal model
kn-keyword=Animal model
END

start-ver=1.4
cd-journal=joma
no-vol=60
cd-vols=
no-issue=10
article-no=
start-page=1138
end-page=1149
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240606
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=S100A11 is involved in the progression of colorectal cancer through the desmosome-catenin-TCF signaling pathway
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Compiling evidence has indicated that S100A11 expression at high levels is closely associated with various cancer species. Consistent with the results reported elsewhere, we have also revealed that S100A11 is highly expressed in squamous cell carcinoma, mesothelioma, and pancreatic cancers and plays a crucial role in cancer progression when secreted into extracellular fluid. Those studies are all focused on the extracellular role of S100A11. However, most of S100A11 is still present within cancer cells, although the intracellular role of S100A11 in cancer cells has not been fully elucidated. Thus, we aimed to investigate S100A11 functions within cancer cells, primarily focusing on colorectal cancer cells, whose S100A11 is abundantly present in cells and still poorly studied cancer for the protein. Our efforts revealed that overexpression of S100A11 promotes proliferation and migration, and downregulation inversely dampens those cancer behaviors. To clarify how intracellular S100A11 aids cancer cell activation, we tried to identify S100A11 binding proteins, resulting in novel binding partners in the inner membrane, many of which are desmosome proteins. Our molecular approach defined that S100A11 regulates the expression level of DSG1, a component protein of desmosome, by which S100A11 activates the TCF pathway via promoting nuclear translocation of γ-catenin from the desmosome. The identified new pathway greatly helps to comprehend S100A11’s nature in colorectal cancers and others.
en-copyright=
kn-copyright=

en-aut-name=ZhouJin
en-aut-sei=Zhou
en-aut-mei=Jin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=MizutaNaoko
en-aut-sei=Mizuta
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamakawaAtsuko
en-aut-sei=Yamakawa
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
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=7
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=8
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 Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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=Department of Cell Biology, 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 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=
en-keyword=S100A11
kn-keyword=S100A11
en-keyword=Desmosome
kn-keyword=Desmosome
en-keyword=TCF signaling
kn-keyword=TCF signaling
en-keyword=Colorectal cancer
kn-keyword=Colorectal cancer
END

start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=7
article-no=
start-page=394
end-page=407
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240531
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The specific shapes of capillaries are associated with worse prognosis in patients with invasive breast cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Angiogenesis is considered essential for tumor progression; however, whether histological counting of blood vessel numbers, expressed as microvessel density (MVD), can be a prognostic factor in breast cancer remains controversial. It has been suggested that the specific morphology of blood vessels such as glomeruloid microvascular proliferation (GMP) is associated with clinical parameters. Here, we aimed to clarify the significance of MVD with revised immunohistochemistry and to identify new blood vessel shapes that predict prognosis in breast cancer. Four hundred and eleven primary breast cancer specimens were collected, and the sections were immunohistochemically stained with CD31 (single staining) and CD31 and Collagen IV (double staining). The prognosis of patients was examined based on the MVD value, and the presence of GMP and other blood vessels with other specific shapes. As a result, high MVD value and the presence of GMP were not associated with worse prognosis. By contrast, patients with deep-curved capillaries surrounding tumor cell nests (C-shaped) or excessively branched capillaries near tumor cell nests showed a significantly poor prognosis. The presence of these capillaries was also correlated with clinicopathological parameters such as Ki-67 index. Thus, the morphology of capillaries rather than MVD can be a better indicator of tumor aggressiveness.
en-copyright=
kn-copyright=

en-aut-name=SweHnin‐Wint‐Wint
en-aut-sei=Swe
en-aut-mei=Hnin‐Wint‐Wint
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=KomatsubaraYu
en-aut-sei=Komatsubara
en-aut-mei=Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
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=6
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=7
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 Breast and Endocrine Surgery, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=angiogenesis
kn-keyword=angiogenesis
en-keyword=blood vessels
kn-keyword=blood vessels
en-keyword=breast cancer
kn-keyword=breast cancer
en-keyword=CD31 antigen
kn-keyword=CD31 antigen
en-keyword=immunohistochemistry
kn-keyword=immunohistochemistry
en-keyword=microvessel density
kn-keyword=microvessel density
en-keyword=survival analysis
kn-keyword=survival analysis
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=12
cd-vols=
no-issue=10
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231031
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance.<br>
Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC.<br>
Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation.<br>
Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC.
en-copyright=
kn-copyright=

en-aut-name=HaraNaofumi
en-aut-sei=Hara
en-aut-mei=Naofumi
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=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
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=6
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=7
ORCID=

en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=

en-aut-name=AbeMasaya
en-aut-sei=Abe
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
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=12
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=13
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=14
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=15
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=16
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=17
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=18
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=19
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=20
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 Respiratory Medicine, Japanese Red Cross Okayama Hospital
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 Hematology, Oncology and Respiratory Medicine, 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 Hematology and Oncology, Okayama University Hospital
kn-affil=

affil-num=12
en-affil=Center for Comprehensive Genomic 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 Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=15
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=16
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=17
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=18
en-affil=Center for Clinical Oncology, Okayama University 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 Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=Epidermal growth factor receptor (EGFR)
kn-keyword=Epidermal growth factor receptor (EGFR)
en-keyword=non-small cell lung cancer (NSCLC)
kn-keyword=non-small cell lung cancer (NSCLC)
en-keyword=cell cycle
kn-keyword=cell cycle
en-keyword=CDK4/6 inhibitor
kn-keyword=CDK4/6 inhibitor
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=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=115
cd-vols=
no-issue=4
article-no=
start-page=1317
end-page=1332
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240126
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Antitumor activity of α-pinene in T-cell tumors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeu-tic agents have been developed, their therapeutic effects are suboptimal. α- Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic ma-lignancies. This report provides a comprehensive analysis of the potential benefits of using α- pinene as an antitumor agent for the treatment of T-cell tumors. We found that α- pinene inhibited the proliferation of hematologic malignancies, especially in T-  cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and re-active oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α- pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted.
en-copyright=
kn-copyright=

en-aut-name=AbeMasaya
en-aut-sei=Abe
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=FukuiChie
en-aut-sei=Fukui
en-aut-mei=Chie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamadaDaisuke
en-aut-sei=Yamada
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=MiyakeMasayuki
en-aut-sei=Miyake
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TakaradaTakeshi
en-aut-sei=Takarada
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=

en-aut-name=AoeMichinori
en-aut-sei=Aoe
en-aut-mei=Michinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
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=12
ORCID=

en-aut-name=MoriyamaTakashi
en-aut-sei=Moriyama
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=MatsumuraAkifumi
en-aut-sei=Matsumura
en-aut-mei=Akifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
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=15
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 and  Oncology, 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=Division of Hematology, Department of  Medicine, Kobe University Hospital
kn-affil=

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

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

affil-num=7
en-affil=Division of Medical Support, Okayama  University Hospital
kn-affil=

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

affil-num=10
en-affil=Division of Medical Support, 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=

affil-num=12
en-affil=Department of Hematology, Oncology  and Respiratory Medicine, Okayama  University Graduate School of Medicine,  Dentistry and Pharmaceutical Sciences
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, Oncology  and Respiratory Medicine, Okayama  University Graduate School of Medicine,  Dentistry and Pharmaceutical Sciences
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=
en-keyword=alpha-pinene
kn-keyword=alpha-pinene
en-keyword=apoptosis
kn-keyword=apoptosis
en-keyword=hematologic malignancies
kn-keyword=hematologic malignancies
en-keyword=lymphoblastic leukemia, acute, T-cell
kn-keyword=lymphoblastic leukemia, acute, T-cell
en-keyword=T-cell lymphoma
kn-keyword=T-cell lymphoma
END

start-ver=1.4
cd-journal=joma
no-vol=34
cd-vols=
no-issue=
article-no=
start-page=102054
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231212
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Gemcitabine is an effective chemotherapeutic agent for biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). However, few other effective agents are currently available, particularly for GEM-refractory BTCs. We previously identified microRNA-451a (miR-451a) as a potential therapeutic target in GBC. To elucidate the antineoplastic effects of miR-451a and its underlying mechanisms, we transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cell lines. Furthermore, mimicking in vivo conditions, tumorigenic GBC organoids and three-dimensional (3D) cell culture systems were employed to investigate the anti-proliferative effects of miR-451a on BTCs, and its effect on stem cell properties. We found that miR-451a significantly inhibited cell proliferation, induced apoptosis, and reduced chemoresistant phenotypes, such as epithelial-mesenchymal transition, in both GBC and GR-GBC. The principal mechanism is probably the negative regulation of the phosphatidylinositol 3-kinase/AKT pathway, partially accomplished by directly downregulating macrophage migration inhibitory factor. The Gene Expression Omnibus database revealed that miR-451a was the most significantly downregulated microRNA in CCA tissues. The introduction of miR-451a resulted in similar antineoplastic effects in GR-CCA. Furthermore, miR-451a reduced cell viability in 3D spheroid models and tumorigenic GBC organoids. These findings suggest that the supplementation of miR-451a is a potential treatment strategy for GEM-refractory BTCs.
en-copyright=
kn-copyright=

en-aut-name=ObataTaisuke
en-aut-sei=Obata
en-aut-mei=Taisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TsutsumiKoichiro
en-aut-sei=Tsutsumi
en-aut-mei=Koichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=UetaEijiro
en-aut-sei=Ueta
en-aut-mei=Eijiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OdaTakashi
en-aut-sei=Oda
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KikuchiTatsuya
en-aut-sei=Kikuchi
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AkoSoichiro
en-aut-sei=Ako
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FujiiYuki
en-aut-sei=Fujii
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YamazakiTatsuhiro
en-aut-sei=Yamazaki
en-aut-mei=Tatsuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UchidaDaisuke
en-aut-sei=Uchida
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MatsumotoKazuyuki
en-aut-sei=Matsumoto
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=HoriguchiShigeru
en-aut-sei=Horiguchi
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KatoHironari
en-aut-sei=Kato
en-aut-mei=Hironari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
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=14
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
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 Graduate School of Medicine, Dentistry, and Pharmaceutical Science
kn-affil=

affil-num=5
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
kn-affil=

affil-num=6
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=12
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=13
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
kn-affil=

affil-num=14
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=24
cd-vols=
no-issue=24
article-no=
start-page=17294
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231209
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.
en-copyright=
kn-copyright=

en-aut-name=HoangLoc Dinh
en-aut-sei=Hoang
en-aut-mei=Loc Dinh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AoyamaEriko
en-aut-sei=Aoyama
en-aut-mei=Eriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HiasaMiki
en-aut-sei=Hiasa
en-aut-mei=Miki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OmoteHiroshi
en-aut-sei=Omote
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
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=6
ORCID=

en-aut-name=TakigawaMasaharu
en-aut-sei=Takigawa
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

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

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

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

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

affil-num=7
en-affil=Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=S-adenosylmethionine
kn-keyword=S-adenosylmethionine
en-keyword=chondrocyte differentiation
kn-keyword=chondrocyte differentiation
en-keyword=CCN2
kn-keyword=CCN2
en-keyword=polyamine
kn-keyword=polyamine
en-keyword=ODC
kn-keyword=ODC
en-keyword=gene expression
kn-keyword=gene expression
END

start-ver=1.4
cd-journal=joma
no-vol=155
cd-vols=
no-issue=
article-no=
start-page=105797
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202311
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Ruxolitinib altered IFN-β induced necroptosis of human dental pulp stem cells during osteoblast differentiation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objective: This study aimed to evaluate the role of ruxolitinib in the interferon beta (IFN-β) mediated osteoblast differentiation using human dental pulp stem cells (hDPSCs).<br>
Design: hDPSCs from five deciduous teeth of healthy patients were stimulated by adding human recombinant IFN-β protein (1 or 2 ng/ml) to the osteogenic differentiation induction medium. Substrate formation was determined using Alizarin Red staining, calcium concentration, and osteoblast marker expression levels. Ruxolitinib was used to inhibit the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway. Apoptosis was detected using terminal deoxynucleotidyl nick-end labeling (TUNEL) staining, and necroptosis was detected using propidium iodide staining and phosphorylated mixed lineage kinase domain-like protein (pMLKL) expression.<br>
Results: In the IFN-β-treated group, substrate formation was inhibited by a reduction in alkaline phosphatase (ALP) expression in a concentration-dependent manner. Although the proliferation potency was unchanged between the IFN-β-treated and control groups, the cell number was significantly reduced in the experimental group. TUNEL-positive cell number was not significantly different; however, the protein level of necroptosis markers, interleukin-6 (IL-6) and pMLKL were significantly increased in the substrate formation. Cell number and ALP expression level were improved in the group administered ruxolitinib, a JAK-STAT inhibitor. Additionally, ruxolitinib significantly suppressed IL-6 and pMLKL levels.<br>
Conclusion: Ruxolitinib interfered with the IFN-β-mediated necroptosis and osteogenic differentiation via the JAK-STAT pathway.
en-copyright=
kn-copyright=

en-aut-name=TanakaAtsuko
en-aut-sei=Tanaka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HayanoSatoru
en-aut-sei=Hayano
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NagataMasayo
en-aut-sei=Nagata
en-aut-mei=Masayo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KosamiTakahiro
en-aut-sei=Kosami
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=KamiokaHiroshi
en-aut-sei=Kamioka
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

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

affil-num=2
en-affil=Department of Orthodontics, Okayama University Hospital
kn-affil=

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

affil-num=4
en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Type-I interferon
kn-keyword=Type-I interferon
en-keyword=Janus kinase/signal transducers and activators of transcription pathway
kn-keyword=Janus kinase/signal transducers and activators of transcription pathway
en-keyword=Osteoblast
kn-keyword=Osteoblast
en-keyword=Necroptosis
kn-keyword=Necroptosis
en-keyword=Singleton-Merten Syndrome
kn-keyword=Singleton-Merten Syndrome
END

start-ver=1.4
cd-journal=joma
no-vol=24
cd-vols=
no-issue=5
article-no=
start-page=382
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=Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line‑derived xenograft model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The cancer stroma regulates bone invasion in oral squamous cell carcinoma (OSCC). However, data on normal stroma are limited. In the present study, the effects of gingival and periodontal ligament tissue‑derived stromal cells (G‑SCs and P‑SCs, respectively) and human dermal fibroblasts (HDFs) on bone resorption and osteoclast activation were assessed using hematoxylin and eosin and tartrate‑resistant acid phosphatase staining in a cell line‑derived xenograft model. The results demonstrated that G‑SCs promoted bone invasion and osteoclast activation and inhibited osteoclast proliferation following crosstalk with the human OSCC HSC‑3 cell line, whereas P‑SCs inhibited bone resorption and promoted osteoclast proliferation in vitro but had a minimal effect on osteoclast activation both in vitro and in vivo following crosstalk with HSC‑3 cells. Furthermore, the effects of G‑SCs, P‑SCs and HDFs on protein expression levels of matrix metalloproteinase (MMP)‑9, membrane type 1 MMP (MT1‑MMP), Snail, parathyroid hormone‑related peptide (PTHrP) and receptor activator of NF‑κB ligand (RANKL) in HSC‑3 cells in OSCC bone invasion regions were assessed using immunohistochemistry. The results demonstrated that G‑SCs had a more prominent effect on the expression of MMP‑9, MT1‑MMP, Snail, PTHrP, and RANKL, whereas P‑SCs only promoted RANKL and PTHrP expression and exerted a minimal effect on MMP‑9, MT1‑MMP and Snail expression. The potential genes underlying the differential effects of G‑SCs and P‑SCs on bone invasion in OSCC were evaluated using a microarray, which indicated that cyclin‑dependent kinase 1, insulin, aurora kinase A, cyclin B1 and DNA topoisomerase II alpha underlaid these differential effects. Therefore, these results demonstrated that G‑SCs promoted bone invasion in OSCC by activating osteoclasts on the bone surface, whereas P‑SCs exerted an inhibitory effect. These findings could indicate a potential regulatory mechanism for bone invasion in OSCC.
en-copyright=
kn-copyright=

en-aut-name=ShanQiusheng
en-aut-sei=Shan
en-aut-mei=Qiusheng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=OmoriHaruka
en-aut-sei=Omori
en-aut-mei=Haruka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
ORCID=

en-aut-name=SukegawaShintaro
en-aut-sei=Sukegawa
en-aut-mei=Shintaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FujiiMasae
en-aut-sei=Fujii
en-aut-mei=Masae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=InadaYasunori
en-aut-sei=Inada
en-aut-mei=Yasunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SanoSho
en-aut-sei=Sano
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=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=

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

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

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

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

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

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

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

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

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

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

affil-num=11
en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=oral squamous cell carcinoma
kn-keyword=oral squamous cell carcinoma
en-keyword=bone invasion
kn-keyword=bone invasion
en-keyword=gingival ligament tissue‑derived stromal cell
kn-keyword=gingival ligament tissue‑derived stromal cell
en-keyword=periodontal ligament tissue‑derived stromal cell
kn-keyword=periodontal ligament tissue‑derived stromal cell
en-keyword=xenograft model
kn-keyword=xenograft model
en-keyword=microarray
kn-keyword=microarray
END

start-ver=1.4
cd-journal=joma
no-vol=60
cd-vols=
no-issue=6
article-no=
start-page=78
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Crosstalk between cancer and different cancer stroma subtypes promotes the infiltration of tumor‑associated macrophages into the tumor microenvironment of oral squamous cell carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Tumor‑associated macrophages (TAMs) are linked to the progression of numerous types of cancer. However, the effects of the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC), particularly the cancer stroma on TAMs, remains to be elucidated. In the present study, the effects of verrucous SCC‑associated stromal cells (VSCC‑SCs), SCC‑associated stromal cells (SCC‑SCs) and human dermal fibroblasts (HDFs) on the differentiation, proliferation and migration of macrophages in vitro was assayed using Giemsa staining, and immunofluorescence, MTS and Transwell (migration) assays, respectively. The combined results suggested that both VSCC‑SCs and SCC‑SCs promoted the differentiation of macrophages into M2 type TAMs, as well as the proliferation and migration of macrophages following crosstalk with HSC‑3 cells in vitro. Moreover, the SCC‑SCs exerted a more prominent effect on TAMs than the VSCC‑SCs. Immunohistochemical staining was used to examine the expression of CD34, CD45, CD11b and CD163 to assay the effects of VSCC‑SCs, SCC‑SCs and HDFs on microvessel density (MVD) and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type macrophages. The results suggested that both VSCC‑SCs and SCC‑SCs promoted MVD and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type TAMs into the TME of OSCC following crosstalk with HSC‑3 cells in vivo. The SCC‑SCs exerted a more prominent promoting effect than the VSCC‑SCs. Finally, the potential genes underlying the differential effects of VSCC‑SCs and SCC‑SCs on the infiltration of TAMs were investigated using microarray analysis. The results revealed that interleukin 1β, bone morphogenetic protein 4, interleukin 6 and C‑X‑C motif chemokine ligand 12 had great potential to mediate the differential effects of VSCC‑SCs and SCC‑SCs on TAM infiltration. On the whole, the findings presented herein, demonstrate that both VSCC‑SCs and SCC‑SCs promote the infiltration of TAMs into the TME of OSCC following crosstalk with HSC‑3 cells; the SCC‑SCs were found to exert a more prominent promoting effect. This may represent a potential regulatory mechanism for the infiltration of TAMs into the TME of OSCC.
en-copyright=
kn-copyright=

en-aut-name=ShanQiusheng
en-aut-sei=Shan
en-aut-mei=Qiusheng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=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=SukegawaShintaro
en-aut-sei=Sukegawa
en-aut-mei=Shintaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujiiMasae
en-aut-sei=Fujii
en-aut-mei=Masae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
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=8
ORCID=

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

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

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

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

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

affil-num=6
en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=

affil-num=7
en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=

affil-num=8
en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
en-keyword=oral squamous cell carcinoma
kn-keyword=oral squamous cell carcinoma
en-keyword=tumor-associated macrophages
kn-keyword=tumor-associated macrophages
en-keyword=cancer stroma
kn-keyword=cancer stroma
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
en-keyword=microvessel density
kn-keyword=microvessel density
en-keyword=microarray
kn-keyword=microarray
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=
article-no=
start-page=1261330
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.<br>
Methods: In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4−), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.<br>
Results: To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4− single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4− SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.<br>
Discussion: Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.
en-copyright=
kn-copyright=

en-aut-name=SaitoYukihiro
en-aut-sei=Saito
en-aut-mei=Yukihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=AkazawaKaoru
en-aut-sei=Akazawa
en-aut-mei=Kaoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KannoTakayuki
en-aut-sei=Kanno
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=SasakiTakanori
en-aut-sei=Sasaki
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AkehiMasaru
en-aut-sei=Akehi
en-aut-mei=Masaru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
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=11
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=12
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=13
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=14
ORCID=

affil-num=1
en-affil=Department of Cardiovascular Medicine, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

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

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

affil-num=5
en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

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

affil-num=13
en-affil=Department of General Internal Medicine 3, Kawasaki Medical School
kn-affil=

affil-num=14
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=sodium/iodide symporter
kn-keyword=sodium/iodide symporter
en-keyword=human induced pluripotent stem cell-derived cardiomyocytes
kn-keyword=human induced pluripotent stem cell-derived cardiomyocytes
en-keyword=single photon emission computed tomography
kn-keyword=single photon emission computed tomography
en-keyword=cell-based therapy
kn-keyword=cell-based therapy
en-keyword=in vivo imaging
kn-keyword=in vivo imaging
END

start-ver=1.4
cd-journal=joma
no-vol=114
cd-vols=
no-issue=11
article-no=
start-page=4343
end-page=4354
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230915
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.
en-copyright=
kn-copyright=

en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
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=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=MoritaAyako
en-aut-sei=Morita
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HaraNaofumi
en-aut-sei=Hara
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=9
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=10
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=11
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=12
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=13
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=14
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=15
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=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=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
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=19
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=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=

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 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 Hematology, Oncology  and Respiratory Medicine, 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=Center for Clinical Oncology, Okayama  University Hospital
kn-affil=

affil-num=12
en-affil=Department of Hematology and  Oncology, Okayama University Hospital
kn-affil=

affil-num=13
en-affil=Department of Allergy and Respiratory  Medicine, Okayama University Hospital
kn-affil=

affil-num=14
en-affil=Department of Allergy and Respiratory  Medicine, Okayama University Hospital
kn-affil=

affil-num=15
en-affil=Department of Allergy and Respiratory  Medicine, Okayama University Hospital
kn-affil=

affil-num=16
en-affil=Department of Allergy and Respiratory  Medicine, Okayama University Hospital
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=

affil-num=18
en-affil=Center for Innovative Clinical Medicine,  Okayama University Hospital
kn-affil=

affil-num=19
en-affil=Center for Clinical Oncology, Okayama  University Hospital
kn-affil=

affil-num=20
en-affil=Department of Hematology, Oncology  and Respiratory Medicine
kn-affil=

affil-num=21
en-affil=Department of Allergy and Respiratory  Medicine, Okayama University Hospital
kn-affil=
en-keyword=alectinib
kn-keyword=alectinib
en-keyword=ALK
kn-keyword=ALK
en-keyword=gilteritinib
kn-keyword=gilteritinib
en-keyword=non-small cell lung cancer
kn-keyword=non-small cell lung cancer
en-keyword=TKI
kn-keyword=TKI
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=4
article-no=
start-page=415
end-page=422
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=Immunohistochemical Expression of Placental Vitamin D Receptors in Pregnancies Complicated by Early and Late-Onset Preeclampsia
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The aim of our study was to determine whether the immunohistochemical expression of placental vitamin D receptors is altered in pregnancies complicated by preeclampsia. Vitamin D receptor expression was immunohistochemically analysed in the placentas of three groups: a control group, and early- and late-onset preeclampsia groups. Total immunohistochemical intensity staining of placentas showed that the control group had a median vitamin D receptor (VDR) expression significantly higher than the placentas of mothers with early- and late-onset preeclampsia. There was no difference among the three groups in a semiquantitative analysis of VDR staining of the stroma only. Vitamin D receptors showed lower median expression in preeclampsia-affected pregnancies, especially early-onset preeclampsia. Therefore, Vitamin D receptor expression may be an important marker for normal placentation and preeclampsia onset.
en-copyright=
kn-copyright=

en-aut-name=JelcicDzenis
en-aut-sei=Jelcic
en-aut-mei=Dzenis
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=PuzovicVelibor
en-aut-sei=Puzovic
en-aut-mei=Velibor
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=BenzonBenjamin
en-aut-sei=Benzon
en-aut-mei=Benjamin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=PaladaIvan
en-aut-sei=Palada
en-aut-mei=Ivan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=JerkovićJelena
en-aut-sei=Jerković
en-aut-mei=Jelena
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=VulicMarko
en-aut-sei=Vulic
en-aut-mei=Marko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Gynecology and Obstetrics, University Hospital of Split
kn-affil=

affil-num=2
en-affil=General Hospital Dubrovnik, Department of Pathology and Cytology
kn-affil=

affil-num=3
en-affil=University of Split School of Medicine
kn-affil=

affil-num=4
en-affil=University Department of Health Studies of the University of Split
kn-affil=

affil-num=5
en-affil=Department of Gynecology and Obstetrics, University Hospital of Split
kn-affil=

affil-num=6
en-affil=Department of Gynecology and Obstetrics, University Hospital of Split
kn-affil=
en-keyword=vitamin D receptor
kn-keyword=vitamin D receptor
en-keyword=immunohistochemistry
kn-keyword=immunohistochemistry
en-keyword=early and late-onset preeclampsia
kn-keyword=early and late-onset preeclampsia
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=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=14
cd-vols=
no-issue=1
article-no=
start-page=621
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230204
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-l-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated. Here, we show that protein S-nitrosylation of a cysteine residue in DNMT3B attenuates DNMT3B enzymatic activity and consequent aberrant upregulation of gene expression. These genes include Cyclin D2 (Ccnd2), which is required for neoplastic cell proliferation in some tumor types. In cell-based and in vivo cancer models, only DNMT3B enzymatic activity, and not DNMT1 or DNMT3A, affects Ccnd2 expression. Using structure-based virtual screening, we discovered chemical compounds that specifically inhibit S-nitrosylation without directly affecting DNMT3B enzymatic activity. The lead compound, designated DBIC, inhibits S-nitrosylation of DNMT3B at low concentrations (IC50 <= 100nM). Treatment with DBIC prevents nitric oxide (NO)-induced conversion of human colonic adenoma to adenocarcinoma in vitro. Additionally, in vivo treatment with DBIC strongly attenuates tumor development in a mouse model of carcinogenesis triggered by inflammation-induced generation of NO. Our results demonstrate that de novo DNA methylation mediated by DNMT3B is regulated by NO, and DBIC protects against tumor formation by preventing aberrant S-nitrosylation of DNMT3B.
en-copyright=
kn-copyright=

en-aut-name=OkudaKosaku
en-aut-sei=Okuda
en-aut-mei=Kosaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NakaharaKengo
en-aut-sei=Nakahara
en-aut-mei=Kengo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ItoAkihiro
en-aut-sei=Ito
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IijimaYuta
en-aut-sei=Iijima
en-aut-mei=Yuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NomuraRyosuke
en-aut-sei=Nomura
en-aut-mei=Ryosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KumarAshutosh
en-aut-sei=Kumar
en-aut-mei=Ashutosh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FujikawaKana
en-aut-sei=Fujikawa
en-aut-mei=Kana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AdachiKazuya
en-aut-sei=Adachi
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ShimadaYuki
en-aut-sei=Shimada
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujioSatoshi
en-aut-sei=Fujio
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YamamotoReina
en-aut-sei=Yamamoto
en-aut-mei=Reina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TakasugiNobumasa
en-aut-sei=Takasugi
en-aut-mei=Nobumasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OnumaKunishige
en-aut-sei=Onuma
en-aut-mei=Kunishige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=OsakiMitsuhiko
en-aut-sei=Osaki
en-aut-mei=Mitsuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=OkadaFutoshi
en-aut-sei=Okada
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=UkegawaTaichi
en-aut-sei=Ukegawa
en-aut-mei=Taichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=TakeuchiYasuo
en-aut-sei=Takeuchi
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=YasuiNorihisa
en-aut-sei=Yasui
en-aut-mei=Norihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=YamashitaAtsuko
en-aut-sei=Yamashita
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=MarusawaHiroyuki
en-aut-sei=Marusawa
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=MatsushitaYosuke
en-aut-sei=Matsushita
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=KatagiriToyomasa
en-aut-sei=Katagiri
en-aut-mei=Toyomasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=ShibataTakahiro
en-aut-sei=Shibata
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=UchidaKoji
en-aut-sei=Uchida
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=NiuSheng-Yong
en-aut-sei=Niu
en-aut-mei=Sheng-Yong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

en-aut-name=LangNhi B.
en-aut-sei=Lang
en-aut-mei=Nhi B.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=

en-aut-name=NakamuraTomohiro
en-aut-sei=Nakamura
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
ORCID=

en-aut-name=ZhangKam Y. J.
en-aut-sei=Zhang
en-aut-mei=Kam Y. J.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=28
ORCID=

en-aut-name=LiptonStuart A.
en-aut-sei=Lipton
en-aut-mei=Stuart A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=29
ORCID=

en-aut-name=UeharaTakashi
en-aut-sei=Uehara
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=30
ORCID=

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

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

affil-num=3
en-affil=Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science
kn-affil=

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

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

affil-num=6
en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN
kn-affil=

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

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

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

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

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

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

affil-num=13
en-affil=Division of Experimental Pathology, Faculty of Medicine, Tottori University
kn-affil=

affil-num=14
en-affil=Division of Experimental Pathology, Faculty of Medicine, Tottori University
kn-affil=

affil-num=15
en-affil=Division of Experimental Pathology, Faculty of Medicine, Tottori University
kn-affil=

affil-num=16
en-affil=Department of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

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

affil-num=18
en-affil=Laboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=19
en-affil=Laboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=20
en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University
kn-affil=

affil-num=21
en-affil=Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University
kn-affil=

affil-num=22
en-affil=Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University
kn-affil=

affil-num=23
en-affil=Graduate School of Bioagricultural Sciences, Nagoya University
kn-affil=

affil-num=24
en-affil=Laboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo
kn-affil=

affil-num=25
en-affil=Broad Institute of MIT and Harvard
kn-affil=

affil-num=26
en-affil=Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute
kn-affil=

affil-num=27
en-affil=Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute
kn-affil=

affil-num=28
en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN
kn-affil=

affil-num=29
en-affil=Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute
kn-affil=

affil-num=30
en-affil=Department of Medicinal Pharmacology, Graduate School 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=11
article-no=
start-page=2971
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230530
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Conventional Cancer Therapies Can Accelerate Malignant Potential of Cancer Cells by Activating Cancer-Associated Fibroblasts in Esophageal Cancer Models
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors.
en-copyright=
kn-copyright=

en-aut-name=KomotoSatoshi
en-aut-sei=Komoto
en-aut-mei=Satoshi
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=KobayashiTeruki
en-aut-sei=Kobayashi
en-aut-mei=Teruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=NarusakaToru
en-aut-sei=Narusaka
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SatoHiroaki
en-aut-sei=Sato
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KatsuraYuki
en-aut-sei=Katsura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=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=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=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=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=
en-keyword=cancer-associated fibroblast
kn-keyword=cancer-associated fibroblast
en-keyword=chemotherapy
kn-keyword=chemotherapy
en-keyword=radiotherapy
kn-keyword=radiotherapy
en-keyword=esophageal cancer
kn-keyword=esophageal cancer
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=3
article-no=
start-page=243
end-page=254
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202306
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Brown Adipose Tissue PPARγ Is Required for the Insulin-Sensitizing Action of Thiazolidinediones
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Brown adipose tissue (BAT) plays a critical role in metabolic homeostasis. BAT dysfunction is associated with the development of obesity through an imbalance between energy expenditure and energy intake. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis. However, the roles of PPARγ and thiazolidinediones (TZDs) in the regulation of BAT metabolism remain unclear. TZDs, which are selective PPARγ activators, improve systemic insulin resistance in animals and humans. In the present study, we generated brown adipocyte-specific PPARγ-deficient mice (BATγKO) to examine the in vivo roles of PPARγ and TZDs in BAT metabolism. In electron microscopic examinations, brown adipocyte-specific PPARγ deletion promoted severe whitening of brown fat and morphological alteration of mitochondria. Brown adipocyte-specific PPARγ deletion also reduced mRNA expression of BAT-selective genes. Although there was no difference in energy expenditure between control and BATγKO mice in calorimetry, norepinephrine-induced thermogenesis was impaired in BATγKO mice. Moreover, pioglitazone treatment improved diet-induced insulin resistance in the control mice but not in the BATγKO mice. These findings suggest that BAT PPARγ is necessary for the maintenance of brown adipocyte function and for the insulin-sensitizing action of TZDs.
en-copyright=
kn-copyright=

en-aut-name=ShibataYusuke
en-aut-sei=Shibata
en-aut-mei=Yusuke
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=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 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=
en-keyword=PPARγ
kn-keyword=PPARγ
en-keyword=brown adipose tissue
kn-keyword=brown adipose tissue
en-keyword=thiazolidinediones
kn-keyword=thiazolidinediones
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=21
cd-vols=
no-issue=
article-no=
start-page=52
end-page=61
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=Development of hydroxyapatite-coated nonwovens for efficient isolation of somatic stem cells from adipose tissues
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Adipose-derived stem cells (ASCs) are an attractive cell source for cell therapy. Despite the increasing number of clinical applications, the methodology for ASC isolation is not optimized for every individual. In this study, we developed an effective material to stabilize explant cultures from small-fragment adipose tissues.<br>
Methods: Polypropylene/polyethylene nonwoven sheets were coated with hydroxyapatite (HA) particles. Adipose fragments were then placed on these sheets, and their ability to trap tissue was monitored during explant culture. The yield and properties of the cells were compared to those of cells isolated by conventional collagenase digestion.<br>
Results: Hydroxyapatite-coated nonwovens immediately trapped adipose fragments when placed on the sheets. The adhesion was stable even in culture media, leading to cell migration and proliferation from the tissue along with the nonwoven fibers. A higher fiber density further enhanced cell growth. Although cells on nonwoven explants could not be fully collected with cell dissociation enzymes, the cell yield was significantly higher than that of conventional monolayer culture without impacting stem cell properties.<br>
Conclusions: Hydroxyapatite-coated nonwovens are useful for the effective primary explant culture of connective tissues without enzymatic cell dissociation.


en-copyright=
kn-copyright=

en-aut-name=ChijimatsuRyota
en-aut-sei=Chijimatsu
en-aut-mei=Ryota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakedaTaiga
en-aut-sei=Takeda
en-aut-mei=Taiga
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TsujiShinsaku
en-aut-sei=Tsuji
en-aut-mei=Shinsaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SasakiKohei
en-aut-sei=Sasaki
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KatoKoichi
en-aut-sei=Kato
en-aut-mei=Koichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KojimaRie
en-aut-sei=Kojima
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MichihataNoriko
en-aut-sei=Michihata
en-aut-mei=Noriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TsubakiToshiya
en-aut-sei=Tsubaki
en-aut-mei=Toshiya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MatuiAya
en-aut-sei=Matui
en-aut-mei=Aya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=WatanabeMiharu
en-aut-sei=Watanabe
en-aut-mei=Miharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TanakaSakae
en-aut-sei=Tanaka
en-aut-mei=Sakae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SaitoTaku
en-aut-sei=Saito
en-aut-mei=Taku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Okayama University Hospital, Center for Comprehensive Genomic Medicine
kn-affil=

affil-num=2
en-affil=The University of Tokyo, Bone and Cartilage Regenerative Medicine, Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=CPC Corporation
kn-affil=

affil-num=4
en-affil=Japan Vilene Company, Ltd., Central Research Laboratory
kn-affil=

affil-num=5
en-affil=Japan Vilene Company, Ltd., Central Research Laboratory
kn-affil=

affil-num=6
en-affil=Japan Vilene Company, Ltd., Central Research Laboratory
kn-affil=

affil-num=7
en-affil=Japan Vilene Company, Ltd., Central Research Laboratory
kn-affil=

affil-num=8
en-affil=The University of Tokyo, Sensory and Motor System Medicine, Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=CPC Corporation
kn-affil=

affil-num=10
en-affil=CPC Corporation
kn-affil=

affil-num=11
en-affil=The University of Tokyo, Sensory and Motor System Medicine, Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=The University of Tokyo, Sensory and Motor System Medicine, Graduate School of Medicine
kn-affil=
en-keyword=Adipose stem cells
kn-keyword=Adipose stem cells
en-keyword=Explant culture
kn-keyword=Explant culture
en-keyword=Nonwovens
kn-keyword=Nonwovens
en-keyword=Hydroxyapatite
kn-keyword=Hydroxyapatite
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=20230123
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Enzyme-Cleaved Bone Marrow Transplantation Improves the Engraftment of Bone Marrow Mesenchymal Stem Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Mesenchymal stem cell (MSC) therapy is a promising approach to curing bone diseases and disorders. In treating genetic bone dis-orders, MSC therapy is local or systemic transplantation of isolated and in vitro proliferated MSC rather than bone marrow transplan-tation. Recent evidence showed that bone marrow MSC engraftment to bone regeneration has been controversial in animal and human studies. Here, our modified bone marrow transplantation (BMT) method solved this problem. Like routine BMT, our modified method involves three steps: (i) isolation of bone marrow cells from the donor, (ii) whole-body lethal irradiation to the recipient, and (iii) injection of isolated bone marrow cells into irradiated recipient mice via the tail vein. The significant modification is imported at the bone marrow isolation step. While the bone marrow cells are flushed out from the bone marrow with the medium in routine BMT, we applied the enzymes' (collagenase type 4 and dispase) integrated medium to wash out the bone marrow cells. Then, cells were incubated in enzyme integrated solution at 37 degrees C for 10 minutes. This modification designated BMT as collagenase-integrated BMT (c-BMT). Notably, successful engraftment of bone marrow MSC to the new bone formation, such as osteoblasts and chondrocytes, occurs in c-BMT mice, whereas routine BMT mice do not recruit bone marrow MSC. Indeed, flow cytometry data showed that c-BMT includes a higher proportion of LepR(+), CD51(+), or RUNX2(+) non-hematopoietic cells than BMT. These findings suggested that c-BMT is a time-efficient and more reliable technique that ensures the disaggregation and collection of bone marrow stem cells and engraftment of bone marrow MSC to the recipient. Hence, we proposed that c-BMT might be a promising approach to curing genetic bone disorders. (c) 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
en-copyright=
kn-copyright=

en-aut-name=KawaiHotaka
en-aut-sei=Kawai
en-aut-mei=Hotaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=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=TosaIkue
en-aut-sei=Tosa
en-aut-mei=Ikue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

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=6
ORCID=

en-aut-name=SanouSho
en-aut-sei=Sanou
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=FushimiShigeko
en-aut-sei=Fushimi
en-aut-mei=Shigeko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SukegawaShintaro
en-aut-sei=Sukegawa
en-aut-mei=Shintaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=

en-aut-name=TakeshiTakarada
en-aut-sei=Takeshi
en-aut-mei=Takarada
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
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 Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

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

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

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

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

affil-num=12
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=BONE FORMATION
kn-keyword=BONE FORMATION
en-keyword=BONE MARROW MESENCHYMAL STEM CELLS
kn-keyword=BONE MARROW MESENCHYMAL STEM CELLS
en-keyword=BONE MARROW TRANSPLANTATION MODEL
kn-keyword=BONE MARROW TRANSPLANTATION MODEL
en-keyword=OSTEOBLASTS
kn-keyword=OSTEOBLASTS
en-keyword=SYSTEM BIOLOGY-BONE INTERACTOR
kn-keyword=SYSTEM BIOLOGY-BONE INTERACTOR
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=1
article-no=
start-page=65
end-page=70
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=Effect of a Cyclooxygenase-2 Inhibitor in Combination with (−)-Epigallocatechin Gallate or Polyphenon E on Cisplatin-Induced Lung Tumorigenesis in A/J Mice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We investigated the effects of celecoxib combined with (−)-epigallocatechin-3-gallate (EGCG) or polyphenon E in a cisplatin-induced lung tumorigenesis model. Four-week-old female A/J mice were divided into seven groups: (i) Control, (ii) 150 mg/kg celecoxib (150Cel), (iii) 1,500 mg/kg celecoxib (1500Cel), (iv) EGCG+150 mg/kg celecoxib (EGCG+150Cel), (v) EGCG+1,500 mg/kg celecoxib (EGCG+1500Cel), (vi) polyphenon E+150 mg/kg celecoxib (PolyE+150Cel), and (vii) polyphenon E+1,500 mg/kg celecoxib (PolyE+1500Cel). All mice were administered cisplatin (1.62 mg/kg of body weight, i.p.) 1×/week for 10 weeks and sacrificed at week 30; the numbers of tumors on the lung surface were then determined. The tumor incidence and multiplicity (no. of tumors/mouse, mean±SD) were respectively 95% and 2.15±1.50 in Control, 95% and 2.10±1.29 in 150Cel, 86% and 1.67±1.20 in 1500Cel, 71% and 1.38±1.24 in EGCG+150Cel, 67% and 1.29±1.38 in EGCG+1500Cel, 80% and 1.95±1.36 in PolyE+150Cel, and 65% and 1.05±0.10 in PolyE+1500Cel. The combination of high-dose celecoxib with EGCG or polyphenon E significantly reduced multiplicity in cisplatin-induced lung tumors.
en-copyright=
kn-copyright=

en-aut-name=SatoKen
en-aut-sei=Sato
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=KatayamaHideki
en-aut-sei=Katayama
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=OkadaToshiaki
en-aut-sei=Okada
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HisamotoAkiko
en-aut-sei=Hisamoto
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MimotoJunko
en-aut-sei=Mimoto
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=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=UeokaHiroshi
en-aut-sei=Ueoka
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TanimotoMitsune
en-aut-sei=Tanimoto
en-aut-mei=Mitsune
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MaedaYoshionobu
en-aut-sei=Maeda
en-aut-mei=Yoshionobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
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=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 General Internal Medicine 4, Kawasaki Medical School
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 Medicine, Yamaguchi-Ube Medical Center
kn-affil=

affil-num=5
en-affil=Department of Medicine, Yamaguchi-Ube Medical Center
kn-affil=

affil-num=6
en-affil=Department of Hematology, Oncology, and Respiratory Medicine, 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 General Internal Medicine 4, Kawasaki Medical School
kn-affil=

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

affil-num=11
en-affil=Department of Medicine, Yamaguchi-Ube Medical Center
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=

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, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=celecoxib
kn-keyword=celecoxib
en-keyword=cisplatin
kn-keyword=cisplatin
en-keyword=EGCG
kn-keyword=EGCG
en-keyword=lung tumor
kn-keyword=lung tumor
en-keyword=polyphenon E
kn-keyword=polyphenon E
END

start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=2
article-no=
start-page=353
end-page=359
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230206
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Do not overwork: cellular communication network factor 3 for life in cartilage
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cellular communication network factor (CCN) 3, which is one of the founding members of the CCN family, displays diverse functions. However, this protein generally represses the proliferation of a variety of cells. Along with skeletal development, CCN3 is produced in cartilaginous anlagen, growth plate cartilage and epiphysial cartilage. Interestingly, CCN3 is drastically induced in the growth plates of mice lacking CCN2, which promotes endochondral ossification. Notably, chondrocytes in these mutant mice with elevated CCN3 production also suffer from impaired glycolysis and energy metabolism, suggesting a critical role of CCN3 in cartilage metabolism. Recently, CCN3 was found to be strongly induced by impaired glycolysis, and in our study, we located an enhancer that mediated CCN3 regulation via starvation. Subsequent investigations specified regulatory factor binding to the X-box 1 (RFX1) as a transcription factor mediating this CCN3 regulation. Impaired glycolysis is a serious problem, resulting in an energy shortage in cartilage without vasculature. CCN3 produced under such starved conditions restricts energy consumption by repressing cell proliferation, leading chondrocytes to quiescence and survival. This CCN3 regulatory system is indicated to play an important role in articular cartilage maintenance, as well as in skeletal development. Furthermore, CCN3 continues to regulate cartilage metabolism even during the aging process, probably utilizing this regulatory system. Altogether, CCN3 seems to prevent "overwork" by chondrocytes to ensure their sustainable life in cartilage by sensing energy metabolism. Similar roles are suspected to exist in relation to systemic metabolism, since CCN3 is found in the bloodstream.
en-copyright=
kn-copyright=

en-aut-name=KubotaSatoshi
en-aut-sei=Kubota
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawakiHarumi
en-aut-sei=Kawaki
en-aut-mei=Harumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=PerbalBernard
en-aut-sei=Perbal
en-aut-mei=Bernard
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakigawaMasaharu
en-aut-sei=Takigawa
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KawataKazumi
en-aut-sei=Kawata
en-aut-mei=Kazumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=NishidaTakashi
en-aut-sei=Nishida
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 Biochemistry and Molecular Dentistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Oral Biochemistry, Asahi University School of Dentistry
kn-affil=

affil-num=3
en-affil=International CCN Society
kn-affil=

affil-num=4
en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences/Dental School
kn-affil=

affil-num=5
en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

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

affil-num=7
en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=CCN family
kn-keyword=CCN family
en-keyword=CCN3
kn-keyword=CCN3
en-keyword=cartilage
kn-keyword=cartilage
en-keyword=chondrocytes
kn-keyword=chondrocytes
en-keyword=energy metabolism
kn-keyword=energy metabolism
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=2
article-no=
start-page=468
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230112
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Simple Summary Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate the possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo lung metastatic model. We found that highly metastatic TNBC cells have limited iron metabolism and can be more effectively targeted by iron chelators. Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate a possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo. Lung metastasis was further significantly reduced, leading to the hypothesis that iron metabolism between metastatic and non-metastatic cells may be different. An analysis of existing database demonstrated that the expression of iron-uptake genes was significantly suppressed in TNBC cells that metastasized to lymph nodes or lungs compared to those in primary tumors. A highly metastatic clone of the murine 4T1 TNBC cells (4T1-HM) did not proliferate well under iron-rich or iron-depleted conditions by iron chelators compared to a low-metastatic clone (4T1-LM). Bulk RNA-seq analysis of RNA from 4T1-HM and 4T1-LM cells suggested that the PI3K-AKT pathway might be responsible for this difference. Indeed, DFX suppressed the proliferation via the AKT-mTOR pathway in 4T1-HM and the human MDA-MB-231 cells, a human mesenchymal-like TNBC cell line. DFX also suppressed the growth of 4T1-HM tumors in comparison to 4T1-LM tumors, and reduced lung metastases after surgical resection of primary 4T1 tumors. These results indicated, for the first time, that highly metastatic TNBC cells have limited iron metabolism, and they can be more effectively targeted by iron chelators.
en-copyright=
kn-copyright=

en-aut-name=WangYuze
en-aut-sei=Wang
en-aut-mei=Yuze
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=ChenYuehua
en-aut-sei=Chen
en-aut-mei=Yuehua
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

en-aut-name=LiChunning
en-aut-sei=Li
en-aut-mei=Chunning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
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=7
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=8
ORCID=

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

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

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

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

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

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

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

affil-num=8
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=triple-negative breast cancer
kn-keyword=triple-negative breast cancer
en-keyword=iron metabolism
kn-keyword=iron metabolism
en-keyword=iron chelator
kn-keyword=iron chelator
en-keyword=phosphoinositide-3-kinase-protein kinase
kn-keyword=phosphoinositide-3-kinase-protein kinase
en-keyword=heterogeneity
kn-keyword=heterogeneity
en-keyword=metastasis
kn-keyword=metastasis
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=24
article-no=
start-page=3993
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=SCAND1 Reverses Epithelial-to-Mesenchymal Transition (EMT) and Suppresses Prostate Cancer Growth and Migration
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epithelial-mesenchymal transition (EMT) is a reversible cellular program that transiently places epithelial (E) cells into pseudo-mesenchymal (M) cell states. The malignant progression and resistance of many carcinomas depend on EMT activation, partial EMT, or hybrid E/M status in neoplastic cells. EMT is activated by tumor microenvironmental TGF beta signal and EMT-inducing transcription factors, such as ZEB1/2, in tumor cells. However, reverse EMT factors are less studied. We demonstrate that prostate epithelial transcription factor SCAND1 can reverse the cancer cell mesenchymal and hybrid E/M phenotypes to a more epithelial, less invasive status and inhibit their proliferation and migration in DU-145 prostate cancer cells. SCAND1 is a SCAN domain-containing protein and hetero-oligomerizes with SCAN-zinc finger transcription factors, such as MZF1, for accessing DNA and the transcriptional co-repression of target genes. We found that SCAND1 expression correlated with maintaining epithelial features, whereas the loss of SCAND1 was associated with mesenchymal phenotypes of tumor cells. SCAND1 and MZF1 were mutually inducible and coordinately included in chromatin with hetero-chromatin protein HP1 gamma. The overexpression of SCAND1 reversed hybrid E/M status into an epithelial phenotype with E-cadherin and beta-catenin relocation. Consistently, the co-expression analysis in TCGA PanCancer Atlas revealed that SCAND1 and MZF1 expression was negatively correlated with EMT driver genes, including CTNNB1, ZEB1, ZEB2 and TGFBRs, in prostate adenocarcinoma specimens. In addition, SCAND1 overexpression suppressed tumor cell proliferation by reducing the MAP3K-MEK-ERK signaling pathway. Of note, in a mouse tumor xenograft model, SCAND1 overexpression significantly reduced Ki-67(+) and Vimentin(+) tumor cells and inhibited migration and lymph node metastasis of prostate cancer. Kaplan-Meier analysis showed high expression of SCAND1 and MZF1 to correlate with better prognoses in pancreatic cancer and head and neck cancers, although with poorer prognosis in kidney cancer. Overall, these data suggest that SCAND1 induces expression and coordinated heterochromatin-binding of MZF1 to reverse the hybrid E/M status into an epithelial phenotype and, inhibits tumor cell proliferation, migration, and metastasis, potentially by repressing the gene expression of EMT drivers and the MAP3K-MEK-ERK signaling pathway.
en-copyright=
kn-copyright=

en-aut-name=EguchiTakanori
en-aut-sei=Eguchi
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=CsizmadiaEva
en-aut-sei=Csizmadia
en-aut-mei=Eva
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=ShetaMona
en-aut-sei=Sheta
en-aut-mei=Mona
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YoshidaKunihiro
en-aut-sei=Yoshida
en-aut-mei=Kunihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=PrinceThomas L.
en-aut-sei=Prince
en-aut-mei=Thomas L.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=WegielBarbara
en-aut-sei=Wegiel
en-aut-mei=Barbara
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=CalderwoodStuart K.
en-aut-sei=Calderwood
en-aut-mei=Stuart K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

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

affil-num=2
en-affil=Division of Surgical Sciences, Department of Surgery, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School
kn-affil=

affil-num=3
en-affil=Department of Oral Pathology and Medicine, 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=

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

affil-num=6
en-affil=Ranok Therapeutics
kn-affil=

affil-num=7
en-affil=Division of Surgical Sciences, Department of Surgery, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School
kn-affil=

affil-num=8
en-affil=Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School
kn-affil=
en-keyword=epithelial-to-mesenchymal transition (EMT)
kn-keyword=epithelial-to-mesenchymal transition (EMT)
en-keyword=hybrid E/M
kn-keyword=hybrid E/M
en-keyword=partial EMT
kn-keyword=partial EMT
en-keyword=SCAND1
kn-keyword=SCAND1
en-keyword=MZF1
kn-keyword=MZF1
en-keyword=SCAN zinc finger transcription factors
kn-keyword=SCAN zinc finger transcription factors
en-keyword=gene expression
kn-keyword=gene expression
en-keyword=cancer prognosis
kn-keyword=cancer prognosis
en-keyword=collective migration
kn-keyword=collective migration
en-keyword=metastasis
kn-keyword=metastasis
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=6
article-no=
start-page=723
end-page=730
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=Serum miR-377 Can Be Used as a Diagnostic Marker for Acute Coronary Syndrome and Can Regulate Proinflammatory Factors and Endothelial Injury Markers
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The diagnostic value of microRNA-377 (miR-377) in patients with acute coronary syndrome (ACS) and explored miR-377’s potential mechanisms. We performed an qRT-PCR to assess serum miR-377 levels in ACS patients and coronary artery ligation rat models. The diagnostic value of miR-377 was evaluated by determining the ROC curve. An ELISA assay was conducted to detect the model rat endothelial damage markers von Willebrand factor (vWF) and heart-type fatty acid binding protein (H-FABP), and proinflammatory cytokines TNF-α, IL-6, and IL-1β. The serum miR-377 level was elevated in the ACS patients and significantly increased in the ACS rats. MiR-377 has a high diagnostic value in ACS patients, with a 0.844 ROC, 76.47% specificity, and 87.10% sensitivity. MiR-377 was positively correlated with the expressions of vWF, H-FABP, cTnI, TNF-α, IL-6, and IL-1β. In ACS rats, reducing the expression of miR-377 significantly inhibited the increases in vWF, H-FABP, TNF-α, IL-6, and IL-1β. An elevated miR-377 level can be used as a diagnostic marker in patients with ACS. A reduction of miR-377 may alleviate ACS by improving myocardial damage such as endothelial injury and the inflammatory response.
en-copyright=
kn-copyright=

en-aut-name=ZhangQuan
en-aut-sei=Zhang
en-aut-mei=Quan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YangLixia
en-aut-sei=Yang
en-aut-mei=Lixia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WanGuozhen
en-aut-sei=Wan
en-aut-mei=Guozhen
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZhangXiaoqiang
en-aut-sei=Zhang
en-aut-mei=Xiaoqiang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WangYing
en-aut-sei=Wang
en-aut-mei=Ying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ZhaoGuannan
en-aut-sei=Zhao
en-aut-mei=Guannan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College
kn-affil=

affil-num=2
en-affil=Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College
kn-affil=

affil-num=4
en-affil=Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College
kn-affil=

affil-num=5
en-affil=Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College
kn-affil=

affil-num=6
en-affil=Department of Dermatological, Pingliang Traditional Chinese Medicine Hospital
kn-affil=
en-keyword=microRNA-377
kn-keyword=microRNA-377
en-keyword=acute coronary syndrome
kn-keyword=acute coronary syndrome
en-keyword=diagnosis
kn-keyword=diagnosis
en-keyword=endothelial injury
kn-keyword=endothelial injury
en-keyword=inflammatory
kn-keyword=inflammatory
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=6
article-no=
start-page=625
end-page=633
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=Knockdown of LncRNA SBF2-AS1 Inhibited Gastric Cancer Tumorigenesis via the Wnt/LRP5 Signaling Pathway
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=This investigation aimed to uncover the impact of a long noncoding RNA, SET-binding factor 2 antisense RNA1 (SBF2-AS1) on the malignant progression of gastric cancer (GC) and to further explore its underlying mechanism. SBF2-AS1 expression was quantified by qRT-PCR in GC cell lines and GC tissues. In vitro loss-of-function studies of SBF2-AS1, accompanied by flow cytometry, CCK-8, and cell invasion tests, were applied to elucidate the impact of SBF2-AS1 on the tumor progression of GC cells. Finally, Western blotting and a luciferase assay were used to detect WNT/LRP5 signaling pathway activation. SBF2-AS1 was aberrantly expressed in GC cell lines (p<0.05) and GC tissues (p<0.05). Cell invasive and proliferative capabilities were inhibited via SBF2-AS1 knockdown, resulting in apoptosis of NCI-N87 and MKN74 cells. Additionally, online database analysis uncovered a positive correlation between SBF2-AS1 and the Wnt/LRP5 signaling pathway (p<0.05). SBF2-AS1 knockdown blocked the Wnt/LRP5 signaling pathway, whereas the effects of SBF2-AS1 knockdown on the malignant genotype of MKN74 as well as NCI-N87 cells were partially restored by triggering the Wnt/ LRP5 signaling pathway. High expression of SBF2-AS1 was found in GC, the malignant progression of which was repressed via SBF2-AS1 knockdown by inhibiting the Wnt/LRP5 signaling pathway.
en-copyright=
kn-copyright=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=LiuZhisheng
kn-aut-sei=Liu
kn-aut-mei=Zhisheng
aut-affil-num=1
ORCID=

en-aut-name=LiQingmei
en-aut-sei=Li
en-aut-mei=Qingmei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WangYe
en-aut-sei=Wang
en-aut-mei=Ye
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=GeYunjie
en-aut-sei=Ge
en-aut-mei=Yunjie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of General surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine)
kn-affil=

affil-num=2
en-affil=Department of General surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine)
kn-affil=

affil-num=3
en-affil=Department of General surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine)
kn-affil=

affil-num=4
en-affil=Department of Healthcare Internal Medicine, Affiliated Qingdao Municipal Hospital of Qingdao University
kn-affil=
en-keyword=gastric cancer (GC)
kn-keyword=gastric cancer (GC)
en-keyword=SET-binding factor 2 antisense RNA1 (SBF2-AS1)
kn-keyword=SET-binding factor 2 antisense RNA1 (SBF2-AS1)
en-keyword=invasion
kn-keyword=invasion
en-keyword=proliferation
kn-keyword=proliferation
en-keyword=signaling
kn-keyword=signaling
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=23
cd-vols=
no-issue=18
article-no=
start-page=10301
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=Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease that is not related to KSHV/HHV8 infection. Currently, iMCD is classified into iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) and iMCD-NOS (not otherwise specified). The former has been established as a relatively homogeneous disease unit that has been recently re-defined, while the latter is considered to be a heterogeneous disease that could be further divided into several subtypes. In 1980, Mori et al. proposed the concept of idiopathic plasmacytic lymphadenopathy (IPL), a disease presenting with polyclonal hypergammaglobulinemia and a sheet-like proliferation of mature plasma cells in the lymph nodes. Some researchers consider IPL to be a part of iMCD-NOS, although it has not been clearly defined to date. This is the first paper to analyze iMCD-NOS clinicopathologically, to examine whether IPL forms a uniform disease unit in iMCD. Histologically, the IPL group showed prominent plasmacytosis and the hyperplasia of germinal centers, while the non-IPL group showed prominent vascularity. Clinically, the IPL group showed significant thrombocytosis and elevated serum IgG levels compared to the non-IPL group (p = 0.007, p < 0.001, respectively). Pleural effusion and ascites were less common in the IPL group (p < 0.001). The IPL group was more likely to have an indolent clinical course and a good response to the anti-IL-6 receptor antibody, while the non-IPL counterpart frequently required more aggressive medical interventions. Thus, the IPL group is a clinicopathologically uniform entity that forms an independent subtype of iMCD.
en-copyright=
kn-copyright=

en-aut-name=NishikoriAsami
en-aut-sei=Nishikori
en-aut-mei=Asami
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=NishimuraYoshito
en-aut-sei=Nishimura
en-aut-mei=Yoshito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

en-aut-name=MaehamaKanna
en-aut-sei=Maehama
en-aut-mei=Kanna
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OhsawaKumiko
en-aut-sei=Ohsawa
en-aut-mei=Kumiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=NakamuraNaoya
en-aut-sei=Nakamura
en-aut-mei=Naoya
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 Molecular Hematopathology, Okayama University Graduate School of Health 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 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 Molecular Hematopathology, Okayama University Graduate School 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 Pathology, Tokai University School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=
en-keyword=Castleman disease
kn-keyword=Castleman disease
en-keyword=idiopathic multicentric Castleman disease
kn-keyword=idiopathic multicentric Castleman disease
en-keyword=idiopathic plasmacytic lymphadenopathy
kn-keyword=idiopathic plasmacytic lymphadenopathy
en-keyword=plasma cell morphology
kn-keyword=plasma cell morphology
END

start-ver=1.4
cd-journal=joma
no-vol=6
cd-vols=
no-issue=10
article-no=
start-page=1
end-page=8
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202285
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effects of Wnt-β-Catenin Signaling and Sclerostin on the Phenotypes of Rat Pheochromocytoma PC12 Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pheochromocytomas and paragangliomas (PPGLs) are classified into 3 major categories with distinct driver genes: pseudohypoxia, kinase signaling, and Wnt-altered subtypes. PPGLs in the Wnt-altered subtype are sporadic and tend to be aggressive with metastasis, where somatic gene fusions affecting mastermind-like 3 (MAML3) and somatic mutations in cold shock domain containing E1 (CSDE1) cause overactivation of Wnt-β-catenin signaling. However, the relation between Wnt-β-catenin signaling and the biological behavior of PPGLs remains unexplored. In rat pheochromocytoma PC12 cells, Wnt3a treatment enhanced cell proliferation and suppressed mRNA expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis, and dopamine secretion. We identified the expression of sclerostin in PC12 cells, which is known as an osteocyte-derived negative regulator for Wnt signaling-driven bone formation. Inhibition of endogenous Wnt pathway by XAV939 or sclerostin resulted in attenuated cell proliferation and increased TH expression. Furthermore, Wnt3a pretreatment suppressed bone morphogenetic protein (BMP)-induced Smad1/5/9 phosphorylation whereas BMPs enhanced sclerostin expression in PC12 cells. In the Wnt-altered subtype, the increased Wnt-β-catenin pathway may contribute the aggressive clinical behavior with reduced catecholamine production. Furthermore, upregulated expression of sclerostin by BMPs may explain the osteolytic metastatic lesions observed in metastatic PPGLs.
en-copyright=
kn-copyright=

en-aut-name=MorimotoEisaku
en-aut-sei=Morimoto
en-aut-mei=Eisaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=InagakiKenichi
en-aut-sei=Inagaki
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KomatsubaraMotoshi
en-aut-sei=Komatsubara
en-aut-mei=Motoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TerasakaTomohiro
en-aut-sei=Terasaka
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ItohYoshihiko
en-aut-sei=Itoh
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujisawaSatoshi
en-aut-sei=Fujisawa
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SasakiErika
en-aut-sei=Sasaki
en-aut-mei=Erika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NishiyamaYuki
en-aut-sei=Nishiyama
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HaraTakayuki
en-aut-sei=Hara
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
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=
en-keyword=Wnt-β-catenin signaling
kn-keyword=Wnt-β-catenin signaling
en-keyword=sclerostin
kn-keyword=sclerostin
en-keyword=catecholamine
kn-keyword=catecholamine
en-keyword=PPGL
kn-keyword=PPGL
en-keyword=PC12
kn-keyword=PC12
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=4
article-no=
start-page=473
end-page=477
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=Genomic Profiling of a Case of Glioneuronal Tumor with Neuropil-like Islands
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Glioneuronal tumor with neuropil-like islands (GNTNI) is a very rare subtype of glioneuronal tumor. We present a case of a 62-year-old man with GNTNI. Two adjacent lesions in the left parietal lobe were removed by left parietal craniotomy. The histological findings were glial cell proliferation and scattered rosettes consisting of synaptophysin-positive and NeuN-positive cells, leading to the diagnosis of GNTNI. Target sequencing revealed a genetic alteration similar to glioblastoma, IDH-wild type, which suggested adjuvant therapies. There are few previous reports on the treatment of this disease, and the patient should be followed carefully.
en-copyright=
kn-copyright=

en-aut-name=TsuboiNobushige
en-aut-sei=Tsuboi
en-aut-mei=Nobushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=ShimazuYosuke
en-aut-sei=Shimazu
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=EdakiHisanori
en-aut-sei=Edaki
en-aut-mei=Hisanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UnedaAtsuhito
en-aut-sei=Uneda
en-aut-mei=Atsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=FujiiKentaro
en-aut-sei=Fujii
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=9
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=10
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=11
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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

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

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

affil-num=9
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=glioneuronal tumor with neuropil-like islands
kn-keyword=glioneuronal tumor with neuropil-like islands
en-keyword= genomic profiling
kn-keyword= genomic profiling
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=4
article-no=
start-page=415
end-page=421
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=5-Nitro-2-(3-phenylpropylamino) Benzoic Acid Inhibits the Proliferation and Migration of Lens Epithelial Cells by Blocking CaMKII Signaling
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Posterior capsule opacification (PCO) is a post-surgery complication of cataract surgery, and lens epithelial cells (LECs) are involved in its development. A suppressive effect on LECs is exerted by the non specific chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) exerts. Herein, the growth and migration inhibitory effects of NPPB on LECs were assessed, and the mechanism underlying the effects were investigated by focusing on Ca2+/CaMKII signaling. LECs were treated with different concentrations of NPPB, and the changes in cell viability, cell-cycle distribution, anchorage-dependent growth, migration, Ca2+ level, and CaMKII expression were evaluated. NPPB inhibited LECs’ proliferation and induced G1 cell-cycle arrest in the cells. Regarding LECs’ mobility, NPPB suppressed the cells’ anchorage-dependent growth ability and inhibited their migration. Changes in cell phenotypes were associated with an increased intracellular Ca2+ level and down-regulation of CaMKII. Together these results confirmed the inhibitory effect of NPPB on the proliferation and migration of LECs, and the effect was shown to be associated with the induced level of Ca2+ and the inhibition of CaMKII signaling transduction.
en-copyright=
kn-copyright=

en-aut-name=KangHaijun
en-aut-sei=Kang
en-aut-mei=Haijun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HuangDongmei
en-aut-sei=Huang
en-aut-mei=Dongmei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KangGangjin
en-aut-sei=Kang
en-aut-mei=Gangjin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YangXu
en-aut-sei=Yang
en-aut-mei=Xu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=LiHeng
en-aut-sei=Li
en-aut-mei=Heng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=LiuSiyuan
en-aut-sei=Liu
en-aut-mei=Siyuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=GouWenjun
en-aut-sei=Gou
en-aut-mei=Wenjun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LiuLinglin
en-aut-sei=Liu
en-aut-mei=Linglin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=QiuYuyan
en-aut-sei=Qiu
en-aut-mei=Yuyan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Ophthalmology, Suining Central Hospital
kn-affil=

affil-num=2
en-affil=Department of Cardiovascular, Suining Central Hospital
kn-affil=

affil-num=3
en-affil=Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University
kn-affil=

affil-num=4
en-affil=Department of Ophthalmology, Suining Central Hospital
kn-affil=

affil-num=5
en-affil=Department of Ophthalmology, Suining Central Hospital
kn-affil=

affil-num=6
en-affil=Department of Ophthalmology, Suining Central Hospital
kn-affil=

affil-num=7
en-affil=Department of Ophthalmology, Suining Central Hospital
kn-affil=

affil-num=8
en-affil=Department of Ophthalmology, Suining Central Hospital
kn-affil=

affil-num=9
en-affil=Department of Ophthalmology, Suining Central Hospital
kn-affil=
en-keyword=5-nitro-2-(3-phenylpropylamino) benzoic acid
kn-keyword=5-nitro-2-(3-phenylpropylamino) benzoic acid
en-keyword=CaMKII
kn-keyword=CaMKII
en-keyword=lens epithelial cell
kn-keyword=lens epithelial cell
en-keyword=migration
kn-keyword=migration
en-keyword=proliferation
kn-keyword=proliferation
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=9
cd-vols=
no-issue=
article-no=
start-page=904215
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220630
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, on AAA formation and rupture. <br>
Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE(-)(/)(-) mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). <br>
Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-alpha in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPAR alpha significantly attenuated the anti-oxidative effect of pemafibrate. <br>
Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.
en-copyright=
kn-copyright=

en-aut-name=AmiokaNaofumi
en-aut-sei=Amioka
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=KondoMegumi
en-aut-sei=Kondo
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
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=6
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=7
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=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=

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

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

affil-num=3
en-affil=Department of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

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

affil-num=5
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

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

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

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

affil-num=9
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=pemafibrate
kn-keyword=pemafibrate
en-keyword=angiotensin II
kn-keyword=angiotensin II
en-keyword=abdominal aortic aneurysm
kn-keyword=abdominal aortic aneurysm
en-keyword=oxidative stress
kn-keyword=oxidative stress
en-keyword=catalase
kn-keyword=catalase
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=3
article-no=
start-page=323
end-page=328
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=A Case of a Solitary Cortical Tuber with No Other Manifestations of Tuberous Sclerosis Complex Mimicking Focal Cortical Dysplasia Type II with Calcification
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case.
en-copyright=
kn-copyright=

en-aut-name=HosomotoKakeru
en-aut-sei=Hosomoto
en-aut-mei=Kakeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SasakiTatsuya
en-aut-sei=Sasaki
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KawaiKoji
en-aut-sei=Kawai
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OkazakiYosuke
en-aut-sei=Okazaki
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HyodoYuki
en-aut-sei=Hyodo
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShibataTakashi
en-aut-sei=Shibata
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SasadaSusumu
en-aut-sei=Sasada
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YasuharaTakao
en-aut-sei=Yasuhara
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KobayashiKatsuhiro
en-aut-sei=Kobayashi
en-aut-mei=Katsuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
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=11
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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

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

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

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

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

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

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

affil-num=11
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cortical tuber
kn-keyword=cortical tuber
en-keyword=epilepsy
kn-keyword=epilepsy
en-keyword=focal cortical dysplasia
kn-keyword=focal cortical dysplasia
en-keyword=transmantle sign
kn-keyword=transmantle sign
en-keyword=tuberous sclerosis complex
kn-keyword=tuberous sclerosis complex
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=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=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=149
cd-vols=
no-issue=8
article-no=
start-page=dev199916
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211109
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Toll signalling promotes blastema cell proliferation during cricket leg regeneration via insect macrophages
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hemimetabolous insects, such as the two-spotted cricket Gryllus bimaculatus, can recover lost tissues, in contrast to the limited regenerative abilities of human tissues. Following cricket leg amputation, the wound surface is covered by the wound epidermis, and plasmatocytes, which are insect macrophages, accumulate in the wound region. Here, we studied the function of Toll-related molecules identified by comparative RNA sequencing during leg regeneration. Of the 11 Toll genes in the Gryllus genome, expression of Toll2-1, Toll2-2 and Toll2-5 was upregulated during regeneration. RNA interference (RNAi) of Toll, Toll2-1, Toll2-2, Toll2-3 or Toll2-4 produced regeneration defects in more than 50% of crickets. RNAi of Toll2-2 led to a decrease in the ratio of S- and M-phase cells, reduced expression of JAK/STAT signalling genes, and reduced accumulation of plasmatocytes in the blastema. Depletion of plasmatocytes in crickets using clodronate also produced regeneration defects, as well as fewer proliferating cells in the regenerating legs. Plasmatocyte depletion also downregulated the expression of Toll and JAK/STAT signalling genes in the regenerating legs. These results suggest that Spz-Toll-related signalling in plasmatocytes promotes leg regeneration through blastema cell proliferation by regulating the Upd-JAK/STAT signalling pathway.
en-copyright=
kn-copyright=

en-aut-name=BandoTetsuya
en-aut-sei=Bando
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OkumuraMisa
en-aut-sei=Okumura
en-aut-mei=Misa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=BandoYuki
en-aut-sei=Bando
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HagiwaraMarou
en-aut-sei=Hagiwara
en-aut-mei=Marou
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HamadaYoshimasa
en-aut-sei=Hamada
en-aut-mei=Yoshimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IshimaruYoshiyasu
en-aut-sei=Ishimaru
en-aut-mei=Yoshiyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MitoTaro
en-aut-sei=Mito
en-aut-mei=Taro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KawaguchiEri
en-aut-sei=Kawaguchi
en-aut-mei=Eri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=InoueTakeshi
en-aut-sei=Inoue
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=AgataKiyokazu
en-aut-sei=Agata
en-aut-mei=Kiyokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NojiSumihare
en-aut-sei=Noji
en-aut-mei=Sumihare
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=

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

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

affil-num=3
en-affil=Faculty of Medicine, Okayama University Medical School
kn-affil=

affil-num=4
en-affil=Faculty of Medicine, Okayama University Medical School
kn-affil=

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

affil-num=6
en-affil=Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University
kn-affil=

affil-num=7
en-affil=Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University
kn-affil=

affil-num=8
en-affil=Division of Biological Science, Graduate School of Science, Kyoto University
kn-affil=

affil-num=9
en-affil=Division of Biological Science, Graduate School of Science, Kyoto University
kn-affil=

affil-num=10
en-affil=Division of Biological Science, Graduate School of Science, Kyoto University
kn-affil=

affil-num=11
en-affil=Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University
kn-affil=

affil-num=12
en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Regeneration
kn-keyword=Regeneration
en-keyword=Toll-related signalling
kn-keyword=Toll-related signalling
en-keyword=JAK/STAT signalling
kn-keyword=JAK/STAT signalling
en-keyword=Macrophages
kn-keyword=Macrophages
en-keyword=Blastema
kn-keyword=Blastema
en-keyword=Gryllus bimaculatus
kn-keyword=Gryllus bimaculatus
END

start-ver=1.4
cd-journal=joma
no-vol=44
cd-vols=
no-issue=4
article-no=
start-page=1539
end-page=1551
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220405
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Laminin 511-E8 Fragment Offers Superior Adhesion Properties for Gastric Cancer Cells Compared with Full-Length Laminin 511
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Simple Summary Numerous studies over the past few decades have revealed that the interactions of gastric cancer cells with laminins through integrins play important roles in tumor cell proliferation, infiltration, and metastasis. However, the association between gastric cancer cells and the laminin E8 fragment, which is the smallest integrin-binding component, has not been investigated. In this study, we revealed that the laminin 511-E8 fragment had a greater impact on the adhesion, morphology, and proliferation of gastric cancer cells than full-length laminin 511. Thus, the laminin 511-E8 fragment is considered to be suitable for investigating the interaction between gastric cancer cells and extracellular matrices in tumor invasion and metastasis. Further, the involvement of Cdc42 in the laminin 511-E8 fragment-induced enhanced adhesion of gastric cancer cells was suggested. Background: The interaction between cancer cells and laminin (Ln) is a key event in tumor invasion and metastasis. Previously, we determined the effect of full-length Ln511 on gastric cancer cells. However, the interactions between the Ln511-E8 fragment, a truncated protein of Ln511, and gastric cancer cells have not been investigated. Methods: We investigated the adhesion properties of gastric cancer cells to full-length Ln511 and Ln511-E8 fragments. Results: The proliferation of four gastric cancer cell lines (SH-10-TC, MKN74, SC-6-JCK, and MKN45) was highest on the Ln511-E8 fragment. Further, a larger cytoplasm was observed in SH-10-TC and MKN74 cells cultured on full-length Ln511 or Ln511-E8 fragments. The percentage of adhesive cells was highest on the Ln511-E8 fragment in all four cell lines. Moreover, adhesion of the gastric cancer cells to Ln511-E8 fragment-coated plates was reduced by the Cdc42 GTPase inhibitor in a dose-dependent manner, suggesting the involvement of Cdc42 in the Ln511-E8 fragment-induced enhanced adhesion of gastric cancer cells. Conclusions: The Ln511-E8 fragment had a greater impact on the adhesion, morphology, and proliferation of gastric cancer cells than full-length laminin. Thus, the Ln511-E8 fragment is suitable for investigating the interaction between gastric cancer cells and extracellular matrices in tumor invasion and metastasis.
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=ShirahaHidenori
en-aut-sei=Shiraha
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KobashiMayu
en-aut-sei=Kobashi
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HoriguchiShigeru
en-aut-sei=Horiguchi
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=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 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=

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 Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cancer progression
kn-keyword=cancer progression
en-keyword=extracellular matrix
kn-keyword=extracellular matrix
en-keyword=gastric cancer cells
kn-keyword=gastric cancer cells
en-keyword=laminin 511-E8 fragment
kn-keyword=laminin 511-E8 fragment
en-keyword=laminin isoforms
kn-keyword=laminin isoforms
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=2711
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220217
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cells (CSCs) are suggested to be responsible for drug resistance and aggressive phenotypes of tumors. Mechanisms of CSC induction are still under investigation. Our lab has established a novel method to generate CSCs from iPSCs under a cancerous microenvironment mimicked by the conditioned medium (CM) of cancer-derived cells. Here, we analyzed the transcriptome of CSCs, which were converted from iPSCs with CM from pancreatic ductal adenocarcinoma cells. The differentially expressed genes were identified and used to explore pathway enrichment. From the comparison of the CSCs with iPSCs, genes with elevated expression were related to the ErbB2/3 signaling pathway. Inhibition of either ErbB2 with lapatinib as a tyrosine kinase inhibitor or ErbB3 with TX1-85-1 or siRNAs arrested cell proliferation, inhibited the in vitro tumorigenicity, and lead to loss of stemness in the converting cells. The self-renewal and tube formation abilities of cells were also abolished while CD24 and Oct3/4 levels were reduced, and the MAPK pathway was overactivated. This study shows a potential involvement of the ErbB2/ErbB3 pathway in CSC generation and could lead to new insight into the mechanism of tumorigenesis and the way of cancer prevention.
en-copyright=
kn-copyright=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

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

affil-num=2
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=1
article-no=
start-page=523
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220104
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Ataxia-telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.
en-copyright=
kn-copyright=

en-aut-name=UenoSayaka
en-aut-sei=Ueno
en-aut-mei=Sayaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SudoTamotsu
en-aut-sei=Sudo
en-aut-mei=Tamotsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HirasawaAkira
en-aut-sei=Hirasawa
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

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

affil-num=2
en-affil=Section of Translational Research, Hyogo Cancer Center
kn-affil=

affil-num=3
en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=hereditary tumors
kn-keyword=hereditary tumors
en-keyword=ATM
kn-keyword=ATM
en-keyword=DNA damage
kn-keyword=DNA damage
en-keyword=redox homeostasis
kn-keyword=redox homeostasis
en-keyword=tumor profiling
kn-keyword=tumor profiling
en-keyword=precision therapy
kn-keyword=precision therapy
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=1
article-no=
start-page=63
end-page=70
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202202
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Chidamide and Decitabine in Combination with a HAG Priming Regimen for Acute Myeloid Leukemia with TP53 Mutation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We analyzed the treatment effects of chidamide and decitabine in combination with a HAG (homoharringtonine, cytarabine, G-CSF) priming regimen (CDHAG) in acute myeloid leukemia (AML) patients with TP53 mutation. Seven TP53 mutated AML patients were treated with CDHAG. The treatment effects were assessed using hemogram detection and bone marrow aspirate. The possible side effects were evaluated based on both hematological and non-hematological toxicity. Four of the seven patients were classified as having achieved complete remission after CDHAG treatment; one patient was considered to have achieved partial remission, and the remaining two patients were considered in non-remission. The overall response rate (ORR) to CDHAG was 71.4%. Regarding the side effects, the hematological toxicity level of the seven patients ranged from level III to level IV, and infections that occurred at lung, blood, and skin were recorded. Nausea, vomiting, liver injury, and kidney injury were also detected. However, all side effects were attenuated by proper management. The CDHAG regimen clearly improved the ORR (71.4%) of TP53-mutated AML patients, with no severe side effects.
en-copyright=
kn-copyright=

en-aut-name=ZhangBei
en-aut-sei=Zhang
en-aut-mei=Bei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=PeiZhixin
en-aut-sei=Pei
en-aut-mei=Zhixin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WangHongxia
en-aut-sei=Wang
en-aut-mei=Hongxia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WuHuimin
en-aut-sei=Wu
en-aut-mei=Huimin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WangJunjie
en-aut-sei=Wang
en-aut-mei=Junjie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=BaiJunjun
en-aut-sei=Bai
en-aut-mei=Junjun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SongQinglin
en-aut-sei=Song
en-aut-mei=Qinglin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Hematology, Jiaozuo People’s Hospital
kn-affil=

affil-num=2
en-affil=Department of Hematology, Jiaozuo People’s Hospital
kn-affil=

affil-num=3
en-affil=Department of Hematology, Jiaozuo People’s Hospital
kn-affil=

affil-num=4
en-affil=Department of Hematology, Jiaozuo People’s Hospital
kn-affil=

affil-num=5
en-affil=Department of Hematology, Jiaozuo People’s Hospital
kn-affil=

affil-num=6
en-affil=Department of Hematology, Jiaozuo People’s Hospital
kn-affil=

affil-num=7
en-affil=Department of Hematology, Jiaozuo People’s Hospital
kn-affil=
en-keyword=acute myeloid leukemia
kn-keyword=acute myeloid leukemia
en-keyword=chidamide
kn-keyword=chidamide
en-keyword=decitabine
kn-keyword=decitabine
en-keyword=HAG
kn-keyword=HAG
en-keyword=TP53 mutation
kn-keyword=TP53 mutation
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=1
article-no=
start-page=25
end-page=32
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202202
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Development and Evaluation of a Short-time Imaging Method for the Clinical Study of the Apparent Diffusion Coefficient Subtraction Method
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The apparent diffusion coefficient subtraction method (ASM) was developed as a new restricted diffusionweighted imaging technique for magnetic resonance imaging (MRI). The usefulness of the ASM has been established by in vitro basic research using a bio-phantom, and clinical research on the application of the ASM for the human body is needed. Herein, we developed a short-time sequence for ASM imaging of the heads of healthy volunteers (n=2), and we investigated the similarity between the obtained ASM images and diffusion kurtosis (DK) images to determine the utility of the ASM for clinical uses. This study appears to be the first to report ASM images of the human head. We observed that the short-time sequence for the ASM imaging of the head can be scanned in approx. 3 min at 1.5T MRI. The noise reduction effect of median filter processing was confirmed on the ASM images scanned by this sequence. The obtained ASM images showed a weak correlation with the DK images, indicating that the ASM images are restricted diffusion-weighted images. The new shorttime imaging sequence could thus be used in clinical studies applying the ASM.
en-copyright=
kn-copyright=

en-aut-name=SugimotoKohei
en-aut-sei=Sugimoto
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaMasahiro
en-aut-sei=Kuroda
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YoshimuraYuuki
en-aut-sei=Yoshimura
en-aut-mei=Yuuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HamadaKentaro
en-aut-sei=Hamada
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KhasawnehAbdullah
en-aut-sei=Khasawneh
en-aut-mei=Abdullah
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=BarhamMajd
en-aut-sei=Barham
en-aut-mei=Majd
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TekikiNouha
en-aut-sei=Tekiki
en-aut-mei=Nouha
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KonishiKohei
en-aut-sei=Konishi
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IshizakaHinata
en-aut-sei=Ishizaka
en-aut-mei=Hinata
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ShimizuYudai
en-aut-sei=Shimizu
en-aut-mei=Yudai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NakamitsuYuki
en-aut-sei=Nakamitsu
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=Al-HammadWlla E. 
en-aut-sei=Al-Hammad
en-aut-mei=Wlla E. 
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KamizakiRyo
en-aut-sei=Kamizaki
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KanazawaSusumu
en-aut-sei=Kanazawa
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=AsaumiJunichi
en-aut-sei=Asaumi
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

affil-num=1
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

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

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

affil-num=7
en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

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

affil-num=9
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

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

affil-num=11
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

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

affil-num=13
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

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

affil-num=15
en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=apparent diffusion coefficient
kn-keyword=apparent diffusion coefficient
en-keyword=apparent diffusion coefficient subtraction method
kn-keyword=apparent diffusion coefficient subtraction method
en-keyword=diffusion kurtosis imaging
kn-keyword=diffusion kurtosis imaging
en-keyword=restricted diffusion
kn-keyword=restricted diffusion
en-keyword=short-time imaging
kn-keyword=short-time imaging
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=11
article-no=
start-page=e0254289
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211124
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Aberrant activation of the Ras/Raf/ERK (extracellular-signal-regulated kinase)-MAPK (mitogen-activated protein kinase) pathway is involved in the progression of cancer, including urothelial carcinoma; but the negative regulation remains unclear. In the present study, we investigated pathological expression of Spred2 (Sprouty-related EVH1 domain-containing protein 2), a negative regulator of the Ras/Raf/ERK-MAPK pathway, and the relation to ERK activation and Ki67 index in various categories of 275 urothelial tumors obtained from clinical patients. In situ hybridization demonstrated that Spred2 mRNA was highly expressed in high-grade non-invasive papillary urothelial carcinoma (HGPUC), and the expression was decreased in carcinoma in situ (CIS) and infiltrating urothelial carcinoma (IUC). Immunohistochemically, membranous Spred2 expression, important to interact with Ras/Raf, was preferentially found in HGPUC. Interestingly, membranous Spred2 expression was decreased in CIS and IUC relative to HGPUC, while ERK activation and the expression of the cell proliferation marker Ki67 index were increased. HGPUC with membranous Spred2 expression correlated significantly with lower levels of ERK activation and Ki67 index as compared to those with negative Spred2 expression. Thus, our pathological findings suggest that Spred2 counters cancer progression in non-invasive papillary carcinoma possibly through inhibiting the Ras/Raf/ERK-MAPK pathway, but this regulatory mechanism is lost in cancers with high malignancy. Spred2 appears to be a key regulator in the progression of non-invasive bladder carcinoma.
en-copyright=
kn-copyright=

en-aut-name=OdaShinsuke
en-aut-sei=Oda
en-aut-mei=Shinsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=LiChunning
en-aut-sei=Li
en-aut-mei=Chunning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ItoToshihiro
en-aut-sei=Ito
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamaguchiTakahiro
en-aut-sei=Yamaguchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
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=7
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 Immunology, Nara Medical 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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=347
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The efficacy of PI3K gamma and EGFR inhibitors on the suppression of the characteristics of cancer stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cells (CSCs) are capable of continuous proliferation, self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. We have established a model of CSCs that was originally developed from mouse induced pluripotent stem cells (miPSCs) by proposing miPSCs to the conditioned medium (CM) of cancer derived cells, which is a mimic of carcinoma microenvironment. Further research found that not only PI3K-Akt but also EGFR signaling pathway was activated during converting miPSCs into CSCs. In this study, we tried to observe both of PI3K gamma inhibitor Eganelisib and EGFR inhibitor Gefitinib antitumor effects on the models of CSCs derived from miPSCs (miPS-CSC) in vitro and in vivo. As the results, targeting these two pathways exhibited significant inhibition of cell proliferation, self-renewal, migration and invasion abilities in vitro. Both Eganelisib and Gefitinib showed antitumor effects in vivo while Eganelisib displayed more significant therapeutic efficacy and less side effects than Gefitinib on all miPS-CSC models. Thus, these data suggest that the inhibitiors of PI3K and EGFR, especially PI3K gamma, might be a promising therapeutic strategy against CSCs defeating cancer in the near future.
en-copyright=
kn-copyright=

en-aut-name=XuYanning
en-aut-sei=Xu
en-aut-mei=Yanning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=DuJuan
en-aut-sei=Du
en-aut-mei=Juan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=LiuBingbing
en-aut-sei=Liu
en-aut-mei=Bingbing
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=WangQing
en-aut-sei=Wang
en-aut-mei=Qing
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=LiHanbo
en-aut-sei=Li
en-aut-mei=Hanbo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LiuYixin
en-aut-sei=Liu
en-aut-mei=Yixin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FuXiaoying
en-aut-sei=Fu
en-aut-mei=Xiaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ZhuZhengmao
en-aut-sei=Zhu
en-aut-mei=Zhengmao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ChenLing
en-aut-sei=Chen
en-aut-mei=Ling
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Etiology, Shanxi Provincial Cancer Hospital
kn-affil=

affil-num=4
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation
kn-affil=

affil-num=5
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Genetics and Cell Biology, College of Life Sciences, Nankai University
kn-affil=

affil-num=7
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation
kn-affil=

affil-num=8
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation
kn-affil=

affil-num=9
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Genetics and Cell Biology, College of Life Sciences, Nankai University
kn-affil=

affil-num=11
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation
kn-affil=

affil-num=12
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=9
article-no=
start-page=4528
end-page=4540
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210930
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Repurposing of posaconazole as a hedgehog/SMO signaling inhibitor for embryonal rhabdomyosarcoma therapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Posaconazole (POS) is a novel antifungal agent, which has been repurposed as an anti-tumor drug for its potential inhibition of Hedgehog signaling pathway. Hedgehog pathway is reported to be abnormally activated in embryonal rhabdomyosarcoma (ERMS), this study aimed to reveal whether POS could inhibit Hedgehog signaling pathway in ERMS. Following POS treatment, XTT viability assay was used to determine the cell proliferation of ERMS cell lines. Protein changes related to Hedgehog signaling, cell cycle and autophagy were detected by Western blot. The cell cycle distribution was analyzed by flow cytometry. Moreover, a subcutaneous tumor mouse model of ERMS was established to assess the anti-tumor effect of POS. POS was found to inhibit tumor progression by inducing G0/G1 arrest and autophagy of RD, RMS-YM, and KYM-1 cells dose-dependently. Western blot demonstrated that POS downregulated the expressions of SMO, Gli1, c-Myc, CDK4, and CDK6, while upregulated the expressions of autophagy-related proteins. Immunofluorescence microscopy revealed a significant increase of LC3B puncta in POS-treated ERMS cells. Furthermore, POS treatment led to a significant inhibition of tumor growth in mice bearing ERMS. Our findings could provide a theoretical basis and have important clinical implications in developing POS as a promising agent against ERMS by targeting Hedgehog pathway.
en-copyright=
kn-copyright=

en-aut-name=SunJingkai
en-aut-sei=Sun
en-aut-mei=Jingkai
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=LiChaoming
en-aut-sei=Li
en-aut-mei=Chaoming
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=XueRuizhi
en-aut-sei=Xue
en-aut-mei=Ruizhi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=HuHao
en-aut-sei=Hu
en-aut-mei=Hao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=

en-aut-name=LiNa
en-aut-sei=Li
en-aut-mei=Na
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=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=

en-aut-name=XuAbai
en-aut-sei=Xu
en-aut-mei=Abai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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=Laboratory of Medical Systems Biology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University
kn-affil=

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

affil-num=9
en-affil=Laboratory of Medical Systems Biology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University
kn-affil=

affil-num=10
en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University
kn-affil=

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

affil-num=12
en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University
kn-affil=

affil-num=13
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Posaconazole
kn-keyword=Posaconazole
en-keyword=cell cycle
kn-keyword=cell cycle
en-keyword=autophagy
kn-keyword=autophagy
en-keyword=rhabdomyosarcoma
kn-keyword=rhabdomyosarcoma
en-keyword=hedgehog proteins
kn-keyword=hedgehog proteins
END

start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=6
article-no=
start-page=677
end-page=684
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=EG-VEGF Induces Invasion of a Human Trophoblast Cell Line via PROKR2
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Extravillous trophoblast (EVT) invasion is important for embryo implantation, placental development, and successful remodeling of the uterine spiral artery. Endocrine gland derived-vascular endothelial growth factor (EG-VEGF) and matrix metalloproteinases (MMPs) are implicated in EVT invasion; however, the high con-centrations found in pregnancy pathologies have not been investigated in non-tumor trophoblasts. The roles of EG-VEGF, prokineticin receptors (PROKR1/2), MMP-2, and MMP-9 in EVT invasion during spiral artery remodeling were evaluated using human EVT from HTR-8/SVneo cell lines. The expression of MMP-2, MMP-9, and mitogen-activated protein kinase (MAPK), and Akt pathways in HTR-8/SVneo cells treated with recom-binant EG-VEGF alongside anti-PROKR1 and/or anti-PROKR2 antibodies was evaluated using quantitative reverse transcription-PCR and western blotting. Wound-healing and cell invasion assays were performed to assess the migration and invasion of these treated cells. Interestingly, 20 nM EG-VEGF activated ERK1/2 sig-naling and upregulated MMP-2 and MMP-9. This effect was suppressed by anti-PROKR2 antibody via ERK1/2 downregulation. Anti-PROKR2 antibody inhibited the migration and invasion of EG-VEGF-stimulated HTR-8/SVneo cells. Elevated concentrations of EG-VEGF enhance EVT invasion in a human trophoblast cell line by upregulating MMP-2 and MMP-9 via PROKR2. These new insights into the regulation of epithelial cell invasion may help in developing therapeutic interventions for placental-related diseases during pregnancy.
en-copyright=
kn-copyright=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=TaniKazumasa
kn-aut-sei=Tani
kn-aut-mei=Kazumasa
aut-affil-num=1
ORCID=

en-aut-name=MitsuiTakashi
en-aut-sei=Mitsui
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MishimaSakurako
en-aut-sei=Mishima
en-aut-mei=Sakurako
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=MakiJota
en-aut-sei=Maki
en-aut-mei=Jota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
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=7
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=8
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=9
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=

affil-num=9
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=endocrine gland-derived vascular endothelial growth factor
kn-keyword=endocrine gland-derived vascular endothelial growth factor
en-keyword=prokineticin
kn-keyword=prokineticin
en-keyword=extravillous trophoblast
kn-keyword=extravillous trophoblast
en-keyword=matrix metalloproteinase
kn-keyword=matrix metalloproteinase
en-keyword=obstetric diseases
kn-keyword=obstetric diseases
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=12
cd-vols=
no-issue=
article-no=
start-page=713358
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210830
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Harnessing Treg Homeostasis to Optimize Posttransplant Immunity: Current Concepts and Future Perspectives
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are functionally distinct subsets of mature T cells with broad suppressive activity and have been shown to play an important role in the establishment of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs exhibit an activated phenotype from the stage of emigration from the thymus and maintain continuous proliferation in the periphery. The distinctive feature in homeostasis enables Tregs to respond sensitively to small environmental changes and exert necessary and sufficient immune suppression; however, on the other hand, it also predisposes Tregs to be susceptible to apoptosis in the inflammatory condition post-transplant. Our studies have attempted to define the intrinsic and extrinsic factors affecting Treg homeostasis from the acute to chronic phases after allogeneic HSCT. We have found that altered cytokine environment in the prolonged post-HSCT lymphopenia or peri-transplant use of immune checkpoint inhibitors could hamper Treg reconstitution, leading to refractory graft-versus-host disease. Using murine models and clinical trials, we have also demonstrated that proper intervention with low-dose interleukin-2 or post-transplant cyclophosphamide could restore Treg homeostasis and further amplify the suppressive function after HSCT. The purpose of this review is to reconsider the distinctive characteristics of post-transplant Treg homeostasis and discuss how to harness Treg homeostasis to optimize posttransplant immunity for developing a safe and efficient therapeutic strategy.</p>
en-copyright=
kn-copyright=

en-aut-name=IkegawaShuntaro
en-aut-sei=Ikegawa
en-aut-mei=Shuntaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

affil-num=1
en-affil=Department of Hematology and Oncology, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Hematology and Oncology, Okayama University
kn-affil=
en-keyword=regulatory T cell
kn-keyword=regulatory T cell
en-keyword=graft-versus-host disease
kn-keyword=graft-versus-host disease
en-keyword=interleukin 2
kn-keyword=interleukin 2
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=post-transplant cyclophosphamide
kn-keyword=post-transplant cyclophosphamide
END

start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=17
article-no=
start-page=9204
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210825
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effect of Angiotensin II on Chondrocyte Degeneration and Protection via Differential Usage of Angiotensin II Receptors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The renin-angiotensin system (RAS) controls not only systemic functions, such as blood pressure, but also local tissue-specific events. Previous studies have shown that angiotensin II receptor type 1 (AT(1)R) and type 2 (AT(2)R), two RAS components, are expressed in chondrocytes. However, the angiotensin II (ANG II) effects exerted through these receptors on chondrocyte metabolism are not fully understood. In this study, we investigated the effects of ANG II and AT(1)R blockade on chondrocyte proliferation and differentiation. Firstly, we observed that ANG II significantly suppressed cell proliferation and glycosaminoglycan content in rat chondrocytic RCS cells. Additionally, ANG II decreased CCN2, which is an anabolic factor for chondrocytes, via increased MMP9. In Agtr1a-deficient RCS cells generated by the CRISPR-Cas9 system, Ccn2 and Aggrecan (Acan) expression increased. Losartan, an AT(1)R antagonist, blocked the ANG II-induced decrease in CCN2 production and Acan expression in RCS cells. These findings suggest that AT(1)R blockade reduces ANG II-induced chondrocyte degeneration. Interestingly, AT(1)R-positive cells, which were localized on the surface of the articular cartilage of 7-month-old mice expanded throughout the articular cartilage with aging. These findings suggest that ANG II regulates age-related cartilage degeneration through the ANG II-AT(1)R axis.
en-copyright=
kn-copyright=

en-aut-name=NishidaTakashi
en-aut-sei=Nishida
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AkashiSho
en-aut-sei=Akashi
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakigawaMasaharu
en-aut-sei=Takigawa
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

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

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

affil-num=3
en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Biochemistry and Molecular Dentistry, 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
en-keyword=angiotensin II
kn-keyword=angiotensin II
en-keyword=cellular communication network factor 2 (CCN2)
kn-keyword=cellular communication network factor 2 (CCN2)
en-keyword=renin-angiotensin system (RAS)
kn-keyword=renin-angiotensin system (RAS)
en-keyword=losartan
kn-keyword=losartan
en-keyword=angiotensin II type I receptor (AT(1)R)
kn-keyword=angiotensin II type I receptor (AT(1)R)
END

start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=4
article-no=
start-page=403
end-page=413
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202108
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Surgical Treatment of Epiretinal Membrane
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epiretinal membrane (ERM) is a common retinal disease characterized by cellular proliferation and metaplasia that lead to the formation of a pathological fibrocellular membrane immediately superjacent to the inner retinal surface. The vast majority of ERMs are considered idiopathic. However, ERM formation can result from various primary intraocular diseases, including retinal breaks and detachment, retinal vascular diseases, and vitreoretinal inflammatory conditions. Although ERMs are generally asymptomatic or cause mild metamorphopsia and/or a modest decrease in visual acuity, some can cause severe macular distortion and macular edema, resulting in significantly impaired function. Surgical removal of ERM is the only treatment, and improvements in vitrectomy systems have enabled less invasive treatment. However, there are currently no standardized criteria for ERM surgery, and the indications for surgery are determined from the patient’s subjective symptoms. Another problem with ERM surgery is that not all patients show satisfactory postoperative recovery of visual function. Thus, further research is needed to determine the criteria for ERM surgery and methods to improve the postoperative prognosis.
en-copyright=
kn-copyright=

en-aut-name=MatobaRyo
en-aut-sei=Matoba
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MorizaneYuki
en-aut-sei=Morizane
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

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

affil-num=2
en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=epiretinal membrane
kn-keyword=epiretinal membrane
en-keyword=vitrectomy
kn-keyword=vitrectomy
en-keyword=optical coherence tomography
kn-keyword=optical coherence tomography
en-keyword=internal limiting membrane
kn-keyword=internal limiting membrane
en-keyword=lamellar macular hole
kn-keyword=lamellar macular hole
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=2021814
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PolyI:C suppresses TGF-β1-induced Akt phosphorylation and reduces the motility of A549 lung carcinoma cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Backgrounds: Epithelial mesenchymal transition (EMT) is a critical process involved in the invasion and metastasis of cancer, including lung cancer (LC). Transforming growth factor (TGF)-β is one of factors capable of inducing EMT. Polyinosinic-polycytidylic acid (polyI:C), a synthetic agonist for toll-like receptor (TLR) 3, can enhance immune responses and has been used as an adjuvant for cancer vaccines; however, it remains unclear whether it influences other process, such as EMT. In the present study, we examined the effects of polyI:C on TGF-β-treated A549 human LC cells.<br>
Methods and results: By in vitro cell proliferation assay, polyI:C showed no effect on the growth of A549 cells treated with TGF-β1 at the concentration range up to 10 μg/ml; however, it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-β1-induced Ak strain transforming (Akt) phosphorylation and increased phosphatase and tensin homologue (PTEN) expression without affecting the Son of mothers against decapentaplegic (Smad) 3 phosphorylation or the expression level of E-cadherin, N-cadherin or Snail, indicating that polyI:C suppressed cell motility independently of the ‘cadherin switching’. The Akt inhibitor perifosine inhibited TGF-β1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C.<br>
Conclusion: PolyI:C has a novel function to suppress the motility of LC cells undergoing EMT by targeting the phosphatidylinositol 3-kinase /Akt pathway partly via PTEN and may prevent or reduce the metastasis of LC cells.
en-copyright=
kn-copyright=

en-aut-name=YamaguchiTakahiro
en-aut-sei=Yamaguchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
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=4
ORCID=

en-aut-name=TongGao
en-aut-sei=Tong
en-aut-mei=Gao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Toll-like receptors
kn-keyword=Toll-like receptors
en-keyword=cell migration
kn-keyword=cell migration
en-keyword= metastasis
kn-keyword= metastasis
en-keyword=epithelial mesenchymal transformation
kn-keyword=epithelial mesenchymal transformation
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=14
article-no=
start-page=3491
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210712
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Origin of Stroma Influences the Biological Characteristics of Oral Squamous Cell Carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Simple Summary Normal stromal cells play a significant role in the progression of cancers but are poorly investigated in oral squamous cell carcinoma (OSCC). In this study, we found that stromal cells derived from the gingival and periodontal ligament tissues could inhibit differentiation and promote the proliferation, invasion, and migration of OSCC both in vitro and in vivo. Furthermore, microarray data suggested that genes, such as CDK1, BUB1B, TOP2A, DLGAP5, BUB1, and CCNB2, probably play a role in influencing the different effects of gingival stromal tissue cells (G-SCs) and periodontal ligament stromal cells (P-SCs) on the progression of OSCC. Therefore, both G-SCs and P-SCs could promote the progression of OSCC, which could be a potential regulatory mechanism in the progression of OSCC. Normal stromal cells surrounding the tumor parenchyma, such as the extracellular matrix (ECM), normal fibroblasts, mesenchymal stromal cells, and osteoblasts, play a significant role in the progression of cancers. However, the role of gingival and periodontal ligament tissue-derived stromal cells in OSCC progression is unclear. In this study, the effect of G-SCs and P-SCs on the differentiation, proliferation, invasion, and migration of OSCC cells in vitro was examined by Giemsa staining, Immunofluorescence (IF), (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS), invasion, and migration assays. Furthermore, the effect of G-SCs and P-SCs on the differentiation, proliferation, and bone invasion by OSCC cells in vivo was examined by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Finally, microarray data and bioinformatics analyses identified potential genes that caused the different effects of G-SCs and P-SCs on OSCC progression. The results showed that both G-SCs and P-SCs inhibited the differentiation and promoted the proliferation, invasion, and migration of OSCC in vitro and in vivo. In addition, genes, including CDK1, BUB1B, TOP2A, DLGAP5, BUB1, and CCNB2, are probably involved in causing the different effects of G-SCs and P-SCs on OSCC progression. Therefore, as a potential regulatory mechanism, both G-SCs and P-SCs can promote OSCC progression.
en-copyright=
kn-copyright=

en-aut-name=OmoriHaruka
en-aut-sei=Omori
en-aut-mei=Haruka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShanQiusheng
en-aut-sei=Shan
en-aut-mei=Qiusheng
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=NakanoKeisuke
en-aut-sei=Nakano
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=SukegawaShintaro
en-aut-sei=Sukegawa
en-aut-mei=Shintaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TsujigiwaHidetsugu
en-aut-sei=Tsujigiwa
en-aut-mei=Hidetsugu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=

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

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

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

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

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

affil-num=6
en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=

affil-num=7
en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=

affil-num=8
en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
en-keyword=gingival ligament tissue-derived stromal cells
kn-keyword=gingival ligament tissue-derived stromal cells
en-keyword=periodontal ligament tissue-derived stromal cells
kn-keyword=periodontal ligament tissue-derived stromal cells
en-keyword=oral squamous cell carcinoma
kn-keyword=oral squamous cell carcinoma
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
en-keyword=biological character
kn-keyword=biological character
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=1
article-no=
start-page=12298
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210610
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Circulating microRNAs (miRNAs) in serum extracellular vesicles (EVs) are a promising biomarker in cancer. We aimed to elucidate the serum EVs miRNA biomarkers to identify patients with gallbladder cancer (GBC) and to clarify their potential roles. One hundred nineteen serum EVs from GBC and non-GBC individuals were isolated by pure-EVs-yieldable size-exclusion chromatography, and then were analyzed using a comprehensive miRNAs array and RT-qPCR-based validation. The functional roles of the identified miRNAs were also investigated using GBC cell lines. Serum EVs miR-1246 and miR-451a were significantly upregulated and downregulated, respectively in GBC patients (P=0.005 and P=0.001), in line with their expression levels in cancer tissue according to an in silico analysis. The combination of CEA and CA19-9 with miR-1246 showed the highest diagnostic power (AUC, 0.816; Sensitivity, 72.0%; Specificity, 90.8%), and miR-1246 was an independent prognostic marker of GBC (Hazard ratio, 3.05; P=0.017) according to a Cox proportional hazards model. In vitro, miR-1246 promoted cell proliferation and invasion, while miR-451a inhibited cell proliferation and induced apoptosis with the targeting of MIF, PSMB8 and CDKN2D. Taken together, miR-1246 in serum EVs has potential application as a diagnostic and prognostic marker and miR-451a may be a novel therapeutic target in GBC.
en-copyright=
kn-copyright=

en-aut-name=UetaEijiro
en-aut-sei=Ueta
en-aut-mei=Eijiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TsutsumiKoichiro
en-aut-sei=Tsutsumi
en-aut-mei=Koichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KatoHironari
en-aut-sei=Kato
en-aut-mei=Hironari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MatsushitaHiroshi
en-aut-sei=Matsushita
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShirahaHidenori
en-aut-sei=Shiraha
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujiiMasakuni
en-aut-sei=Fujii
en-aut-mei=Masakuni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MatsumotoKazuyuki
en-aut-sei=Matsumoto
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HoriguchiShigeru
en-aut-sei=Horiguchi
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=

affil-num=2
en-affil=Department of Gastroenterology, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Gastroenterology, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of Gastroenterology, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Gastroenterology, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital
kn-affil=

affil-num=7
en-affil=Department of Gastroenterology, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Gastroenterology, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=3
article-no=
start-page=391
end-page=395
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202106
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Embedding of Epiretinal Proliferation for a Secondary Lamellar Macular Hole 12 Years after Rhegmatogenous Retinal Detachment Repair
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 58-year-old Japanese man underwent vitrectomy for rhegmatogenous retinal detachment (RRD) in 2002. Twelve years later, optical coherence tomography revealed the development of a lamellar macular hole; the visual acuity was 20/200. Two years later, because metamorphopsia and the foveal retina thinning were aggravated, epiretinal proliferation embedding was performed to restore the foveal structure by transplanting glial cells to the foveal cavity. The patient was followed-up for 4 years, and his macular morphology and visual acuity (20/66) improved. No complications occurred. This appears to be the first report of epiretinal proliferation embedding for a lamellar macular hole post-RRD repair.
en-copyright=
kn-copyright=

en-aut-name=FujiwaraMiyuki
en-aut-sei=Fujiwara
en-aut-mei=Miyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KimuraShuhei
en-aut-sei=Kimura
en-aut-mei=Shuhei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=Morizane HosokawaMio
en-aut-sei=Morizane Hosokawa
en-aut-mei=Mio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ShiodeYusuke
en-aut-sei=Shiode
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=DoiShinichiro
en-aut-sei=Doi
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakahashiKosuke
en-aut-sei=Takahashi
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MatobaRyo
en-aut-sei=Matoba
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KanzakiYuki 
en-aut-sei=Kanzaki
en-aut-mei=Yuki 
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MorizaneYuki
en-aut-sei=Morizane
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

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

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

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

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

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

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

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

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

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

start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=1
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210511
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cellular and transcriptomic analyses reveal two-staged chloroplast biogenesis underpinning photosynthesis build-up in the wheat leaf
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background The developmental gradient in monocot leaves has been exploited to uncover leaf developmental gene expression programs and chloroplast biogenesis processes. However, the relationship between the two is barely understood, which limits the value of transcriptome data to understand the process of chloroplast development. Results Taking advantage of the developmental gradient in the bread wheat leaf, we provide a simultaneous quantitative analysis for the development of mesophyll cells and of chloroplasts as a cellular compartment. This allows us to generate the first biologically-informed gene expression map of this leaf, with the entire developmental gradient from meristematic to fully differentiated cells captured. We show that the first phase of plastid development begins with organelle proliferation, which extends well beyond cell proliferation, and continues with the establishment and then the build-up of the plastid genetic machinery. The second phase is marked by the development of photosynthetic chloroplasts which occupy the available cellular space. Using a network reconstruction algorithm, we predict that known chloroplast gene expression regulators are differentially involved across those developmental stages. Conclusions Our analysis generates both the first wheat leaf transcriptional map and one of the most comprehensive descriptions to date of the developmental history of chloroplasts in higher plants. It reveals functionally distinct plastid and chloroplast development stages, identifies processes occurring in each of them, and highlights our very limited knowledge of the earliest drivers of plastid biogenesis, while providing a basis for their future identification.
en-copyright=
kn-copyright=

en-aut-name=LoudyaNaresh
en-aut-sei=Loudya
en-aut-mei=Naresh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MishraPriyanka
en-aut-sei=Mishra
en-aut-mei=Priyanka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=Uehara-YamaguchiYukiko
en-aut-sei=Uehara-Yamaguchi
en-aut-mei=Yukiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=InoueKomaki
en-aut-sei=Inoue
en-aut-mei=Komaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=BogreLaszlo
en-aut-sei=Bogre
en-aut-mei=Laszlo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=Lopez-JuezEnrique
en-aut-sei=Lopez-Juez
en-aut-mei=Enrique
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Biological Sciences, Royal Holloway University of London
kn-affil=

affil-num=2
en-affil=Department of Biological Sciences, Royal Holloway University of London
kn-affil=

affil-num=3
en-affil=RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=4
en-affil=RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=5
en-affil=RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=6
en-affil=Department of Biological Sciences, Royal Holloway University of London
kn-affil=

affil-num=7
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Biological Sciences, Royal Holloway University of London
kn-affil=
en-keyword=Wheat
kn-keyword=Wheat
en-keyword=Plastid
kn-keyword=Plastid
en-keyword=Chloroplast
kn-keyword=Chloroplast
en-keyword=Leaf development
kn-keyword=Leaf development
END

start-ver=1.4
cd-journal=joma
no-vol=79
cd-vols=
no-issue=1
article-no=
start-page=181
end-page=186
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2008
dt-pub=20080101
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Appearance of Multidrug-Resistant Opportunistic Bacteria on the Gingiva During Leukemia Treatment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Dentists generally recognize the importance of periodontal treatment inpatients with leukemia, with the most attention paid to preventing the development of odontogenic infection. For physicians, the worst type of infection is one caused by multidrug-resistant bacteria. Here, we report a patient with an abnormal increase in multidrug-resistant opportunistic bacteria in the gingiva during hematopoietic cell transplantation (HCT). <br>
<br>
Methods: A 53-year-old woman receiving HCT for leukemia had an insufficient blood cell count for invasive periodontal treatment before HCT. Even brushing caused difficulties with hemostasis. Therefore, frequent pocket irrigation and local minocycline administration were performed. <br>
<br>
Results: The multidrug-resistant opportunistic bacterium Stenotrophomonas maltophilia was detected first in phlegm 2 days before HCT, and it was detected in a gingival smear and a blood sample 7 and I I days after HCT, respectively. The patient developed sepsis on day I I and died 14 days after HCT. Frequent irrigation and local antibiotic application were ineffective against S. maltophilia on the gingiva. Inflammatory gingiva without scaling and root planing showed bleeding tendency, and this interfered with the eradication of this bacterium. <br>
<br>
Conclusions: The gingiva in patients undergoing leukemia treatment acts as sites of proliferation and reservoirs for multidrug-resistant opportunistic bacteria. Severe systemic infection by multidrug-resistant bacteria in such patients with leukemia also may involve the gingiva. To prevent abnormal increases in such bacteria on the gingiva, scaling and/or root planing before chemotherapy, which reduces bleeding on brushing during the neutropenic period caused by chemotherapy, may contribute to infection control in such patients, although it was impossible in this case.
en-copyright=
kn-copyright=

en-aut-name=SogaYoshihiko
en-aut-sei=Soga
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SaitoTakashi
en-aut-sei=Saito
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishimuraFusanori
en-aut-sei=Nishimura
en-aut-mei=Fusanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IshimaruFumihiko
en-aut-sei=Ishimaru
en-aut-mei=Fumihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MineshibaJunji
en-aut-sei=Mineshiba
en-aut-mei=Junji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MineshibaFumi
en-aut-sei=Mineshiba
en-aut-mei=Fumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakayaHirokazu
en-aut-sei=Takaya
en-aut-mei=Hirokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SatoHideaki
en-aut-sei=Sato
en-aut-mei=Hideaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KudoChieko
en-aut-sei=Kudo
en-aut-mei=Chieko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KokeguchiSusumu
en-aut-sei=Kokeguchi
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
ORCID=

en-aut-name=TanimotoMitsune
en-aut-sei=Tanimoto
en-aut-mei=Mitsune
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
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=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 Pathophysiology – Periodontal Science, 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 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=

affil-num=10
en-affil=Department of Global Health and Environmental Sciences – Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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=

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

affil-num=13
en-affil=Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=bacteria
kn-keyword=bacteria
en-keyword=drug resistance
kn-keyword=drug resistance
en-keyword=gingiva
kn-keyword=gingiva
en-keyword=leukemia
kn-keyword=leukemia
en-keyword=opportunistic infections
kn-keyword=opportunistic infections
END

start-ver=1.4
cd-journal=joma
no-vol=36
cd-vols=
no-issue=11
article-no=
start-page=2875
end-page=2877
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210513
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Millifolide A, a dimeric ether of degraded sesquiterpene lactones, inhibited the proliferation of human lung cancer cell line A549
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The inhibitory effect of three degraded sesquiterpene lactones, iso-seco-tanapartholide, arteludooicinolide A and millifolide A isolated from Achillea millefolium L., on anti-human lung cancer cells was examined using MTT and reporter gene assays. Millifolide A has significant inhibitory effects on the proliferation of human lung cancer cells probably through inducing cell apoptosis. 
en-copyright=
kn-copyright=

en-aut-name=YuPan-Pan
en-aut-sei=Yu
en-aut-mei=Pan-Pan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YuFeng
en-aut-sei=Yu
en-aut-mei=Feng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LiWen-Zhe
en-aut-sei=Li
en-aut-mei=Wen-Zhe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WangSi-Ming
en-aut-sei=Wang
en-aut-mei=Si-Ming
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WangChuan
en-aut-sei=Wang
en-aut-mei=Chuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=DongMei
en-aut-sei=Dong
en-aut-mei=Mei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NiZhi-Yu
en-aut-sei=Ni
en-aut-mei=Zhi-Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LiYong
en-aut-sei=Li
en-aut-mei=Yong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KiyotaHiromasa
en-aut-sei=Kiyota
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification
kn-affil=

affil-num=2
en-affil=College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification
kn-affil=

affil-num=3
en-affil=College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification
kn-affil=

affil-num=4
en-affil=The Fourth Hospital of Hebei Medical 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=

affil-num=8
en-affil=The Fourth Hospital of Hebei Medical University
kn-affil=

affil-num=9
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=
en-keyword=Achillea millefolium L
kn-keyword=Achillea millefolium L
en-keyword=millifolide A
kn-keyword=millifolide A
en-keyword=human lung cancer cells
kn-keyword=human lung cancer cells
en-keyword=antiproliferation
kn-keyword=antiproliferation
en-keyword=apoptosis 
kn-keyword=apoptosis 
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=2021511
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Comparison of posterior root remnant cells and horn cells of the medial meniscus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose/Aim of the study: Previous studies have noted distinctions between medial meniscus posterior root and horn cells. However, the characteristics of root remnant cells have not been explored in detail. The purpose of this study was to evaluate the gene expression levels, proliferation, and resistance to mechanical stress of remnant and horn cells. Materials and Methods: Medial meniscus tissue samples were obtained from patients who underwent total or uni-compartmental knee arthroplasty. Cellular morphology, sry-type HMG box 9, type II collagen, and chondromodulin-I gene expression levels were analyzed. Collagen synthesis was assessed by immunofluorescence staining. Proliferation analysis after 4 h-cyclic tensile strain was performed. Results: Horn cells displayed triangular morphology, whereas root remnant cells appeared fibroblast-like. sry-type HMG box 9 mRNA expression levels were similar in both cells, but type II collagen and chondromodulin-I mRNA expressions were observed only in horn cells. The ratio of type II collagen-positive cells in horn cells was about 10-fold higher than that in root remnant cells, whereas the ratio of sry-type HMG box 9-positive cells was similar. A significant increase in proliferation was observed in root remnant cells compared to that in horn cells. Further, under cyclic tensile strain, the survival rate was higher in root remnant cells than in horn cells. Conclusions: Medial meniscus root remnant cells showed higher proliferation and resistant properties to cyclic tensile strain than horn cells and showed no chondromodulin-I expression. Preserving the medial meniscus posterior root remnant during pullout repair surgery might maintain mechanical stress-resistant tissue and support healing.
en-copyright=
kn-copyright=

en-aut-name=ZhangXiming
en-aut-sei=Zhang
en-aut-mei=Ximing
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FurumatsuTakayuki
en-aut-sei=Furumatsu
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OkazakiYuki
en-aut-sei=Okazaki
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HiranakaTakaaki
en-aut-sei=Hiranaka
en-aut-mei=Takaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=XueHaowei
en-aut-sei=Xue
en-aut-mei=Haowei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KintakaKeisuke
en-aut-sei=Kintaka
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MiyazawaShinichi
en-aut-sei=Miyazawa
en-aut-mei=Shinichi
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 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=
en-keyword=Medial meniscus
kn-keyword=Medial meniscus
en-keyword=posterior root remnant cells
kn-keyword=posterior root remnant cells
en-keyword=posterior horn cells
kn-keyword=posterior horn cells
en-keyword=collagen synthesis
kn-keyword=collagen synthesis
en-keyword=anti-angiogenic gene
kn-keyword=anti-angiogenic gene
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=e13312
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202153
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Roles of Porphyromonas gulae proteases in bacterial and host cell biology
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Porphyromonas gulae, an animal-derived periodontal pathogen, expresses several virulence factors, including fimbria, lipopolysaccharide (LPS) and proteases. We previously reported that its invasive efficiency was dependent on fimbriae types. In addition, P. gulae LPS increased inflammatory responses via toll-like receptors. The present study was conducted to investigate the involvement of P. gulae proteases in bacterial and host cell biology. Porphyromonas gulae strains showed an ability to agglutinate mouse erythrocytes and also demonstrated co-aggregation with Actinomyces viscosus, while the protease inhibitors antipain, PMSF, TLCK and leupeptin diminished P. gulae proteolytic activity, resulting in inhibition of haemagglutination and co-aggregation with A. viscosus. In addition, specific proteinase inhibitors were found to reduce bacterial cell growth. Porphyromonas gulae inhibited Ca9-22 cell proliferation in a multiplicity of infection- and time-dependent manner. Additionally, P. gulae-induced decreases in cell contact and adhesion-related proteins were accompanied by a marked change in cell morphology from well spread to rounded. In contrast, inhibition of protease activity prevented degradation of proteins, such as E-cadherin, beta-catenin and focal adhesion kinase, and also blocked inhibition of cell proliferation. Together, these results indicate suppression of the amount of human proteins, such as gamma-globulin, fibrinogen and fibronectin, by P. gulae proteases, suggesting that a novel protease complex contributes to bacterial virulence.
en-copyright=
kn-copyright=

en-aut-name=UrmiAlam Saki
en-aut-sei=Urmi
en-aut-mei=Alam Saki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=InabaHiroaki
en-aut-sei=Inaba
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NomuraRyota
en-aut-sei=Nomura
en-aut-mei=Ryota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YoshidaShoko
en-aut-sei=Yoshida
en-aut-mei=Shoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=AsaiFumitoshi
en-aut-sei=Asai
en-aut-mei=Fumitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NakanoKazuhiko
en-aut-sei=Nakano
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=Matsumoto‐NakanoMichiyo
en-aut-sei=Matsumoto‐Nakano
en-aut-mei=Michiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

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

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

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

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

affil-num=5
en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and the Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Pharmacology, School of Veterinary Medicine Azabu University
kn-affil=

affil-num=7
en-affil=Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry
kn-affil=

affil-num=8
en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=coaggregation
kn-keyword=coaggregation
en-keyword=haemagglutination
kn-keyword=haemagglutination
en-keyword=P. gulae
kn-keyword=P. gulae
en-keyword=protease
kn-keyword=protease
en-keyword=protein degradation
kn-keyword=protein degradation
END

start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=2
article-no=
start-page=139
end-page=145
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202104
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Evaluation of the Imaging Process for a Novel Subtraction Method Using Apparent Diffusion Coefficient Values
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Diffusion-weighted imaging may be used to obtain the apparent diffusion coefficient (ADC), which aids the diagnosis of cerebral infarction and tumors. An ADC reflects elements of free diffusion. Diffusion kurtosis imaging (DKI) has attracted attention as a restricted diffusion imaging technique. The ADC subtraction method (ASM) was developed to visualize restricted diffusion with high resolution by using two ADC maps taken with different diffusion times. We conducted the present study to provide a bridge between the reported basic ASM research and clinical research. We developed new imaging software for clinical use and evaluated its performance herein. This software performs the imaging process automatically and continuously at the pixel level, using ImageJ software. The new software uses a macro or a plugin which is compatible with various operating systems via a Java Virtual Machine. We tested the new imaging software’s performance by using a Jurkat cell bio-phantom, and the statistical evaluation of the performance clarified that the ASM values of 99.98% of the pixels in the bio-phantom and physiological saline were calculated accurately (p<0.001). The new software may serve as a useful tool for future clinical applications and restricted diffusion imaging research.
en-copyright=
kn-copyright=

en-aut-name=HamadaKentaro
en-aut-sei=Hamada
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaMasahiro
en-aut-sei=Kuroda
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YoshimuraYuuki 
en-aut-sei=Yoshimura
en-aut-mei=Yuuki 
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KhasawnehAbdullah
en-aut-sei=Khasawneh
en-aut-mei=Abdullah
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=BarhamMajd
en-aut-sei=Barham
en-aut-mei=Majd
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TekikiNouha
en-aut-sei=Tekiki
en-aut-mei=Nouha
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SugiantoIrfan
en-aut-sei=Sugianto
en-aut-mei=Irfan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=BamgboseBabatunde O.
en-aut-sei=Bamgbose
en-aut-mei=Babatunde O.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KonishiKohei
en-aut-sei=Konishi
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SugimotoKohei
en-aut-sei=Sugimoto
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=IshizakaHinata
en-aut-sei=Ishizaka
en-aut-mei=Hinata
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KurozumiAkira
en-aut-sei=Kurozumi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MatsushitaToshi 
en-aut-sei=Matsushita
en-aut-mei=Toshi 
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=OhnoSeiichiro
en-aut-sei=Ohno
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=KanazawaSusumu
en-aut-sei=Kanazawa
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=AsaumiJunichi
en-aut-sei=Asaumi
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=12
en-affil=Central Division of Radiology, Okayama University Hospital
kn-affil=

affil-num=13
en-affil=Central Division of Radiology, Okayama University Hospital
kn-affil=

affil-num=14
en-affil=Central Division of Radiology, Okayama University Hospital
kn-affil=

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

affil-num=16
en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital
kn-affil=
en-keyword=apparent diffusion coefficient
kn-keyword=apparent diffusion coefficient
en-keyword=ADC subtraction method
kn-keyword=ADC subtraction method
en-keyword=restricted diffusion
kn-keyword=restricted diffusion
en-keyword=ImageJ
kn-keyword=ImageJ
en-keyword=plugin
kn-keyword=plugin
END

start-ver=1.4
cd-journal=joma
no-vol=61
cd-vols=
no-issue=1
article-no=
start-page=1
end-page=9
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=2021
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immune reconstitution after T-cell replete HLA haploidentical hematopoietic stem cell transplantation using high-dose post-transplant cyclophosphamide
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=As HLA haploidentical related donors are quickly available, HLA haploidentical hematopoietic stem cell transplantation (haploHSCT) using high-dose post-transplant cyclophosphamide (PTCy) is now widely used. Recent basic and clinical studies revealed the details of immune reconstitution after T-cell replete haploHSCT using PTCy. T cells and NK cells in the graft proliferate abundantly at day 3 post-haploHSCT, and the PTCy eliminates these proliferating cells. After ablation of proliferating mature cells, donor-derived NK cell reconstitution occurs after the second week; however, recovering NK cells remain functionally impaired for at least several months after haploHSCT. PTCy depletes proliferating cells, resulting in the preferential accumulation of Treg and CD4+ T cells, especially the memory stem T cell (T-SCM) phenotype. T-SCM capable of both self-renewal and differentiation into effector T cells may play an important role in the first month of immune reconstitution. Subsequently, de novo T cells progressively recover but their levels remain well below those of donor CD4+ T cells at the first year after haploHSCT. The phenotype of recovering T cells after HSCT is predominantly effector memory, whereas B cells are predominantly phenotypically naive throughout the first year after haploHSCT. B cell recovery depends on de novo generation and they are not detected until week 4 after haploHSCT. At week 5, recovering B cells mostly exhibit an unconventional transitional cell phenotype and the cell subset undergoes maturation. Recent advances in immune reconstitution have improved our understanding of the relationship between haploHSCT with PTCy and the clinical outcome.
en-copyright=
kn-copyright=

en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
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=Immune reconstitution
kn-keyword=Immune reconstitution
en-keyword=haploidentical hematopoietic stem cell transplantation
kn-keyword=haploidentical hematopoietic stem cell transplantation
en-keyword=post-transplant cyclophosphamide
kn-keyword=post-transplant cyclophosphamide
END

start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=8
article-no=
start-page=1824
end-page=1830
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210219
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Potential role of myeloid-derived suppressor cells in transition from reaction to repair phase of bone healing process
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with immunosuppressive functions; these cells play a key role in infection, immunization, chronic inflammation, and cancer. Recent studies have reported that immunosuppression plays an important role in the healing process of tissues and that Treg play an important role in fracture healing. MDSCs suppress active T cell proliferation and reduce the severity of arthritis in mice and humans. Together, these findings suggest that MDSCs play a role in bone biotransformation. In the present study, we examined the role of MDSCs in the bone healing process by creating a bone injury at the tibial epiphysis in mice. MDSCs were identified by CD11b and GR1 immunohistochemistry and their role in new bone formation was observed by detection of Runx2 and osteocalcin expression. Significant numbers of MDSCs were observed in transitional areas from the reactionary to repair stages. Interestingly, MDSCs exhibited Runx2 and osteocalcin expression in the transitional area but not in the reactionary area. And at the same area, cllagene-1 and ALP expression level increased in osteoblast progenitor cells. These data is suggesting that MDSCs emerge to suppress inflammation and support new bone formation. Here, we report, for the first time (to our knowledge), the role of MDSCs in the initiation of bone formation. MDSC appeared at the transition from inflammation to bone making and regulates bone healing by suppressing inflammation.
en-copyright=
kn-copyright=

en-aut-name=KawaiHotaka
en-aut-sei=Kawai
en-aut-mei=Hotaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=TsujigiwaHidetsugu
en-aut-sei=Tsujigiwa
en-aut-mei=Hidetsugu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
ORCID=

en-aut-name=SukegawaShintaro 
en-aut-sei=Sukegawa
en-aut-mei=Shintaro 
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
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 Life Science, Faculty of Science, Okayama University of Science
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 Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Oral Pathology and Medicine, 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=
en-keyword=myeloid-derived suppressor cells (MDSC)
kn-keyword=myeloid-derived suppressor cells (MDSC)
en-keyword=bone healing
kn-keyword=bone healing
en-keyword=transition period
kn-keyword=transition period
en-keyword=new bone formation
kn-keyword=new bone formation
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=81
end-page=91
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202114
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Bipartite regulation of cellular communication network factor 2 and fibroblast growth factor 1 genes by fibroblast growth factor 1 through histone deacetylase 1 and fork head box protein A1
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Fibroblast growth factor 1 (FGF-1) is the first FGF family member, and it induces proliferation of fibroblasts and other types of the cells. However, recent studies are uncovering unexpected functions of this molecule. Our previous study redefined this growth factor as a catabolic molecule produced in cartilage upon metabolic insult. Indeed, FGF-1 was found to repress the gene expression of cellular communication network factor 2 (CCN2), which protects and regenerates cartilage, amplifying its own production through positive feedback regulation. In the present study, we investigated the molecular mechanism of this bipartite CCN2 repression and FGF1 activation by FGF-1 in chondrocytes. Repression of CCN2 and induction of FGF1 in human chondrocytic cells were both partly abolished by valproic acid, an inhibitor of histone deacetylase 1 (HDAC1), indicating the involvement of chromatin remodeling by histone acetylation in this system. In contrast, RNA degradation analysis suggested no contribution of post-transcriptional regulation of the mRNA stability to the effects conferred by FGF-1. Suspecting a regulation by a specific transcription factor, we next sought a candidate in silico from a large dataset. As a result, we found fork head box protein A1 (FOXA1) as the transcription factor that bound to both CCN2 and FGF1 loci. Functional analysis demonstrated that FOXA1 silencing significantly attenuated the CCN2 repression and FGF1 induction caused by FGF1. These findings collectively indicate that the bipartite regulation by FGF-1 is enabled by the combination of chromatin remodeling by HDACs and transcriptional modulation by FOXA1 with unknown transcriptional coactivators of opposite functionalities.
en-copyright=
kn-copyright=

en-aut-name=ElseoudiAbdellatif
en-aut-sei=Elseoudi
en-aut-mei=Abdellatif
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishidaTakashi
en-aut-sei=Nishida
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MizukawaTomomi
en-aut-sei=Mizukawa
en-aut-mei=Tomomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

en-aut-name=KawataKazumi
en-aut-sei=Kawata
en-aut-mei=Kazumi
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=TakigawaMasaharu
en-aut-sei=Takigawa
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=

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

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

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

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

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

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

affil-num=7
en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Biochemistry and Molecular Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=FGF-1
kn-keyword=FGF-1
en-keyword=CCN2
kn-keyword=CCN2
en-keyword=Osteoarthritis
kn-keyword=Osteoarthritis
en-keyword=Chondrocytes
kn-keyword=Chondrocytes
en-keyword=Cartilage 
kn-keyword=Cartilage 
END

start-ver=1.4
cd-journal=joma
no-vol=60
cd-vols=
no-issue=4
article-no=
start-page=124
end-page=129
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=2020
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas, including mantle cell lymphoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) accounts for approximately 1% of all lymphomas in our department. In this article, we describe the differential diagnosis of CLL/SLL from other indolent lymphomas, with special reference to follicular lymphoma, marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, and mantle cell lymphoma, although the latter is considered to be aggressive. CLL/SLL often exhibits proliferation centers, similar to follicular lymphoma. Immunohistological examination can easily distinguish these two lymphomas. The most important characteristic of CLL/SLL is CD5 and CD23 positivity. Mantle cell lymphoma is also CD5-positive and there are some CD23-positive cases. Such cases should be carefully distinguished from CLL/SLL. Some marginal zone lymphomas are also positive for CD5 and such cases are often disseminated. Lymphoplasmacytic lymphoma should also be a differential diagnosis for CLL/SLL. It frequently demonstrates MYD88 L265P, which is a key differential finding. By immunohistological examination, the expression of lymphoid enhancer-binding factor 1 is specific for CLL/SLL and can be a good marker in the differential diagnosis.
en-copyright=
kn-copyright=

en-aut-name=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
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=SatoYasuharu
en-aut-sei=Sato
en-aut-mei=Yasuharu
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
kn-affil=

affil-num=2
en-affil=Department of Pathology, Okayama University Graduate School
kn-affil=

affil-num=3
en-affil=Department of Pathology, Okayama University Graduate School
kn-affil=
en-keyword=chronic lymphocytic leukemia/small lymphocytic lymphoma
kn-keyword=chronic lymphocytic leukemia/small lymphocytic lymphoma
en-keyword=differential diagnosis
kn-keyword=differential diagnosis
en-keyword=indolent lymphoma
kn-keyword=indolent lymphoma
END

start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=3
article-no=
start-page=1053
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210121
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Epstein-Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. EBVMCU is a unifocal mucosal or cutaneous ulcer that often occurs after local trauma in patients with immunosuppression; the patients generally have a good prognosis. It is histologically characterized by proliferating EBV-positive atypical B cells accompanied by ulcers. On the basis of conventional pathologic criteria, EBVMCU may be misdiagnosed as EBV-positive diffuse large B-cell lymphoma or other lymphomas. However, its prognosis differs from that of EBV-associated lymphomas, in that patients with EBVMCU frequently show spontaneous regression or complete remission without chemotherapy. Therefore, EBVMCU is now recognized as a low-grade malignancy or a pseudo-malignant lesion. Avoiding unnecessary chemotherapy by distinguishing EBVMCU from other EBV-associated lymphomas will reduce the burden and unnecessary harm on patients. On the basis of these facts, EBVMCU was first described as a new clinicopathological entity by the World Health Organization in 2017. In this review, we discuss the clinicopathological characteristics of previously reported EBVMCU cases, while focusing on up-to-date clinical, pathological, and genetic aspects.
en-copyright=
kn-copyright=

en-aut-name=IkedaTomoka
en-aut-sei=Ikeda
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=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=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
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=Division of Pathophysiology, Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=3
en-affil=Department of General Medicine, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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=
en-keyword=EBV-positive mucocutaneous ulcer
kn-keyword=EBV-positive mucocutaneous ulcer
en-keyword=clinical features
kn-keyword=clinical features
en-keyword=pathological features
kn-keyword=pathological features
en-keyword=immunosuppression
kn-keyword=immunosuppression
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=2020
dt-pub=20201227
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Spred2欠損は肺上皮細胞の増殖を高め、ブレオマイシン誘発肺線維症を緩和させる
kn-title=Spred2-Deficiency Enhances the Proliferation of Lung Epithelial Cells and Alleviates Pulmonary Fibrosis Induced by Bleomycin
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=KawaraAkina
en-aut-sei=Kawara
en-aut-mei=Akina
kn-aut-name=河原明奈
kn-aut-sei=河原
kn-aut-mei=明奈
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=14
cd-vols=
no-issue=1
article-no=
start-page=100960
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202101
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PRRX1 promotes malignant properties in human osteosarcoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Paired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma.
en-copyright=
kn-copyright=

en-aut-name=JokoRyoji
en-aut-sei=Joko
en-aut-mei=Ryoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YamadaDaisuke
en-aut-sei=Yamada
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakamuraMasahiro
en-aut-sei=Nakamura
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

en-aut-name=TakihiraShota
en-aut-sei=Takihira
en-aut-mei=Shota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakaoTomoka
en-aut-sei=Takao
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=LuMing
en-aut-sei=Lu
en-aut-mei=Ming
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SatoKohei
en-aut-sei=Sato
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ItoTatsuo
en-aut-sei=Ito
en-aut-mei=Tatsuo
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=NakataEiji
en-aut-sei=Nakata
en-aut-mei=Eiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=

en-aut-name=TakaradaTakeshi
en-aut-sei=Takarada
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

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

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

affil-num=3
en-affil=Precision Health, Department of Bioengineering, Graduate School of Engineering, The University of Tokyo
kn-affil=

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

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

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

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

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

affil-num=9
en-affil=Department of Hygiene, Kawasaki Medical School
kn-affil=

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

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

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

affil-num=13
en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=PRRX1
kn-keyword=PRRX1
en-keyword=Osteosarcoma
kn-keyword=Osteosarcoma
en-keyword=Tumor malignancy
kn-keyword=Tumor malignancy
en-keyword=Invasion
kn-keyword=Invasion
en-keyword=Drug resistance
kn-keyword=Drug resistance
en-keyword=Connectivity map analysis
kn-keyword=Connectivity map analysis
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=19959
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201117
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Follistatin expressed in mechanically-damaged salivary glands of male mice induces proliferation of CD49f(+) cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Salivary glands (SGs) are very important for maintaining the physiological functions of the mouth. When SGs regenerate and repair from various damages, including mechanical, radiological, and immune diseases, acinar and granular duct cells originate from intercalated duct cells. However, the recovery is often insufficient because of SGs' limited self-repair function. Furthermore, the precise repair mechanism has been unclear. Here, we focused on CD49f, one of the putative stem cell markers, and characterized CD49f positive cells (CD49f(+) cells) isolated from male murine SGs. CD49f(+) cells possess self-renewal ability and express epithelial and pluripotent markers. Compared to CD49f negative cells, freshly isolated CD49f(+) cells highly expressed inhibin beta A and beta B, which are components of activin that has anti-proliferative effects. Notably, an inhibitor of activin, follistatin was expressed in mechanically-damaged SGs, meanwhile no follistatin was expressed in normal SGs in vivo. Moreover, sub-cultured CD49f(+) cells highly expressed both Follistatin and a series of proliferative genes, expressions of which were decreased by Follistatin siRNA. These findings indicated that the molecular interaction between activin and follistatin may induce CD49f(+) cells proliferation in the regeneration and repair of mouse SGs.
en-copyright=
kn-copyright=

en-aut-name=IkedaA.
en-aut-sei=Ikeda
en-aut-mei=A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YamamotoT.
en-aut-sei=Yamamoto
en-aut-mei=T.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MineshibaJ.
en-aut-sei=Mineshiba
en-aut-mei=J.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakashibaS.
en-aut-sei=Takashiba
en-aut-mei=S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Periodontics and Endodontics, Okayama University Hospital
kn-affil=

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

affil-num=3
en-affil=Hanamizuki Dental Clinic
kn-affil=

affil-num=4
en-affil=Department of Pathophysiology ‑ Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=56
cd-vols=
no-issue=1
article-no=
start-page=119
end-page=126
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201009
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cellular communication network factor 2 (CCN2) is a cysteine-rich secreted matricellular protein that regulates various cellular functions including cell differentiation. CCN2 is highly expressed under several types of mechanical stress, such as stretch, compression, and shear stress, in mesenchymal cells including chondrocytes, osteoblasts, and fibroblasts. In particular, CCN2 not only promotes cell proliferation and differentiation of various cells but also regulates the stability of mRNA of TRPV4, a mechanosensitive ion channel in chondrocytes. Of note, CCN2 behaves like a biomarker to sense suitable mechanical stress, because CCN2 expression is down-regulated when chondrocytes are subjected to excessive mechanical stress. These findings suggest that CCN2 is a mechano-sensing regulator. CCN2 expression is regulated by the activation of various mechano-sensing signaling pathways, e.g., mechanosensitive ion channels, integrin-focal adhesion-actin dynamics, Rho GTPase family members, Hippo-YAP signaling, and G protein-coupled receptors. This review summarizes the characterization of mechanoreceptors involved in CCN2 gene regulation and discusses the role of CCN2 as a mechano-sensing regulator of mesenchymal cell differentiation, with particular focus on chondrocytes.
en-copyright=
kn-copyright=

en-aut-name=NishidaTakashi
en-aut-sei=Nishida
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

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

affil-num=2
en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Mechanoreceptors
kn-keyword=Mechanoreceptors
en-keyword=Cellular communication network factor 2 (CCN2)
kn-keyword=Cellular communication network factor 2 (CCN2)
en-keyword=Mechanical stress
kn-keyword=Mechanical stress
en-keyword=Chondrocytes
kn-keyword=Chondrocytes
END

start-ver=1.4
cd-journal=joma
no-vol=330
cd-vols=
no-issue=
article-no=
start-page=788
end-page=196
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201111
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture t (BNCT)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Boron neutron capture therapy (BNCT) is a tumor selective therapy, the effectiveness of which depends on sufficient 10B delivery to and accumulation in tumors. In this study, we used self-assembling A6K peptide nanotubes as boron carriers and prepared new boron agents by simple mixing of A6K and BSH. BSH has been used to treat malignant glioma patients in clinical trials and its drug safety and availability have been confirmed; however, its contribution to BNCT efficacy is low. A6K nanotube delivery improved two major limitations of BSH, including absence of intracellular transduction and non-specific drug delivery to tumor tissue. Varying the A6K peptide and BSH mixture ratio produced materials with different morphologies—determined by electron microscopy—and intracellular transduction efficiencies. We investigated the A6K/BSH 1:10 mixture ratio and found high intracellular boron uptake with no toxicity. Microscopy observation showed intracellular localization of A6K/BSH in the perinuclear region and endosome in human glioma cells. The intracellular boron concentration using A6K/BSH was almost 10 times higher than that of BSH. The systematic administration of A6K/BSH via mouse tail vein showed tumor specific accumulation in a mouse brain tumor model with immunohistochemistry and pharmacokinetic study. Neutron irradiation of glioma cells treated with A6K/BSH showed the inhibition of cell proliferation in a colony formation assay. Boron delivery using A6K peptide provides a unique and simple strategy for next generation BNCT drugs.
en-copyright=
kn-copyright=

en-aut-name=MichiueHiroyuki
en-aut-sei=Michiue
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=FukunagaAsami
en-aut-sei=Fukunaga
en-aut-mei=Asami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TsuboiNobushige
en-aut-sei=Tsuboi
en-aut-mei=Nobushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=MatsushitaHiroaki
en-aut-sei=Matsushita
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=KasaiTomonari
en-aut-sei=Kasai
en-aut-mei=Tomonari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=

en-aut-name=MatsuiHideki
en-aut-sei=Matsui
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=FuruyaShuichi
en-aut-sei=Furuya
en-aut-mei=Shuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Applied Chemistry, Kindai University
kn-affil=

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

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

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

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

affil-num=7
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=

affil-num=8
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=

affil-num=9
en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University
kn-affil=

affil-num=10
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=

affil-num=11
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=
en-keyword=Malignant brain tumor
kn-keyword=Malignant brain tumor
en-keyword=Boron neutron capture therapy (BNCT)
kn-keyword=Boron neutron capture therapy (BNCT)
en-keyword=Peptide nanotube
kn-keyword=Peptide nanotube
en-keyword=Boron drug
kn-keyword=Boron drug
en-keyword=Drug delivery system (DDS)
kn-keyword=Drug delivery system (DDS)
en-keyword=A6K peptide
kn-keyword=A6K peptide
END

start-ver=1.4
cd-journal=joma
no-vol=56
cd-vols=
no-issue=1
article-no=
start-page=119
end-page=126
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202011
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cellular communication network factor 2 (CCN2) is a cysteine-rich secreted matricellular protein that regulates various cellular functions including cell differentiation. CCN2 is highly expressed under several types of mechanical stress, such as stretch, compression, and shear stress, in mesenchymal cells including chondrocytes, osteoblasts, and fibroblasts. In particular, CCN2 not only promotes cell proliferation and differentiation of various cells but also regulates the stability of mRNA of TRPV4, a mechanosensitive ion channel in chondrocytes. Of note, CCN2 behaves like a biomarker to sense suitable mechanical stress, because CCN2 expression is down-regulated when chondrocytes are subjected to excessive mechanical stress. These findings suggest that CCN2 is a mechano-sensing regulator. CCN2 expression is regulated by the activation of various mechano-sensing signaling pathways, e.g., mechanosensitive ion channels, integrin-focal adhesion-actin dynamics, Rho GTPase family members, Hippo-YAP signaling, and G protein-coupled receptors. This review summarizes the characterization of mechanoreceptors involved in CCN2 gene regulation and discusses the role of CCN2 as a mechano-sensing regulator of mesenchymal cell differentiation, with particular focus on chondrocytes.
en-copyright=
kn-copyright=

en-aut-name=NishidaTakashi
en-aut-sei=Nishida
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

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

affil-num=2
en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Mechanoreceptors
kn-keyword=Mechanoreceptors
en-keyword=Cellular communication network factor 2 (CCN2)
kn-keyword=Cellular communication network factor 2 (CCN2)
en-keyword=Mechanical stress
kn-keyword=Mechanical stress
en-keyword=Chondrocytes
kn-keyword=Chondrocytes
END

start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=20
article-no=
start-page=7714
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201018
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Impact of the Stroma on the Biological Characteristics of the Parenchyma in Oral Squamous Cell Carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Solid tumors consist of the tumor parenchyma and stroma. The standard concept of oncology is that the tumor parenchyma regulates the tumor stroma and promotes tumor progression, and that the tumor parenchyma represents the tumor itself and defines the biological characteristics of the tumor tissue. Thus, the tumor stroma plays a pivotal role in assisting tumor parenchymal growth and invasiveness and is regarded as a supporter of the tumor parenchyma. The tumor parenchyma and stroma interact with each other. However, the influence of the stroma on the parenchyma is not clear. Therefore, in this study, we investigated the effect of the stroma on the parenchyma in oral squamous cell carcinoma (OSCC). We isolated tumor stroma from two types of OSCCs with different invasiveness (endophytic type OSCC (ED-st) and exophytic type OSCC (EX-st)) and examined the effect of the stroma on the parenchyma in terms of proliferation, invasion, and morphology by co-culturing and co-transplanting the OSCC cell line (HSC-2) with the two types of stroma. Both types of stroma were partially positive for alpha-smooth muscle actin. The tumor stroma increased the proliferation and invasion of tumor cells and altered the morphology of tumor cells in vitro and in vivo. ED-st exerted a greater effect on the tumor parenchyma in proliferation and invasion than EX-st. Morphological analysis showed that ED-st changed the morphology of HSC-2 cells to the invasive type of OSCC, and EX-st altered the morphology of HSC-2 cells to verrucous OSCC. This study suggests that the tumor stroma influences the biological characteristics of the parenchyma and that the origin of the stroma is strongly associated with the biological characteristics of the tumor.
en-copyright=
kn-copyright=

en-aut-name=TakabatakeKiyofumi
en-aut-sei=Takabatake
en-aut-mei=Kiyofumi
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=OmoriHaruka
en-aut-sei=Omori
en-aut-mei=Haruka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=QiushengShan
en-aut-sei=Qiusheng
en-aut-mei=Shan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=SukegawaShintaro 
en-aut-sei=Sukegawa
en-aut-mei=Shintaro 
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=TsujigiwaHidetsugu
en-aut-sei=Tsujigiwa
en-aut-mei=Hidetsugu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=

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

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

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

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

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

affil-num=6
en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=

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

affil-num=9
en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=
en-keyword=tumor stroma
kn-keyword=tumor stroma
en-keyword=tumor parenchyma
kn-keyword=tumor parenchyma
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
en-keyword=biological characteristics
kn-keyword=biological characteristics
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=16490
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201005
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Spred2-deficiency enhances the proliferation of lung epithelial cells and alleviates pulmonary fibrosis induced by bleomycin
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2−/− mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2−/− lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2−/− and WT macrophages produced similar levels of TNFα and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2−/− fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of naïve WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2−/− mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF.
en-copyright=
kn-copyright=

en-aut-name=KawaraAkina
en-aut-sei=Kawara
en-aut-mei=Akina
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=ItoToshihiro
en-aut-sei=Ito
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=LiChunning
en-aut-sei=Li
en-aut-mei=Chunning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NakamuraKaoru
en-aut-sei=Nakamura
en-aut-mei=Kaoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SunCuiming
en-aut-sei=Sun
en-aut-mei=Cuiming
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KuwabaraMasaki
en-aut-sei=Kuwabara
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KitabatakeMasahiro
en-aut-sei=Kitabatake
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
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=11
ORCID=

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

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

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

affil-num=4
en-affil=Department of Immunology, Nara Medical University
kn-affil=

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

affil-num=6
en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=

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

affil-num=9
en-affil=Department of Immunology, Nara Medical University
kn-affil=

affil-num=10
en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科

affil-num=11
en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
kn-affil=
en-keyword=Cell signalling
kn-keyword=Cell signalling
en-keyword=Mechanisms of disease
kn-keyword=Mechanisms of disease
END

start-ver=1.4
cd-journal=joma
no-vol=46
cd-vols=
no-issue=
article-no=
start-page=101865
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202007
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Adult kidney stem/progenitor cells contribute to regeneration through the secretion of trophic factors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Adult kidney stem cells are known to have important roles in renal regeneration after acute kidney injury. Although trophic factors from tissue stem cells have been reported to promote the regeneration of other organs, there is limited number of evidence of this phenomenon in the kidneys. Here, we explored the effects of secreted factors from kidney stem cells. We intraperitoneally administered culture supernatant obtained from adult rat kidney stem/progenitor cells into rat kidney ischemia/reperfusion injury models, and the treatment significantly ameliorated renal tubulointerstitial injury, suppressed tubular cell apoptosis, diminished inflammation and promoted the proliferation of both residual renal cells and immature cells. In vitro, treatment with culture supernatant from kidney stem cells significantly promoted cell proliferation and suppressed cisplatin-induced cell apoptosis in both normal rat kidney cells and kidney stem cells. In addition, treatment with culture supernatant increased the expression of nestin in normal rat kidney cells, suggesting the dedifferentiation of tubular cells into stem-like cells. Analysis of the culture supernatant revealed that it contained a variety of growth factors. Taken together, the results suggest that these factors together lead to renal regeneration. In conclusion, adult kidney stem cells contribute to renal regeneration indirectly through the secretion of regenerative factors.
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=KitamuraShinji
en-aut-sei=Kitamura
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SangYizhen
en-aut-sei=Sang
en-aut-mei=Yizhen
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=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=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=
en-keyword=Kidney stem cell
kn-keyword=Kidney stem cell
en-keyword=Regeneration
kn-keyword=Regeneration
en-keyword=Acute kidney injury
kn-keyword=Acute kidney injury
en-keyword=Growth factor
kn-keyword=Growth factor
END

start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=4
article-no=
start-page=335
end-page=343
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202008
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Recurrence of Solitary Fibrous Tumor/Hemangiopericytoma Could Be Predicted by Ki-67 Regardless of Its Origin
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Since the discovery of the NAB2-STAT6 gene fusion in 2013, solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) have been considered the same disease. STAT6 nuclear stain is approved as a highly sensitive and specific marker to diagnose SFT/HPC from other tumors with similar histology. As the next step, detection of fusion variants that may predict clinical malignancy of SFT/HPC has been attempted. However, no fusion variants with a clear relation to malignancy have been identified. In this study, the clinical and histological backgrounds of 23 Japanese patients diagnosed with SFT/HPC from 2000 to 2019 at Kochi University Hospital were examined to identify factors potentially related to recurrence. A significant relationship to recurrence was detected for mitosis ≥ 1/10 HPF (400×), necrosis, and Ki-67>5%. These findings indicate that a deliberate investigation of histological features such as mitosis and necrosis is crucial for the clinical observation of SFT/ HPC patients. In addition, Ki-67 was revealed to be a useful parameter to predict recurrence in SFT/HPC patients.
en-copyright=
kn-copyright=

en-aut-name=YamamotoYumiko
en-aut-sei=Yamamoto
en-aut-mei=Yumiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HayashiYoshihiro
en-aut-sei=Hayashi
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MurakamiIchiro
en-aut-sei=Murakami
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Diagnostic Pathology, Kochi University
kn-affil=

affil-num=2
en-affil=Department of Equipment of Support Planning Office, Kochi University
kn-affil=

affil-num=3
en-affil=Department of Diagnostic Pathology, Kochi University
kn-affil=
en-keyword=solitary fibrous tumor
kn-keyword=solitary fibrous tumor
en-keyword=hemangiopericytoma
kn-keyword=hemangiopericytoma
en-keyword=Ki-67
kn-keyword=Ki-67
en-keyword=NAB2-STAT6
kn-keyword=NAB2-STAT6
en-keyword=WHO classification
kn-keyword=WHO classification
en-keyword=WHO grading criteria
kn-keyword=WHO grading criteria
en-keyword=Marseille Grading System
kn-keyword=Marseille Grading System
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=
article-no=
start-page=1461
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200714
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=High Mobility Group Box 1 Expression in Oral Inflammation and Regeneration
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein of about 30 kDa. It is released from a variety of cells into the extracellular milieu in response to inflammatory stimuli and acts on specific cell-surface receptors, such as receptors for advanced glycation end-products (RAGE), Toll-like receptor (TLR)2, TLR4, with or without forming a complex with other molecules. HMGB1 mediates various mechanisms such as inflammation, cell migration, proliferation, and differentiation. On the other hand, HMGB1 enhances chemotaxis acting through the C-X-C motif chemokine ligand (CXCL)12/C-X-C chemokine receptor (CXCR)4 axis and is involved in regeneration. In the oral cavity, high levels of HMGB1 have been detected in the gingival tissue from periodontitis and peri-implantitis patients, and it has been shown that secreted HMGB1 induces pro-inflammatory cytokine expression, such as interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha, which prolong inflammation. In contrast, wound healing after tooth extraction or titanium dental implant osseointegration requires an initial acute inflammation, which is regulated by secreted HMGB1. This indicates that secreted HMGB1 regulates angiogenesis and bone remodeling by osteoclast and osteoblast activation and promotes bone healing in oral tissue repair. Therefore, HMGB1 can prolong inflammation in the periodontal tissue and, conversely, can regenerate or repair damaged tissues in the oral cavity. In this review, we highlight the role of HMGB1 in the oral cavity by comparing its function and regulation with its function in other diseases. We also discuss the necessity for further studies in this field to provide more specific scientific evidence for dentistry.
en-copyright=
kn-copyright=

en-aut-name=YamashiroKeisuke
en-aut-sei=Yamashiro
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IdeguchiHidetaka
en-aut-sei=Ideguchi
en-aut-mei=Hidetaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AoyagiHiroaki
en-aut-sei=Aoyagi
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=Yoshihara-HirataChiaki
en-aut-sei=Yoshihara-Hirata
en-aut-mei=Chiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HiraiAnna
en-aut-sei=Hirai
en-aut-mei=Anna
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=Suzuki-KyoshimaRisa
en-aut-sei=Suzuki-Kyoshima
en-aut-mei=Risa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ZhangYao
en-aut-sei=Zhang
en-aut-mei=Yao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=9
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=10
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=11
ORCID=

affil-num=1
en-affil=Department of Periodontics and Endodontics, Okayama University Hospital
kn-affil=

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

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

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

affil-num=11
en-affil=Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=high mobility group box 1
kn-keyword=high mobility group box 1
en-keyword=inflammation
kn-keyword=inflammation
en-keyword=periodontal regeneration
kn-keyword=periodontal regeneration
en-keyword=periodontitis
kn-keyword=periodontitis
en-keyword=osseointegration
kn-keyword=osseointegration
en-keyword=tooth movement
kn-keyword=tooth movement
en-keyword=wound healing
kn-keyword=wound healing
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=6
article-no=
start-page=1360
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200526
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Paclitaxel and Sorafenib: The Effective Combination of Suppressing the Self-Renewal of Cancer Stem Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Combination therapy, which is a treatment modality combining two or more therapeutic agents, is considered a cornerstone of cancer therapy. The combination of anticancer drugs, of which functions are different from the other, enhances the efficiency compared to the monotherapy because it targets cancer cells in a synergistic or an additive manner. In this study, the combination of paclitaxel and sorafenib in low concentration was evaluated to target cancer stem cells, miPS-BT549cmP and miPS-Huh7cmP cells, developed from mouse induced pluripotent stem cells. The synergistic effect of paclitaxel and sorafenib on cancer stem cells was assessed by the inhibition of proliferation, self-renewal, colony formation, and differentiation. While the IC(50)values of paclitaxel and sorafenib were approximately ranging between 250 and 300 nM and between 6.5 and 8 mu M, respectively, IC(50)of paclitaxel reduced to 20 and 25 nM, which was not toxic in a single dose, in the presence of 1 mu M sorafenib, which was not toxic to the cells. Then, the synergistic effect was further assessed for the potential of self-renewal of cancer stem cells by sphere formation ability. As a result, 1 mu M of sorafenib significantly enhanced the effect of paclitaxel to suppress the number of spheres. Simultaneously, paclitaxel ranging in 1 to 4 nM significantly suppressed not only the colony formation but also the tube formation of the cancer stem cells in the presence of 1 mu M sorafenib. These results suggest the combination therapy of paclitaxel and sorafenib in low doses should be an attractive approach to target cancer stem cells with fewer side effects.
en-copyright=
kn-copyright=

en-aut-name=NawaraHend M.
en-aut-sei=Nawara
en-aut-mei=Hend M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AtallahMarwa N.
en-aut-sei=Atallah
en-aut-mei=Marwa N.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MansourHager
en-aut-sei=Mansour
en-aut-mei=Hager
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=Abu QuoraHagar A.
en-aut-sei=Abu Quora
en-aut-mei=Hagar A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AlamMd Jahangir
en-aut-sei=Alam
en-aut-mei=Md Jahangir
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OsmanAmira
en-aut-sei=Osman
en-aut-mei=Amira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KakutaHiroki
en-aut-sei=Kakuta
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=HamadaHiroki
en-aut-sei=Hamada
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=妹尾彬正
kn-aut-sei=妹尾
kn-aut-mei=彬正
aut-affil-num=12
ORCID=

en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=妹尾昌治
kn-aut-sei=妹尾
kn-aut-mei=昌治
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Vertebrates Embryology and Comparative Anatomy, Zoology Department, Faculty of Science, Menoufia University
kn-affil=

affil-num=6
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

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

affil-num=8
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

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

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

affil-num=11
en-affil=Department of Life Science, Faculty of Science, Okayama University of Science
kn-affil=

affil-num=12
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=combination therapy
kn-keyword=combination therapy
en-keyword=paclitaxel
kn-keyword=paclitaxel
en-keyword=sorafenib
kn-keyword=sorafenib
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=10418
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200626
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Decreased miR-200b-3p in cancer cells leads to angiogenesis in HCC by enhancing endothelial ERG expression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Transcription factor ERG (erythroblast transformation-specific (ETS)-related gene) is essential in endothelial differentiation and angiogenesis, in which microRNA (miR)-200b-3p targeting site is expected by miRNA target prediction database. miR-200b is known decreased in hepatocellular carcinoma (HCC), however, the functional relation between ERG and miR-200b-3p, originating from pre-miR-200b, in HCC angiogenesis remains unclear. We investigated whether hepatocyte-derived miR-200b-3p governs angiogenesis in HCC by targeting endothelial ERG. Levels of miR-200b-3p in HCC tissues were significantly lower than those in adjacent non-HCC tissues. Poorly differentiated HCC cell line expressed lower level of miR-200b-3p compared to well-differentiated HCC cell lines. The numbers of ERG-positive endothelial cells were higher in HCC tissues than in adjacent non-HCC tissues. There was a negative correlation between the number of ERG-positive cells and miR-200b-3p expression in HCC tissues. Culture supernatants of HCC cell lines with miR-200b-3p-overexpression reduced cell migration, proliferation and tube forming capacity in endothelial cells relative to the control, while those with miR-200b-3p-inhibition augmented the responses. Exosomes isolated from HCC culture supernatants with miR-200b-3p overexpression suppressed endothelial ERG expression. These results suggest that exosomal miR-200b-3p from hepatocytes suppresses endothelial ERG expression, and decreased miR-200b-3p in cancer cells promotes angiogenesis in HCC tissues by enhancing endothelial ERG expression.	
en-copyright=
kn-copyright=

en-aut-name=Moh-Moh-AungAye
en-aut-sei=Moh-Moh-Aung
en-aut-mei=Aye
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=ItoSachio
en-aut-sei=Ito
en-aut-mei=Sachio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KatayamaHiroshi
en-aut-sei=Katayama
en-aut-mei=Hiroshi
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=OtaYoko
en-aut-sei=Ota
en-aut-mei=Yoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
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=8
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 Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

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

affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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=
en-keyword=Molecular medicine
kn-keyword=Molecular medicine
en-keyword=Tumour angiogenesis
kn-keyword=Tumour angiogenesis
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=9323
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200609
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Neural regulation in tooth regeneration of Ambystoma mexicanum
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration.
en-copyright=
kn-copyright=

en-aut-name=MakanaeAki
en-aut-sei=Makanae
en-aut-mei=Aki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TajikaYuki
en-aut-sei=Tajika
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishimuraKoki
en-aut-sei=Nishimura
en-aut-mei=Koki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SaitoNanami
en-aut-sei=Saito
en-aut-mei=Nanami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TanakaJun-Ichi
en-aut-sei=Tanaka
en-aut-mei=Jun-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SatohAkira
en-aut-sei=Satoh
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS)
kn-affil=

affil-num=2
en-affil=Gunma University, Department of Anatomy, Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS)
kn-affil=

affil-num=4
en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS)
kn-affil=

affil-num=5
en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS)
kn-affil=

affil-num=6
en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS)
kn-affil=
en-keyword=Cell proliferation
kn-keyword=Cell proliferation
en-keyword=Differentiation
kn-keyword=Differentiation
en-keyword=Morphogenesis
kn-keyword=Morphogenesis
END

start-ver=1.4
cd-journal=joma
no-vol=33
cd-vols=
no-issue=12
article-no=
start-page=2437
end-page=2448
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200619
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL.
en-copyright=
kn-copyright=

en-aut-name=IkedaTomoka
en-aut-sei=Ikeda
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=SakamotoMisa
en-aut-sei=Sakamoto
en-aut-mei=Misa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TachibanaTomoyasu
en-aut-sei=Tachibana
en-aut-mei=Tomoyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=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=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=SatoYasuharu
en-aut-sei=Sato
en-aut-mei=Yasuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

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

affil-num=2
en-affil=Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=3
en-affil=Okayama University Graduate School of Health Sciences
kn-affil=

affil-num=4
en-affil=Department of Otolaryngology, Japanese Red Cross Society Himeji Hospital
kn-affil=

affil-num=5
en-affil= Okayama University Graduate School of Health Sciences
kn-affil=

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

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

affil-num=8
en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Lymphoid tissues
kn-keyword=Lymphoid tissues
en-keyword=Lymphoma
kn-keyword=Lymphoma
END

start-ver=1.4
cd-journal=joma
no-vol=44
cd-vols=
no-issue=9
article-no=
start-page=1919
end-page=1933
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200521
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=G‐CSF‐dependent neutrophil differentiation requires downregulation of MAPK activities through the Gab2 signaling pathway
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Granulocyte colony‐stimulating factor (G‐CSF) stimulation of myeloid cells induced tyrosine‐phosphorylation of cellular proteins. One of the tyrosine‐phosphorylated proteins was found to be a scaffold protein, Grb2‐associated binding protein 2 (Gab2). Another member of Gab family protein, Gab3, was exogenously overexpressed in neutrophil progenitor cells to make the Gab3 protein to compete with the endogenous Gab2 for the G‐CSF‐dependent signaling. In Gab3‐overexpressed cells, the level of tyrosine phosphorylation of endogenous Gab2 by G‐CSF stimulation was markedly downregulated, while the phosphorylation of Gab3 was significantly enhanced. The Gab3‐overexpressed cells continuously proliferated in the medium containing G‐CSF and lost the ability to differentiate to the mature neutrophil, characterized by the lobulated nucleus. The G‐CSF stimulation‐dependent tyrosine phosphorylation of Gab3, the association of SHP2 to Gab3 and the following mitogen‐activated protein kinase (MAPK) activation were prolonged in the Gab3‐overexpressed cells, compared to the parental cells, where the binding of SHP2 to Gab2 protein and thereby the activation of MAPK were not sustained after G‐CSF stimulation. Inhibition of MAPK by pharmaceutical inhibitor restored the Gab3‐overexpressed cells to the ability to differentiate to mature neutrophil. Therefore, G‐CSF‐dependent Gab2 phosphorylation and following its downregulation led the short‐term MAPK activation. The downregulation of MAPK after transient Gab2 phosphorylation was necessary for the consequent neutrophil differentiation induced by G‐CSF stimulation.
en-copyright=
kn-copyright=

en-aut-name=ZhaoXianglin
en-aut-sei=Zhao
en-aut-mei=Xianglin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawanoShun‐ichiro
en-aut-sei=Kawano
en-aut-mei=Shun‐ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
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=4
ORCID=

affil-num=1
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Natural Science and Technology, 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 Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=granulocyte
kn-keyword=granulocyte
en-keyword=MAP kinase
kn-keyword=MAP kinase
en-keyword=negative feedback
kn-keyword=negative feedback
en-keyword=phosphorylation
kn-keyword=phosphorylation
en-keyword=scaffold protein
kn-keyword=scaffold protein
en-keyword=SHP2
kn-keyword=SHP2
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=5
article-no=
start-page=1260
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200516
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (200-1000 nm) and small EVs (50-200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 led to a significant reduction in tumoroid size and the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. Moreover, CD63, another member of the tetraspanin family, was significantly reduced only in the EVs fractions of the MMP3-KO cells compared to their counterpart. These weakened phenotypes of MMP3-KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3, resulting in increasing the proliferation and tumorigenesis, indicating crucial roles of MMP3 in tumor progression.
en-copyright=
kn-copyright=

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=1
ORCID=

en-aut-name=SogawaChiharu
en-aut-sei=Sogawa
en-aut-mei=Chiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OkushaYuka
en-aut-sei=Okusha
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
ORCID=

en-aut-name=ElseoudiAbdellatif
en-aut-sei=Elseoudi
en-aut-mei=Abdellatif
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
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=8
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=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=OkamotoKuniaki
en-aut-sei=Okamoto
en-aut-mei=Kuniaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=

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

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

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

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

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

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

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

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

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

affil-num=10
en-affil=Department of Medical Bioengineering, Okayama University Graduate School of Natural Science and Technology
kn-affil=

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

affil-num=12
en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=matrix metalloproteinase 3 (MMP3)
kn-keyword=matrix metalloproteinase 3 (MMP3)
en-keyword=extracellular vesicles (EVs)
kn-keyword=extracellular vesicles (EVs)
en-keyword=tumoroid
kn-keyword=tumoroid
en-keyword=tumor organoid
kn-keyword=tumor organoid
en-keyword=tumorigenesis
kn-keyword=tumorigenesis
en-keyword=three-dimensional (3D) culture system
kn-keyword=three-dimensional (3D) culture system
END

start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=3
article-no=
start-page=237
end-page=243
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202006
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Serum REIC/Dickkopf-3 Protein Level Predicts Disease-Free Survival in Patients with Hepatocellular Carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The physiological role of the reduced expression of immortalized cells (REIC)/Dickkopf-3 (Dkk-3) protein in patients with hepatocellular carcinoma (HCC) remains unclear. In this study, we evaluated the effect of the REIC/Dkk-3 protein on HCC cell proliferation and assessed the relationship between the serum REIC/Dkk-3 protein level and the prognosis in patients with HCC. We evaluated the REIC/Dkk-3 protein-induced anticancer effects on Huh7 and Hep3B cells (HCC cell lines) in the presence of peripheral blood mononuclear cells (PBMCs), and found that combination treatment with REIC/Dkk-3 protein and PBMCs reduced the proliferation of HCC cells (Hep3B: 82.0%±16.3%; Huh7: 72.6%±9.1%). We also studied 194 HCC patients who underwent primary liver resection or primary radiofrequency ablation from 2008 to 2017. Serum REIC/Dkk-3 protein levels were measured by an enzyme-linked immunosorbent assay and compared to the prognostic data. The 3-year disease-free survival of the REIC/Dkk-3 high group was significantly higher than that in the REIC/Dkk-3 low group. In conclusion, this is the first study investigating the relationship between HCC patient survival and serum REIC/Dkk-3 protein levels in a large population. Based on the results, the serum REIC/Dkk-3 protein level should be considered a new prognostic marker for patients with HCC.
en-copyright=
kn-copyright=

en-aut-name=OyamaAtsushi
en-aut-sei=Oyama
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=UchidaDaisuke
en-aut-sei=Uchida
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ShirahaHidenori
en-aut-sei=Shiraha
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SawaharaHiroaki
en-aut-sei=Sawahara
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KatoRyo
en-aut-sei=Kato
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=HoriguchiShigeru
en-aut-sei=Horiguchi
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=

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=

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

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

affil-num=8
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=enzyme-linked immunosorbent assay
kn-keyword=enzyme-linked immunosorbent assay
en-keyword=liver resection
kn-keyword=liver resection
en-keyword=primary radiofrequency ablation
kn-keyword=primary radiofrequency ablation
en-keyword=Huh7
kn-keyword=Huh7
en-keyword=Hep3B
kn-keyword=Hep3B
END

start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=3
article-no=
start-page=185
end-page=190
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202006
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Stem Cell Therapy in Heart Disease: Limitations and Future Possibilities
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Heart diseases are one of the major causes of morbidity and mortality worldwide. Despite major advances in drug and interventional therapies, surgical procedures, and organ transplantation, further research into new therapeutic options is still necessary. Stem cell therapy has emerged as one option for the treatment of a variety of heart diseases. Although a large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach, the results obtained from these clinical studies are inconsistent, and stem cell-based improvements of heart performance and cardiac remodeling were found to be quite limited. Since the precise mechanisms underlying the therapeutic actions of stem cells are still under debate, researchers have developed a variety of strategies to improve and boost the potency of stem cells in repair. In this review, we summarize both the current therapeutic strategies using stem cells and future directions for enhancing stem cell potency.
en-copyright=
kn-copyright=

en-aut-name=SanoToshikazu
en-aut-sei=Sano
en-aut-mei=Toshikazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IshigamiShuta
en-aut-sei=Ishigami
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ItoTatsuo
en-aut-sei=Ito
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SanoShunji
en-aut-sei=Sano
en-aut-mei=Shunji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San Francisco
kn-affil=

affil-num=2
en-affil=Department of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San Francisco
kn-affil=

affil-num=3
en-affil=Department of Hygiene, Kawasaki Medical University
kn-affil=

affil-num=4
en-affil=Department of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San Francisco
kn-affil=
en-keyword=heart disease
kn-keyword=heart disease
en-keyword=stem cell
kn-keyword=stem cell
en-keyword=myocardial regeneration
kn-keyword=myocardial regeneration
END

start-ver=1.4
cd-journal=joma
no-vol=90
cd-vols=
no-issue=9
article-no=
start-page=1043
end-page=1052
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190319
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Acceleration of bone regeneration of horizontal bone defect in rats using collagen‐binding basic fibroblast growth factor combined with collagen scaffolds
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background</br>
Basic fibroblast growth factor (bFGF) has been applied for periodontal regeneration. However, the application depends on bone defect morphology because bFGF diffuses rapidly from defect sites. In a previous study, collagen‐binding bFGF (CB‐bFGF) has been shown to enhance bone formation by collagen‐anchoring in the orthopedic field. The aim of this study is to demonstrate the efficacy of CB‐bFGF with collagen scaffolds in bone regeneration of horizontal bone defect.</br>
Methods</br>
Cell proliferation activity and collagen binding activity of CB‐bFGF was confirmed by WST‐8 assay and collagen binding assay, respectively. The retention of CB‐bFGF in the collagen sheet (CS) was measured by fluorescence imaging. The rat horizontal alveolar bone defect model was employed to investigate the efficacy of CB‐bFGF with collagen powder (CP). After 4 and 8 weeks, the regenerative efficacy was evaluated by microcomputed tomography, histological, and immunohistochemical analyses.</br>
Results</br>
CB‐bFGF had a comparable proliferation activity to bFGF and a collagen binding activity. CB‐bFGF was retained in CS longer than bFGF. At 8 weeks postoperation, bone volume, bone mineral content, and new bone area in CB‐bFGF/CP group were significantly increased compared with those in other groups. Furthermore, epithelial downgrowth was significantly suppressed in CB‐bFGF/CP group. At 4 weeks, the numbers of osteocalcin, proliferating cell nuclear antigen, and osteopontin‐positive cells at the regeneration site in CB‐bFGF/CP group were greater than those in other groups.</br>
Conclusions</br>
CB‐bFGF/CP effectively promoted bone regeneration of horizontal bone defect possibly by sustained release of bFGF. The potential of CB‐bFGF composite material for improved periodontal regeneration in vertical axis was shown.
en-copyright=
kn-copyright=

en-aut-name=NakamuraShin
en-aut-sei=Nakamura
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ItoTakashi
en-aut-sei=Ito
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OkamotoKentaro
en-aut-sei=Okamoto
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MimaTakehiko
en-aut-sei=Mima
en-aut-mei=Takehiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UchidaKentaro
en-aut-sei=Uchida
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SiddiquiYasir D.
en-aut-sei=Siddiqui
en-aut-mei=Yasir D.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ItoMasahiro
en-aut-sei=Ito
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TaiMasako
en-aut-sei=Tai
en-aut-mei=Masako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
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=10
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=11
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=12
ORCID=

en-aut-name=MatsushitaOsamu
en-aut-sei=Matsushita
en-aut-mei=Osamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
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=14
ORCID=

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

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

affil-num=3
en-affil=Department of Pathophysiology‐Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

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

affil-num=5
en-affil=Department of Orthopedic Surgery, Kitasato University School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Pathophysiology‐Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Department of Pathophysiology‐Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=8
en-affil=Department of Pathophysiology‐Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Pathophysiology‐Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=10
en-affil=Department of Pathophysiology‐Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Department of Periodontics and Endodontics, Okayama University Hospital
kn-affil=

affil-num=12
en-affil=Department of Periodontics and Endodontics, Okayama University Hospital
kn-affil=

affil-num=13
en-affil=Department of Bacteriology, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Pathophysiology‐Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
en-keyword=bone regeneration
kn-keyword=bone regeneration
en-keyword=collagen
kn-keyword=collagen
en-keyword=drug delivery systems
kn-keyword=drug delivery systems
en-keyword=growth factors
kn-keyword=growth factors
en-keyword=periodontitis
kn-keyword=periodontitis
en-keyword=tissue engineering
kn-keyword=tissue engineering
END

start-ver=1.4
cd-journal=joma
no-vol=26
cd-vols=
no-issue=2
article-no=
start-page=230
end-page=236
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200326
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Differences between the root and horn cells of the human medial meniscus from the osteoarthritic knee in cellular characteristics and responses to mechanical stress
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background</br>
Many histological, mechanical, and clinical studies have been performed on the medial meniscus posterior root attachment, as it often tears in patients with osteoarthritic knee. Medial meniscal root repair is recommended in clinical situations; however, to date, no studies have examined the differences between meniscal root and horn cells. The aim of this study was, therefore, to investigate the morphology, reaction to cyclic tensile strain, and gene expression levels of medial meniscal root and horn cells.</br>
Methods</br>
Meniscal samples were obtained from the medial knee compartments of 10 patients with osteoarthritis who underwent total knee arthroplasty. Root and horn cells were cultured in Dulbecco's modified Eagle's medium without enzymes. The morphology, distribution, and proliferation of medial meniscal root and horn cells, as well as the gene and protein expression levels of Sry-type HMG box 9 and type II collagen, were determined after cyclic tensile strain treatment.</br>
Results</br>
Horn cells had a triangular morphology, whereas root cells were fibroblast-like. The number of horn cells positive for Sry-type HMG box 9 and type II collagen was considerably higher than that of root cells. Although root and horn cells showed similar levels of proliferation after 48, 72, or 96 h of culture, more horn cells than root cells were lost following a 2-h treatment with 5% and 10% cyclic tensile. Sry-type HMG box 9 and α1(II) collagen mRNA expression levels were significantly enhanced in both cells after 2- and 4-h cyclic tensile strain (5%) treatment.</br>
Conclusions</br>
Medial meniscal root and horn cells have distinct morphologies, reactions to mechanical stress, and cellular phenotypes. Our results suggest that physiological tensile strain is important to activate extracellular matrix production in horn cells.
en-copyright=
kn-copyright=

en-aut-name=OkazakiYuki
en-aut-sei=Okazaki
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FurumatsuTakayuki
en-aut-sei=Furumatsu
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KamatsukiYusuke
en-aut-sei=Kamatsuki
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NishidaKeiichiro
en-aut-sei=Nishida
en-aut-mei=Keiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NasuYoshihisa
en-aut-sei=Nasu
en-aut-mei=Yoshihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NakaharaRyuichi
en-aut-sei=Nakahara
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SaitoTaichi
en-aut-sei=Saito
en-aut-mei=Taichi
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=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

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

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

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

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

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

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

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

start-ver=1.4
cd-journal=joma
no-vol=138
cd-vols=
no-issue=
article-no=
start-page=105654
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200531
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Enhanced expression of nicotinamide nucleotide transhydrogenase (NNT) and its role in a human T cell line continuously exposed to asbestos
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The effects of asbestos fibers on human immune cells have not been well documented. We have developed a continuously exposed cell line model using the human T-lymphotropic virus 1 (HTLV-1)-immortalized human T cell line MT-2. Sublines continuously exposed to chrysotile (CH) or crocidolite (CR) showed acquired resistance to asbestos-induced apoptosis following transient and high-dose re-exposure with fibers. These sublines in addition to other immune cells such as natural killer cells or cytotoxic T lymphocytes exposed to asbestos showed a reduction in anti-tumor immunity. In this study, the expression of genes and molecules related to antioxidative stress was examined. Furthermore, complexes related to oxidative phosphorylation were investigated since the production of reactive oxygen species (ROS) is important when considering the effects of asbestos in carcinogenesis and the mechanisms involved in resistance to asbestos-induced apoptosis. In sublines continuously exposed to CH or CR, the expression of thioredoxin decreased. Interestingly, nicotinamide nucleotide transhydrogenase (NNT) expression was markedly enhanced. Thus, knockdown of NNT was then performed. Although the knockdown clones did not show any changes in proliferation or occurrence of apoptosis, these clones showed recovery of ROS production with returning NADPH/NADP+ ratio that increased with decreased production of ROS in continuously exposed sublines. These results indicated that NNT is a key factor in preventing ROS-induced cytotoxicity in T cells continuously exposed to asbestos. Considering that these sublines showed a reduction in anti-tumor immunity, modification of NNT may contribute to recovery of the anti-tumor effects in asbestos-exposed T cells.
en-copyright=
kn-copyright=

en-aut-name=YamamotoShoko
en-aut-sei=Yamamoto
en-aut-mei=Shoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=LeeSuni
en-aut-sei=Lee
en-aut-mei=Suni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MatsuzakiHidenori
en-aut-sei=Matsuzaki
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=Kumagai-TakeiNaoko
en-aut-sei=Kumagai-Takei
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YoshitomeKei
en-aut-sei=Yoshitome
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SadaNagisa
en-aut-sei=Sada
en-aut-mei=Nagisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ShimizuYurika
en-aut-sei=Shimizu
en-aut-mei=Yurika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ItoTastsuo
en-aut-sei=Ito
en-aut-mei=Tastsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NishimuraYasumitsu
en-aut-sei=Nishimura
en-aut-mei=Yasumitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OtsukiTakemi
en-aut-sei=Otsuki
en-aut-mei=Takemi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=2
en-affil=Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=3
en-affil=Department of Life Science, Faculty of Life and Environmental Science, Prefectural University of Hiroshima
kn-affil=

affil-num=4
en-affil=Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=5
en-affil=Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=6
en-affil=Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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 Hygiene, Kawasaki Medical School
kn-affil=

affil-num=9
en-affil=Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=10
en-affil=Department of Hygiene, Kawasaki Medical School
kn-affil=
en-keyword=Asbestos
kn-keyword=Asbestos
en-keyword=Continuous exposure
kn-keyword=Continuous exposure
en-keyword=Oxidative phosphorylation
kn-keyword=Oxidative phosphorylation
en-keyword=T cell
kn-keyword=T cell
en-keyword=nicotinamide nucleotide transhydrogenase (NNT)
kn-keyword=nicotinamide nucleotide transhydrogenase (NNT)
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=1
article-no=
start-page=42
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200405
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Annexin A2-STAT3-Oncostatin M receptor axis drives phenotypic and mesenchymal changes in glioblastoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Glioblastoma (GBM) is characterized by extensive tumor cell invasion, angiogenesis, and proliferation. We previously established subclones of GBM cells with distinct invasive phenotypes and identified annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we further explored the role of ANXA2 in regulating phenotypic transition in GBM. We identified oncostatin M receptor (OSMR) as a key ANXA2 target gene in GBM utilizing microarray analysis and hierarchical clustering analysis of the Ivy Glioblastoma Atlas Project and The Cancer Genome Atlas datasets. Overexpression of ANXA2 in GBM cells increased the expression of OSMR and phosphorylated signal transducer and activator of transcription 3 (STAT3) and enhanced cell invasion, angiogenesis, proliferation, and mesenchymal transition. Silencing of OSMR reversed the ANXA2-induced phenotype, and STAT3 knockdown reduced OSMR protein expression. Exposure of GBM cells to hypoxic conditions activated the ANXA2-STAT3-OSMR signaling axis. Mice bearing ANXA2-overexpressing GBM exhibited shorter survival times compared with control tumor-bearing mice, whereas OSMR knockdown increased the survival time and diminished ANXA2-mediated tumor invasion, angiogenesis, and growth. Further, we uncovered a significant relationship between ANXA2 and OSMR expression in clinical GBM specimens, and demonstrated their correlation with tumor histopathology and patient prognosis. Our results indicate that the ANXA2-STAT3-OSMR axis regulates malignant phenotypic changes and mesenchymal transition in GBM, suggesting that this axis is a promising therapeutic target to treat GBM aggressiveness.
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=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=FujimuraAtsushi
en-aut-sei=Fujimura
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujiiKentaro
en-aut-sei=Fujii
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TomitaYusuke
en-aut-sei=Tomita
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HattoriYasuhiko
en-aut-sei=Hattori
en-aut-mei=Yasuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UnedaAtsuhito
en-aut-sei=Uneda
en-aut-mei=Atsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TsuboiNobushige
en-aut-sei=Tsuboi
en-aut-mei=Nobushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KanedaKeisuke
en-aut-sei=Kaneda
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=MakinoKeigo
en-aut-sei=Makino
en-aut-mei=Keigo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
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, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

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

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

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

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

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

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

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

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

affil-num=13
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=ANXA2
kn-keyword=ANXA2
en-keyword=OSMR
kn-keyword=OSMR
en-keyword=Invasion
kn-keyword=Invasion
en-keyword=Mesenchymal transition
kn-keyword=Mesenchymal transition
en-keyword=Glioblastoma
kn-keyword=Glioblastoma
END

start-ver=1.4
cd-journal=joma
no-vol=59
cd-vols=
no-issue=2
article-no=
start-page=64
end-page=6471
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190628
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (EBVMCUs) were first described as a lymphoproliferative disorder in 2010. Clinically, EBVMCUs are shallow, sharply circumscribed, unifocal mucosal or cutaneous ulcers that occur in immunosuppressed patients, including those with advanced age-associated immunosenescence, iatrogenic immunosuppression, primary immune disorders, and HIV/AIDS-associated immune deficiencies. In general, patients exhibit indolent disease progression and spontaneous regression. Histologically, EBVMCUs are characterized by the proliferation of EBV-positive, variable-sized, atypical B-cells. According to conventional histopathologic criteria, EBVMCUs may diagnosed as lymphomas. However, EBVMCUs are recognized as pseudomalignant lesions because they spontaneously regress without anti-cancer treatment. Therefore, overtreatment must be carefully avoided and multilateral differentiation is important. In this article, we reviewed previously reported EBVMCUs focusing on their clinical and pathological aspects in comparison with other EBV-positive B-cell neoplasms.
en-copyright=
kn-copyright=

en-aut-name=IkedaTomoka
en-aut-sei=Ikeda
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
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=4
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=Division of Pathophysiology, Okayama University Graduate School of Health 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=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=EBV-positive mucocutaneous ulcer
kn-keyword=EBV-positive mucocutaneous ulcer
en-keyword=clinical features
kn-keyword=clinical features
en-keyword=immunosuppression
kn-keyword=immunosuppression
en-keyword=pathological features
kn-keyword=pathological features
END

start-ver=1.4
cd-journal=joma
no-vol=54
cd-vols=
no-issue=1
article-no=
start-page=283
end-page=294
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2018
dt-pub=20181112
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Nicotine promotes lymph node metastasis and cetuximab resistance in head and neck squamous cell carcinoma.
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epidermal growth factor (EGF) is overexpressed in many cancers and is associated with worse prognosis. EGF binds to its cell surface receptor (EGFR), which induces EGFR phosphorylation. Phosphorylated EGFR (p‑EGFR) is translocated into the nucleus, which increases cancer cell activity. Nicotine, which is one of the main components of tobacco, is absorbed through pulmonary alveoli and mucosal epithelia in the head and neck region by smoking and moves into the blood. Nicotine in blood binds to nicotinic acetylcholine receptor (nAChR) in the central nervous system and serves a crucial role in tobacco addiction. Although nAChR localization is thought to be limited in the nervous system, nAChR is present in a wide variety of non‑neuronal cells, including cancer cells. Recent studies suggest that nicotine contributes to the metastasis and resistance to anti‑cancer drugs of various cancer cells. However, it remains unknown whether head and neck squamous cell carcinoma (HNSCC) cells can utilize nicotine‑nAChR signaling to metastasize and acquire resistance to anti‑cancer drugs, even though the mucosal epithelia of the head and neck region are the primary sites of exposure to tobacco smoke. To the best of our knowledge, the present study is the first to demonstrate the role of nicotine in metastasis and anti‑EGFR‑therapy resistance of HNSCC. The present findings demonstrated that nicotine increased proliferation, migration, invasion, p‑EGFR nuclear translocation and protein kinase B (Akt) phosphorylation in HNSCC cells. It was also demonstrated that nicotine restored cetuximab‑inhibited proliferation, migration and invasion of HNSCC cells. Finally, an in vivo experiment revealed that nicotine increased lymph node metastasis of xenografted tumors, whereas an nAChR inhibitor suppressed lymph node metastasis and p‑EGFR nuclear localization of xenografted tumors. Taken together, these results demonstrated that nicotine induced nuclear accumulation of p‑EGFR, and activation of Akt signaling. These signaling pathways elevated the activities of HNSCC cells, causing lymph node metastasis and serving a role in cetuximab resistance.
en-copyright=
kn-copyright=

en-aut-name=ShimizuRieko
en-aut-sei=Shimizu
en-aut-mei=Rieko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=KuwajimaDaisuke
en-aut-sei=Kuwajima
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KodamaShinichi
en-aut-sei=Kodama
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishiokaTakashi
en-aut-sei=Nishioka
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OkuiTatsuo
en-aut-sei=Okui
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ObataKyoichi
en-aut-sei=Obata
en-aut-mei=Kyoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
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=10
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=11
ORCID=

en-aut-name=OkamotoKuniaki
en-aut-sei=Okamoto
en-aut-mei=Kuniaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
ORCID=

en-aut-name=SasakiAkira
en-aut-sei=Sasaki
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

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

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

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

affil-num=6
en-affil=Department of Oral Diagnosis, Tohoku University Graduate School of Dentistry
kn-affil=

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

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

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

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

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

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

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

affil-num=14
en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=nicotine
kn-keyword=nicotine
en-keyword=head and neck squamous cell carcinoma
kn-keyword=head and neck squamous cell carcinoma
en-keyword=lymph node metastasis
kn-keyword=lymph node metastasis
en-keyword=cetuximab
kn-keyword=cetuximab
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=8866
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=2019620
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Yeast screening system reveals the inhibitory mechanism of cancer cell proliferation by benzyl isothiocyanate through down-regulation of Mis12
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Benzyl isothiocyanate (BITC) is a naturally-occurring isothiocyanate derived from cruciferous vegetables. BITC has been reported to inhibit the proliferation of various cancer cells, which is believed to be important for the inhibition of tumorigenesis. However, the detailed mechanisms of action remain unclear. In this study, we employed a budding yeast Saccharomyces cerevisiae as a model organism for screening. Twelve genes including MTW1 were identified as the overexpression suppressors for the antiproliferative effect of BITC using the genome-wide multi-copy plasmid collection for S. cerevisiae. Overexpression of the kinetochore protein Mtw1 counteracts the antiproliferative effect of BITC in yeast. The inhibitory effect of BITC on the proliferation of human colon cancer HCT-116 cells was consistently suppressed by the overexpression of Mis12, a human orthologue of Mtw1, and enhanced by the knockdown of Mis12. We also found that BITC increased the phosphorylated and ubiquitinated Mis12 level with consequent reduction of Mis12, suggesting that BITC degrades Mis12 through an ubiquitin-proteasome system. Furthermore, cell cycle analysis showed that the change in the Mis12 level affected the cell cycle distribution and the sensitivity to the BITC-induced apoptosis. These results provide evidence that BITC suppresses cell proliferation through the post-transcriptional regulation of the kinetochore protein Mis12.
en-copyright=
kn-copyright=

en-aut-name=Abe-KanohNaomi
en-aut-sei=Abe-Kanoh
en-aut-mei=Naomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KunisueNarumi
en-aut-sei=Kunisue
en-aut-mei=Narumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MyojinTakumi
en-aut-sei=Myojin
en-aut-mei=Takumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ChinoAyako
en-aut-sei=Chino
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
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=6
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=7
ORCID=

en-aut-name=MoriyaHisao
en-aut-sei=Moriya
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
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=Research Core for Interdisciplinary Sciences, 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 Natural Science and Technology, Okayama University
kn-affil=

affil-num=8
en-affil=Research Core for Interdisciplinary Sciences, Okayama University
kn-affil=

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

start-ver=1.4
cd-journal=joma
no-vol=73
cd-vols=
no-issue=5
article-no=
start-page=433
end-page=440
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=201910
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Relationship between Intracellular Signaling of the (Pro)renin Receptor and the Pathogenesis of Preeclampsia
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= An association between preeclampsia and (pro)renin was recently reported. Intracellular signaling of the (pro) renin receptor [(P)RR] increases the expressions of TGF-β and PAI-1. In this study we sought to clarify the involvement of (pro)renin in the pathogenesis of preeclampsia via the intracellular signaling of (P)RR on preeclampsia placentas. Activated (pro)renin plasma concentrations were compared between pregnant women with (n=15) and without (n=28) preeclampsia. The placentas were immunohistochemically evaluated with anti-HIF-1α and anti-(P)RR antibodies. HTR-8/SVneo cells were cultured under hypoxic conditions and treated with human recombinant (pro)renin. The mRNA expressions of HIF-1α, (P)RR, PAI-1, TGF-β, and ET-1 were also examined by real-time RCR. The activated (pro)renin plasma concentration was significantly higher in the third vs. the second trimester in the preeclampsia patients. HIF-1α and (P)RR expressions were significantly increased in the preeclampsia placentas. The mRNA expressions of PAI-1, TGF-β, and ET-1 were significantly increased in the experiments using recombinant (pro)renin vs. hypoxic conditions. (P)RR expression in preeclampsia placentas is increased by persistent hypoxia through the second and third trimesters, and PAI-1, TGF-β, and ET-1 production is increased via (P)RR. Our results suggest that ET-1 production via the intracellular signaling of (P)RR is important in the pathogenesis of preeclampsia.
en-copyright=
kn-copyright=

en-aut-name=TamadaShoko
en-aut-sei=Tamada
en-aut-mei=Shoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MitsuiTakashi
en-aut-sei=Mitsui
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
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=4
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=5
ORCID=

en-aut-name=EguchiTakeshi
en-aut-sei=Eguchi
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
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=8
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=9
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=

affil-num=9
en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=preeclampsia
kn-keyword=preeclampsia
en-keyword=(pro)renin
kn-keyword=(pro)renin
en-keyword=(pro)renin receptor
kn-keyword=(pro)renin receptor
en-keyword=endothelin-1
kn-keyword=endothelin-1
en-keyword=HTR-8/SVneo
kn-keyword=HTR-8/SVneo
END

start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=
article-no=
start-page=100619
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=201907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Convenient methodology for extraction and subsequent selective propagation of mouse melanocytes in culture from adult mouse skin tissue
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Mouse melanoma B16-BL6 cells are useful cells for cancer metastatic studies. To understand the metastatic principle at molecular levels, it is necessary to carry out experiments in which cancer cells and their normal counterparts are compared. However, unlike normal human melanocytes, preparation of normal mouse melanocytes is quite difficult due to the lack of marketing and insufficient information on an established protocol for primary culture of mouse melanocytes. In this study, we aimed to establish a convenient method for primary culture of mouse melanocytes on the basis of the protocol for human melanocytes. The main obstacles to preparing pure mouse melanocytes are how to digest mouse skin tissue and how to reduce the contamination of keratinocytes and fibroblasts. The obstacles were overcome by collagenase digestion for skin specimens, short time trypsinization for separating melanocytes and keratinocytes, and use of 12-O-Tetradecanoylphorbol 13-acetate (TPA) and cholera toxin in the culture medium. These supplements act to prevent the proliferation of keratinocytes and fibroblasts, respectively. The convenient procedure enabled us to prepare a pure culture of normal mouse melanocytes. Using enriched normal mouse melanocytes and cancerous B16-BL6 cells, we compared the expression levels of melanoma cell adhesion molecule (MCAM), an important membrane protein for melanoma metastasis, in the cells. The results showed markedly higher expression of MCAM in B16-BL6 cells than in normal mouse melanocytes.
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=SumardikaI. Wayan
en-aut-sei=Sumardika
en-aut-mei=I. Wayan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
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=6
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=7
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=8
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=9
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 Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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=Faculty of Science and Technology, Division of Molecular Science, Gunma University, Kiryu
kn-affil=

affil-num=6
en-affil=Department of Biochemistry, Kawasaki Medical School
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=
en-keyword=Melanocytes
kn-keyword=Melanocytes
en-keyword=Melanoma
kn-keyword=Melanoma
en-keyword=Metastasis
kn-keyword=Metastasis
en-keyword=Primary culture
kn-keyword=Primary culture
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=
article-no=
start-page=243
end-page=252
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190614
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We recently demonstrated the generation of mouse induced tissue-specific stem (iTS) cells through transient overexpression of reprogramming factors combined with tissue-specific selection. Here we induced expandable tissue-specific progenitor (iTP) cells from human pancreatic tissue through transient expression of genes encoding the reprogramming factors OCT4 (octamer-binding transcription factor 4), p53 small hairpin RNA (shRNA), SOX2 (sex-determining region Y-box 2), KLF4 (Kruppel-like factor 4), L-MYC, and LIN28. Transfection of episomal plasmid vectors into human pancreatic tissue efficiently generated iTP cells expressing genetic markers of endoderm and pancreatic progenitors. The iTP cells differentiated into insulin-producing cells more efficiently than human induced pluripotent stem cells (iPSCs). iTP cells continued to proliferate faster than pancreatic tissue cells until days 100–120 (passages 15–20). iTP cells subcutaneously inoculated into immunodeficient mice did not form teratomas. Genomic bisulfite nucleotide sequence analysis demonstrated that the OCT4 and NANOG promoters remained partially methylated in iTP cells. We compared the global gene expression profiles of iPSCs, iTP cells, and pancreatic cells (islets >80%). Microarray analyses revealed that the gene expression profiles of iTP cells were similar, but not identical, to those of iPSCs but different from those of pancreatic cells. The generation of human iTP cells may have important implications for the clinical application of stem/progenitor cells.
en-copyright=
kn-copyright=

en-aut-name=NoguchiHirofumi
en-aut-sei=Noguchi
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=Miyagi-ShiohiraChika
en-aut-sei=Miyagi-Shiohira
en-aut-mei=Chika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakashimaYoshiki
en-aut-sei=Nakashima
en-aut-mei=Yoshiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KinjoTakao
en-aut-sei=Kinjo
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KobayashiNaoya
en-aut-sei=Kobayashi
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SaitohIssei
en-aut-sei=Saitoh
en-aut-mei=Issei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=ShapiroA. M. James
en-aut-sei=Shapiro
en-aut-mei=A. M. James
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KinTatsuya
en-aut-sei=Kin
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus
kn-affil=

affil-num=2
en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus
kn-affil=

affil-num=3
en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus
kn-affil=

affil-num=4
en-affil=Department of Basic Laboratory Sciences, School of Health Sciences in Faculty of Medicine, University of the Ryukyus
kn-affil=

affil-num=5
en-affil=Okayama Saidaiji Hospital
kn-affil=

affil-num=6
en-affil=Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University
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=Clinical Islet Transplant Program and Department of Surgery, University of Alberta
kn-affil=

affil-num=9
en-affil=Clinical Islet Transplant Program and Department of Surgery, University of Alberta
kn-affil=
en-keyword=induced tissue-specific progenitor cells
kn-keyword=induced tissue-specific progenitor cells
en-keyword=iTP
kn-keyword=iTP
en-keyword=induced tissue-specific stem cells
kn-keyword=induced tissue-specific stem cells
en-keyword=iTS
kn-keyword=iTS
en-keyword=induced pluripotent stem cells
kn-keyword=induced pluripotent stem cells
en-keyword=iPSCs
kn-keyword=iPSCs
en-keyword=reprogramming factors
kn-keyword=reprogramming factors
en-keyword=pancreas
kn-keyword=pancreas
END

start-ver=1.4
cd-journal=joma
no-vol=73
cd-vols=
no-issue=4
article-no=
start-page=285
end-page=297
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=201908
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dynamic Reorganization of Microtubule and Glioma Invasion
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion.
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=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 Neurosurgery, The University of Texas Health Science Center at Houston
kn-affil=

affil-num=2
en-affil=Department of Neurosurgery, Kagawa Prefectural Central Hospital
kn-affil=

affil-num=3
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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=cytoskeletons
kn-keyword=cytoskeletons
en-keyword=invasion
kn-keyword=invasion
en-keyword=microtubules
kn-keyword=microtubules
END

start-ver=1.4
cd-journal=joma
no-vol=119
cd-vols=
no-issue=9
article-no=
start-page=7363
end-page=7376
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2018
dt-pub=20180515
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Members of matrix metalloproteinase (MMP) family promote cancer cell migration, invasion, and metastasis through alteration of the tumor milieu, intracellular signaling pathways, and transcription. We examined gene expression signatures of colon adenocarcinoma cell lines with different metastatic potentials and found that rapidly metastatic cells powerfully expressed genes encoding MMP3 and MMP9. The non-proteolytic PEX isoform and proteolytic isoforms of MMPs were significantly expressed in the metastatic cells in vitro. Knockdown of MMP3 attenuated cancer cell migration and invasion in vitro and lung metastasis in vivo. Profound nuclear localization of MMP3/PEX was found in tumor-stroma marginal area. In contrast, MMP9 was localized in central area of subcutaneous tumors. Overexpression of the PEX isoform of MMP3 promoted proliferation and migration of the rapidly metastatic cells in vitro. Taken together, the non-proteolytic PEX isoform of MMPs locating in cell nuclei involves proliferation, migration, and subsequent metastasis of aggressive adenocarcinoma cells.
en-copyright=
kn-copyright=

en-aut-name=OkushaYuka
en-aut-sei=Okusha
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=SogawaChiharu
en-aut-sei=Sogawa
en-aut-mei=Chiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OkuiTatsuo
en-aut-sei=Okui
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

en-aut-name=OkamotoKuniaki
en-aut-sei=Okamoto
en-aut-mei=Kuniaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KozakiKen‐Ichi
en-aut-sei=Kozaki
en-aut-mei=Ken‐Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

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

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

affil-num=5
en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry andPharmaceutical Sciences, Okayama University
kn-affil=

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

affil-num=7
en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=PEX domain
kn-keyword=PEX domain
en-keyword=cancer metastasis
kn-keyword=cancer metastasis
en-keyword=non-proteolytic MMP
kn-keyword=non-proteolytic MMP
en-keyword=nuclear MMP
kn-keyword=nuclear MMP
en-keyword=tumor stroma
kn-keyword=tumor stroma
END

start-ver=1.4
cd-journal=joma
no-vol=72
cd-vols=
no-issue=3
article-no=
start-page=309
end-page=313
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2018
dt-pub=201806
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Pulmonary Tumor Thrombotic Microangiopathy Induced by Prostate Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal, malignancy-related respiratory complication; we herein report a PTTM case induced by metastatic prostate cancer. An 81-year-old Japanese man developed dyspnea. High-resolution computed tomography (HRCT) revealed ground-glass opacities spread across bilateral lung fields. Pulmonary microvascular aspiration cytology detected prostate cancer cells. As PTTM was highly suspected, docetaxel chemotherapy was performed immediately. His respiratory condition and HRCT findings improved temporarily, but he died approx. 6 weeks after admission. Autopsy showed fibrocellular intimal proliferation of small pulmonary arterioles, which confirmed the diagnosis of PTTM induced by prostate cancer. As in the present case, it is often difficult to confirm the presence of not only tumor embolization but also fibrocellular intimal proliferation before the patient’s death.
en-copyright=
kn-copyright=

en-aut-name=KatayamaSatoshi
en-aut-sei=Katayama
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakenakaTadasu
en-aut-sei=Takenaka
en-aut-mei=Tadasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakamuraAya
en-aut-sei=Nakamura
en-aut-mei=Aya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SakoSinichi
en-aut-sei=Sako
en-aut-mei=Sinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=BesshoAkihiro
en-aut-sei=Bessho
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OharaNobuya
en-aut-sei=Ohara
en-aut-mei=Nobuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Urology, St.Mary's Hospital
kn-affil=

affil-num=2
en-affil=Department of Urology, Red Cross Okayama Hospital
kn-affil=

affil-num=3
en-affil=Department of Urology, Okayama Saiseikai General Hospital
kn-affil=

affil-num=4
en-affil=Department of Urology, Okayama Saiseikai General Hospital
kn-affil=

affil-num=5
en-affil=Department of Respiratory Medicine, Red Cross Okayama Hospital
kn-affil=

affil-num=6
en-affil=Department of Pathology, Kagawa Rosai Hospital
kn-affil=
en-keyword=autopsy
kn-keyword=autopsy
en-keyword=dyspnea
kn-keyword=dyspnea
en-keyword=prostate neoplasm
kn-keyword=prostate neoplasm
en-keyword=metastatic lung cancer
kn-keyword=metastatic lung cancer
en-keyword=thrombotic microangiopathy
kn-keyword=thrombotic microangiopathy
END

start-ver=1.4
cd-journal=joma
no-vol=34
cd-vols=
no-issue=
article-no=
start-page=17
end-page=20
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2018
dt-pub=201804
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Avian coccidiosis : Toward the understanding of pathophysiology in Eimeria tenella infection
kn-title=鶏コクシジウム症：アイメリア・テネラ感染メカニズムの解明に向けて
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Avian coccidiosis is most important entero-parasitic disease in the world. Eimeria parasite is causative agent of this disease. In Japan, this parasite species were widely spread and the positive rates are about 50 in layer and 70 % in broiler. The symptoms of coccidiosis are diarrhea, bloody excretion, weight loss, and die. Eimeria tenella is the most pathogenic protozoa. The sporozoites, infection form of this parasite, entry to epithelial cells around the crypt of cecum in early infection. After infection, parasites proliferate in epithelial cells, and form to sexual stage finally. However, we have less information about the pathophysiology, especially invasive mechanisms and infection route, by E. tenella infection. We have focused to analyze the invasive mechanism and route of this parasite because this phenomenon is first event to cause the pathophysiological changes in the infection. I would like to inform about Eimeria parasite and introduce our research in this paper.
en-copyright=
kn-copyright=

en-aut-name=HatabuToshimitsu
en-aut-sei=Hatabu
en-aut-mei=Toshimitsu
kn-aut-name=畑生俊光
kn-aut-sei=畑生
kn-aut-mei=俊光
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate school of Environmental and Life Sciences, Okayama University
kn-affil=岡山大学大学院環境生命科学研究科
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=2017
dt-pub=20170929
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=腎がん細胞における外因性タンパクDKK-3/REICはwnt/β-catenin経路と細胞増殖を抑制する
kn-title=Exogenous DKK-3/REIC inhibits Wnt/β-catenin signaling and cell proliferation in human kidney cancer KPK1
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=XuJiaqi
en-aut-sei=Xu
en-aut-mei=Jiaqi
kn-aut-name=許家琪
kn-aut-sei=許
kn-aut-mei=家琪
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=2017
dt-pub=20170929
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=ヒト膀胱癌細胞におけるREIC/Dkk-3の強発現により、CD147の発現および細胞増殖が抑制された
kn-title=Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=HorikawaYuhei
en-aut-sei=Horikawa
en-aut-mei=Yuhei
kn-aut-name=堀川雄平
kn-aut-sei=堀川
kn-aut-mei=雄平
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=51
cd-vols=
no-issue=2
article-no=
start-page=625
end-page=632
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2017
dt-pub=20170621
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor κβ ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Furthermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion.
en-copyright=
kn-copyright=

en-aut-name=TakadaHiroyuki
en-aut-sei=Takada
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=OkuiTatsuo
en-aut-sei=Okui
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ObataKyoichi
en-aut-sei=Obata
en-aut-mei=Kyoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MasuiMasanori
en-aut-sei=Masui
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MorisawaAyaka
en-aut-sei=Morisawa
en-aut-mei=Ayaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=9
ORCID=

en-aut-name=YoshiokaNorie
en-aut-sei=Yoshioka
en-aut-mei=Norie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=Nur Mohammad Monsur Hassan
en-aut-sei=Nur Mohammad Monsur Hassan
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ShimoTsuyoshi
en-aut-sei=Shimo
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=HuGuo-Fu
en-aut-sei=Hu
en-aut-mei=Guo-Fu
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=

en-aut-name=SasakiAkira
en-aut-sei=Sasaki
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

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

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

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

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

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

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

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

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

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

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

affil-num=11
en-affil=School of Dentistry and Health Sciences, Charles Sturt University
kn-affil=

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

affil-num=13
en-affil=Molecular Oncology Research Institute, Tufts Medical Center
kn-affil=

affil-num=14
en-affil=Departments of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

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

start-ver=1.4
cd-journal=joma
no-vol=50
cd-vols=
no-issue=6
article-no=
start-page=2024
end-page=2032
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2017
dt-pub=20170509
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes (CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules such as granzyme B and perforin, as well as suppressed proliferation of CTLs. Additionally, analysis of T helper cells showed that surface CXCR3, chemokine receptor, and the productive potential of interferon (IFN)γ were reduced following asbestos exposure in an in vitro cell line model and in peripheral CD4+ cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos exposure enhanced regulatory T cell (Treg) function. This study also focused on CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell receptor and co-culture with various concentrations of chrysotile fibers using freshly isolated CD4+ surface CXCR3 positive and negative fractions, the intracellular expression of CXCR3, IFNγ and IL-17 remained unchanged when co-cultured with chrysotile. However, subsequent re-stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production and expression, particularly in CD4+ surface CXCR3 positive cells. These results indicated that the balance and polarization between Treg and Th-17 fractions play an important role with respect to the immunological effects of asbestos and the associated reduction in antitumor immunity.
en-copyright=
kn-copyright=

en-aut-name=MaedaMegumi
en-aut-sei=Maeda
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ChenYing
en-aut-sei=Chen
en-aut-mei=Ying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LeeSuni
en-aut-sei=Lee
en-aut-mei=Suni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=Kumagai-TakeiNaoko
en-aut-sei=Kumagai-Takei
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YoshitomeKei
en-aut-sei=Yoshitome
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MatsuzakiHidenori
en-aut-sei=Matsuzaki
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YamamotoShoko
en-aut-sei=Yamamoto
en-aut-mei=Shoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HatayamaTamayo
en-aut-sei=Hatayama
en-aut-mei=Tamayo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IkedaMiho
en-aut-sei=Ikeda
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NishimuraYasumitsu
en-aut-sei=Nishimura
en-aut-mei=Yasumitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=OtsukiTakemi
en-aut-sei=Otsuki
en-aut-mei=Takemi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology
kn-affil=

affil-num=2
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=3
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=4
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=5
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=6
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=7
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=8
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=9
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=10
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=

affil-num=11
en-affil= Department of Hygiene, Kawasaki Medical School
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=313
cd-vols=
no-issue=1
article-no=
start-page=169
end-page=174
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2017
dt-pub=201707
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=In vitro analysis of radioprotective effect of monoterpenes
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Monoterpenes are naturally occurring hydrocarbons composed of two units of isoprenes. They exhibit antioxidant activity to scavenge reactive oxygen species, such as hydroxyl radicals. We investigated the potential of monoterpenes such as thymol, linalool, and menthol to act as radioprotectants. The proliferation of EL4 cells, a mouse lymphoma cell line, treated with linalool at a concentration of 500 μM or more was not affected by X-ray irradiation. Plasmid-nicking assay performed using formamidopyrimidine-DNA glycosylase showed that linalool prevented single strand breaks and oxidized purines on pUC19 plasmid DNA. These findings indicate that linalool has the ability to scavenge reactive oxygen species and is a potential radioprotector.
en-copyright=
kn-copyright=

en-aut-name=KudoKen-ichi
en-aut-sei=Kudo
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HanafusaTadashi
en-aut-sei=Hanafusa
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OnoToshiro
en-aut-sei=Ono
en-aut-mei=Toshiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=
kn-affil=

affil-num=2
en-affil=Department of Radiation Research, Advanced Science Research CenterOkayama University
kn-affil=

affil-num=3
en-affil=Department of Radiation Research, Advanced Science Research CenterOkayama University
kn-affil=
en-keyword=Monoterpenes
kn-keyword=Monoterpenes
en-keyword= Linalool 
kn-keyword= Linalool 
en-keyword=X-ray irradiation
kn-keyword=X-ray irradiation
en-keyword= Reactive oxygen species
kn-keyword= Reactive oxygen species
en-keyword= SSB 
kn-keyword= SSB 
END

start-ver=1.4
cd-journal=joma
no-vol=128
cd-vols=
no-issue=2
article-no=
start-page=103
end-page=109
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=20160801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Identification of the adipokine ‘vaspin’ and its significance in metabolic syndrome
kn-title=アディポカイン「バスピン」の同定とメタボリックシンドロームにおける意義
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=和田淳
kn-aut-sei=和田
kn-aut-mei=淳
aut-affil-num=1
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=岡山大学大学院医歯薬学総合研究科　腎・免疫・内分泌代謝内科学
en-keyword=metabolic syndrome
kn-keyword=metabolic syndrome
en-keyword=adipokine
kn-keyword=adipokine
en-keyword=atherosclerosis
kn-keyword=atherosclerosis
en-keyword=endothelial cells
kn-keyword=endothelial cells
en-keyword=apoptosis
kn-keyword=apoptosis
END

start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=1
article-no=
start-page=13
end-page=24
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201602
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Function of β2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Intact β2-glycoprotein I (iβ2GPI) is a glycoprotein that regulates coagulation and fibrinolysis. Nicked β2GPI (nβ2GPI) possesses an angiogenic property at a relatively low concentration, and an antiangiogenic property at a high concentration. Here we investigated the functions of βi 2GPI and nβ2GPI in vascular endothelial growth factor (VEGF)-A-induced endothelial cell proliferation and tube formation. We used noninvasive PET imaging to analyze the in vivo distribution of intravenously injected β2GPI variants in tumor lesions in mice. iβ2GPI was incubated with plasmin to obtain nβ2GPI, and its N-terminal sequence was analyzed. nβ2GPI had at least one other cleavage site upstream of the β2GPIʼs domain V, whereas the former plasmin-cleavage site locates between K317 and T318. Both of intact and nicked β2GPI significantly inhibited the VEGF-A-induced cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs). PET imaging visualized considerably distributed intensities of all tested β2GPI variants in tumor lesions of pancreatic tumor cell-xenografts. These results indicate that β2GPI may be physiologically and pathophysiologically important in the regulation of not only coagulation and fibrinolysis, but also angiogenesis.
en-copyright=
kn-copyright=

en-aut-name=Arum Tri Wahyuningsih
en-aut-sei=Arum Tri Wahyuningsih
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShenLianhua
en-aut-sei=Shen
en-aut-mei=Lianhua
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KobayashiKazuko
en-aut-sei=Kobayashi
en-aut-mei=Kazuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SasakiTakanori
en-aut-sei=Sasaki
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakenakaFumiaki
en-aut-sei=Takenaka
en-aut-mei=Fumiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HanadaTakahisa
en-aut-sei=Hanada
en-aut-mei=Takahisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AkehiMasaru
en-aut-sei=Akehi
en-aut-mei=Masaru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AkahoshiAkiya
en-aut-sei=Akahoshi
en-aut-mei=Akiya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OzekiEiichi
en-aut-sei=Ozeki
en-aut-mei=Eiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=AndoEiji
en-aut-sei=Ando
en-aut-mei=Eiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
ORCID=

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

affil-num=2
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=6
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=8
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=9
en-affil=
kn-affil=Technology Research Laboratory, Shimadzu Corporation

affil-num=10
en-affil=
kn-affil=Life Science Business Department, Shimadzu Corporation

affil-num=11
en-affil=
kn-affil=Department of Cell Chemistry , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=β2-glycoprotein I (β2GPI)
kn-keyword=β2-glycoprotein I (β2GPI)
en-keyword=angiogenesis
kn-keyword=angiogenesis
en-keyword=vascular endothelial growth factor-A (VEGF-A)
kn-keyword=vascular endothelial growth factor-A (VEGF-A)
en-keyword=positron emission tomography (PET) imaging
kn-keyword=positron emission tomography (PET) imaging
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=1
article-no=
start-page=e85594
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140122
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Nuclear hormone receptors (NHRs) are transcription factors that regulate carbohydrate and lipid metabolism, immune responses, and inflammation. Although several NHRs, including peroxisome proliferator-activated receptor-γ (PPARγ) and PPARα, demonstrate a renoprotective effect in the context of diabetic nephropathy (DN), the expression and role of other NHRs in the kidney are still unrecognized. To investigate potential roles of NHRs in the biology of the kidney, we used quantitative real-time polymerase chain reaction to profile the expression of all 49 members of the mouse NHR superfamily in mouse kidney tissue (C57BL/6 and db/m), and cell lines of mesangial (MES13), podocyte (MPC), proximal tubular epithelial (mProx24) and collecting duct (mIMCD3) origins in both normal and high-glucose conditions. In C57BL/6 mouse kidney cells, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and COUP-TFIII were highly expressed. During hyperglycemia, the expression of the NHR 4A subgroup including neuron-derived clone 77 (Nur77), nuclear receptor-related factor 1, and neuron-derived orphan receptor 1 significantly increased in diabetic C57BL/6 and db/db mice. In renal cell lines, PPARδ was highly expressed in mesangial and proximal tubular epithelial cells, while COUP-TFs were highly expressed in podocytes, proximal tubular epithelial cells, and collecting duct cells. High-glucose conditions increased the expression of Nur77 in mesangial and collecting duct cells, and liver x receptor α in podocytes. These data demonstrate NHR expression in mouse kidney cells and cultured renal cell lines and suggest potential therapeutic targets in the kidney for the treatment of DN.
en-copyright=
kn-copyright=

en-aut-name=OgawaDaisuke
en-aut-sei=Ogawa
en-aut-mei=Daisuke
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=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=TeramiNaoto
en-aut-sei=Terami
en-aut-mei=Naoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HatanakaTakashi
en-aut-sei=Hatanaka
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TachibanaHiromi
en-aut-sei=Tachibana
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=Sato HoriguchiChikage
en-aut-sei=Sato Horiguchi
en-aut-mei=Chikage
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NishiiNaoko
en-aut-sei=Nishii
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=

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

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

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

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

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

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

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

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

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

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

start-ver=1.4
cd-journal=joma
no-vol=142
cd-vols=
no-issue=17
article-no=
start-page=2916
end-page=2927
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=201509
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Leg regeneration is epigenetically regulated by histone H3K27 methylation in the cricket Gryllus bimaculatus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hemimetabolous insects such as the cricket Gryllus bimaculatus regenerate lost tissue parts using blastemal cells, a population of dedifferentiated proliferating cells. The expression of several factors that control epigenetic modification is upregulated in the blastema compared with differentiated tissue, suggesting that epigenetic changes in gene expression might control the differentiation status of blastema cells during regeneration. To clarify the molecular basis of epigenetic regulation during regeneration, we focused on the function of the Gryllus Enhancer of zeste [Gb'E(z)] and Ubiquitously transcribed tetratricopeptide repeat gene on the X chromosome (Gb'Utx) homologues, which regulate methylation and demethylation of histone H3 lysine 27 (H3K27), respectively. Methylated histone H3K27 in the regenerating leg was diminished by Gb'E(z)RNAi and was increased by Gb'UtxRNAi. Regenerated Gb'E(z)RNAi cricket legs exhibited extra leg segment formation between the tibia and tarsus, and regenerated Gb'UtxRNAi cricket legs showed leg joint formation defects in the tarsus. In the Gb'E(z)RNAi regenerating leg, the Gb'dac expression domain expanded in the tarsus. By contrast, in the Gb'UtxRNAi regenerating leg, Gb'Egfr expression in the middle of the tarsus was diminished. These results suggest that regulation of the histone H3K27 methylation state is involved in the repatterning process during leg regeneration among cricket species via the epigenetic regulation of leg patterning gene expression.
en-copyright=
kn-copyright=

en-aut-name=HamadaYoshimasa
en-aut-sei=Hamada
en-aut-mei=Yoshimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=BandoTetsuya
en-aut-sei=Bando
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakamuraTaro
en-aut-sei=Nakamura
en-aut-mei=Taro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IshimaruYoshiyasu
en-aut-sei=Ishimaru
en-aut-mei=Yoshiyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MitoTaro
en-aut-sei=Mito
en-aut-mei=Taro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NojiSumihare
en-aut-sei=Noji
en-aut-mei=Sumihare
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TomiokaKenji
en-aut-sei=Tomioka
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=

affil-num=1
en-affil=
kn-affil=Graduate School of Natural Science and Technology, Okayama University

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

affil-num=3
en-affil=
kn-affil=Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School

affil-num=4
en-affil=
kn-affil=Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School

affil-num=5
en-affil=
kn-affil=Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School

affil-num=6
en-affil=
kn-affil=Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School

affil-num=7
en-affil=
kn-affil=Graduate School of Natural Science and Technology, Okayama University

affil-num=8
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
en-keyword=Regeneration
kn-keyword=Regeneration
en-keyword=Epigenetics
kn-keyword=Epigenetics
en-keyword=Histone H3K27
kn-keyword=Histone H3K27
en-keyword=Gryllus bimaculatus
kn-keyword=Gryllus bimaculatus
en-keyword=Polycomb
kn-keyword=Polycomb
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=12
article-no=
start-page=e83545
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20131227
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=miRNA-720 Controls Stem Cell Phenotype, Proliferation and Differentiation of Human Dental Pulp Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Dental pulp cells (DPCs) are known to be enriched in stem/progenitor cells but not well characterized yet. Small non-coding microRNAs (miRNAs) have been identified to control protein translation, mRNA stability and transcription, and have been reported to play important roles in stem cell biology, related to cell reprogramming, maintenance of stemness and regulation of cell differentiation. In order to characterize dental pulp stem/progenitor cells and its mechanism of differentiation, we herein sorted stem-cell-enriched side population (SP) cells from human DPCs and periodontal ligament cells (PDLCs), and performed a locked nucleic acid (LNA)-based miRNA array. As a result, miR-720 was highly expressed in the differentiated main population (MP) cells compared to that in SP cells. In silico analysis and a reporter assay showed that miR-720 targets the stem cell marker NANOG, indicating that miR-720 could promote differentiation of dental pulp stem/progenitor cells by repressing NANOG. Indeed, gain-and loss-of-function analyses showed that miR-720 controls NANOG transcript and protein levels. Moreover, transfection of miR-720 significantly decreased the number of cells positive for the early stem cell marker SSEA-4. Concomitantly, mRNA levels of DNA methyltransferases (DNMTs), which are known to play crucial factors during stem cell differentiation, were also increased by miR-720 through unknown mechanism. Finally, miR-720 decreased DPC proliferation as determined by immunocytochemical analysis against ki-67, and promoted odontogenic differentiation as demonstrated by alizarin red staining, as well as alkaline phosphatase and osteopontin mRNA levels. Our findings identify miR-720 as a novel miRNA regulating the differentiation of DPCs.
en-copyright=
kn-copyright=

en-aut-name=HaraEmilio Satoshi
en-aut-sei=Hara
en-aut-mei=Emilio Satoshi
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=EguchiTakanori
en-aut-sei=Eguchi
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

en-aut-name=HaiThanh Pham
en-aut-sei=Hai
en-aut-mei=Thanh Pham
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SonoyamaWataru
en-aut-sei=Sonoyama
en-aut-mei=Wataru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TajimaShoji
en-aut-sei=Tajima
en-aut-mei=Shoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TakigawaMasaharu
en-aut-sei=Takigawa
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=Stuart K.Calderwood
en-aut-sei=Stuart K.
en-aut-mei=Calderwood
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=

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

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

affil-num=3
en-affil=
kn-affil=Department of Radiation Oncology, Division of Molecular and Cellular Biology, Beth Israel Deaconess Medical Center, Harvard Medical School

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

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

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=
kn-affil=Laboratory of Epigenetics, Institute for Protein Research, Osaka University

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

affil-num=9
en-affil=
kn-affil=Department of Radiation Oncology, Division of Molecular and Cellular Biology, Beth Israel Deaconess Medical Center, Harvard Medical School

affil-num=10
en-affil=
kn-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=12
article-no=
start-page=e84186
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20131227
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Proliferation of Luteal Steroidogenic Cells in Cattle
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The rapid growth of the corpus luteum (CL) after ovulation is believed to be mainly due to an increase in the size of luteal cells (hypertrophy) rather than an increase in their number. However, the relationship between luteal growth and the proliferation of luteal steroidogenic cells (LSCs) is not fully understood. One goal of the present study was to determine whether LSCs proliferate during CL growth. A second goal was to determine whether luteinizing hormone (LH), which is known have roles in the proliferation and differentiation of follicular cells, also affects the proliferation of LSCs. Ki-67 (a cell proliferation marker) was expressed during the early, developing and mid luteal stages and some Ki-67-positive cells co-expressed HSD3B (a steroidogenic marker). DNA content in LSCs isolated from the developing CL increased much more rapidly (indicating rapid growth) than did DNA content in LSCs isolated from the mid CL. The cell cycle-progressive genes CCND2 (cyclin D2) and CCNE1 (cyclin E1) mRNA were expressed more strongly in the small luteal cells than in the large luteal cells. LH decreased the rate of increase of DNA in LSCs isolated from the mid luteal stage but not in LSCs from the developing stage. LH suppressed CCND2 expression in LSCs from the mid luteal stage but not from the developing luteal stage. Furthermore, LH receptor (LHCGR) mRNA expression was higher at the mid luteal stage than at the developing luteal stage. The overall results suggest that the growth of the bovine CL is due to not only hypertrophy of LSCs but also an increase in their number, and that the proliferative ability of luteal steroidogenic cells decreases between the developing and mid luteal stages.
en-copyright=
kn-copyright=

en-aut-name=YoshiokaShin
en-aut-sei=Yoshioka
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AbeHironori
en-aut-sei=Abe
en-aut-mei=Hironori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SakumotoRyosuke
en-aut-sei=Sakumoto
en-aut-mei=Ryosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OkudaKiyoshi
en-aut-sei=Okuda
en-aut-mei=Kiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=
kn-affil=Graduate School of Natural Science and Technology, Okayama University

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

affil-num=3
en-affil=
kn-affil=Reproductive Biology Research Unit, National Institute of Agrobiological Sciences

affil-num=4
en-affil=
kn-affil=Graduate School of Natural Science and Technology, Okayama University
END

start-ver=1.4
cd-journal=joma
no-vol=127
cd-vols=
no-issue=3
article-no=
start-page=209
end-page=212
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=20151201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=A primary diffuse large B-cell lymphoma of the liver treated with R-CHOP regimen
kn-title=Rituximab併用CHOP療法が奏効した肝原発びまん性大細胞型Ｂ細胞リンパ腫の１例
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=　A 78-year-old Japanese man was referred to our hospital after experiencing black feces. No abnormal finding was detected in the endoscopic examination of his stomach and large intestines. Computed tomography (CT) of the abdomen revealed a tumor lesion in the right lobe of the liver. A needle biopsy of the tumor under ultrasound guidance was performed. A pathological examination of the biopsy specimen showed a diffuse proliferation of lymphoma cells, which was compatible with diffuse large B-cell lymphoma (DLBCL). F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT demonstrated increased FDG uptake only in the liver tumor. We made the diagnosis of primary DLBCL of the liver. After six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), the patient achieved complete remission and has maintained remission for 2 years since the diagnosis. The R-CHOP regimen might be effective therapy for primary DLBCL of the liver.
en-copyright=
kn-copyright=

en-aut-name=OkadaHiroshi
en-aut-sei=Okada
en-aut-mei=Hiroshi
kn-aut-name=岡田博
kn-aut-sei=岡田
kn-aut-mei=博
aut-affil-num=1
ORCID=

en-aut-name=FujiiSoichiro
en-aut-sei=Fujii
en-aut-mei=Soichiro
kn-aut-name=藤井総一郎
kn-aut-sei=藤井
kn-aut-mei=総一郎
aut-affil-num=2
ORCID=

en-aut-name=WatanabeKentaro
en-aut-sei=Watanabe
en-aut-mei=Kentaro
kn-aut-name=渡邉謙太郎
kn-aut-sei=渡邉
kn-aut-mei=謙太郎
aut-affil-num=3
ORCID=

en-aut-name=ShigematuTerunobu
en-aut-sei=Shigematu
en-aut-mei=Terunobu
kn-aut-name=重松照伸
kn-aut-sei=重松
kn-aut-mei=照伸
aut-affil-num=4
ORCID=

en-aut-name=MiyashitaKatsuhiro
en-aut-sei=Miyashita
en-aut-mei=Katsuhiro
kn-aut-name=宮下雄博
kn-aut-sei=宮下
kn-aut-mei=雄博
aut-affil-num=5
ORCID=

en-aut-name=OkazakiMorihiro
en-aut-sei=Okazaki
en-aut-mei=Morihiro
kn-aut-name=岡崎守宏
kn-aut-sei=岡崎
kn-aut-mei=守宏
aut-affil-num=6
ORCID=

en-aut-name=KobashiHaruhiko
en-aut-sei=Kobashi
en-aut-mei=Haruhiko
kn-aut-name=小橋春彦
kn-aut-sei=小橋
kn-aut-mei=春彦
aut-affil-num=7
ORCID=

en-aut-name=YokoyamaMotohiro
en-aut-sei=Yokoyama
en-aut-mei=Motohiro
kn-aut-name=横山元浩
kn-aut-sei=横山
kn-aut-mei=元浩
aut-affil-num=8
ORCID=

en-aut-name=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
kn-aut-name=吉野正
kn-aut-sei=吉野
kn-aut-mei=正
aut-affil-num=9
ORCID=

affil-num=1
en-affil=
kn-affil=岡山赤十字病院

affil-num=2
en-affil=
kn-affil=岡山赤十字病院

affil-num=3
en-affil=
kn-affil=岡山赤十字病院

affil-num=4
en-affil=
kn-affil=岡山赤十字病院

affil-num=5
en-affil=
kn-affil=岡山赤十字病院

affil-num=6
en-affil=
kn-affil=岡山赤十字病院

affil-num=7
en-affil=
kn-affil=岡山赤十字病院

affil-num=8
en-affil=
kn-affil=岡山赤十字病院

affil-num=9
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科
en-keyword=びまん性大細胞型Ｂ細胞リンパ腫（diffuse large B-cell lymphoma）
kn-keyword=びまん性大細胞型Ｂ細胞リンパ腫（diffuse large B-cell lymphoma）
en-keyword=肝臓（liver）
kn-keyword=肝臓（liver）
en-keyword=R-CHOP療法（R-CHOP regimen）
kn-keyword=R-CHOP療法（R-CHOP regimen）
END

start-ver=1.4
cd-journal=joma
no-vol=5
cd-vols=
no-issue=
article-no=
start-page=14812
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=2015
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Regulation of the unfolded protein response via S-nitrosylation of sensors of endoplasmic reticulum stress
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Protein S-nitrosylation modulates important cellular processes, including neurotransmission, vasodilation, proliferation, and apoptosis in various cell types. We have previously reported that protein disulfide isomerase (PDI) is S-nitrosylated in brains of patients with sporadic neurodegenerative diseases. This modification inhibits PDI enzymatic activity and consequently leads to the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) lumen. Here, we describe S-nitrosylation of additional ER pathways that affect the unfolded protein response (UPR) in cell-based models of Parkinson's disease (PD). We demonstrate that nitric oxide (NO) can S-nitrosylate the ER stress sensors IRE1α and PERK. While S-nitrosylation of IRE1α inhibited its ribonuclease activity, S-nitrosylation of PERK activated its kinase activity and downstream phosphorylation/inactivation or eIF2α. Site-directed mutagenesis of IRE1α(Cys931) prevented S-nitrosylation and inhibition of its ribonuclease activity, indicating that Cys931 is the predominant site of S-nitrosylation. Importantly, cells overexpressing mutant IRE1α(C931S) were resistant to NO-induced damage. Our findings show that nitrosative stress leads to dysfunctional ER stress signaling, thus contributing to neuronal cell death.
en-copyright=
kn-copyright=

en-aut-name=RyosukeNakato
en-aut-sei=Ryosuke
en-aut-mei=Nakato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YuOhkubo
en-aut-sei=Yu
en-aut-mei=Ohkubo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AkariKonishi
en-aut-sei=Akari
en-aut-mei=Konishi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MariShibata
en-aut-sei=Mari
en-aut-mei=Shibata
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YukiKaneko
en-aut-sei=Yuki
en-aut-mei=Kaneko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakaoIwawaki
en-aut-sei=Takao
en-aut-mei=Iwawaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TomohiroNakamura
en-aut-sei=Tomohiro
en-aut-mei=Nakamura
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=Stuart A.Lipton
en-aut-sei=Stuart A.
en-aut-mei=Lipton
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TakashiUehara
en-aut-sei=Takashi
en-aut-mei=Uehara
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

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

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

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

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

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

affil-num=6
en-affil=
kn-affil=Iwawaki laboratory, Education and Research Support Center, Graduate School of Medicine, Gunma University

affil-num=7
en-affil=
kn-affil=Neuroscience and Aging Research Center, Sanford-Burnham-Prebys Medical Discovery Institute

affil-num=8
en-affil=
kn-affil=Neuroscience and Aging Research Center, Sanford-Burnham-Prebys Medical Discovery Institute

affil-num=9
en-affil=
kn-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
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=2015
dt-pub=20150325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=半月板inner領域におけるChondromodulin-Iの血管内皮細胞増殖抑制効果
kn-title=Chondromodulin-I Derived from the Inner Meniscus Prevents Endothelial Cell Proliferation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=FujiiMasataka
en-aut-sei=Fujii
en-aut-mei=Masataka
kn-aut-name=藤井政孝
kn-aut-sei=藤井
kn-aut-mei=政孝
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院
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=2015
dt-pub=20150325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=MafAは膵β細胞の生後の増殖に必要である
kn-title=MafA Is Required for Postnatal Proliferation of Pancreatic β-Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=EtoKoki
en-aut-sei=Eto
en-aut-mei=Koki
kn-aut-name=衛藤弘城
kn-aut-sei=衛藤
kn-aut-mei=弘城
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院
END

start-ver=1.4
cd-journal=joma
no-vol=5
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20141120
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Benzyl isothiocyanate (BITC), a dietary isothiocyanate derived from cruciferous vegetables, inhibits the proliferation of colorectal cancer cells, most of which overexpress β-catenin as a result of mutations in the genes for adenomatous polyposis coli or mutations in β-catenin itself. Because nuclear factor-κB (NF-κB) is a plausible target of BITC signaling in inflammatory cell models, we hypothesized that it is also involved in BITC-inhibited proliferation of colorectal cancer cells. siRNA-mediated knockdown of the NF-κB p65 subunit significantly decreased the BITC sensitivity of human colorectal cancer HT-29 cells with mutated p53 tumor suppressor protein. Treating HT-29 cells with BITC induced the phosphorylation of IκB kinase, IκB-α and p65, the degradation of IκB-α, the translocation of p65 to the nucleus and the upregulation of NF-κB transcriptional activity. BITC also decreased β-catenin binding to a positive cis element of the cyclin D1 promoter and thus inhibited β-catenin-dependent cyclin D1 transcription, possibly through a direct interaction between p65 and β-catenin. siRNA-mediated knockdown of p65 confirmed that p65 negatively affects cyclin D1 expression. On the other hand, when human colorectal cancer HCT-116 cells with wild-type p53 were treated with BITC, translocation of p65 to the nucleus was inhibited rather than enhanced. p53 knockout increased the BITC sensitivity of HCT-116 cells in a p65-dependent manner, suggesting that p53 negatively regulates p65-dependent effects. Together, these results identify BITC as a novel type of antiproliferative agent that regulates the NF-κB pathway in p53-deficient colorectal cancer cells.
en-copyright=
kn-copyright=

en-aut-name=AbeN
en-aut-sei=Abe
en-aut-mei=N
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HouD-X
en-aut-sei=Hou
en-aut-mei=D-X
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MunemasaS
en-aut-sei=Munemasa
en-aut-mei=S
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MurataY
en-aut-sei=Murata
en-aut-mei=Y
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NakamuraY
en-aut-sei=Nakamura
en-aut-mei=Y
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

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

affil-num=2
en-affil=
kn-affil=Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University

affil-num=3
en-affil=
kn-affil=Graduate School of Environmental and Life Science, Okayama University

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

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

start-ver=1.4
cd-journal=joma
no-vol=7
cd-vols=
no-issue=2
article-no=
start-page=292
end-page=302
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=201404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Glioblastoma is known to secrete high levels of vascular endothelial growth factor (VEGF), and clinical studies with bevacizumab, a monoclonal antibody to VEGF, have demonstrated convincing therapeutic benefits in glioblastoma patients. However, its induction of invasive proliferation has also been reported. We examined the effects of treatment with cilengitide, an integrin inhibitor, on bevacizumab-induced invasive changes in glioma. U87 Delta EGFR cells were stereotactically injected into the brain of nude mice or rats. Five days after tumor implantation, cilengitide and bevacizumab were administered intraperitoneally three times a week. At 18 days after tumor implantation, the brains were removed and observed histopathologically. Next, the bevacizumab and cilengitide combination group was compared to the bevacizumab monotherapy group using microarray analysis. Bevacizumab treatment led to increased cell invasion in spite of decreased angiogenesis. When the rats were treated with a combination of bevacizumab and cilengitide, the depth of tumor invasion was significantly less than with only bevacizumab. Pathway analysis demonstrated the inhibition of invasion-associated genes such as the integrin-mediated cell adhesion pathway in the combination group. This study showed that the combination of bevacizumab with cilengitide exerted its anti-invasive effect. The elucidation of this mechanism might contribute to the treatment of bevacizumab-refractory glioma.
en-copyright=
kn-copyright=

en-aut-name=IshidaJoji
en-aut-sei=Ishida
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OnishiManabu
en-aut-sei=Onishi
en-aut-mei=Manabu
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=IchikawaTomotsugu
en-aut-sei=Ichikawa
en-aut-mei=Tomotsugu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujiiKentaro
en-aut-sei=Fujii
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShimazuYosuke
en-aut-sei=Shimazu
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OkaTetsuo
en-aut-sei=Oka
en-aut-mei=Tetsuo
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=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
END

start-ver=1.4
cd-journal=joma
no-vol=126
cd-vols=
no-issue=3
article-no=
start-page=203
end-page=208
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20141201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Modulation of neuronal function and neuroprotection by astrocytes
kn-title=アストロサイトによる神経機能修飾とパーキンソン病での神経保護
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=AsanumaMasato
en-aut-sei=Asanuma
en-aut-mei=Masato
kn-aut-name=浅沼幹人
kn-aut-sei=浅沼
kn-aut-mei=幹人
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　神経ゲノム学
en-keyword=アストロサイト
kn-keyword=アストロサイト
en-keyword=抗酸化防御機構
kn-keyword=抗酸化防御機構
en-keyword=パーキンソン病
kn-keyword=パーキンソン病
en-keyword=メタロチオネイン
kn-keyword=メタロチオネイン
en-keyword=Nrf2
kn-keyword=Nrf2
END

start-ver=1.4
cd-journal=joma
no-vol=19
cd-vols=
no-issue=23
article-no=
start-page=6495
end-page=6505
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20131201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Genetically Engineered Oncolytic Adenovirus Decoys and Lethally Traps Quiescent Cancer Stem-like Cells in S/G(2)/M Phases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose: Because chemoradiotherapy selectively targets proliferating cancer cells, quiescent cancer stem-like cells are resistant. Mobilization of the cell cycle in quiescent leukemia stem cells sensitizes them to cell death signals. However, it is unclear that mobilization of the cell cycle can eliminate quiescent cancer stem-like cells in solid cancers. Thus, we explored the use of a genetically-engineered telomerase-specific oncolytic adenovirus, OBP-301, to mobilize the cell cycle and kill quiescent cancer stem-like cells. 

Experimental Design: We established CD133(+) cancer stem-like cells from human gastric cancer MKN45 and MKN7 cells. We investigated the efficacy of OBP-301 against quiescent cancer stem-like cells. We visualized the treatment dynamics of OBP-301 killing of quiescent cancer stem-like cells in dormant tumor spheres and xenografts using a fluorescent ubiquitination cell-cycle indicator (FUCCI). 

Results: CD133(+) gastric cancer cells had stemness properties. OBP-301 efficiently killed CD133(+) cancer stem-like cells resistant to chemoradiotherapy. OBP-301 induced cell-cycle mobilization from G(0)-G(1) to S/G(2)/M phases and subsequent cell death in quiescent CD133(+) cancer stem-like cells by mobilizing cell-cycle-related proteins. FUCCI enabled visualization of quiescent CD133(+) cancer stem-like cells and proliferating CD133(-) non-cancer stem-like cells. Three-dimensional visualization of the cell-cycle behavior in tumor spheres showed that CD133(+) cancer stem-like cells maintained stemness by remaining in G(0)-G(1) phase. We showed that OBP-301 mobilized quiescent cancer stem-like cells in tumor spheres and xenografts into S/G(2)/M phases where they lost viability and cancer stem-like cell properties and became chemosensitive. 

Conclusion: Oncolytic adenoviralinfection is an effective mechanism of cancer cell killing in solid cancer and can be a new therapeutic paradigm to eliminate quiescent cancer stem-like cells.
en-copyright=
kn-copyright=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
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=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
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=6
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=7
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NagasakaTakeshi
en-aut-sei=Nagasaka
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
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=11
ORCID=

en-aut-name=HoffmanRobert M.
en-aut-sei=Hoffman
en-aut-mei=Robert M.
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=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=2
en-affil=
kn-affil=Okayama Univ Hosp, Ctr Innovat Clin Med

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=10
en-affil=
kn-affil=Oncolys BioPharma Inc

affil-num=11
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=12
en-affil=
kn-affil=Univ Calif San Diego, Dept Surg

affil-num=13
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
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=2014
dt-pub=20140325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=ウシ黄体ステロイド合成細胞の増殖能に関する研究
kn-title=Study on the proliferation of bovine luteal steroidogenic cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=YoshiokaShin
en-aut-sei=Yoshioka
en-aut-mei=Shin
kn-aut-name=吉岡伸
kn-aut-sei=吉岡
kn-aut-mei=伸
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
END

start-ver=1.4
cd-journal=joma
no-vol=37
cd-vols=
no-issue=1
article-no=
start-page=159
end-page=165
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201301
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Comparison between normal and loose fragment chondrocytes in proliferation and redifferentiation potential
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Loose fragments in osteochondritis dissecans (OCD) of the knee require internal fixation. On the other hand, loose fragments derived from spontaneous osteonecrosis of the knee (SONK) are usually removed. However, the difference in healing potential between OCD- and SONK-related loose fragments has not been elucidated. In this study, we investigated proliferative activity and redifferentiation potential of normal cartilage-derived and loose fragment-derived chondrocytes. 

Cells were prepared from normal articular cartilages and loose fragment cartilages derived from knee OCD and SONK. Cellular proliferation was compared. Redifferentiation ability of pellet-cultured chondrocytes was assessed by real-time PCR analyses. Mesenchymal differentiation potential was investigated by histological analyses. Positive ratio of a stem cell marker CD166 was evaluated in each cartilaginous tissue. 

Normal and OCD chondrocytes showed a higher proliferative activity than SONK chondrocytes. Chondrogenic pellets derived from normal and OCD chondrocytes produced a larger amount of safranin O-stained proteoglycans compared with SONK-derived pellets. Expression of chondrogenic marker genes was inferior in SONK pellets. The CD166-positive ratio was higher in normal cartilages and OCD loose fragments than in SONK loose fragments. 

The OCD chondrocytes maintained higher proliferative activity and redifferentiation potential compared with SONK chondrocytes. Our results suggest that chondrogenic properties of loose fragment-derived cells and the amount of CD166-positive cells may affect the repair process of osteochondral defects.
en-copyright=
kn-copyright=

en-aut-name=SakataKenichiro
en-aut-sei=Sakata
en-aut-mei=Kenichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FurumatsuTakayuki
en-aut-sei=Furumatsu
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MiyazawaShinichi
en-aut-sei=Miyazawa
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OkadaYukimasa
en-aut-sei=Okada
en-aut-mei=Yukimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujiiMasataka
en-aut-sei=Fujii
en-aut-mei=Masataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Orthopaed Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Orthopaed Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=3
en-affil=
kn-affil=Okayama Univ, Dept Orthopaed Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Orthopaed Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=5
en-affil=
kn-affil=Okayama Univ, Dept Orthopaed Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=6
en-affil=
kn-affil=Okayama Univ, Dept Orthopaed Surg, Grad Sch Med Dent & Pharmaceut Sci
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=10
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20131009
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Truncated SSX Protein Suppresses Synovial Sarcoma Cell Proliferation by Inhibiting the Localization of SS18-SSX Fusion Protein
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Synovial sarcoma is a relatively rare high-grade soft tissue sarcoma that often develops in the limbs of young people and induces the lung and the lymph node metastasis resulting in poor prognosis. In patients with synovial sarcoma, specific chromosomal translocation of t(X; 18) (p11.2; q11.2) is observed, and SS18-SSX fusion protein expressed by this translocation is reported to be associated with pathogenesis. However, role of the fusion protein in the pathogenesis of synovial sarcoma has not yet been completely clarified. In this study, we focused on the localization patterns of SS18-SSX fusion protein. We constructed expression plasmids coding for the full length SS18-SSX, the truncated SS18 moiety (tSS18) and the truncated SSX moiety (tSSX) of SS18-SSX, tagged with fluorescent proteins. These plasmids were transfected in synovial sarcoma SYO-1 cells and we observed the expression of these proteins using a fluorescence microscope. The SS18-SSX fusion protein showed a characteristic speckle pattern in the nucleus. However, when SS18-SSX was co-expressed with tSSX, localization of SS18-SSX changed from speckle patterns to the diffused pattern similar to the localization pattern of tSSX and SSX. Furthermore, cell proliferation and colony formation of synovial sarcoma SYO-1 and YaFuSS cells were suppressed by exogenous tSSX expression. Our results suggest that the characteristic speckle localization pattern of SS18-SSX is strongly involved in the tumorigenesis through the SSX moiety of the SS18-SSX fusion protein. These findings could be applied to further understand the pathogenic mechanisms, and towards the development of molecular targeting approach for synovial sarcoma.
en-copyright=
kn-copyright=

en-aut-name=YonedaYasushi
en-aut-sei=Yoneda
en-aut-mei=Yasushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ItoSachio
en-aut-sei=Ito
en-aut-mei=Sachio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=MorimotoYuki
en-aut-sei=Morimoto
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KanzakiHirotaka
en-aut-sei=Kanzaki
en-aut-mei=Hirotaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=ShimizuKenji
en-aut-sei=Shimizu
en-aut-mei=Kenji
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=

en-aut-name=OuchidaMamoru
en-aut-sei=Ouchida
en-aut-mei=Mamoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthoped Surg

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Genet

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med Mat Musculoskeletal Reconstruct

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthoped Surg

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Genet

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthoped Surg

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Genet

affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthoped Surg

affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Genet
END

start-ver=1.4
cd-journal=joma
no-vol=126
cd-vols=
no-issue=1
article-no=
start-page=11
end-page=15
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=A preoperative SUVmax greater than the ADCmin of the primary tumour : A predictor of disease recurrence and survival in patients with endometrial cancer
kn-title=PET/CT SUVmaxは子宮体癌の予後不良因子になりうる
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=NakamuraKeiichiro
en-aut-sei=Nakamura
en-aut-mei=Keiichiro
kn-aut-name=中村圭一郎
kn-aut-sei=中村
kn-aut-mei=圭一郎
aut-affil-num=1
ORCID=

en-aut-name=JojaIkuo
en-aut-sei=Joja
en-aut-mei=Ikuo
kn-aut-name=上者郁夫
kn-aut-sei=上者
kn-aut-mei=郁夫
aut-affil-num=2
ORCID=

en-aut-name=FukushimaChikako
en-aut-sei=Fukushima
en-aut-mei=Chikako
kn-aut-name=福島千加子
kn-aut-sei=福島
kn-aut-mei=千加子
aut-affil-num=3
ORCID=

en-aut-name=HarumaTomoko
en-aut-sei=Haruma
en-aut-mei=Tomoko
kn-aut-name=春間朋子
kn-aut-sei=春間
kn-aut-mei=朋子
aut-affil-num=4
ORCID=

en-aut-name=HayashiChiaki
en-aut-sei=Hayashi
en-aut-mei=Chiaki
kn-aut-name=林千晶
kn-aut-sei=林
kn-aut-mei=千晶
aut-affil-num=5
ORCID=

en-aut-name=KusumotoTomoyuki
en-aut-sei=Kusumoto
en-aut-mei=Tomoyuki
kn-aut-name=楠本知行
kn-aut-sei=楠本
kn-aut-mei=知行
aut-affil-num=6
ORCID=

en-aut-name=SekiNoriko
en-aut-sei=Seki
en-aut-mei=Noriko
kn-aut-name=関典子
kn-aut-sei=関
kn-aut-mei=典子
aut-affil-num=7
ORCID=

en-aut-name=HongoAtsushi
en-aut-sei=Hongo
en-aut-mei=Atsushi
kn-aut-name=本郷淳司
kn-aut-sei=本郷
kn-aut-mei=淳司
aut-affil-num=8
ORCID=

en-aut-name=HiramatsuYuji
en-aut-sei=Hiramatsu
en-aut-mei=Yuji
kn-aut-name=平松祐司
kn-aut-sei=平松
kn-aut-mei=祐司
aut-affil-num=9
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　産科婦人科学

affil-num=2
en-affil=
kn-affil=岡山大学大学院保健学研究科　放射線技術科学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　産科婦人科学

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　産科婦人科学

affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　産科婦人科学

affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　産科婦人科学

affil-num=7
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　産科婦人科学

affil-num=8
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　産科婦人科学

affil-num=9
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　産科婦人科学
en-keyword=endometrial cancer
kn-keyword=endometrial cancer
en-keyword=SUVmax
kn-keyword=SUVmax
en-keyword=PET/CT
kn-keyword=PET/CT
en-keyword=predictor of poor prognosis
kn-keyword=predictor of poor 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=2013
dt-pub=20131231
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=ミゾリビンは腎臓再生の過程において腎臓幹/前駆細胞をG1/S期に休止させることによりその増殖を抑制する
kn-title=Mizoribine inhibits the proliferation of renal stem / progenitor cells by G1/S arrest during renal regeneration
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=HorimotoNaoya
en-aut-sei=Horimoto
en-aut-mei=Naoya
kn-aut-name=堀元直哉
kn-aut-sei=堀元
kn-aut-mei=直哉
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
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=2013
dt-pub=20131231
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=truncated SSXは転座型融合蛋白SS18-SSXの局在を阻害することで滑膜肉腫細胞の増殖を抑制する
kn-title=Truncated SSX Protein Suppresses Synovial Sarcoma Cell Proliferation by Inhibiting the Localization of SS18-SSX Fusion Protein
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=YonedaYasushi
en-aut-sei=Yoneda
en-aut-mei=Yasushi
kn-aut-name=米田泰史
kn-aut-sei=米田
kn-aut-mei=泰史
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
END

start-ver=1.4
cd-journal=joma
no-vol=68
cd-vols=
no-issue=1
article-no=
start-page=7
end-page=15
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=201402
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mizoribine Inhibits the Proliferation of Renal Stem/Progenitor Cells by G1/S Arrest during Renal Regeneration
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immunosuppressive agents are generally administered to treat kidney diseases. However, it is unclear whether renal stem/progenitor cells are directly affected by the immunosuppressive agents. We used normal rat kidney cells, ureteric bud cells and rat kidney stem/progenitor cells in this study. Mizoribine (MZR), cyclophosphamide (CPA) and cyclosporine (CyA) were added to the culture media of these cells. We evaluated the effects of these immunosuppressive agents on cell proliferation using an electrical cell-substrate impedance sensing system (ECIS) and their effects on the process of renal regeneration using the ischemia-reperfusion (I/R) injury rat model. The ECIS data showed that proliferation
of each of the 3 types of cells was significantly suppressed by MZR. MZR treatment enhanced renal tubular injury in ischemia-reperfusion (I/R) injured rats, and significantly decreased levels of M-phase cells and Nestin-positive cells. These results suggested that MZR inhibits the cell cycle of renal stem/progenitor cells;thus, physicians should take note that MZR might affect not only inflammation but also renal regeneration.
en-copyright=
kn-copyright=

en-aut-name=HorimotoNaoya
en-aut-sei=Horimoto
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
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=4
ORCID=

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

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

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

affil-num=4
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=cell biology
kn-keyword=cell biology
en-keyword=immunosuppression
kn-keyword=immunosuppression
en-keyword=stem cells
kn-keyword=stem cells
END

start-ver=1.4
cd-journal=joma
no-vol=463
cd-vols=
no-issue=5
article-no=
start-page=697
end-page=711
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201311
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Polycomb group (PcG) proteins are important for the regulation of hematopoiesis by regulating chromatin compaction and silencing genes related to differentiation and cell cycle. Overexpression of enhancer of zeste homologue 2 (Ezh2) and Bmi-1/PCGF4 has been implicated in solid organ cancers, while Mel-18/PCGF2 has been reported as a tumor suppressor. Detailed expression profiles of PcG proteins and their diagnostic significance in malignant lymphomas are still unknown. In this study, we analyzed the expression levels of Ezh2, Bmi-1, Mel-18, and Ki67 in 197 Hodgkin's and non-Hodgkin's lymphoma patient samples and in lymphoma cell lines using immunohistochemistry, fluorescent immunocytochemistry, and Western blotting. Immunohistochemical staining showed that Ezh2 expression was significantly increased in aggressive compared to indolent subtypes of B cell neoplasms (P = 0.000-0.030), while no significant differences in Bmi-1 expression were found between these subtypes. Compared to the normal counterpart, T cell lymphomas showed significant overexpression of Bmi-1 (P = 0.011) and Ezh2 (P = 0.000). The Ki67 labeling index showed a positive correlation with Ezh2 expression in B cell lymphomas (correlation coefficient (Co) = 0.983, P = 0.000) and T/NK cell lymphomas (Co = 0.629, P = 0.000). Fluorescent immunohistochemical staining showed coexpression of Ezh2 and Ki67 in the same tumor cells, indicating that Ezh2 expression correlates with cell proliferation. Both B and T/NK cell neoplasms showed low expression of Mel-18 and high expression of both Bmi-1 and Ezh2. In conclusion, in aggressive lymphoma variants, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2. Coexpression of Bmi-1 and Ezh2 is a characteristic of aggressive lymphomas. Ezh2 correlates with the proliferation and aggressive nature of non-Hodgkin's lymphomas.
en-copyright=
kn-copyright=

en-aut-name=Abd Al KaderLamia
en-aut-sei=Abd Al Kader
en-aut-mei=Lamia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OkaTakashi
en-aut-sei=Oka
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakataKatsuyoshi
en-aut-sei=Takata
en-aut-mei=Katsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SunXu
en-aut-sei=Sun
en-aut-mei=Xu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SatoHiaki
en-aut-sei=Sato
en-aut-mei=Hiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MurakamiIchiro
en-aut-sei=Murakami
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TojiTomohiro
en-aut-sei=Toji
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ManabeAkihiro
en-aut-sei=Manabe
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KimuraHiroshi
en-aut-sei=Kimura
en-aut-mei=Hiroshi
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=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=3
en-affil=
kn-affil=Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=4
en-affil=
kn-affil=Dalian Med Univ, Dept Pathol, Affiliated Hosp 1

affil-num=5
en-affil=
kn-affil=Okayama Univ, Dept Med Technol, Grad Sch Hlth Sci

affil-num=6
en-affil=
kn-affil=Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=7
en-affil=
kn-affil=Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=8
en-affil=
kn-affil=Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=9
en-affil=
kn-affil=Osaka Univ, Grad Sch Frontier Sci

affil-num=10
en-affil=D
kn-affil=Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci
en-keyword=Ezh2
kn-keyword=Ezh2
en-keyword=Bmi-1
kn-keyword=Bmi-1
en-keyword=Mel-18
kn-keyword=Mel-18
en-keyword=Malignant lymphoma
kn-keyword=Malignant lymphoma
en-keyword=PRC1.2
kn-keyword=PRC1.2
en-keyword=PRC1.4
kn-keyword=PRC1.4
END

start-ver=1.4
cd-journal=joma
no-vol=27
cd-vols=
no-issue=10
article-no=
start-page=1602
end-page=1608
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Des-gamma-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background and Aim: Hepatocellular carcinoma (HCC) is a hypervascular tumor, and angiogenesis plays an important role in its development. Previously, we demonstrated that des-gamma-carboxyl prothrombin (DCP) promotes both cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) by inducing the autophosphorylation of kinase insert domain receptor (KDR). In the present study, DCP-associated tumor angiogenesis was assessed by comparing hypovascular and common hypervascular HCC. Methods: The solitary HCCs of 827 patients were classified into two groups according to the tumor density at the arterial phase of a dynamic computed tomography scan; the initial clinical data of patients with the hyper- and hypovascular types were compared. The HCC tissues from 95 tumors were analyzed by immunohistochemical staining for DCP and phosphorylated KDR, and intratumoral microvessel density (MVD) was analyzed to evaluate microvessel angiogenesis. Results: The serum DCP levels (320 +/- 3532 mAU/mL) and tumor size (18.4 +/- 9.0 mm) of patients with hypervascular HCC were significantly greater than those with hypovascular HCC (38.7 +/- 80 mAU/mL and 14.6 +/- 5.2 mm, P < 0.001). Immunohistochemical analysis revealed that the expressions of DCP and phospho-KDR were significantly greater in hypervascular HCC (71.4% and 31.0%, respectively) than in hypovascular HCC (7.6% and 5.7%, respectively). Intratumoral MVD was significantly correlated with DCP (r = 0.48, P < 0.0001). Conclusions: des-gamma-carboxyl prothrombin production is associated with tumor angiogenesis in HCC.
en-copyright=
kn-copyright=

en-aut-name=MatsubaraMinoru
en-aut-sei=Matsubara
en-aut-mei=Minoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShirahaHidenori
en-aut-sei=Shiraha
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KataokaJyunro
en-aut-sei=Kataoka
en-aut-mei=Jyunro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

en-aut-name=HoriguchiShigeru
en-aut-sei=Horiguchi
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishinaShin-ichi
en-aut-sei=Nishina
en-aut-mei=Shin-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakaokaNobuyuki
en-aut-sei=Takaoka
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UemuraMasayuki
en-aut-sei=Uemura
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=

en-aut-name=NakamuraShinichiro
en-aut-sei=Nakamura
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KobayashiYoshiyuki
en-aut-sei=Kobayashi
en-aut-mei=Yoshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=NousoKazuhiro
en-aut-sei=Nouso
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=YamamotoKazuhide
en-aut-sei=Yamamoto
en-aut-mei=Kazuhide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=2
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=3
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=4
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=5
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=6
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=7
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=8
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=9
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=10
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=11
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=12
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol

affil-num=13
en-affil=
kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol
en-keyword=des-gamma-carboxyl prothrombin
kn-keyword=des-gamma-carboxyl prothrombin
en-keyword=hepatocellular carcinoma
kn-keyword=hepatocellular carcinoma
en-keyword=intratumoral microvessel density
kn-keyword=intratumoral microvessel density
en-keyword=kinase insert domain receptor
kn-keyword=kinase insert domain receptor
END

start-ver=1.4
cd-journal=joma
no-vol=125
cd-vols=
no-issue=3
article-no=
start-page=229
end-page=234
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20131202
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Roles for a tissue morphogenetic factor, Fgf10
kn-title=組織形成因子Fgf10
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=OhuchiHideyo
en-aut-sei=Ohuchi
en-aut-mei=Hideyo
kn-aut-name=大内淑代
kn-aut-sei=大内
kn-aut-mei=淑代
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　細胞組織学
en-keyword=Fgf10
kn-keyword=Fgf10
en-keyword=線維芽細胞増殖因子
kn-keyword=線維芽細胞増殖因子
en-keyword=上皮間葉相互作用
kn-keyword=上皮間葉相互作用
en-keyword=組織形成
kn-keyword=組織形成
en-keyword=シスエレメント
kn-keyword=シスエレメント
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=3
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130328
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cartilage-Specific Over-Expression of CCN Family Member 2/Connective Tissue Growth Factor (CCN2/CTGF) Stimulates Insulin-Like Growth Factor Expression and Bone Growth
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Previously we showed that CCN family member 2/connective tissue growth factor (CCN2) promotes the proliferation, differentiation, and maturation of growth cartilage cells in vitro. To elucidate the specific role and molecular mechanism of CCN2 in cartilage development in vivo, in the present study we generated transgenic mice overexpressing CCN2 and analyzed them with respect to cartilage and bone development. Transgenic mice were generated expressing a ccn2/lacZ fusion gene in cartilage under the control of the 6 kb-Col2a1-enhancer/promoter. Changes in cartilage and bone development were analyzed histologically and immunohistologically and also by micro CT. Primary chondrocytes as well as limb bud mesenchymal cells were cultured and analyzed for changes in expression of cartilage-related genes, and non-transgenic chondrocytes were treated in culture with recombinant CCN2. Newborn transgenic mice showed extended length of their long bones, increased content of proteoglycans and collagen II accumulation. Micro-CT analysis of transgenic bones indicated increases in bone thickness and mineral density. Chondrocyte proliferation was enhanced in the transgenic cartilage. In in vitro short-term cultures of transgenic chondrocytes, the expression of col2a1, aggrecan and ccn2 genes was substantially enhanced; and in long-term cultures the expression levels of these genes were further enhanced. Also, in vitro chondrogenesis was strongly enhanced. IGF-I and IGF-II mRNA levels were elevated in transgenic chondrocytes, and treatment of non-transgenic chondrocytes with recombinant CCN2 stimulated the expression of these mRNA. The addition of CCN2 to non-transgenic chondrocytes induced the phosphorylation of IGFR, and ccn2-overexpressing chondrocytes showed enhanced phosphorylation of IGFR. Our data indicates that the observed effects of CCN2 may be mediated in part by CCN2-induced overexpression of IGF-I and IGF-II. These findings indicate that CCN2-overexpression in transgenic mice accelerated the endochondral ossification processes, resulting in increased length of their long bones. Our results also indicate the possible involvement of locally enhanced IGF-I or IGF-II in this extended bone growth.
en-copyright=
kn-copyright=

en-aut-name=TomitaNao
en-aut-sei=Tomita
en-aut-mei=Nao
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=ItohShinsuke
en-aut-sei=Itoh
en-aut-mei=Shinsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AoyamaEriko
en-aut-sei=Aoyama
en-aut-mei=Eriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YaoMayumi
en-aut-sei=Yao
en-aut-mei=Mayumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YamashiroTakashi
en-aut-sei=Yamashiro
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakigawaMasaharu
en-aut-sei=Takigawa
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Sch Dent, Dept Biochem & Mol Dent

affil-num=2
en-affil=
kn-affil=Okayama Univ, Sch Dent, Dept Biochem & Mol Dent

affil-num=3
en-affil=
kn-affil=Okayama Univ, Sch Dent, Dept Biochem & Mol Dent

affil-num=4
en-affil=
kn-affil=Okayama Univ, Sch Dent, Biodent Res Ctr

affil-num=5
en-affil=
kn-affil=Okayama Univ, Sch Dent, Dept Biochem & Mol Dent

affil-num=6
en-affil=
kn-affil=Okayama Univ, Sch Dent, Dept Orthodont, Grad Sch Med Dent & Pharmaceut Sci

affil-num=7
en-affil=
kn-affil=Okayama Univ, Sch Dent, Dept Biochem & Mol Dent
END

start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=3
article-no=
start-page=230
end-page=236
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201303
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Esophageal squamous cell carcinoma (ESCC) remains one of the most aggressive cancers with poor prognosis regardless of a several reports that indicate a better therapeutic efficacy using some new chemotherapeutic agents. Recent drug development has contributed to an improved specificity to suppress mTOR activity by which many types of malignancies can be explosively progressed. Temsirolimus (CCI-779, TricelTM) is one of recently synthesized analogs of rapamycin and has provided better outcomes for patients with renal cell carcinoma. In this study, we experimentally evaluated an efficacy of targeting mTOR by temsirolimus for ESCC treatment, with an assessment of its survival advantage using an advanced ESCC animal model. 

First, we confirmed that the expression of phosphorylated mTOR was increased in 46 of 58 clinical ESCC tumor tissues (79.3%) and appeared to get strengthened with tumor progression. All of ESCC cell lines used in this study revealed an increase of mTOR phosphorylation, accompanied with the upregulation of hypoxia inducible factor-I alpha (HIF-1 alpha), one of the critical effectors regulated by mTOR. Temsirolimus treatment apparently suppressed the activation of mTOR and its downstream effectors, resulting in the reduced ability of ESCC cell proliferation. Finally, the weekly administration of temsirolimus significantly diminished the size of subcutaneous tumors (vehicle, 3261.6 +/- 722.0; temsirolimus, 599.2 +/- 122.9; p = 0.007) in nude mice and effectively prolonged orthotopic esophageal cancer-bearing mice (median survival periods: control, 31 d; temsirolimus, 43 d; p = 0.0024). 

These data suggests that targeting mTOR by temsirolimus may become a therapeutic alternative for esophageal cancer, with a contribution to a better outcome.
en-copyright=
kn-copyright=

en-aut-name=NishikawaToshio
en-aut-sei=Nishikawa
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakaokaMunenori
en-aut-sei=Takaoka
en-aut-mei=Munenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=TomonoYasuko
en-aut-sei=Tomono
en-aut-mei=Yasuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HaoHuifang
en-aut-sei=Hao
en-aut-mei=Huifang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=BaoXiaohong
en-aut-sei=Bao
en-aut-mei=Xiaohong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FukazawaTakuya
en-aut-sei=Fukazawa
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=WangZhigang
en-aut-sei=Wang
en-aut-mei=Zhigang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SakuramaKazufumi
en-aut-sei=Sakurama
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraYasuhiro
en-aut-sei=Fujiwara
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MotokiTakayuki
en-aut-sei=Motoki
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=

en-aut-name=YamatsujiTomoki
en-aut-sei=Yamatsuji
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=TanakaNoriaki
en-aut-sei=Tanaka
en-aut-mei=Noriaki
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=

en-aut-name=NaomotoYoshio
en-aut-sei=Naomoto
en-aut-mei=Yoshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=4
en-affil=
kn-affil=Shigei Med Res Inst

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=8
en-affil=
kn-affil=Inner Mongolia Univ, Coll Life Sci, Dept Biol

affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=11
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=12
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=13
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=14
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=15
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol

affil-num=16
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol
en-keyword=temsirolimus
kn-keyword=temsirolimus
en-keyword=esophageal cancer
kn-keyword=esophageal cancer
en-keyword=mTOR
kn-keyword=mTOR
en-keyword=prolonged survival
kn-keyword=prolonged survival
en-keyword=molecular-targeted therapy
kn-keyword=molecular-targeted therapy
END

start-ver=1.4
cd-journal=joma
no-vol=103
cd-vols=
no-issue=10
article-no=
start-page=1889
end-page=1897
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Tumor growth inhibitory effect of ADAMTS1 is accompanied by the inhibition of tumor angiogenesis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Angiogenesis plays an important role in tumor progression. Several reports have demonstrated that a disintegrin and metalloproteinase with thrombospondin motifs1 (ADAMTS1) inhibited angiogenesis via multiple mechanisms. The aim of this study was to investigate the effect of ADAMTS1 on endothelial cells in vitro and on tumor growth with regard to angiogenesis in vivo. We examined the effects of the transfection of ADAMTS1 using two constructs, full-length ADAMTS1 (full ADAMTS1) and catalytic domain-deleted ADAMTS1 (delta ADAMTS1). Transfection of both the full ADAMTS1 and delta ADAMTS1 gene constructs demonstrated the secretion of tagged-ADAMTS1 protein into the conditioned medium, so we examined the effects of ADAMTS1-containing conditioned medium on endothelial cells. Both types of conditioned media inhibited endothelial tube formation, and this effect was completely abolished after immunoprecipitation of the secreted protein from the medium. Both types of conditioned media also inhibited endothelial cell migration and proliferation. We then examined the impact of ADAMTS1 on endothelial cell apoptosis. Both conditioned media increased the number of Annexin V-positive endothelial cells and caspase-3 activity and this effect was attenuated when z-vad was added. These results indicated that ADAMTS1 induced endothelial cell apoptosis. We next examined the effects of ADAMTS1 gene transfer into tumor-bearing mice. Both full ADAMTS1 and delta ADAMTS1 significantly inhibited the subcutaneous tumor growth. Collectively, our results demonstrated that ADAMTS1 gene transfer inhibited angiogenesis in vitro and in vivo, likely as a result of the induction of endothelial cell apoptosis by ADAMTS1 that occurs independent of the protease activity.
en-copyright=
kn-copyright=

en-aut-name=ObikaMasanari
en-aut-sei=Obika
en-aut-mei=Masanari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=TakahashiKatsuyuki
en-aut-sei=Takahashi
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=LiJiayi
en-aut-sei=Li
en-aut-mei=Jiayi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

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=5
ORCID=

en-aut-name=CilekMehmet Zeynel
en-aut-sei=Cilek
en-aut-mei=Mehmet Zeynel
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=InagakiJunko
en-aut-sei=Inagaki
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OhtsukiTakashi
en-aut-sei=Ohtsuki
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KusachiShozo
en-aut-sei=Kusachi
en-aut-mei=Shozo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NinomiyaYoshifumi
en-aut-sei=Ninomiya
en-aut-mei=Yoshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Hlth Sci, Dept Med Technol

affil-num=11
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem

affil-num=12
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
END

start-ver=1.4
cd-journal=joma
no-vol=90
cd-vols=
no-issue=2
article-no=
start-page=99
end-page=110
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201302
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Morphologic, flow cytometric, functional, and molecular analyses of S100B positive lymphocytes, unique cytotoxic lymphocytes containing S100B protein
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Little is known about the S100B+ lymphocytes, which are unique human peripheral blood lymphocytes (PBL) containing the S100B protein. It has recently been shown that S100B is released from various types of S100B+ cells and exhibits varied cytokine-like activities. In this study, we precisely characterized the S100B+ lymphocytes of healthy adults with respect to the proportion in the whole PBL, immunophenotypes, function, and their S100B mRNA expression and also evaluated their S100B-releasing activity upon stimulation. S100B+ lymphocytes were detected in all individuals examined, and the proportion of S100B+ lymphocytes in the whole PBL ranged from 0.42% to 16.15% (mean, 4.21%). In addition, two subtypes of S100B+ lymphocytes, a CTL subtype (CD3+ CD8+ CD16-) and a NK subtype (CD3- CD8- CD16+), were detected. The majority of the CTL subtype of S100B+ lymphocytes expressed the alpha beta-T-cell receptor. Surprisingly, S100B mRNA was detected not only in S100B+ lymphocytes, but also in every S100B- lymphocytes, although the expression levels of S100B mRNA in S100B- lymphocytes were much lower than those of S100B+ lymphocytes. The CTL subtype of S100B+ lymphocytes exhibited blastic morphological changes, proliferated and released S100B upon stimulation with phytohemagglutinin. The NK subtype of S100B+ lymphocytes exhibited morphological NK activity when cocultivated with NK-sensitive target, K-562 cells. Thus, the CTL subtype of S100B+ lymphocytes exhibit the biological characteristics of T cells, while the NK subtype of S100B+ lymphocytes exhibit the characteristics of NK cells. These results suggest that S100B+ lymphocytes are a particular subtype of cytotoxic lymphocytes that play a unique role in antitumor immunity.
en-copyright=
kn-copyright=

en-aut-name=MikiYukari
en-aut-sei=Miki
en-aut-mei=Yukari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=MukaeYuriko
en-aut-sei=Mukae
en-aut-mei=Yuriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HayashiAtsushi
en-aut-sei=Hayashi
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SatoHiaki
en-aut-sei=Sato
en-aut-mei=Hiaki
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=TakahashiKiyoshi
en-aut-sei=Takahashi
en-aut-mei=Kiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Hlth Sci, Dept Med Technol

affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=3
en-affil=
kn-affil=Kawasaki Coll Allied Hlth Profess, Dept Med Technol

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Hlth Sci, Dept Med Technol

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Hlth Sci, Dept Med Technol

affil-num=6
en-affil=
kn-affil=Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Hlth Sci, Dept Med Technol
en-keyword=S100B
kn-keyword=S100B
en-keyword=peripheral blood
kn-keyword=peripheral blood
en-keyword=cytotoxic T cells
kn-keyword=cytotoxic T cells
en-keyword=NK cells
kn-keyword=NK cells
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=1
article-no=
start-page=26
end-page=31
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201204
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Strong anti-tumor effect of NVP-AUY922, a novel Hsp90 inhibitor, on non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The anti-tumor activity of a newly developed Hsp90 inhibitor, NVP-AUY922 (AUY922), against non-small cell lung cancer (NSCLC) was examined. Twenty-one NSCLC cell lines were used, the somatic alterations of which were characterized. Cell proliferation was analyzed using a modified MTS assay. Expression of the client proteins was assessed using Western blotting. The cell cycle was analyzed using flow cytometry. The IC50 value of AUY922 for the NSCLC cell lines ranged from 5.2 to 860 nM (median, 20.4 nM). Based on previous data, cells with an IC50 of less than 50 nM were classified as sensitive cells and 19 of the 21 NSCLC cell lines were judged to be sensitive. The IC50 of five malignant pleural mesothelioma (MPM) cell lines revealed that the MPM cells had a significantly higher IC50 value (median, 89.2 nM; range, 22.2-24, 100 nM) than the NSCLC cells (p = 0.015). There was significant depletion of both the total and phosphorylated client proteins - EGFR, MET, HERZ and ART - at low drug concentrations (50-100 nM) in drug-sensitive cell lines. Cell-cycle analysis was performed for two sensitive cell lines, H1975 and H838. Following AUY922 treatment, an increase in the sub-G(0)-G(1) cell population, as well as appearance of cleaved PARP expression, indicated the induction of apoptosis. In conclusion, AUY922 was effective against most NSCLC cell lines, independent of the type of known molecular alteration, and appears to be a promising new drug for the treatment of NSCLC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
en-copyright=
kn-copyright=

en-aut-name=UenoTsuyoshi
en-aut-sei=Ueno
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TsukudaKazunori
en-aut-sei=Tsukuda
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=AndoMidori
en-aut-sei=Ando
en-aut-mei=Midori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakaokaMunenori
en-aut-sei=Takaoka
en-aut-mei=Munenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AsanoHiroaki
en-aut-sei=Asano
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MakiYuho
en-aut-sei=Maki
en-aut-mei=Yuho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MuraokaTakayuki
en-aut-sei=Muraoka
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TanakaNorimitsu
en-aut-sei=Tanaka
en-aut-mei=Norimitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FurukawaMasashi
en-aut-sei=Furukawa
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=YamatsujiTomoki
en-aut-sei=Yamatsuji
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
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=14
ORCID=

en-aut-name=NaomotoYoshio
en-aut-sei=Naomoto
en-aut-mei=Yoshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=MiyoshiShinichiro
en-aut-sei=Miyoshi
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=3
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=5
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Surg

affil-num=6
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=7
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=8
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=9
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=10
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=11
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=12
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=13
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Surg

affil-num=14
en-affil=
kn-affil=Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci

affil-num=15
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Surg

affil-num=16
en-affil=
kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
en-keyword=NSCLC
kn-keyword=NSCLC
en-keyword=Hsp90
kn-keyword=Hsp90
en-keyword=AUY922
kn-keyword=AUY922
en-keyword=EGFR
kn-keyword=EGFR
en-keyword=EGFR-TKI
kn-keyword=EGFR-TKI
en-keyword=Mesothelioma
kn-keyword=Mesothelioma
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=1
article-no=
start-page=32
end-page=38
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201204
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Frequent methylation and oncogenic role of microRNA-34b/c in small-cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Small-cell lung cancer (SCLC) is an aggressive tumor with a dismal prognosis among primary lung cancers. MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human malignancy. The miR-34 family is comprised of tumor-suppressive miRNAs, and its reduced expression by methylation has been reported in various cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the alteration and tumor-suppressive impact of miR-34s in SCLC. The methylation of miR-34a and miR-34b/c was observed in 4 (36%) and 7 (64%) of 11 SCLC cell lines, respectively. Among the 27 SCLC clinical specimens, miR-34a and miR-34b/c were methylated in 4(15%) and 18 (67%), respectively. In contrast, 13 (28%) miR-34a methylated cases and 12 (26%) miR-34b/c methylated cases were found in 47 NSCLC primary tumors. The frequency of miR-34b/c methylation was significantly higher in SCLC than in NSCLC (p < 0.001). The expressions of miR-34s were reduced in methylated cell lines and tumors and restored after 5-aza-2'-deoxycytidine treatment, indicating that methylation was responsible for the reduced expression of miR-34s. Because the frequency of methylation was higher in miR-34b/c, we focused on miR-34b/c for a functional analysis. We examined the effect of miR-34b/c introduction on cell proliferation, migration and invasion. The transfection of miR-34b/c to two SCLC cell lines (H1048 and SBC5) resulted in the significant inhibition of cell growth, migration, and invasion, compared with control transfectants. Our results indicate that the aberrant methylation of miR-34b/c plays an important role in the pathogenesis of SCLC, implying that miR-34b/c may be a useful therapeutic target for SCLC.
en-copyright=
kn-copyright=

en-aut-name=TanakaNorimitsu
en-aut-sei=Tanaka
en-aut-mei=Norimitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KuboTakafumi
en-aut-sei=Kubo
en-aut-mei=Takafumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MakiYuho
en-aut-sei=Maki
en-aut-mei=Yuho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MuraokaTakayuki
en-aut-sei=Muraoka
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FurukawaMasashi
en-aut-sei=Furukawa
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UenoTsuyoshi
en-aut-sei=Ueno
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=AsanoHiroaki
en-aut-sei=Asano
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TsukudaKazunori
en-aut-sei=Tsukuda
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
ORCID=

en-aut-name=MiyoshiShinichiro
en-aut-sei=Miyoshi
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=3
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=5
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=6
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=7
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=8
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=9
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=10
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=11
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=12
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=13
en-affil=
kn-affil=Natl Hosp Org Yamaguchi Ube Med Ctr, Dept Med Oncol

affil-num=14
en-affil=
kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
en-keyword=Methylation
kn-keyword=Methylation
en-keyword=MicroRNA
kn-keyword=MicroRNA
en-keyword=MicroRNA-34b/c
kn-keyword=MicroRNA-34b/c
en-keyword=Small cell lung cancer
kn-keyword=Small cell lung cancer
en-keyword=Non-small cell lung cancer
kn-keyword=Non-small cell lung cancer
en-keyword=p53
kn-keyword=p53
END

start-ver=1.4
cd-journal=joma
no-vol=430
cd-vols=
no-issue=2
article-no=
start-page=592
end-page=597
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130111
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PML tumor suppressor protein is required for HCV production
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.
en-copyright=
kn-copyright=

en-aut-name=KurokiMisao
en-aut-sei=Kuroki
en-aut-mei=Misao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=HijikataMakoto
en-aut-sei=Hijikata
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
ORCID=

en-aut-name=WakitaTakaji
en-aut-sei=Wakita
en-aut-mei=Takaji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ShimotohnoKunitada
en-aut-sei=Shimotohno
en-aut-mei=Kunitada
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci

affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci

affil-num=3
en-affil=
kn-affil=Kyoto Univ, Dept Viral Oncol, Inst Virus Res

affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci

affil-num=5
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci

affil-num=6
en-affil=
kn-affil=Natl Inst Infect Dis, Dept Virol 2

affil-num=7
en-affil=
kn-affil=Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol

affil-num=8
en-affil=
kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci
en-keyword=Hepatitis C virus
kn-keyword=Hepatitis C virus
en-keyword=PML
kn-keyword=PML
en-keyword=INI1
kn-keyword=INI1
en-keyword=DDX5
kn-keyword=DDX5
en-keyword=Tumor suppressor
kn-keyword=Tumor suppressor
en-keyword=Lipid droplet
kn-keyword=Lipid droplet
END

start-ver=1.4
cd-journal=joma
no-vol=67
cd-vols=
no-issue=3
article-no=
start-page=129
end-page=134
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201306
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cell Cycle Abnormality in Metabolic Syndrome and Nuclear Receptors as an Emerging Therapeutic Target
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=In recent years, many researchers have emphasized the importance of metabolic syndrome based on its increasing prevalence and its adverse prognosis due to associated chronic vascular complications. Upstream of a cluster of metabolic and vascular disorders is the accumulation of visceral adipose tissue, which plays a central role in the pathophysiology. In the accumulation of adipose tissues, cell cycle regulation is tightly linked to cellular processes such as proliferation, hypertrophy and apoptosis. In addition, various cell cycle abnormalities have also been observed in other tissues, such as kidneys and the cardiovascular system, and they are critically involved in the progression of disease. Here, we discuss cell cycle abnormalities in metabolic syndrome in various tissues. Furthermore, we describe the role of nuclear receptors in cell growth and survival, and glucose and lipid metabolism in the whole body. Therapeutic strategies for modulating various cell cycles in metabolic disorders by targeting nuclear receptors may overcome obesity and its chronic vascular complications in the future.
en-copyright=
kn-copyright=

en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
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=

en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

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

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

affil-num=3
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=nuclear receptor
kn-keyword=nuclear receptor
en-keyword=cell cycle
kn-keyword=cell cycle
en-keyword=metabolic syndrome
kn-keyword=metabolic syndrome
en-keyword=diabetic nephropathy
kn-keyword=diabetic nephropathy
END

start-ver=1.4
cd-journal=joma
no-vol=6
cd-vols=
no-issue=3
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2011
dt-pub=20110514
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Expression of a Constitutively Active Calcineurin Encoded by an Intron-Retaining mRNA in Follicular Keratinocytes
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hair growth is a highly regulated cyclical process. Immunosuppressive immunophilin ligands such as cyclosporin A (CsA) and FK506 are known as potent hair growth modulatory agents in rodents and humans that induce active hair growth and inhibit hair follicle regression. The immunosuppressive effectiveness of these drugs has been generally attributed to inhibition of T cell activation through well-characterized pathways. Specifically, CsA and FK506 bind to intracellular proteins, principally cyclophilin A and FKBP12, respectively, and thereby inhibit the phosphatase calcineurin (Cn). The calcineurin (Cn)/NFAT pathway has an important, but poorly understood, role in the regulation of hair follicle development. Here we show that a novel-splicing variant of calcineurin A beta CnA beta-FK, which is encoded by an intron-retaining mRNA and is deficient in the autoinhibitory domain, is predominantly expressed in mature follicular keratinocytes but not in the proliferating keratinocytes of rodents. CnA beta-FK was weakly sensitive to Ca(2+) and dephosphorylated NFATc2 under low Ca(2+) levels in keratinocytes. Inhibition of Cn/NFAT induced hair growth in nude mice. Cyclin G2 was identified as a novel target of the Cn/NFATc2 pathway and its expression in follicular keratinocytes was reduced by inhibition of Cn/NFAT. Overexpression of cyclin G2 arrested the cell cycle in follicular keratinocytes in vitro and the Cn inhibitor, cyclosporin A, inhibited nuclear localization of NFATc2, resulting in decreased cyclin G2 expression in follicular keratinocytes of rats in vivo. We therefore suggest that the calcineurin/NFAT pathway has a unique regulatory role in hair follicle development.
en-copyright=
kn-copyright=

en-aut-name=FujimuraAtsushi
en-aut-sei=Fujimura
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

en-aut-name=NishikiTei-ichi
en-aut-sei=Nishiki
en-aut-mei=Tei-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OhmoriIori
en-aut-sei=Ohmori
en-aut-mei=Iori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WeiFanyan
en-aut-sei=Wei
en-aut-mei=Fanyan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MatsuiHideki
en-aut-sei=Matsui
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TomizawaKazuhito
en-aut-sei=Tomizawa
en-aut-mei=Kazuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=3
en-affil=
kn-affil=Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=5
en-affil=
kn-affil=Kumamoto Univ, Dept Mol Physiol, Fac Life Sci

affil-num=6
en-affil=
kn-affil=Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=7
en-affil=
kn-affil=Kumamoto Univ, Dept Mol Physiol, Fac Life Sci
END

start-ver=1.4
cd-journal=joma
no-vol=423
cd-vols=
no-issue=4
article-no=
start-page=744
end-page=749
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120713
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken together, a possible strategy for inhibiting peritoneal dissemination by targeting FAK with TAE226 appears to be applicable through anti-proliferative and anti-invasion/anti-migration mechanisms.
en-copyright=
kn-copyright=

en-aut-name=HaoHui-fang
en-aut-sei=Hao
en-aut-mei=Hui-fang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakaokaMunenori
en-aut-sei=Takaoka
en-aut-mei=Munenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=BaoXiao-hong
en-aut-sei=Bao
en-aut-mei=Xiao-hong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WangZhi-gang
en-aut-sei=Wang
en-aut-mei=Zhi-gang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TomonoYasuko
en-aut-sei=Tomono
en-aut-mei=Yasuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SakuramaKazufumi
en-aut-sei=Sakurama
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=FukazawaTakuya
en-aut-sei=Fukazawa
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YamatsujiTomoki
en-aut-sei=Yamatsuji
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=

en-aut-name=NaomotoYoshio
en-aut-sei=Naomoto
en-aut-mei=Yoshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=2
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Surg

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=4
en-affil=
kn-affil=Inner Mongolia Univ, Coll Life Sci, Key Lab Mammal Reprod Biol & Biotechnol, Minist Educ

affil-num=5
en-affil=
kn-affil=Shigei Med Res Inst, Div Mol & Cell Biol

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=8
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Surg

affil-num=9
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Surg

affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=11
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Surg
en-keyword=Focal adhesion kinase
kn-keyword=Focal adhesion kinase
en-keyword=TAE226
kn-keyword=TAE226
en-keyword=Peritoneal dissemination
kn-keyword=Peritoneal dissemination
en-keyword=Prolonged survival
kn-keyword=Prolonged survival
en-keyword=Anti-proliferation
kn-keyword=Anti-proliferation
en-keyword=Colon cancer
kn-keyword=Colon cancer
END

start-ver=1.4
cd-journal=joma
no-vol=348
cd-vols=
no-issue=1
article-no=
start-page=224
end-page=232
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120102
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Peroxisome proliferator-activated receptor activity is involved in the osteoblastic differentiation regulated by bone morphogenetic proteins and tumor necrosis factor-α.
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Recent studies have suggested possible adverse effects of thiazolidinediones on bone metabolism. However, the detailed mechanism by which the activity of PPAR affects bone formation has not been elucidated. Impaired osteoblastic function due to cytokines is critical for the progression of inflammatory bone diseases. In the present study, we investigated the cellular mechanism by which PPAR actions interact with osteoblast differentiation regulated by BMP and TNF-alpha using mouse myoblastic C2C12 cells. BMP-2 and -4 potently induced the expression of various bone differentiation markers including Runx2, osteocalcin, type-1 collagen and alkaline phosphatase (ALP) in C2C12 cells. When administered in combination with a PPAR alpha agonist (fenofibric acid) but not with a PPAR gamma agonist (pioglitazone), BMP-4 enhanced osteoblast differentiation through the activity of PPAR alpha. The osteoblastic changes induced by BMP-4 were readily suppressed by treatment with TNF-alpha. Interestingly, the activities of PPAR alpha and PPAR gamma agonists reversed the suppression by TNF-alpha of osteoblast differentiation induced by BMP-4. Furthermore, TNF-alpha-induced phosphorylation of MAPKs, NF kappa B, I kappa B and Stat pathways was inhibited in the presence of PPAR alpha and PPAR gamma agonists with reducing TNF-alpha receptor expression. In view of the finding that inhibition of SAPK/JNK. Stat and NF kappa B pathways reversed the TNF-alpha suppression of osteoblast differentiation, we conclude that these cascades are functionally involved in the actions of PPARs that antagonize TNF-alpha-induced suppression of osteoblast differentiation. It was further discovered that the PPAR alpha agonist enhanced BMP-4-induced Smad1/5/8 signaling through downregulation of inhibitory Smad6/7 expression, whereas the PPAR gamma agonist impaired this activity by suppressing BMPRII expression. On the other hand, BMPs increased the expression levels of PPAR alpha and PPAR gamma in the process of osteoblast differentiation. Thus, PPAR alpha actions promote BMP-induced osteoblast differentiation, while both activities of PPAR alpha and PPAR gamma suppress TNF-alpha actions. Collectively, our present data establishes that PPAR activities are functionally involved in modulating the interaction between the BMP system and TNF-alpha receptor signaling that is crucial for bone metabolism.
en-copyright=
kn-copyright=

en-aut-name=TakanoMariko
en-aut-sei=Takano
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=InagakiKenichi
en-aut-sei=Inagaki
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakedaMasaya
en-aut-sei=Takeda
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NakamuraEri
en-aut-sei=Nakamura
en-aut-mei=Eri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TsukamotoNaoko
en-aut-sei=Tsukamoto
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MiyoshiTomoko
en-aut-sei=Miyoshi
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
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=10
ORCID=

affil-num=1
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=

affil-num=2
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=

affil-num=3
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=

affil-num=4
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=

affil-num=5
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=

affil-num=6
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=

affil-num=7
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=

affil-num=8
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=

affil-num=9
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=

affil-num=10
en-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
kn-affil=
en-keyword=Bone morphogenetic protein (BMP)
kn-keyword=Bone morphogenetic protein (BMP)
en-keyword=Peroxisome proliferator-activated receptor (PPAR)
kn-keyword=Peroxisome proliferator-activated receptor (PPAR)
en-keyword=Osteoblast
kn-keyword=Osteoblast
en-keyword=Tumor necrosis factor-alpha (TNF-alpha)
kn-keyword=Tumor necrosis factor-alpha (TNF-alpha)
END

start-ver=1.4
cd-journal=joma
no-vol=7
cd-vols=
no-issue=4
article-no=
start-page=e33544
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120412
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5'-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model.
en-copyright=
kn-copyright=

en-aut-name=ChenLing
en-aut-sei=Chen
en-aut-mei=Ling
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KasaiTomonari
en-aut-sei=Kasai
en-aut-mei=Tomonari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LiYueguang
en-aut-sei=Li
en-aut-mei=Yueguang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SugiiYuh
en-aut-sei=Sugii
en-aut-mei=Yuh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=JinGuoliang
en-aut-sei=Jin
en-aut-mei=Guoliang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OkadaMasashi
en-aut-sei=Okada
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=VaidyanathArun
en-aut-sei=Vaidyanath
en-aut-mei=Arun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MizutaniAkifumi
en-aut-sei=Mizutani
en-aut-mei=Akifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=

en-aut-name=KudohTakayuki
en-aut-sei=Kudoh
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=HendrixMary J. C.
en-aut-sei=Hendrix
en-aut-mei=Mary J. C.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SalomonDavid S
en-aut-sei=Salomon
en-aut-mei=David S
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FuLi
en-aut-sei=Fu
en-aut-mei=Li
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ

affil-num=2
en-affil=
kn-affil=Okayama Univ

affil-num=3
en-affil=
kn-affil=Tianjin 4th Ctr Hosp

affil-num=4
en-affil=
kn-affil=Okayama Univ

affil-num=5
en-affil=
kn-affil=Okayama Univ

affil-num=6
en-affil=
kn-affil=Okayama Univ

affil-num=7
en-affil=
kn-affil=Okayama Univ

affil-num=8
en-affil=
kn-affil=Okayama Univ

affil-num=9
en-affil=
kn-affil=Okayama Univ

affil-num=10
en-affil=
kn-affil=Okayama Univ

affil-num=11
en-affil=
kn-affil=Northwestern Univ

affil-num=12
en-affil=
kn-affil=NCI

affil-num=13
en-affil=
kn-affil=Tianjin Med Univ

affil-num=14
en-affil=
kn-affil=Okayama Univ
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2011
dt-pub=20110104
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC). 

Methods: RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. 

Results: RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 +/- 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 +/- 4% and 4 +/- 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. 

Conclusion: RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.
en-copyright=
kn-copyright=

en-aut-name=NakanishiYutaka
en-aut-sei=Nakanishi
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShirahaHidenori
en-aut-sei=Shiraha
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishinaShin-ichi
en-aut-sei=Nishina
en-aut-mei=Shin-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TanakaShigetomi
en-aut-sei=Tanaka
en-aut-mei=Shigetomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MatsubaraMinoru
en-aut-sei=Matsubara
en-aut-mei=Minoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HoriguchiShigeru
en-aut-sei=Horiguchi
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

en-aut-name=TakaokaNobuyuki
en-aut-sei=Takaoka
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UemuraMasayuki
en-aut-sei=Uemura
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KuwakiKenji
en-aut-sei=Kuwaki
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=HagiharaHiroaki
en-aut-sei=Hagihara
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ToshimoriJunichi
en-aut-sei=Toshimori
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OhnishiHideki
en-aut-sei=Ohnishi
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
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=14
ORCID=

en-aut-name=NakamuraShinichiro
en-aut-sei=Nakamura
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KobayashiYoshiyuki
en-aut-sei=Kobayashi
en-aut-mei=Yoshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=NousoKazuhiro
en-aut-sei=Nouso
en-aut-mei=Kazuhiro
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=YamamotoKazuhide
en-aut-sei=Yamamoto
en-aut-mei=Kazuhide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ

affil-num=2
en-affil=
kn-affil=Okayama Univ

affil-num=3
en-affil=
kn-affil=Okayama Univ

affil-num=4
en-affil=
kn-affil=Okayama Univ

affil-num=5
en-affil=
kn-affil=Okayama Univ

affil-num=6
en-affil=
kn-affil=Okayama Univ

affil-num=7
en-affil=
kn-affil=Okayama Univ

affil-num=8
en-affil=
kn-affil=Okayama Univ

affil-num=9
en-affil=
kn-affil=Okayama Univ

affil-num=10
en-affil=
kn-affil=Okayama Univ

affil-num=11
en-affil=
kn-affil=Okayama Univ

affil-num=12
en-affil=
kn-affil=Okayama Univ

affil-num=13
en-affil=
kn-affil=Okayama Univ

affil-num=14
en-affil=
kn-affil=Okayama Univ

affil-num=15
en-affil=
kn-affil=Okayama Univ

affil-num=16
en-affil=
kn-affil=Okayama Univ

affil-num=17
en-affil=
kn-affil=Okayama Univ

affil-num=18
en-affil=
kn-affil=Okayama Univ

affil-num=19
en-affil=
kn-affil=Okayama Univ
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2009
dt-pub=20090718
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Twist expression promotes migration and invasion in hepatocellular carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Twist, a transcription factor of the basic helix-loop-helix class, is reported to regulate cancer metastasis. It is known to induce epithelial-mesenchymal transition (EMT). In this study, we evaluated the expression of twist and its effect on cell migration in hepatocellular carcinoma (HCC). 

Methods: We examined twist expression using immunohistochemistry in 20 tissue samples of hepatocellular carcinoma, and assessed twist expression in HCC cell lines by RT-PCR and Western blot analysis. Ectopic twist expression was created by introducing a twist construct in the twist-negative HCC cell lines. Endogenous twist expression was blocked by twist siRNA in the twist-positive HCC cell lines. We studied EMT related markers, E-cadherin, Vimentin, and N-cadherin by Western blot analysis. Cell proliferation was measured by MTT assay, and cell migration was measured by in vitro wound healing assay. We used immunofluorescent vinculin staining to visualize focal adhesion. 

Results: We detected strong and intermediate twist expression in 7 of 20 tumor samples, and no significant twist expression was found in the tumor-free resection margins. In addition, we detected twist expression in HLE, HLF, and SK-Hep1 cells, but not in PLC/RPF/5, HepG2, and Huh7 cells. Ectopic twist-expressing cells demonstrated enhanced cell motility, but twist expression did not affect cell proliferation. Twist expression induced epithelial-mesenchymal transition together with related morphologic changes. Focal adhesion contact was reduced significantly in ectopic twist-expressing cells. Twist-siRNA-treated HLE, HLF, and SK-Hep1 cells demonstrated a reduction in cell migration by 50, 40 and 18%, respectively. 

Conclusion: Twist induces migratory effect on hepatocellular carcinoma by causing epithelial-mesenchymal transition.
en-copyright=
kn-copyright=

en-aut-name=MatsuoNoriyuki
en-aut-sei=Matsuo
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShirahaHidenori
en-aut-sei=Shiraha
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FujikawaTatsuya
en-aut-sei=Fujikawa
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakaokaNobuyuki
en-aut-sei=Takaoka
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UedaNaoki
en-aut-sei=Ueda
en-aut-mei=Naoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TanakaShigetomi
en-aut-sei=Tanaka
en-aut-mei=Shigetomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NishinaShinichi
en-aut-sei=Nishina
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NakanishiYutaka
en-aut-sei=Nakanishi
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UemuraMasayuki
en-aut-sei=Uemura
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=

en-aut-name=NakamuraShinichiro
en-aut-sei=Nakamura
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KobayashiYoshiyuki
en-aut-sei=Kobayashi
en-aut-mei=Yoshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=NousoKazuhiro
en-aut-sei=Nouso
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
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=14
ORCID=

en-aut-name=YamamotoKazuhide
en-aut-sei=Yamamoto
en-aut-mei=Kazuhide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ

affil-num=2
en-affil=
kn-affil=Okayama Univ

affil-num=3
en-affil=
kn-affil=Okayama Univ

affil-num=4
en-affil=
kn-affil=Okayama Univ

affil-num=5
en-affil=
kn-affil=Okayama Univ

affil-num=6
en-affil=
kn-affil=Okayama Univ

affil-num=7
en-affil=
kn-affil=Okayama Univ

affil-num=8
en-affil=
kn-affil=Okayama Univ

affil-num=9
en-affil=
kn-affil=Okayama Univ

affil-num=10
en-affil=
kn-affil=Okayama Univ

affil-num=11
en-affil=
kn-affil=Okayama Univ

affil-num=12
en-affil=
kn-affil=Okayama Univ

affil-num=13
en-affil=
kn-affil=Okayama Univ

affil-num=14
en-affil=
kn-affil=Okayama Univ

affil-num=15
en-affil=
kn-affil=Okayama Univ
END

start-ver=1.4
cd-journal=joma
no-vol=124
cd-vols=
no-issue=3
article-no=
start-page=231
end-page=238
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20121203
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=HuH-7 cell line established from a highly differentiated human hepatocellular carcinoma
kn-title=高分化型ヒト肝癌由来細胞株“HuH-7”
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=高分化型ヒト肝癌由来細胞株“HuH-7”は，1982年にCancer Researchにその樹立を報告した．HuH-7は，当時の岡山大学医学部附属癌源研究施設病理部門（故佐藤二郎教授）の下で樹立し，これまで多くの研究分野で利用され，世界的に有名な肝癌細胞株となっている．本稿では，有用性の高い分化機能を有するヒト肝癌細胞株HuH-7について，肝細胞癌の腫瘍マーカーであるα-fetoprotein（AFP）を中心に，この細胞株を用いた研究分野に関する詳細を紹介する．
en-copyright=
kn-copyright=

en-aut-name=NakabayashiHidekazu
en-aut-sei=Nakabayashi
en-aut-mei=Hidekazu
kn-aut-name=中林秀和
kn-aut-sei=中林
kn-aut-mei=秀和
aut-affil-num=1
ORCID=

en-aut-name=TaketaKazuhisa
en-aut-sei=Taketa
en-aut-mei=Kazuhisa
kn-aut-name=武田和久
kn-aut-sei=武田
kn-aut-mei=和久
aut-affil-num=2
ORCID=

affil-num=1
en-affil=
kn-affil=北海道情報大学　医療情報学科

affil-num=2
en-affil=
kn-affil=介護老人保健施設　仁和の里
en-keyword=肝細胞癌
kn-keyword=肝細胞癌
en-keyword=培養細胞
kn-keyword=培養細胞
en-keyword=α-フェトプロテイン
kn-keyword=α-フェトプロテイン
en-keyword=HuH-7
kn-keyword=HuH-7
END

start-ver=1.4
cd-journal=joma
no-vol=53
cd-vols=
no-issue=4
article-no=
start-page=635
end-page=645
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201204
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A chemical biology approach reveals an opposite action between thermospermine and auxin in xylem development in Arabidopsis thaliana
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Thermospermine, a structural isomer of spermine, is produced through the action of ACAULIS5 (ACL5) and suppresses xylem differentiation in Arabidopsis thaliana. To elucidate the molecular basis of the function of thermospermine, we screened chemical libraries for compounds that can modulate xylem differentiation in the acl5 mutant, which is deficient in thermospermine and shows a severe dwarf phenotype associated with excessive proliferation of xylem vessels. We found that the isooctyl ester of a synthetic auxin, 2,4-D, remarkably enhanced xylem vessel differentiation in acl5 seedlings. 2,4-D, 2,4-D analogs and IAA analogs, including 4-chloro IAA (4-Cl-IAA) and IAA ethyl ester, also enhanced xylem vessel formation, while IAA alone had little or no obvious effect on xylem differentiation. These effects of auxin analogs were observed only in the acl5 mutant but not in the wild type, and were suppressed by the anti-auxin, p-chlorophenoxyisobutyric acid (PCIB) and alpha-(phenyl ethyl-2-one)-IAA (PEO-IAA), and also by thermospermine. Furthermore, the suppressor of acaulis51-d (sac51-d) mutation, which causes SAC51 overexpression in the absence of thermospermine and suppresses the dwarf phenotype of acl5, also suppressed the effect of auxin analogs in acl5. These results suggest that the auxin signaling that promotes xylem differentiation is normally limited by SAC51-mediated thermospermine signaling but can be continually stimulated by exogenous auxin analogs in the absence of thermospermine. The opposite action between thermospermine and auxin may fine-tune the timing and spatial pattern of xylem differentiation.
en-copyright=
kn-copyright=

en-aut-name=YoshimotoKaori
en-aut-sei=Yoshimoto
en-aut-mei=Kaori
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=

en-aut-name=HayashiKen-ichiro
en-aut-sei=Hayashi
en-aut-mei=Ken-ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

en-aut-name=TakahashiTaku
en-aut-sei=Takahashi
en-aut-mei=Taku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MotoseHiroyasu
en-aut-sei=Motose
en-aut-mei=Hiroyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Division of Bioscience, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=
kn-affil=

affil-num=3
en-affil=
kn-affil=Okayama Univ Sci

affil-num=4
en-affil=
kn-affil=RIKEN

affil-num=5
en-affil=
kn-affil=Okayama Univ

affil-num=6
en-affil=
kn-affil=Okayama Univ
en-keyword=ACAULIS5
kn-keyword=ACAULIS5
en-keyword=Arabidopsis thaliana
kn-keyword=Arabidopsis thaliana
en-keyword=Auxin
kn-keyword=Auxin
en-keyword=2.4-D
kn-keyword=2.4-D
en-keyword=Thermospermine
kn-keyword=Thermospermine
en-keyword=Xylem differentiation
kn-keyword=Xylem differentiation
END

start-ver=1.4
cd-journal=joma
no-vol=124
cd-vols=
no-issue=2
article-no=
start-page=97
end-page=100
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=RXR antagonism induces G0/G1 cell cycle arrest and ameliorates obesity by up-regulating p53-p21<sup>Cip1</sup> pathway in adipocytes
kn-title=RXR阻害によるp53-p21<sup>Cip1</sup>経路の活性化およびG0/G1細胞周期停止を介した抗肥満作用
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=中司敦子
kn-aut-sei=中司
kn-aut-mei=敦子
aut-affil-num=1
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=和田淳
kn-aut-sei=和田
kn-aut-mei=淳
aut-affil-num=2
ORCID=

en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=槇野博史
kn-aut-sei=槇野
kn-aut-mei=博史
aut-affil-num=3
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　腎・免疫・内分泌代謝内科学

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　腎・免疫・内分泌代謝内科学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　腎・免疫・内分泌代謝内科学
en-keyword=RXR
kn-keyword=RXR
en-keyword=cell cycle
kn-keyword=cell cycle
en-keyword=obesity
kn-keyword=obesity
en-keyword=p53
kn-keyword=p53
en-keyword=p21<sup>Cip1</sup>
kn-keyword=p21<sup>Cip1</sup>
END

start-ver=1.4
cd-journal=joma
no-vol=124
cd-vols=
no-issue=2
article-no=
start-page=111
end-page=114
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Therapeutic effects of mesenchymal stem cell transplantation on rat models of Parkinson’s disease
kn-title=パーキンソン病モデルラットに対する間葉系幹細胞移植の治療効果
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=WangFeifei
en-aut-sei=Wang
en-aut-mei=Feifei
kn-aut-name=王飛霏
kn-aut-sei=王
kn-aut-mei=飛霏
aut-affil-num=1
ORCID=

en-aut-name=YasuharaTakao
en-aut-sei=Yasuhara
en-aut-mei=Takao
kn-aut-name=安原隆雄
kn-aut-sei=安原
kn-aut-mei=隆雄
aut-affil-num=2
ORCID=

en-aut-name=KamedaMasahiro
en-aut-sei=Kameda
en-aut-mei=Masahiro
kn-aut-name=亀田雅博
kn-aut-sei=亀田
kn-aut-mei=雅博
aut-affil-num=3
ORCID=

en-aut-name=DateIsao
en-aut-sei=Date
en-aut-mei=Isao
kn-aut-name=伊達勲
kn-aut-sei=伊達
kn-aut-mei=勲
aut-affil-num=4
ORCID=

affil-num=1
en-affil=
kn-affil=高知大学医学部　先端医療学推進センター

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経外科学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経外科学

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経外科学
en-keyword=Parkinson’s disease
kn-keyword=Parkinson’s disease
en-keyword=mesenchymal stem cell
kn-keyword=mesenchymal stem cell
en-keyword=SDF-1 alfa
kn-keyword=SDF-1 alfa
END

start-ver=1.4
cd-journal=joma
no-vol=124
cd-vols=
no-issue=2
article-no=
start-page=101
end-page=104
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=A constitutively active calcineurin encoded by an intron-containing mRNA is involved in hair cycle regulation
kn-title=恒常活性型カルシニューリンによる毛周期制御機構―新しい機構に基づく発毛促進ペプチドの開発―
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=FujimuraAtsushi
en-aut-sei=Fujimura
en-aut-mei=Atsushi
kn-aut-name=藤村篤史
kn-aut-sei=藤村
kn-aut-mei=篤史
aut-affil-num=1
ORCID=

en-aut-name=TomizawaKazuhito
en-aut-sei=Tomizawa
en-aut-mei=Kazuhito
kn-aut-name=富澤一仁
kn-aut-sei=富澤
kn-aut-mei=一仁
aut-affil-num=2
ORCID=

en-aut-name=MatsuiHideki
en-aut-sei=Matsui
en-aut-mei=Hideki
kn-aut-name=松井秀樹
kn-aut-sei=松井
kn-aut-mei=秀樹
aut-affil-num=3
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　細胞生理学

affil-num=2
en-affil=
kn-affil=熊本大学大学院生命科学研究部　分子生理学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　細胞生理学
en-keyword=calcineurin/NFAT
kn-keyword=calcineurin/NFAT
en-keyword=alternative splicing
kn-keyword=alternative splicing
en-keyword=calcium sensitivity
kn-keyword=calcium sensitivity
en-keyword=hair cycle
kn-keyword=hair cycle
en-keyword=cyclin G2
kn-keyword=cyclin G2
END

start-ver=1.4
cd-journal=joma
no-vol=33
cd-vols=
no-issue=4
article-no=
start-page=1044
end-page=1051
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201202
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The mechanical stimulation of cells in 3D culture within a self-assembling peptide hydrogel
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The aim of this present study was to provide a scaffold as a tool for the investigation of the effect of mechanical stimulation on three-dimensionally cultured cells. For this purpose, we developed an artificial self-assembling peptide (SPG-178) hydrogel scaffold. The structural properties of the SPG-178 peptide were confirmed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and transmission electron microscopy (TEM). The mechanical properties of the SPG-178 hydrogel were studied using rheology measurements. The SPG-178 peptide was able to form a stable, transparent hydrogel in a neutral pH environment In the SPG-178 hydrogel, mouse skeletal muscle cells proliferated successfully (increased by 12.4 +/- 1.5 times during 8 days of incubation; mean +/- SEM). When the scaffold was statically stretched, a rapid phosphorylation of ERK was observed (increased by 2.8 +/- 0.2 times; mean +/- SEM). These results demonstrated that the developed self-assembling peptide gel is non-cytotoxic and is a suitable tool for the investigation of the effect of mechanical stimulation on three-dimensional cell culture.
en-copyright=
kn-copyright=

en-aut-name=NagaiYusuke
en-aut-sei=Nagai
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
en-keyword=Cell proliferation
kn-keyword=Cell proliferation
en-keyword=Self-assembly
kn-keyword=Self-assembly
en-keyword=Hydrogel
kn-keyword=Hydrogel
en-keyword=Scaffold
kn-keyword=Scaffold
en-keyword=Mechanical strain
kn-keyword=Mechanical strain
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=2012
dt-pub=20120323
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=乳癌細胞増殖におけるFGF-8・BMPおよびEstrogen受容体の機能連関
kn-title=Functional interaction of fibroblast growth factor-8, bone morphogenetic protein and estrogen receptor in breast cancer cell proliferation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=MasudaHiroko
en-aut-sei=Masuda
en-aut-mei=Hiroko
kn-aut-name=増田紘子
kn-aut-sei=増田
kn-aut-mei=紘子
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
END

start-ver=1.4
cd-journal=joma
no-vol=124
cd-vols=
no-issue=1
article-no=
start-page=27
end-page=34
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Telomere biology towards cardiac stem cell therapy in patients with heart failure
kn-title=テロメア生物学から心筋再生医療の実用化へ
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=OhHidemasa
en-aut-sei=Oh
en-aut-mei=Hidemasa
kn-aut-name=王英正
kn-aut-sei=王
kn-aut-mei=英正
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学病院　新医療研究開発センター　再生医療部
en-keyword=stem cells
kn-keyword=stem cells
en-keyword=heart failure
kn-keyword=heart failure
en-keyword=telomere
kn-keyword=telomere
en-keyword=regeneration
kn-keyword=regeneration
en-keyword=cardiac function
kn-keyword=cardiac function
END

start-ver=1.4
cd-journal=joma
no-vol=46
cd-vols=
no-issue=1
article-no=
start-page=119
end-page=126
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2009
dt-pub=200904
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Induction of hepatocyte growth factor production in human dermal fibroblasts and their proliferation by the extract of bitter melon pulp
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hepatocyte growth factor (HGF) is useful as a potential therapeutic agent for hepatic and renal fibrosis and cardiovascular diseases through inducing proliferation of epithelial and endothelial cells. HGF inducers may also be useful as therapeutic agents for these diseases. However, there have been no reports on induction of HGF production by plant extracts or juices. An extract of bitter melon (Momordica charantia L.) pulp markedly induced HGF production. There was a time lag of 72 h before induction of HGF production after the extract addition. Its stimulatory effect was accompanied by upregulation of HGF gene expression. Increases in mitogen-activated protein kinases (MAPKs) were observed from 72 h after the extract addition. Inhibitors of MAPKs suppressed the extract-induced HGF production. The extract also stimulated cell proliferation. Both activities for induction of HGF production and cell proliferation were eluted together in a single peak with 14,000 Da on gel filtration. The results indicate that bitter melon pulp extract induced HGF production and cell proliferation of human dermal fibroblasts and suggest that activation of MAPKs is involved in the HGF induction. Our findings suggest potential usefulness of the extract for tissue regeneration and provide an insight into the molecular mechanism underlying the wound-healing property of bitter melon.
en-copyright=
kn-copyright=

en-aut-name=OnoTakehiro
en-aut-sei=Ono
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TsujiTomoe
en-aut-sei=Tsuji
en-aut-mei=Tomoe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SakaiMiho
en-aut-sei=Sakai
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YukizakiChizuko
en-aut-sei=Yukizaki
en-aut-mei=Chizuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=InoHisatoshi
en-aut-sei=Ino
en-aut-mei=Hisatoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AkagiIsao
en-aut-sei=Akagi
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HiramatsuKaori
en-aut-sei=Hiramatsu
en-aut-mei=Kaori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MatsumotoYohsuke
en-aut-sei=Matsumoto
en-aut-mei=Yohsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SugiuraYoshihiro
en-aut-sei=Sugiura
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UtoHirofumi
en-aut-sei=Uto
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TsubouchiHirohito
en-aut-sei=Tsubouchi
en-aut-mei=Hirohito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=GohdaEiichi
en-aut-sei=Gohda
en-aut-mei=Eiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

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

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

affil-num=3
en-affil=
kn-affil=Miyazaki Prefectural Food R&D Center

affil-num=4
en-affil=
kn-affil=Miyazaki Prefectural Food R&D Center

affil-num=5
en-affil=
kn-affil=Miyazaki Agricultural Research Institute

affil-num=6
en-affil=
kn-affil=Miyazaki Prefectural Industrial Support Foundation

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

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

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

affil-num=10
en-affil=
kn-affil=Department of Digestive Disease and Life-style Related Diseases, Health Research Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences

affil-num=11
en-affil=
kn-affil=Department of Digestive Disease and Life-style Related Diseases, Health Research Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences

affil-num=12
en-affil=
kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=Hepatocyte growth factor
kn-keyword=Hepatocyte growth factor
en-keyword=Bitter melon
kn-keyword=Bitter melon
en-keyword=Extracellular signal-regulated kinase
kn-keyword=Extracellular signal-regulated kinase
en-keyword=Cell proliferation
kn-keyword=Cell proliferation
en-keyword=Dermal fibroblast
kn-keyword=Dermal fibroblast
END

start-ver=1.4
cd-journal=joma
no-vol=26
cd-vols=
no-issue=2
article-no=
start-page=131
end-page=138
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2009
dt-pub=200902
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Estradiol, Progesterone, and Transforming Growth Factor α Regulate Insulin-Like Growth Factor Binding Protein-3 (IGFBP3) Expression in Mouse Endometrial Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Insulin-like growth factor 1 (IGF1) Is Involved in the proliferation of mouse and rat endometrial cells in a paracrine or autocrine manner. Insulin-like growth factor binding protein-3 (IGFBP3) modulates actions of IGFs directly or indirectly. The present study aimed to determine whether IGFBP3 is Involved In the regulation of proliferation of mouse endometrial cells. Mouse endometrial epithelial cells and stromal cells were isolated, and cultured In a serum free medium. IGF1 stimulated DNA synthesis by endometrial epithelial and stromal cells, and IGFBP3 Inhibited IGF1-induced DNA synthesis. Estradiol-17 beta (E2) decreased the Igfbp3 mRNA level in endometrial stromal cells, whereas It Increased the Igf1 mRNA level. Transforming growth factor alpha (TGF alpha) significantly decreased IGFBP3 expression at both the mRNA and secreted protein levels in endometrial stromal cells. Progesterone (134) did not affect the E2-induced down-regulation of Igfbp3 mRNA expression in endometrial stromal cells, although P4 alone increased Igfbp3 mRNA levels. The present findings suggest that in mouse endometrial stromal cells E2 enhances IGF1 action through enhancement of IGF1 synthesis and reduction of IGFBP3 synthesis, and that TGF alpha affects IGF1 actions through modulation of IGFBP3 levels.
en-copyright=
kn-copyright=

en-aut-name=MaekawaTetsuya
en-aut-sei=Maekawa
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakeuchiSakae
en-aut-sei=Takeuchi
en-aut-mei=Sakae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayamaMunetoshi
en-aut-sei=Kanayama
en-aut-mei=Munetoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakahashiSumio
en-aut-sei=Takahashi
en-aut-mei=Sumio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Biology, Graduate School of Natural Science and Technology, Okayama University

affil-num=2
en-affil=
kn-affil=Department of Biology, Graduate School of Natural Science and Technology, Okayama University

affil-num=3
en-affil=
kn-affil=Department of Biology, Graduate School of Natural Science and Technology, Okayama University

affil-num=4
en-affil=
kn-affil=Department of Biology, Graduate School of Natural Science and Technology, Okayama University
en-keyword=IGFBP3
kn-keyword=IGFBP3
en-keyword=IGF1
kn-keyword=IGF1
en-keyword=estrogen
kn-keyword=estrogen
en-keyword=mouse
kn-keyword=mouse
en-keyword=uterus
kn-keyword=uterus
END