start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=2 article-no= start-page=473 end-page=479.e1 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.
Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the interferon signature for neonatal screening and to gain insight into presymptomatic state of neonates with inborn errors of immunity (IEIs).
Methods: DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs as well as from neonates with viral infections, including some samples obtained during the presymptomatic neonatal period, were examined by nontargeted proteome analyses. Expression of interferon-stimulated genes (ISGs) was evaluated and a DBS-interferon signature was defined. Differential expression/pathway analysis was also performed.
Results: The ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z scores for these as the DBS-interferon signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high interferon signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus?like pathways.
Conclusion: Upregulation of the interferon pathway exists already at birth?not only in neonates with type I interferonopathy but also in other IEIs, including CGD. en-copyright= kn-copyright= en-aut-name=NihiraHiroshi en-aut-sei=Nihira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaDaisuke en-aut-sei=Nakajima en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IzawaKazushi en-aut-sei=Izawa en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawashimaYusuke en-aut-sei=Kawashima en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShibataHirofumi en-aut-sei=Shibata en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonnoRyo en-aut-sei=Konno en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashiguchiMotoko en-aut-sei=Higashiguchi en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoTakayuki en-aut-sei=Miyamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nishitani-IsaMasahiko en-aut-sei=Nishitani-Isa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiejimaEitaro en-aut-sei=Hiejima en-aut-mei=Eitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HondaYoshitaka en-aut-sei=Honda en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsubayashiTadashi en-aut-sei=Matsubayashi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaTakashi en-aut-sei=Ishihara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwataNaomi en-aut-sei=Iwata en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhwadaYoko en-aut-sei=Ohwada en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomotakiSeiichi en-aut-sei=Tomotaki en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaiMasahiko en-aut-sei=Kawai en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MurakamiKosaku en-aut-sei=Murakami en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhnishiHidenori en-aut-sei=Ohnishi en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshimuraMasataka en-aut-sei=Ishimura en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OkadaSatoshi en-aut-sei=Okada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YamashitaMotoi en-aut-sei=Yamashita en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MorioTomohiro en-aut-sei=Morio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HoshinoAkihiro en-aut-sei=Hoshino en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KaneganeHirokazu en-aut-sei=Kanegane en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ImaiKohsuke en-aut-sei=Imai en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakamuraYasuko en-aut-sei=Nakamura en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NonoyamaShigeaki en-aut-sei=Nonoyama en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UchiyamaToru en-aut-sei=Uchiyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OnoderaMasafumi en-aut-sei=Onodera en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=IshikawaTakashi en-aut-sei=Ishikawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawaiToshinao en-aut-sei=Kawai en-aut-mei=Toshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TakitaJunko en-aut-sei=Takita en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NishikomoriRyuta en-aut-sei=Nishikomori en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OharaOsamu en-aut-sei=Ohara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=YasumiTakahiro en-aut-sei=Yasumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= affil-num=1 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University kn-affil= affil-num=15 en-affil=Department of Infection and Immunology, Aichi ChildrenЃfs Health and Medical Center kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neonatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Pediatrics, Gifu University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=23 en-affil=Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=24 en-affil=Laboratory of Immunology and Molecular Medicine, Advanced Research Initiative, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=25 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=26 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=27 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=28 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=29 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=30 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=31 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=32 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=33 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=34 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=35 en-affil=Department of Pediatrics and Child Health, Kurume University School of Medicine kn-affil= affil-num=36 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=37 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= en-keyword=Inborn errors of immunity kn-keyword=Inborn errors of immunity en-keyword=interferonopathy kn-keyword=interferonopathy en-keyword=signature kn-keyword=signature en-keyword=proteome kn-keyword=proteome en-keyword=dried blood spot kn-keyword=dried blood spot en-keyword=CGD kn-keyword=CGD en-keyword=WAS kn-keyword=WAS en-keyword=newborn kn-keyword=newborn en-keyword=neonate kn-keyword=neonate END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=e00110-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)?1ѓА, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1ѓА, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaHiroyuki en-aut-sei=Yamada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotozonoChihiro en-aut-sei=Motozono en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiSho en-aut-sei=Yamasaki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TorrellesJordi B. en-aut-sei=Torrelles en-aut-mei=Jordi B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TurnerJoanne en-aut-sei=Turner en-aut-mei=Joanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=3 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=4 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=5 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=6 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=7 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=8 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=pyroptosis kn-keyword=pyroptosis en-keyword=caspase kn-keyword=caspase en-keyword=RNA-Seq kn-keyword=RNA-Seq en-keyword=cytokine kn-keyword=cytokine en-keyword=fibroblasts kn-keyword=fibroblasts END start-ver=1.4 cd-journal=joma no-vol=351 cd-vols= no-issue= article-no= start-page=199522 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=Evidence for the replication of a plant rhabdovirus in its arthropod mite vector en-subtitle= kn-subtitle= en-abstract= kn-abstract=Transmission of plant viruses that replicate in the insect vector is known as persistent-propagative manner. However, it remains unclear whether such virus-vector relationships also occur between plant viruses and other biological vectors such as arthropod mites. In this study, we investigated the possible replication of orchid fleck virus (OFV), a segmented plant rhabdovirus, within its mite vector (Brevipalpus californicus s.l.) using quantitative RT-qPCR, western blotting and next-generation sequencing. Time-course RT-qPCR and western blot analyses showed an increasing OFV accumulation pattern in mites after virus acquisition. Since OFV genome expression requires the transcription of polyadenylated mRNAs, polyadenylated RNA fractions extracted from the viruliferous mite samples and OFV-infected plant leaves were used for RNA-seq analysis. In the mite and plant datasets, a large number of sequence reads were aligned to genomic regions of OFV RNA1 and RNA2 corresponding to transcribed viral gene mRNAs. This includes the short polyadenylated transcripts originating from the leader and trailer regions at the ends of the viral genome, which are believed to play a crucial role in viral transcription/replication. In contrast, a low number of reads were mapped to the non-transcribed regions (gene junctions). These results strongly suggested that OFV gene expression occurs both in mites and plants. Additionally, deep sequencing revealed the accumulation of OFV-derived small RNAs in mites, although their size profiles differ from those found in plants. Taken together, our results indicated that OFV replicates within a mite vector and is targeted by the RNA-silencing mechanism. en-copyright= kn-copyright= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaMiki en-aut-sei=Fujita en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TelengechPaul en-aut-sei=Telengech en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruyamKazuyuki en-aut-sei=Maruyam en-aut-mei=Kazuyuki 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=TassiAline Daniele en-aut-sei=Tassi en-aut-mei=Aline Daniele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchoaRonald en-aut-sei=Ochoa en-aut-mei=Ronald kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndikaIda Bagus en-aut-sei=Andika en-aut-mei=Ida Bagus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=6 en-affil=Tropical Research and Education Center, University of Florida kn-affil= affil-num=7 en-affil=Systematic Entomology Laboratory, USDA kn-affil= affil-num=8 en-affil=College of Plant Protection, Northwest A&F University kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Rhabdovirus kn-keyword=Rhabdovirus en-keyword=Plant kn-keyword=Plant en-keyword=Mite kn-keyword=Mite en-keyword=Vector kn-keyword=Vector en-keyword=Replication kn-keyword=Replication en-keyword=mRNA kn-keyword=mRNA en-keyword=Small RNA kn-keyword=Small RNA END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=10712 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Shoot-Silicon-Signal protein to regulate root silicon uptake in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plants accumulate silicon to protect them from biotic and abiotic stresses. Especially in rice (Oryza sativa), a typical Si-accumulator, tremendous Si accumulation is indispensable for healthy growth and productivity. Here, we report a shoot-expressed signaling protein, Shoot-Silicon-Signal (SSS), an exceptional homolog of the flowering hormone ЃgflorigenЃh differentiated in Poaceae. SSS transcript is only detected in the shoot, whereas the SSS protein is also detected in the root and phloem sap. When Si is supplied from the root, the SSS transcript rapidly decreases, and then the SSS protein disappears. In sss mutants, root Si uptake and expression of Si transporters are decreased to a basal level regardless of the Si supply. The grain yield of the mutants is decreased to 1/3 due to insufficient Si accumulation. Thus, SSS is a key phloem-mobile protein for integrating root Si uptake and shoot Si accumulation underlying the terrestrial adaptation strategy of grasses. en-copyright= kn-copyright= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Mitani-UenoNamiki en-aut-sei=Mitani-Ueno en-aut-mei=Namiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiToshiki en-aut-sei=Fujii en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinyaTomonori en-aut-sei=Shinya en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShaoJi Feng en-aut-sei=Shao en-aut-mei=Ji Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WatanukiShota en-aut-sei=Watanuki en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitohYasunori en-aut-sei=Saitoh en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture & Forestry 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= affil-num=8 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= 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.) ЃgAkashinrikiЃh 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tumor Microvessels with Specific Morphology as a Prognostic Factor in Esophageal Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Angiogenesis is essential for tumor progression. Microvessel density (MVD) is a widely used histological method to assess angiogenesis using immunostained sections, but its prognostic significance in esophageal cancer remains controversial. Recently, the evaluation of microvascular architecture has gained importance as a method to assess tumor aggressiveness. The present study aimed to identify the histological characteristics of tumor microvessels that are associated with the aggressiveness of esophageal squamous cell carcinoma.
Patients and Methods A total of 108 esophageal squamous cell carcinoma tissues were immunohistochemically stained with blood vessel markers and angiogenesis-related markers, including CD31, alpha smooth muscle actin, vascular endothelial growth factor A (VEGF-A), CD206, and D2-40. MVD, microvessel pericyte coverage index (MPI), and tumor vascular morphology were evaluated by microscopy.
Results MVD was significantly associated with patient outcomes, whereas neither MPI nor VEGF-A expression throughout the tumor showed a significant correlation. In addition, the presence of blood vessels encircling clusters of tumor cells, termed C-shaped microvessels, and excessively branching microvessels, termed X-shaped microvessels, was significantly associated with poor prognosis. These vessel types were also correlated with clinicopathological parameters, including deeper invasion of the primary tumor, presence of lymph node metastasis, advanced pathological stage, and distant metastasis. Focal VEGF-A immunoexpression in tumor cells was higher in areas containing C-shaped or X-shaped microvessels compared with areas lacking these vessel morphologies.
Conclusions The data suggest that tumor microvessels with specific morphologies (C-shaped and X-shaped microvessels) may serve as a promising prognostic factor in esophageal squamous cell carcinoma. en-copyright= kn-copyright= en-aut-name=TunHnin Thida en-aut-sei=Tun en-aut-mei=Hnin Thida 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=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=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 Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Esophageal neoplasms kn-keyword=Esophageal neoplasms en-keyword=Angiogenesis kn-keyword=Angiogenesis en-keyword=Microvessel density kn-keyword=Microvessel density en-keyword=Pericytes kn-keyword=Pericytes en-keyword=VEGF-A kn-keyword=VEGF-A en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry en-keyword=Prognosis kn-keyword=Prognosis END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=7 article-no= start-page=1152 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240717 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metatranscriptomic Sequencing of Sheath Blight-Associated Isolates of Rhizoctonia solani Revealed Multi-Infection by Diverse Groups of RNA Viruses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice sheath blight, caused by the soil-borne fungus Rhizoctonia solani (teleomorph: Thanatephorus cucumeris, Basidiomycota), is one of the most devastating phytopathogenic fungal diseases and causes yield loss. Here, we report on a very high prevalence (100%) of potential virus-associated double-stranded RNA (dsRNA) elements for a collection of 39 fungal strains of R. solani from the rice sheath blight samples from at least four major rice-growing areas in the Philippines and a reference isolate from the International Rice Research Institute, showing different colony phenotypes. Their dsRNA profiles suggested the presence of multiple viral infections among these Philippine R. solani populations. Using next-generation sequencing, the viral sequences of the three representative R. solani strains (Ilo-Rs-6, Tar-Rs-3, and Tar-Rs-5) from different rice-growing areas revealed the presence of at least 36 viruses or virus-like agents, with the Tar-Rs-3 strain harboring the largest number of viruses (at least 20 in total). These mycoviruses or their candidates are believed to have single-stranded RNA or dsRNA genomes and they belong to or are associated with the orders Martellivirales, Hepelivirales, Durnavirales, Cryppavirales, Ourlivirales, and Ghabrivirales based on their coding-complete RNA-dependent RNA polymerase sequences. The complete genome sequences of two novel RNA viruses belonging to the proposed family Phlegiviridae and family Mitoviridae were determined. en-copyright= kn-copyright= en-aut-name=UrzoMichael Louie R. en-aut-sei=Urzo en-aut-mei=Michael Louie R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GuintoTimothy D. en-aut-sei=Guinto en-aut-mei=Timothy D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Eusebio-CopeAna en-aut-sei=Eusebio-Cope en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BudotBernard O. en-aut-sei=Budot en-aut-mei=Bernard O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanoriaMary Jeanie T. en-aut-sei=Yanoria en-aut-mei=Mary Jeanie T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JonsonGilda B. en-aut-sei=Jonson en-aut-mei=Gilda B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArakawaMasao en-aut-sei=Arakawa en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=2 en-affil=Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=3 en-affil=Fit-for-Future Genetic Resources Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=4 en-affil=Institute of Weed Science, Entomology, and Plant Pathology, College of Agriculture and Food Science, University of the Philippines Los Ba?os kn-affil= affil-num=5 en-affil=Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=6 en-affil=Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=7 en-affil=Faculty of Agriculture, Meijo University kn-affil= affil-num=8 en-affil=Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=9 en-affil=Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Rhizoctonia solani kn-keyword=Rhizoctonia solani en-keyword=dsRNA kn-keyword=dsRNA en-keyword=mycovirus kn-keyword=mycovirus en-keyword=RNA virus kn-keyword=RNA virus en-keyword=metatranscriptome kn-keyword=metatranscriptome END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Ћоб‡—Z‰рѓAѓfѓmѓEѓCѓ‹ѓX‚Й‚ж‚й• Ќo“аѓ}ѓNѓЌѓtѓ@Ѓ[ѓW‚М‹@”\“IЌДЌ\’z‚Й‚ж‚иЃA€ЭЉа• –Њ”dЋн‚Й‘О‚·‚йЌRЋоб‡–Ж‰u‚Є‰с•њ‚·‚й kn-title=Functional remodeling of intraperitoneal macrophages by oncolytic adenovirus restores anti-tumor immunity for peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TABUCHIMotoyasu en-aut-sei=TABUCHI en-aut-mei=Motoyasu kn-aut-name=“cџєЉІЌN kn-aut-sei=“cџє kn-aut-mei=ЉІЌN aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И 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.
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.
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.
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=74 cd-vols= no-issue=3 article-no= start-page=96 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression.
Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils.
Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells.
Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach. en-copyright= kn-copyright= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NogiShohei en-aut-sei=Nogi en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiAtsuki en-aut-sei=Taniguchi en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimotoMasashi en-aut-sei=Yoshimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujitaShuto en-aut-sei=Fujita en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Neutrophil kn-keyword=Neutrophil en-keyword=Anti-fibrotic agent kn-keyword=Anti-fibrotic agent en-keyword=Pirfenidone kn-keyword=Pirfenidone END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=3267 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and alpha-smooth muscle (alpha-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with alpha-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and alpha-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC. en-copyright= kn-copyright= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkuraTomohiro en-aut-sei=Okura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= en-aut-name=OhtsukaJunko en-aut-sei=Ohtsuka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhkiRieko en-aut-sei=Ohki en-aut-mei=Rieko 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=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=12 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute 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=Peritoneal metastasis kn-keyword=Peritoneal metastasis en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Interleukin-6 kn-keyword=Interleukin-6 en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Interleukin-6 receptor antibody kn-keyword=Interleukin-6 receptor antibody END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=2 article-no= start-page=249 end-page=260 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD.
Methods: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1?/?) mice.
Results: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LT‚ from Nr4a1?/? donors significantly improved pulmonary graft function compared to wild-type donors. Histological analysis showed decreased microvascular endothelial cell death, neutrophil infiltration, and albumin leakage. Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1?/? donors, correlating with diminished pulmonary edema. However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1?/? recipient.
Conclusions: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD. en-copyright= kn-copyright= en-aut-name=KawanaShinichi en-aut-sei=Kawana en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaueTomohisa en-aut-sei=Sakaue en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoKohei en-aut-sei=Hashimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChoshiHaruki en-aut-sei=Choshi en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhtaniShinji en-aut-sei=Ohtani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=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= 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=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine kn-affil= affil-num=4 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=5 en-affil=Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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= affil-num=9 en-affil=Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 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=lung transplantation kn-keyword=lung transplantation en-keyword=ischemia-reperfusion injury kn-keyword=ischemia-reperfusion injury en-keyword=donation after circulatory death kn-keyword=donation after circulatory death en-keyword=nuclear receptor subfamily 4 group A member 1 kn-keyword=nuclear receptor subfamily 4 group A member 1 en-keyword=endothelial cell kn-keyword=endothelial cell END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=23 article-no= start-page=4089 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frequency and Significance of Body Weight Loss During Immunochemotherapy in Patients with Advanced Non-Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Limited data are available on the frequency and significance of body weight loss during cancer therapy. This study investigated the frequency of patients who experienced body weight loss during immune checkpoint inhibitor (ICI) plus chemotherapy for advanced non-small cell lung cancer (NSCLC) and the impact of weight loss on treatment outcomes. Methods: Using the clinical data of 370 patients with NSCLC who received a combination of ICI and chemotherapy at 13 institutions, this study investigated the frequency of body weight loss > 5% during treatment and determined the impact of body weight loss on patient outcomes. Results: Of the 370 included patients, 141 (38.1%) lost more than 5% of their body weight during ICI plus chemotherapy (WL group). The 2-month landmark analysis showed that patients who experienced body weight loss of >5% during treatment had worse overall survival (OS) and progression-free survival (PFS) than those who did not (OS 14.0 and 31.1 months in the WL non-WL groups, respectively, p < 0.001; PFS 6.8 and 10.9 months in the WL non-WL groups, respectively, p = 0.002). Furthermore, a negative impact of body weight loss on survival was observed even in those who had obesity (body mass index [BMI] >= 25.0) at the start of therapy (OS 12.8 and 25.4 months in the WL non-WL groups, respectively, p < 0.001; PFS 5.7 and 10.7 months in the WL non-WL groups, respectively, p = 0.038). Conclusions: In conclusion, weight loss of >5% during ICI plus chemotherapy negatively influenced patient outcomes. Further and broader studies should investigate the role of nutritional status, specifically weight change and nutritional support, in responsiveness to ICI plus chemotherapy. en-copyright= kn-copyright= en-aut-name=TaokaMasataka en-aut-sei=Taoka en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoAkiko en-aut-sei=Sato en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraKayo en-aut-sei=Nakamura en-aut-mei=Kayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaiHaruyuki en-aut-sei=Kawai en-aut-mei=Haruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OzeIsao en-aut-sei=Oze en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Internal Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Japanese Red Cross Himeji Hospital kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=12 en-affil=Department of General Internal Medicine 4 , Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=16 en-affil=Division of Cancer Information and Control, Aichi Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=body weight loss kn-keyword=body weight loss en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=chemotherapy kn-keyword=chemotherapy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Ќ‚€«ђ«“xЊыЌoќG•ЅЏг”зЉа‚Й‚Ё‚ў‚ДЃACX3CL1‚НѓЉѓ“ѓpЉЗђVђ¶‚р‘ќ‹‚µѓЉѓ“ѓpђЯ“]€Ъ‚ЙЉс—^‚·‚й kn-title=Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Htoo Shwe Eain en-aut-sei=Htoo Shwe Eain en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ђZЏЃђ«“ыЉаЉіЋТ‚Й‚Ё‚Ї‚й–СЌЧЊЊЉЗ‚М“Б’и‚МЊ`Џу‚НЃA—\Њг‚Є€«‚ў‚±‚Ж‚ЖЉЦA‚µ‚Д‚ў‚Ь‚· 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= en-copyright= kn-copyright= en-aut-name=HNIN WINT WINT SWE en-aut-sei=HNIN WINT WINT SWE en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=SPRED2‚НЃAЉМЌЧ–EЉаЌЧ–E‚Ё‚ж‚СђіЏнЉМЌЧ–E‚Й‚Ё‚Ї‚йѓIЃ[ѓgѓtѓ@ѓWЃ[‚МђV‚µ‚ў’ІђЯ€цЋq‚Е‚· kn-title=SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WANGTIANYI en-aut-sei=WANG en-aut-mei=TIANYI kn-aut-name=‰¤“V? kn-aut-sei=‰¤ kn-aut-mei=“V? aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ЉіЋТЋоб‡€ЪђAѓ‚ѓfѓ‹‚Й‘О‚·‚йѓqѓg‰»ЌRFibroblast Atcivation ProteinЌR‘М‚р—p‚ўЉаЉЦAђь€Ы‰иЌЧ–E‚р•W“I‚Ж‚µ‚ЅЊх–Ж‰u—Г–@ kn-title=Near-infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Patient-Derived Xenografts Using a Humanized Anti-Fibroblast Activation Protein Antibody en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KOBAYASHITeruki en-aut-sei=KOBAYASHI en-aut-mei=Teruki kn-aut-name=Џ¬—СЏЖ‹M kn-aut-sei=Џ¬—С kn-aut-mei=ЏЖ‹M aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=V‰»ђь€Ы‰иЌЧ–E‚НIL-8‚МѓNѓЌѓXѓgЃ[ѓN‚р‰о‚µЃA‚С‚Ь‚сђ«€ЭЉаЌЧ–E‚М• –Њ“]€Ъ‚р‘Јђi‚·‚й kn-title=Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8?mediated Crosstalk en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LIYUNCHENG en-aut-sei=LI en-aut-mei=YUNCHENG kn-aut-name=—›‰]ђ¬ kn-aut-sei=—› kn-aut-mei=‰]ђ¬ aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=9 article-no= start-page=212 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mutations in starch BRANCHING ENZYME 2a suppress the traits caused by the loss of ISOAMYLASE1 in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=The genetic interactions among starch biosynthesis genes can be exploited to alter starch properties, but they remain poorly understood due to the various combinations of mutations to be tested. Here, we isolated two novel barley mutants defective in starch BRANCHING ENZYME 2a (hvbe2a-1 and hvbe2a-2) based on the starch granule (SG) morphology. Both hvbe2a mutants showed elongated SGs in the endosperm and increased resistant starch content. hvbe2a-1 had a base change in HvBE2a gene, substituting the amino acid essential for its enzyme activity, while hvbe2a-2 is completely missing HvBE2a due to a chromosomal deletion. Further genetic crosses with barley isoamylase1 mutants (hvisa1) revealed that both hvbe2a mutations could suppress defects in endosperm caused by hvisa1, such as reduction in starch, increase in phytoglycogen, and changes in the glucan chain length distribution. Remarkably, hvbe2a mutations also transformed the endosperm SG morphology from the compound SG caused by hvisa1 to bimodal simple SGs, resembling that of wild-type barley. The suppressive impact was in competition with floury endosperm 6 mutation (hvflo6), which could enhance the phenotype of hvisa1 in the endosperm. In contrast, the compound SG formation induced by the hvflo6 hvisa1 mutation in pollen was not suppressed by hvbe2a mutations. Our findings provide new insights into genetic interactions in the starch biosynthetic pathway, demonstrating how specific genetic alterations can influence starch properties and SG morphology, with potential applications in cereal breeding for desired starch properties. en-copyright= kn-copyright= en-aut-name=MatsushimaRyo en-aut-sei=Matsushima en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimJune-Sik en-aut-sei=Kim en-aut-mei=June-Sik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=McNellyRose en-aut-sei=McNelly en-aut-mei=Rose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OitomeNaoko F. en-aut-sei=Oitome en-aut-mei=Naoko F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SeungDavid en-aut-sei=Seung en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujitaNaoko en-aut-sei=Fujita en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=John Innes Centre, Norwich Research Park kn-affil= affil-num=5 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=6 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=7 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=8 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=136 cd-vols= no-issue=2 article-no= start-page=54 end-page=56 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2023 Incentive Award of the Okayama Medical Association in Cardiovascular and Pulmonary Research (2023 Sunada Prize) kn-title=—Яa‚T”N“x‰ЄЋR€гЉw‰пЏЬЃ@‹№•”ЃEЏzЉВЊ¤‹†Џ§—гЏЬЃiЌ»“cЏЬЃj en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name=ЏјЊґЊd kn-aut-sei=ЏјЊґ kn-aut-mei=Њd aut-affil-num=1 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=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰ИЃ@ЊД‹zЉнЃE“ы‘BЃE“а•Є”еЉO‰ИЉw END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=10 article-no= start-page=1164 end-page=1171 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240716 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cytosolic acidification and oxidation are the toxic mechanisms of SO2 in Arabidopsis guard cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=SO2/H2SO3 can damage plants. However, its toxic mechanism has still been controversial. Two models have been proposed, cytosolic acidification model and cellular oxidation model. Here, we assessed the toxic mechanism of H2SO3 in three cell types of Arabidopsis thaliana, mesophyll cells, guard cells (GCs), and petal cells. The sensitivity of GCs of Chloride channel a (CLCa)-knockout mutants to H2SO3 was significantly lower than those of wildtype plants. Expression of other CLC genes in mesophyll cells and petal cells were different from GCs. Treatment with antioxidant, disodium 4,5-dihydroxy-1,3-benzenedisulfonate (tiron), increased the median lethal concentration (LC50) of H2SO3 in GCs indicating the involvement of cellular oxidation, while the effect was negligible in mesophyll cells and petal cells. These results indicate that there are two toxic mechanisms of SO2 to Arabidopsis cells: cytosolic acidification and cellular oxidation, and the toxic mechanism may vary among cell types. en-copyright= kn-copyright= en-aut-name=MozhganiMahdi en-aut-sei=Mozhgani en-aut-mei=Mahdi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OoiLia en-aut-sei=Ooi en-aut-mei=Lia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EspagneChristelle en-aut-sei=Espagne en-aut-mei=Christelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FilleurSophie en-aut-sei=Filleur en-aut-mei=Sophie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriIzumi C en-aut-sei=Mori en-aut-mei=Izumi C kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=Universit? Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) kn-affil= affil-num=4 en-affil=Universit? Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=cytosolic acidification kn-keyword=cytosolic acidification en-keyword=Arabidopsis kn-keyword=Arabidopsis en-keyword=cellular oxidation kn-keyword=cellular oxidation en-keyword=chloride channel a kn-keyword=chloride channel a en-keyword=sulfur dioxide kn-keyword=sulfur dioxide END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=6 article-no= start-page=2497 end-page=2509 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=Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8?mediated Crosstalk en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. Materials and Methods: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of ѓї?smooth muscle actin (ѓї-SMA), senescence-associated ѓА-galactosidase (SA-ѓА-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. Results: IGC cells significantly induced ѓї-SMA+ myCAFs by secreting transforming growth factor?ѓА, whereas DGC cells induced SA-ѓА-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. Conclusion: sCAFs promote peritoneal metastasis of DGC via IL-8?mediated crosstalk. en-copyright= kn-copyright= en-aut-name=LIYUNCHENG en-aut-sei=LI en-aut-mei=YUNCHENG 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=NAGAIYASUO en-aut-sei=NAGAI en-aut-mei=YASUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FUJITASHUTO en-aut-sei=FUJITA en-aut-mei=SHUTO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OKURATOMOHIRO en-aut-sei=OKURA en-aut-mei=TOMOHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SHOJIRYOHEI en-aut-sei=SHOJI en-aut-mei=RYOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YAMADAMOTOHIKO en-aut-sei=YAMADA en-aut-mei=MOTOHIKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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=11 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=12 ORCID= en-aut-name=KAGAWASHUNSUKE en-aut-sei=KAGAWA en-aut-mei=SHUNSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=peritoneal metastasis kn-keyword=peritoneal metastasis en-keyword=senescent fibroblast kn-keyword=senescent fibroblast en-keyword=IL-8 kn-keyword=IL-8 en-keyword=CXCR1/2 kn-keyword=CXCR1/2 END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=11 article-no= start-page=6269 end-page= 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=SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sprouty-related enabled/vasodilator-stimulated phosphoprotein homology 1 domain containing 2 (SPRED2) is an inhibitor of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and has been shown to promote autophagy in several cancers. Here, we aimed to determine whether SPRED2 plays a role in autophagy in hepatocellular carcinoma (HCC) cells. The Cancer Genome Atlas (TCGA) Liver Cancer Database showed a negative association between the level of SPRED2 and p62, a ubiquitin-binding scaffold protein that accumulates when autophagy is inhibited. Immunohistochemically, accumulation of p62 was detected in human HCC tissues with low SPRED2 expression. Overexpression of SPRED2 in HCC cells increased the number of autophagosomes and autophagic vacuoles containing damaged mitochondria, decreased p62 levels, and increased levels of light-chain-3 (LC3)-II, an autophagy marker. In contrast, SPRED2 deficiency increased p62 levels and decreased LC3-II levels. SPRED2 expression levels were negatively correlated with translocase of outer mitochondrial membrane 20 (TOM20) expression levels, suggesting its role in mitophagy. Mechanistically, SPRED2 overexpression reduced ERK activation followed by the mechanistic or mammalian target of rapamycin complex 1 (mTORC1)-mediated signaling pathway, and SPRED2 deficiency showed the opposite pattern. Finally, hepatic autophagy was impaired in the liver of SPRED2-deficient mice with hepatic lipid droplet accumulation in response to starvation. These results indicate that SPRED2 is a critical regulator of autophagy not only in HCC cells, but also in hepatocytes, and thus the manipulation of this process may provide new insights into liver pathology. en-copyright= kn-copyright= en-aut-name=WangTianyi en-aut-sei=Wang en-aut-mei=Tianyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=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=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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cell Biology, 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= en-keyword=autophagy kn-keyword=autophagy en-keyword=mitophagy kn-keyword=mitophagy en-keyword=SPRED proteins kn-keyword=SPRED proteins en-keyword=MAPK/ERK kn-keyword=MAPK/ERK en-keyword=mTOR kn-keyword=mTOR en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=4610 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An NLR paralog Pit2 generated from tandem duplication of Pit1 fine-tunes Pit1 localization and function en-subtitle= kn-subtitle= en-abstract= kn-abstract=NLR family proteins act as intracellular receptors. Gene duplication amplifies the number of NLR genes, and subsequent mutations occasionally provide modifications to the second gene that benefits immunity. However, evolutionary processes after gene duplication and functional relationships between duplicated NLRs remain largely unclear. Here, we report that the rice NLR protein Pit1 is associated with its paralogue Pit2. The two are required for the resistance to rice blast fungus but have different functions: Pit1 induces cell death, while Pit2 competitively suppresses Pit1-mediated cell death. During evolution, the suppression of Pit1 by Pit2 was probably generated through positive selection on two fate-determining residues in the NB-ARC domain of Pit2, which account for functional differences between Pit1 and Pit2. Consequently, Pit2 lost its plasma membrane localization but acquired a new function to interfere with Pit1 in the cytosol. These findings illuminate the evolutionary trajectory of tandemly duplicated NLR genes after gene duplication. en-copyright= kn-copyright= en-aut-name=LiYuying en-aut-sei=Li en-aut-mei=Yuying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangQiong en-aut-sei=Wang en-aut-mei=Qiong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JiaHuimin en-aut-sei=Jia en-aut-mei=Huimin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KosamiKen-Ichi en-aut-sei=Kosami en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UebaTakahiro en-aut-sei=Ueba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujimotoAtsumi en-aut-sei=Tsujimoto en-aut-mei=Atsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanakaMiki en-aut-sei=Yamanaka en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YabumotoYasuyuki en-aut-sei=Yabumoto en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MikiDaisuke en-aut-sei=Miki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SasakiEriko en-aut-sei=Sasaki en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FukaoYoichiro en-aut-sei=Fukao en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraMasayuki en-aut-sei=Fujiwara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Kaneko-KawanoTakako en-aut-sei=Kaneko-Kawano en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanLi en-aut-sei=Tan en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KojimaChojiro en-aut-sei=Kojima en-aut-mei=Chojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WingRod A. en-aut-sei=Wing en-aut-mei=Rod A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SebastianAlfino en-aut-sei=Sebastian en-aut-mei=Alfino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NishimuraHideki en-aut-sei=Nishimura en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FukadaFumi en-aut-sei=Fukada en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NiuQingfeng en-aut-sei=Niu en-aut-mei=Qingfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShimizuMotoki en-aut-sei=Shimizu en-aut-mei=Motoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YoshidaKentaro en-aut-sei=Yoshida en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TerauchiRyohei en-aut-sei=Terauchi en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ShimamotoKo en-aut-sei=Shimamoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences kn-affil= affil-num=2 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=College of Agronomy, Jiangxi Agricultural University kn-affil= affil-num=4 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=7 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=8 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=9 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=10 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=11 en-affil=Faculty of Science, Kyushu University kn-affil= affil-num=12 en-affil=Department of Bioinformatics, Ritsumeikan University kn-affil= affil-num=13 en-affil=YANMAR HOLDINGS Co., Ltd. kn-affil= affil-num=14 en-affil=College of Pharmaceutical Sciences, Ritsumeikan University kn-affil= affil-num=15 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=16 en-affil=Graduate School of Engineering Science, Yokohama National University kn-affil= affil-num=17 en-affil=Arizona Genomics Institute, School of Plant Sciences, University of Arizona kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=20 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=21 en-affil=Advanced Academy, Anhui Agricultural University, Research Centre for Biological Breeding Technology kn-affil= affil-num=22 en-affil=Iwate Biotechnology Research Center kn-affil= affil-num=23 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=24 en-affil=Iwate Biotechnology Research Center kn-affil= affil-num=25 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=26 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=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=SweHninЃ]WintЃ]Wint en-aut-sei=Swe en-aut-mei=HninЃ]WintЃ]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=9 cd-vols= no-issue=10 article-no= start-page=e174618 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro -tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph -circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC. en-copyright= kn-copyright= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShanQuisheng en-aut-sei=Shan en-aut-mei=Quisheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MizukawaNobuyoshi en-aut-sei=Mizukawa en-aut-mei=Nobuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IidaSeiji en-aut-sei=Iida en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Universit kn-affil= affil-num=6 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=”x€ЪђAЊг‘ЃЉъ€ЪђA”x‹@”\•s‘S‚Й‘О‚·‚йЋЎ—Г‚Ж‚µ‚Д‚М‘М“а”xЉТ—¬ђн—Є kn-title=In vivo lung perfusion for prompt recovery from primary graft dysfunction after lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MATSUBARAKei en-aut-sei=MATSUBARA en-aut-mei=Kei kn-aut-name=ЏјЊґЊd kn-aut-sei=ЏјЊґ kn-aut-mei=Њd aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=p53“‹ЌЪѓeѓЌѓЃѓ‰Ѓ[ѓ[“Б€Щ“IЋоб‡—Z‰рѓAѓfѓmѓEѓCѓ‹ѓX‚М• Ќo“а“Љ—^‚Н‚С‚Ь‚сђ«€ЭЉаЌЧ–E‚Й‚ж‚й• –Њ”dЋн‚р—}ђ§‚·‚й kn-title=Intraperitoneal Administration of p53-armed Oncolytic Adenovirus Inhibits Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HORINaoto en-aut-sei=HORI en-aut-mei=Naoto kn-aut-name=–x’јђl kn-aut-sei=–x kn-aut-mei=’јђl aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol=72 cd-vols= no-issue=11 article-no= start-page=3787 end-page=3802 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the ѓї smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity. en-copyright= kn-copyright= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoTakuya en-aut-sei=Kato en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkaiMasaaki en-aut-sei=Akai en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KobayashiTeruki en-aut-sei=Kobayashi en-aut-mei=Teruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Esophageal cancer kn-keyword=Esophageal cancer en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Programmed cell death 1 kn-keyword=Programmed cell death 1 en-keyword=Program cell death ligand 1 kn-keyword=Program cell death ligand 1 en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=136 cd-vols= no-issue=4 article-no= start-page=94 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=FLOURY ENDOSPERM 6 mutations enhance the sugary phenotype caused by the loss of ISOAMYLASE1 in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Starch is a biologically and commercially important glucose polymer synthesized by plants as semicrystalline starch granules (SGs). Because SG morphology affects starch properties, mutants with altered SG morphology may be useful in breeding crops with desirable starch properties, including potentially novel properties. In this study, we employed a simple screen for mutants with altered SG morphology in barley (Hordeum vulgare). We isolated mutants that formed compound SGs together with the normal simple SGs in the endosperm and found that they were allelic mutants of the starch biosynthesis genes ISOAMYLASE1 (HvISA1) and FLOURY ENDOSPERM 6 (HvFLO6), encoding starch debranching enzyme and CARBOHYDRATE-BINDING MODULE 48-containing protein, respectively. We generated the hvflo6 hvisa1 double mutant and showed that it had significantly reduced starch biosynthesis and developed shrunken grains. In contrast to starch, soluble ѓї-glucan, phytoglycogen, and sugars accumulated to higher levels in the double mutant than in the single mutants. In addition, the double mutants showed defects in SG morphology in the endosperm and in the pollen. This novel genetic interaction suggests that hvflo6 acts as an enhancer of the sugary phenotype caused by hvisa1 mutation. en-copyright= kn-copyright= en-aut-name=MatsushimaRyo en-aut-sei=Matsushima en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GalisIvan en-aut-sei=Galis en-aut-mei=Ivan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiuraSatoko en-aut-sei=Miura en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CroftsNaoko en-aut-sei=Crofts en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakenakaYuto en-aut-sei=Takenaka en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OitomeNaoko F. en-aut-sei=Oitome en-aut-mei=Naoko F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshimizuTakeshi en-aut-sei=Ishimizu en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujitaNaoko en-aut-sei=Fujita en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=5 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=6 en-affil=College of Life Sciences, Ritsumeikan University kn-affil= affil-num=7 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=8 en-affil=College of Life Sciences, Ritsumeikan University kn-affil= affil-num=9 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue= article-no= start-page=127 end-page=148 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240329 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Changes in Local Food Culture in the Northeast of Okayama PrefectureЃ\Cases of the Autumn Festival in the Former Ohara Town and Nishiawakura VillageЃ\ kn-title=‰ЄЋRЊ§–k“Њ•”‚Й‚Ё‚Ї‚й’n€жђH•¶‰»‚М•П‘JЃ\‹Њ‘еЊґ’¬‚Жђј€ѕ‘q‘є‚МЏHЌХ‚и‚рЋ–—б‚Ж‚µ‚ДЃ\ en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HOSHIJIMAShigeko en-aut-sei=HOSHIJIMA en-aut-mei=Shigeko kn-aut-name=ђЇ“‡‚µ‚°Ћq kn-aut-sei=ђЇ“‡ kn-aut-mei=‚µ‚°Ћq aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@ЋР‰п•¶‰»‰ИЉwЊ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=11 article-no= start-page=1562 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Iron Chelators, Super-Polyphenols, Show Antimicrobial Effects against Cariogenic Streptococcus mutans en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dental caries are an oral infectious disease that can affect human health both orally and systemically. It remains an urgent issue to establish a novel antibacterial method to prevent oral infection for a healthy life expectancy. The aim of this study was to evaluate the inhibitory effects of novel iron chelators, super-polyphenols (SPs), on the cariogenic bacterium Streptococcus mutans, in vitro. SPs were developed to reduce the side effects of iron chelation therapy and were either water-soluble or insoluble depending on their isoforms. We found that SP6 and SP10 inhibited bacterial growth equivalent to povidone-iodine, and viability tests indicated that their effects were bacteriostatic. These results suggest that SP6 and SP10 have the potential to control oral bacterial infections such as Streptococcus mutans. en-copyright= kn-copyright= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Periodontics & Endodontics, Division of Dentistry, Okayama University Hospital 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=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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=antimicrobial kn-keyword=antimicrobial en-keyword=iron chelator kn-keyword=iron chelator en-keyword=oral infection kn-keyword=oral infection en-keyword=Streptococcus mutans kn-keyword=Streptococcus mutans en-keyword=super-polyphenols kn-keyword=super-polyphenols END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=619 end-page=625 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trochanteric Claw Plate Fixation for Greater Trochanteric Fracture or Osteotomy in Total Hip Arthroplasty en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study retrospectively evaluated 41 consecutive open reductions and internal fixations following primary or revision total hip arthroplasty, which required trochanteric claw plate fixation for greater trochanteric fracture or osteotomy between January 2008 and December 2020. The mean duration of clinical follow-up was 4.2 years (range, 1-13 years). The patients included 13 men and 28 women, with a mean age of 68 years (range, 32-87 years). The indications for intervention included trochanteric osteotomy, intraoperative fracture, and non-union including postoperative fracture in 6, 9, and 26 cases, respectively. The mean Merle dЃfAubign? Clinical Score improved from 9.4 points (range, 5-15 points) pre-operatively, to 14.3 points (range, 9-18 points) at the last follow-up. Bone union occurred in 35 cases (85%), while implant breakage occurred in four cases. At the last follow-up, the mean Merle dЃfAubign? Clinical Scores of bone union and non-union were 15.3 and 14.1, respectively (p=0.48). The Kaplan-Meier survival rate, with the endpoint being revision surgery for pain, non-union, dislocation, or implant breakage, at 10 years was 80.0% (95% confidence interval: 62.6-97.4%). Greater trochanteric fixation using a trochanteric claw plate yielded successful results. en-copyright= kn-copyright= en-aut-name=OeKenichi en-aut-sei=Oe en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IidaHirokazu en-aut-sei=Iida en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SogawaShohei en-aut-sei=Sogawa en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiFumito en-aut-sei=Kobayashi en-aut-mei=Fumito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraTomohisa en-aut-sei=Nakamura en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoTakanori en-aut-sei=Saito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Kansai Medical University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Kansai Medical University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Kansai Medical University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Kansai Medical University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Kansai Medical University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Kansai Medical University kn-affil= en-keyword=greater trochanteric fracture kn-keyword=greater trochanteric fracture en-keyword=trochanteric osteotomy kn-keyword=trochanteric osteotomy en-keyword=claw plate kn-keyword=claw plate en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=‚Є‚сЉЦAђь€Ы‰иЌЧ–E‚Й‚ж‚йЋоб‡–Ж‰u—}ђ§‚МЌRѓCѓ“ѓ^Ѓ[ѓЌѓCѓLѓ“6Ћу—e‘МЌR‘М‚Й‚ж‚йЌЋ•ћ kn-title=Overcoming cancer?associated fibroblast?induced immunosuppression by anti?interleukin?6 receptor antibody en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NISHIWAKINoriyuki en-aut-sei=NISHIWAKI en-aut-mei=Noriyuki kn-aut-name=ђјe‹I”V kn-aut-sei=ђјe kn-aut-mei=‹I”V aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Ќ‚“]€Ъђ«ѓgѓЉѓvѓ‹ѓlѓKѓeѓBѓu“ыЉаЌЧ–E‚Е‚Н“S‘гЋУ‚Єђ§ЊА‚і‚кЃA“SѓLѓЊЃ[ѓgЌЬ‚МЋЎ—Г•W“I‚Ж‚И‚и“ѕ‚й 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= en-copyright= kn-copyright= en-aut-name=WANGYUZE en-aut-sei=WANG en-aut-mei=YUZE kn-aut-name=‰¤‰F‘т kn-aut-sei=‰¤ kn-aut-mei=‰F‘т aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ЉМЌЧ–EЉа‚МЏг”зЉФ—t“]Љ·‚ЖЉІЌЧ–Eђ«‚МђV‹K’ІђЯ€цЋq: SPRED2 kn-title=SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=GAOTONG en-aut-sei=GAO en-aut-mei=TONG kn-aut-name=Ќ‚‹Л kn-aut-sei=Ќ‚ kn-aut-mei=‹Л aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=3 article-no= start-page=e2021JB023586 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deformation of PostЃ]Spinel Under the Lower Mantle Conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=To study the viscosity of bridgmanite and ferropericlase aggregate, uniaxial compression deformation experiments on pre-synthesized post-spinel phase and bridgmanite two-layered samples were conducted under top lower mantle pressure and 1773 K utilizing DT-Cup apparatus. Up to the strain of 0.25 Ѓ} 0.05, the observed comparable strain of the bridgmanite and post-spinel samples suggests the bridgmanite dominates the bulk viscosity of the post-spinel without strain localization in periclase. The microstructures of the deformed post-spinel samples show evidence of a similar strain of periclase with the bulk strain without strain partitioning. Texture analyses of bridgmanite indicate a dominant slip plane (100), with a steady state fabric strength achieved within the strain of 0.12 Ѓ} 0.01. The current experiment has provided no evidence about an onset of strain localization of ?30 vol.% periclase at 0.25 strain. Our observations provide direct experimental verification of bridgmanite controlled rheology under low strain magnitude, which should be considered in geodynamical models which include mantle compositional and rheological evolution in the lower mantle. en-copyright= kn-copyright= en-aut-name=XuF. en-aut-sei=Xu en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamazakiD. en-aut-sei=Yamazaki en-aut-mei=D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuntS. A. en-aut-sei=Hunt en-aut-mei=S. A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujinoN. en-aut-sei=Tsujino en-aut-mei=N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HigoY. en-aut-sei=Higo en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TangeY. en-aut-sei=Tange en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaK. en-aut-sei=Ohara en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DobsonD. P. en-aut-sei=Dobson en-aut-mei=D. P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Department of Earth Sciences, University College London kn-affil= affil-num=4 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=5 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=6 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=7 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=8 en-affil=Department of Earth Sciences, University College London kn-affil= en-keyword=lower mantle kn-keyword=lower mantle en-keyword=rheology kn-keyword=rheology en-keyword=deformation kn-keyword=deformation en-keyword=post-spinel kn-keyword=post-spinel en-keyword=strain localization kn-keyword=strain localization END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=6 article-no= start-page=1213 end-page=1223 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diagnostic Utility of the PD-L1 Immunostaining in Biopsy Specimens of Patients with Biliary Tract Neoplasms en-subtitle= kn-subtitle= en-abstract= kn-abstract=BackgroundЃ@Anti-programmed death 1/programmed death ligand 1 (PD1/PD-L1) antibodies have been successfully used as treatment agents for several solid tumors; however, it is difficult to predict their effectiveness. We evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue.
MethodsЃ@Among 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. We performed immunohistochemical staining to investigate the PD-L1 expression in both resected and biopsy specimens. The percentage of the positively stained cells was calculated for subsequent use in the correlation investigation.
ResultsЃ@The biopsy methods were endoscopic retrograde cholangiopancreatography (ERCP) in 28 cases, percutaneous liver biopsy in 10 cases, and endoscopic ultrasound fine-needle aspiration in 7 cases. Among the 45 patients, when patients with?>?10% positive tumor cells in surgically resected tissues were regarded as truly positive PD-L1, the positive and negative concordance rates between surgically resected tissues and biopsy samples were 56% (5/9) and 100% (36/36), respectively. With regard to the use of preoperative biopsy as a diagnostic tool, all (5/5) PD-L1-positive patients had a positive resected specimen. The accuracy of each biopsy method was as follows: ERCP, 89% (25/28); fine-needle aspiration, 86% (6/7); and liver biopsy, 100% (10/10).
ConclusionsЃ@Biopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates. en-copyright= kn-copyright= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki 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=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=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, 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 Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Programmed death ligand 1 kn-keyword=Programmed death ligand 1 en-keyword=Bile tract neoplasm kn-keyword=Bile tract neoplasm en-keyword=Biopsy specimen kn-keyword=Biopsy specimen en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=7 article-no= start-page=739 end-page=753 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mixed Response to Cancer Immunotherapy is Driven by Intratumor Heterogeneity and Differential Interlesion Immune Infiltration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some patients experience mixed response to immunotherapy, whose biological mechanisms and clinical impact have been obscure. We obtained two tumor samples from lymph node (LN) metastatic lesions in a same patient. Whole exome sequencing for the both tumors and single-cell sequencing for the both tumor-infiltrating lymphocytes (TIL) demonstrated a significant difference in tumor clonality and TILs' characteristics, especially exhausted T-cell clonotypes, although a close relationship between the tumor cell and T-cell clones were observed as a response of an overlapped exhausted T-cell clone to an overlapped neoantigen. To mimic the clinical setting, we generated a mouse model of several clones from a same tumor cell line. Similarly, differential tumor clones harbored distinct TILs, and one responded to programmed cell death protein 1 (PD-1) blockade but the other did not in this model. We further conducted cohort study (n = 503) treated with PD-1 blockade monotherapies to investigate the outcome of mixed response. Patients with mixed responses to PD-1 blockade had a poor prognosis in our cohort. Particularly, there were significant differences in both tumor and T-cell clones between the primary and LN lesions in a patient who experienced tumor response to anti-PD-1 mAb followed by disease progression in only LN metastasis. Our results underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome.
Significance: Several patients experience mixed responses to immunotherapies, but the biological mechanisms and clinical significance remain unclear. Our results from clinical and mouse studies underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome. en-copyright= kn-copyright= en-aut-name=MorinagaTakao en-aut-sei=Morinaga en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaxNicolas en-aut-sei=Sax en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaKazuo en-aut-sei=Yamashita en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OharaYuuki en-aut-sei=Ohara en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuwataTakeshi en-aut-sei=Kuwata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YukamiHiroki en-aut-sei=Yukami en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawazoeAkihito en-aut-sei=Kawazoe en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShitaraKohei en-aut-sei=Shitara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmedaYoshiyasu en-aut-sei=Umeda en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KawaharaYu en-aut-sei=Kawahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KiniwaYukiko en-aut-sei=Kiniwa en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=EnokidaTomohiro en-aut-sei=Enokida en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TaharaMakoto en-aut-sei=Tahara en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HasegawaYoshinori en-aut-sei=Hasegawa en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=NishikawaHiroyoshi en-aut-sei=Nishikawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=2 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=3 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=KOTAI Biotechnologies Inc kn-affil= affil-num=6 en-affil=KOTAI Biotechnologies Inc kn-affil= affil-num=7 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=8 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=10 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=11 en-affil=Department of Pathology, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Genetic Medicineand Services, National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=14 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=15 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=16 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=17 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=18 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=19 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=20 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=21 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=22 en-affil=Department of Dermatology, Shinshu University School of Medicine kn-affil= affil-num=23 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=24 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=26 en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=27 en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=28 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=29 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=30 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=31 en-affil=Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center kn-affil= affil-num=32 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=8 article-no= start-page=2955 end-page=2971 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=A Method for Estimating Physician Stress Using Wearable Sensor Devices en-subtitle= kn-subtitle= en-abstract= kn-abstract=The idea of Society 5.0 initiative has been proposed to solve various social problems by connecting virtual cyberspace and real physical space through information technology. When applying the idea to improve the work-life balance of physicians in the medical field, we must consider the increased stress owing to their long continuous working hours. Estimating the stress of physicians in their daily lives by the questionnaires is insufficient, because of the difficulty of accurate their activity recalling. By using bio-metric information such as heart rate, physical activity, and sleeping information, it was expected that the daily stress state of physicians with high accuracy. In this paper, we propose a method for estimating physician stress by analyzing bio-metric information acquired by wearing a wearable sensor device. The proposed method estimates the state of stress during daily activities by acquiring data on heart rate variability (HRV) during wakefulness as well as sleep depth during rapid eye movement (REM) and non-REM sleep. Up to seven physicians wore the wearable sensor device for the maximum of eight weeks and the sleep depth and low-/high-frequency (LF/HF) components of HRV were obtained. Our observation showed that physicians' root mean square of successive differences (rMSSDs) were constantly high in their healthy state. Therefore, the decreasing of this index can be used as an indicator of fatigue and stress. In addition, by combining LF/HF components to the rMSSDs, we may estimate the stress state of physicians and find personal stressors. en-copyright= kn-copyright= en-aut-name=ImuraIssei en-aut-sei=Imura en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GotohYusuke en-aut-sei=Gotoh en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaiKoji en-aut-sei=Sakai en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaYu en-aut-sei=Ohara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TazoeJun en-aut-sei=Tazoe en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiuraHiroshi en-aut-sei=Miura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirotaTatsuya en-aut-sei=Hirota en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaAkira en-aut-sei=Uchiyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NomuraYoshinari en-aut-sei=Nomura en-aut-mei=Yoshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=4 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=5 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=6 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=7 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=8 en-affil=Graduate School of Information Science and Technology, Osaka University kn-affil= affil-num=9 en-affil=Faculty of Natural Science and Technology, Okayama University kn-affil= en-keyword=heart rate variability kn-keyword=heart rate variability en-keyword=LF/HF kn-keyword=LF/HF en-keyword=Society 5.0 kn-keyword=Society 5.0 en-keyword=stress kn-keyword=stress en-keyword=wearable sensor devices kn-keyword=wearable sensor devices en-keyword=working style kn-keyword=working style 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 ѓї-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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=‚Є‚сЉЦAђь€Ы‰иЌЧ–E‚Е‚М‚ђ53‚Мђ§Њд‚Н€ЭЉа• –Њ”dЋн‚р—}ђ§‚·‚й kn-title=Modulation of p53 expression in cancer-associated fibroblasts prevents peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OGAWAToshihiro en-aut-sei=OGAWA en-aut-mei=Toshihiro kn-aut-name=Џ¬ђмЏr”Ћ kn-aut-sei=Џ¬ђм kn-aut-mei=Џr”Ћ aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Ћоб‡”чЏ¬ЉВ‹«‰є‚Й‚Ё‚Ї‚йђH“№Ља‚ЖЋоб‡ЉЦAђь€Ы‰иЌЧ–E‚Й‘О‚·‚йЊхђь–Ж‰u—Г–@ kn-title=Dual?targeted near?infrared photoimmunotherapy for esophageal cancer and cancer?associated fbroblasts in the tumor microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SATOHiroaki en-aut-sei=SATO en-aut-mei=Hiroaki kn-aut-name=ЌІ“ЎЌ_–ѕ kn-aut-sei=ЌІ“Ў kn-aut-mei=Ќ_–ѕ aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=21 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230424 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Absence of Cretaceous hairpin in the apparent polar wander path of southwest Japan: consistency in paleomagnetic pole positions en-subtitle= kn-subtitle= en-abstract= kn-abstract=To test the hypothesis that a Cretaceous hairpin turn is absent in the apparent polar wander path (APWP) of the inner arc of southwestern Japanese island (southwest Japan), we refined a mid-Cretaceous (100 Ma) paleomagnetic pole from southwest Japan. Red mudstone samples from the 100 Ma Hayama Formation were collected for paleomagnetic analysis from eight sites in the Hayama area in the central part of southwest Japan. A high-temperature remanent magnetization component carried by hematite was isolated from these sites and was found to be of primary mid-Cretaceous origin. The primary nature of the magnetization is supported by the detrital character of the magnetic carrier. The primary directions provided a paleomagnetic pole (35.0 degrees N, 209.6 degrees E, A(95) = 6.1 degrees, N = 8), which represented southwest Japan at 100 Ma. This pole falls into a cluster of Cretaceous poles in southwest Japan. An APWP for southwest Japan between 110 and 70 Ma was updated to ascertain the stationarity of the pole positions for this region. Therefore, it is unlikely that the APWP for southwest Japan experienced a hairpin turn during the Cretaceous. en-copyright= kn-copyright= en-aut-name=UnoKoji en-aut-sei=Uno en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaHonoka en-aut-sei=Ohara en-aut-mei=Honoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurukawaKuniyuki en-aut-sei=Furukawa en-aut-mei=Kuniyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanamaruTatsuo en-aut-sei=Kanamaru en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Business Administration, Aichi University kn-affil= affil-num=4 en-affil=Department of Earth and Environmental Sciences, Nihon University kn-affil= en-keyword=Apparent polar wander path kn-keyword=Apparent polar wander path en-keyword=Hairpin turn kn-keyword=Hairpin turn en-keyword=Cretaceous kn-keyword=Cretaceous en-keyword=Southwest Japan kn-keyword=Southwest Japan END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=3 article-no= start-page=136 end-page=138 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2021 Incentive Award of the Okayama Medical Association in General Medical Science (2021 Yuuki Prize) kn-title=—Яa‚R”N“x‰ЄЋR€гЉw‰пЏЬЃ@‘ЌЌ‡Њ¤‹†Џ§—гЏЬЃiЊ‹ЏйЏЬЃj en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SunCuiming en-aut-sei=Sun en-aut-mei=Cuiming kn-aut-name=‘·ђ‰–ѕ kn-aut-sei=‘· kn-aut-mei=ђ‰–ѕ aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰ИЃ@•a—ќЉwЃi–Ж‰u•a—ќЃj END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=5 article-no= start-page=4996 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The downregulation of SPRED2, a negative regulator of the ERK1/2 pathway, was previously detected in human cancers; however, the biological consequence remains unknown. Here, we investigated the effects of SPRED2 loss on hepatocellular carcinoma (HCC) cell function. Human HCC cell lines, expressing various levels of SPRED2 and SPRED2 knockdown, increased ERK1/2 activation. SPRED2-knockout (KO)-HepG2 cells displayed an elongated spindle shape with increased cell migration/invasion and cadherin switching, with features of epithelial-mesenchymal transition (EMT). SPRED2-KO cells demonstrated a higher ability to form spheres and colonies, expressed higher levels of stemness markers and were more resistant to cisplatin. Interestingly, SPRED2-KO cells also expressed higher levels of the stem cell surface markers CD44 and CD90. When CD44(+)CD90(+) and CD44(-)CD90(-) populations from WT cells were analyzed, a lower level of SPRED2 and higher levels of stem cell markers were detected in CD44(+)CD90(+) cells. Further, endogenous SPRED2 expression decreased when WT cells were cultured in 3D, but was restored in 2D culture. Finally, the levels of SPRED2 in clinical HCC tissues were significantly lower than those in adjacent non-HCC tissues and were negatively associated with progression-free survival. Thus, the downregulation of SPRED2 in HCC promotes EMT and stemness through the activation of the ERK1/2 pathway, and leads to more malignant phenotypes. en-copyright= kn-copyright= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong 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=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=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangTianyi en-aut-sei=Wang en-aut-mei=Tianyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=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 Cell Biology, 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=cancer stem cells kn-keyword=cancer stem cells en-keyword=epithelial-mesenchymal transition kn-keyword=epithelial-mesenchymal transition en-keyword=ERK1/2-MAPK kn-keyword=ERK1/2-MAPK en-keyword=tumorigenesis kn-keyword=tumorigenesis 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=14 cd-vols= no-issue=24 article-no= start-page=6184 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Effect of Pleural Effusion on Prognosis in Patients with Non-Small Cell Lung Cancer Undergoing Immunochemotherapy: A Retrospective Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Simple Summary Minimal data exists on pleural effusion (PE) for non-small cell lung cancer (NSCLC) patients undergoing combined ICI and chemotherapy. We retrospectively investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival and overall survival than those without PE. In addition, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. In conclusion, PE was associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy. Objectives: Combined immune checkpoint inhibitor (ICI) therapy and chemotherapy has become the standard treatment for advanced non-small-cell lung cancer (NSCLC). Pleural effusion (PE) is associated with poor outcomes among patients with NSCLC undergoing chemotherapy. However, minimal data exists on PE for patients undergoing combined ICI and chemotherapy. Therefore, we investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. Methods: We identified patients with advanced NSCLC undergoing chemotherapy and ICI therapy from the Okayama Lung Cancer Study Group-Immune Chemotherapy Database (OLCSG-ICD) between December 2018 and December 2020; the OLCSG-ICD includes the clinical data of patients with advanced NSCLC from 13 institutions. Then, we analyzed the treatment outcomes based on the presence of PE. Results: We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without PE (median PFS: 6.2 months versus 9.1 months; p < 0.001; median OS: 16.4 months versus 27.7 months; p < 0.001). The negative effect of PE differed based on the patient's programmed cell death-ligand 1 (PD-L1) expression status; with the effect being more evident in patients with high PD-L1 expression. In addition, PFS and OS did not differ between patients who did and did not undergo bevacizumab treatment; thus, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. Conclusion: PE is associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy. en-copyright= kn-copyright= en-aut-name=NishimuraTomoka en-aut-sei=Nishimura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoKen en-aut-sei=Sato en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KishinoDaizo en-aut-sei=Kishino en-aut-mei=Daizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaiHaruyuki en-aut-sei=Kawai en-aut-mei=Haruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=12 en-affil=Department of General Internal Medicine 4, Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=pleural effusion kn-keyword=pleural effusion en-keyword=non-small cell carcinoma kn-keyword=non-small cell carcinoma en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=12 article-no= start-page=1032 end-page=1039 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of number of functional teeth on independence of Japanese older adults en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim
To examine the relationship between the number of present and functional teeth at baseline and future incidence of loss of independence.

Methods
Participants were community-dwelling older individuals who participated in a comprehensive geriatric health examination conducted in Kusatsu town, Japan, between 2009 and 2015. The primary endpoint was the incidence of loss of independence among participants, defined as the first certification of long-term care insurance in Japan. The numbers of present and functional teeth at baseline were determined via an oral examination. Demographics, clinical variables (e.g., history of chronic diseases and psychosocial factors), blood nutritional markers, physical functions, and perceived masticatory function were assessed.

Results
This study included 1121 individuals, and 205 individuals suffered from loss of independence during the follow-up period. Kaplan?Meier estimates of loss of independence for participants with smaller numbers of present and functional teeth were significantly greater than for those with larger numbers of teeth. Cox proportional hazard analyses indicated that a smaller number of present teeth was not a significant risk factor after adjusting for demographic characteristics. However, the number of functional teeth was a significant risk factor after the adjustment (hazard ratio: 1.975 [1.168?3.340]). Additionally, higher hazard ratios were observed in other adjusted models, but they were not statistically significant.

Conclusions
The number of functional teeth may be more closely related to the future incidence of loss of independence than the number of present teeth. This novel finding suggests that prosthodontic rehabilitation for tooth loss possibly prevents the future incidence of this life-event. en-copyright= kn-copyright= en-aut-name=MaekawaKenji en-aut-sei=Maekawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkeuchiTomoko en-aut-sei=Ikeuchi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinkaiShoji en-aut-sei=Shinkai en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiranoHirohiko en-aut-sei=Hirano en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RyuMasahiro en-aut-sei=Ryu en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TamakiKatsushi en-aut-sei=Tamaki en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YataniHirofumi en-aut-sei=Yatani en-aut-mei=Hirofumi 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=KimuraЃ]OnoAya en-aut-sei=KimuraЃ]Ono en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikutaniTakeshi en-aut-sei=Kikutani en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SuganumaTakashi en-aut-sei=Suganuma en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AyukawaYasunori en-aut-sei=Ayukawa en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GondaTomoya en-aut-sei=Gonda en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OgawaToru en-aut-sei=Ogawa en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujisawaMasanori en-aut-sei=Fujisawa en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IshigakiShoichi en-aut-sei=Ishigaki en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WatanabeYutaka en-aut-sei=Watanabe en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KitamuraAkihiko en-aut-sei=Kitamura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TaniguchiYu en-aut-sei=Taniguchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FujiwaraYoshinori en-aut-sei=Fujiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=EdahiroAyako en-aut-sei=Edahiro en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OharaYuki en-aut-sei=Ohara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FuruyaJunichi en-aut-sei=Furuya en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NakajimaJunko en-aut-sei=Nakajima en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=UmekiKento en-aut-sei=Umeki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IgarashiKentaro en-aut-sei=Igarashi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HoribeYasuhiro en-aut-sei=Horibe en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KugimiyaYoshihiro en-aut-sei=Kugimiya en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KawaiYasuhiko en-aut-sei=Kawai en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MatsumuraHideo en-aut-sei=Matsumura en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=IchikawaTetsuo en-aut-sei=Ichikawa en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OhkawaShuji en-aut-sei=Ohkawa en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=BabaKazuyoshi en-aut-sei=Baba en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=Kusatsu ISLE Study Working Group Collaborators en-aut-sei=Kusatsu ISLE Study Working Group Collaborators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=3 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=4 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=5 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=6 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=7 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=8 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=10 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=11 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=12 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=13 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=14 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=15 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=16 en-affil=Research Planning and Promotion Committee Japan Prosthodontic Society kn-affil= affil-num=17 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=18 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=19 en-affil=National Institute for Environmental Studies kn-affil= affil-num=20 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=21 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=22 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=23 en-affil=Showa University School of Dentistry kn-affil= affil-num=24 en-affil=Tokyo Dental College kn-affil= affil-num=25 en-affil=Nihon University School of Dentistry at Matsudo kn-affil= affil-num=26 en-affil=Nihon University School of Dentistry at Matsudo kn-affil= affil-num=27 en-affil=Tokyo Dental College kn-affil= affil-num=28 en-affil=Tokyo Dental College kn-affil= affil-num=29 en-affil=Nihon University School of Dentistry at Matsudo kn-affil= affil-num=30 en-affil=Nihon University School of Dentistry kn-affil= affil-num=31 en-affil=Tokushima University Graduate School Institute of Biomedical Sciences kn-affil= affil-num=32 en-affil=Meikai University School of Dentistry kn-affil= affil-num=33 en-affil=Showa University School of Dentistry kn-affil= affil-num=34 en-affil= kn-affil= en-keyword=community-dwelling older adults kn-keyword=community-dwelling older adults en-keyword=functional teeth kn-keyword=functional teeth en-keyword=loss of independence kn-keyword=loss of independence en-keyword=oral health kn-keyword=oral health en-keyword=present teeth kn-keyword=present teeth END start-ver=1.4 cd-journal=joma no-vol=72 cd-vols= no-issue=5 article-no= start-page=1285 end-page=1300 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic ductal adenocarcinoma (PDAC) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. However, the precise relationship between GEM-resistant PDAC and development of an immunosuppressive tumor microenvironment (TME) remains unclear. In this study, we investigated the immunosuppressive TME in parental and GEM-resistant PDAC tumors and assessed the therapeutic potential of combination therapy with the telomerase-specific replication-competent oncolytic adenovirus OBP-702, which induces tumor suppressor p53 protein and PD-L1 blockade against GEM-resistant PDAC tumors. Mouse PDAC cells (PAN02) and human PDAC cells (MIA PaCa-2, BxPC-3) were used to establish GEM-resistant PDAC lines. PD-L1 expression and the immunosuppressive TME were analyzed using parental and GEM-resistant PDAC cells. A cytokine array was used to investigate the underlying mechanism of immunosuppressive TME induction by GEM-resistant PAN02 cells. The GEM-resistant PAN02 tumor model was used to evaluate the antitumor effect of combination therapy with OBP-702 and PD-L1 blockade. GEM-resistant PDAC cells exhibited higher PD-L1 expression and produced higher granulocyte-macrophage colony-stimulating factor (GM-CSF) levels compared with parental cells, inducing an immunosuppressive TME and the accumulation of myeloid-derived suppressor cells (MDSCs). OBP-702 significantly inhibited GEM-resistant PAN02 tumor growth by suppressing GM-CSF-mediated MDSC accumulation. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation. en-copyright= kn-copyright= en-aut-name=KajiwaraYoshinori en-aut-sei=Kajiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FushimiTakuro en-aut-sei=Fushimi en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Oncolys BioPharma Inc. kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Pancreatic cancer kn-keyword=Pancreatic cancer en-keyword=Chemoresistance kn-keyword=Chemoresistance en-keyword=MDSC kn-keyword=MDSC en-keyword=GM-CSF kn-keyword=GM-CSF en-keyword=Oncolytic virus kn-keyword=Oncolytic virus END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=20152 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual-targeted near-infrared photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in the tumor microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) play a significant role in tumor progression within the tumor microenvironment. Previously, we used near-infrared photoimmunotherapy (NIR-PIT), a next-generation cancer cell-targeted phototherapy, to establish CAF-targeted NIR-PIT. In this study, we investigated whether dual-targeted NIR-PIT, targeting cancer cells and CAFs, could be a therapeutic strategy. A total of 132 cases of esophageal cancer were analyzed for epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and fibroblast activation protein (FAP) expression using immunohistochemistry. Human esophageal cancer cells and CAFs were co-cultured and treated with single- or dual-targeted NIR-PIT in vitro. These cells were co-inoculated into BALB/c-nu/nu mice and the tumors were treated with single-targeted NIR-PIT or dual-targeted NIR-PIT in vivo. Survival analysis showed FAP- or EGFR-high patients had worse survival than patients with low expression of FAP or EGFR (log-rank, P < 0.001 and P = 0.074, respectively), while no difference was observed in HER2 status. In vitro, dual (EGFR/FAP)-targeted NIR-PIT induced specific therapeutic effects in cancer cells and CAFs along with suppressing tumor growth in vivo, whereas single-targeted NIR-PIT did not show any significance. Moreover, these experiments demonstrated that dual-targeted NIR-PIT could treat cancer cells and CAFs simultaneously with a single NIR light irradiation. We demonstrated the relationship between EGFR/FAP expression and prognosis of patients with esophageal cancer and the stronger therapeutic effect of dual-targeted NIR-PIT than single-targeted NIR-PIT in experimental models. Thus, dual-targeted NIR-PIT might be a promising therapeutic strategy for cancer treatment. en-copyright= kn-copyright= en-aut-name=SatoHiroaki en-aut-sei=Sato en-aut-mei=Hiroaki 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=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=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkaiMasaaki en-aut-sei=Akai en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 ORCID= en-aut-name=KomotoSatoshi en-aut-sei=Komoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 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=13 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=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KobayashiHisataka en-aut-sei=Kobayashi en-aut-mei=Hisataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=11 article-no= start-page=673 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Functional Blockage of S100A8/A9 Ameliorates Ischemia-Reperfusion Injury in the Lung en-subtitle= kn-subtitle= en-abstract= kn-abstract=(1) Background: Lung ischemia-reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to identify the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. (2) Methods: Using a mouse hilar clamp model, the combination of RNA sequencing and histological investigations revealed that neutrophil-derived S100A8/A9 plays a central role in inflammatory reactions during lung IR injury. Mice were assigned to sham and IR groups with or without the injection of anti-S100A8/A9 neutralizing monoclonal antibody (mAb). (3) Results: Anti-S100A8/A9 mAb treatment significantly attenuated plasma S100A8/A9 levels compared with control IgG. As evaluated by oxygenation capacity and neutrophil infiltration, the antibody treatment dramatically ameliorated the IR injury. The gene expression levels of cytokines and chemokines induced by IR injury were significantly reduced by the neutralizing antibody. Furthermore, the antibody treatment significantly reduced TUNEL-positive cells, indicating the presence of apoptotic cells. (4) Conclusions: We identified S100A8/A9 as a novel therapeutic target against lung IR injury. en-copyright= kn-copyright= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaueTomohisa en-aut-sei=Sakaue en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomodaYuhei en-aut-sei=Komoda en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimizuDai en-aut-sei=Shimizu en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= 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=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine 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 Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network 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= affil-num=9 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=10 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=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 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=15 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=16 en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ischemia reperfusion injury kn-keyword=ischemia reperfusion injury en-keyword= S100A8/A9 kn-keyword= S100A8/A9 en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=damage-associated molecule patterns kn-keyword=damage-associated molecule patterns END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=705 end-page=713 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=The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus en-subtitle= kn-subtitle= en-abstract= kn-abstract=The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozinЃfs osmotic diuresis mechanism, patientsЃf serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (ѓА1=?0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/eЃf tended to decrease (ѓА1=?0.382, p=0.13, LRA). Compared to the baseline, E/eЃf was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/eЃf group (E/eЃf?10, n=34), E/eЃf decreased significantly (ѓА1=?0.63, p<0.05, LRA). ѓўE/eЃf was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/eЃf in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function. en-copyright= kn-copyright= en-aut-name=HigashikawaToshihiro en-aut-sei=Higashikawa en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoTomohiko en-aut-sei=Ito en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizunoTakurou en-aut-sei=Mizuno en-aut-mei=Takurou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshigamiKeiichiro en-aut-sei=Ishigami en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurokiKengo en-aut-sei=Kuroki en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaekawaNaoto en-aut-sei=Maekawa en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UsudaDaisuke en-aut-sei=Usuda en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IzumidaToshihide en-aut-sei=Izumida en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaShinya en-aut-sei=Yamada en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SangenRyusho en-aut-sei=Sangen en-aut-mei=Ryusho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HamadaKazu en-aut-sei=Hamada en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KiyosawaJun en-aut-sei=Kiyosawa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SaitoAtsushi en-aut-sei=Saito en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IguchiMasaharu en-aut-sei=Iguchi en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KasamakiYuji en-aut-sei=Kasamaki en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakahashiTakeshi en-aut-sei=Nakahashi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukudaAkihiro en-aut-sei=Fukuda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SaitoHitoshi en-aut-sei=Saito en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KandaTsugiyasu en-aut-sei=Kanda en-aut-mei=Tsugiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OkuroMasashi en-aut-sei=Okuro en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=2 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=3 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=4 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=5 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=6 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=7 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=8 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=9 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=10 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=11 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=12 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=13 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=14 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=15 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=16 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=17 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=18 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=19 en-affil=Kanazawa Medical University Himi Municipal Hospital kn-affil= affil-num=20 en-affil=Department of Geriatric Medicine, Kanazawa Medical University kn-affil= en-keyword=tofogliflozin kn-keyword=tofogliflozin en-keyword=SGLT2 inhibitor kn-keyword=SGLT2 inhibitor en-keyword=elderly patient kn-keyword=elderly patient en-keyword=HbA1c kn-keyword=HbA1c en-keyword=cardiac diastolic function kn-keyword=cardiac diastolic function END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Ћоб‡ЉФЋї—R—€CCL2‚НЌњђ‘—R—€–Ж‰u—}ђ§ЌЧ–E‚МЋоб‡”чЏ¬ЉВ‹«‚Ц‚М“®€х‚ЙЉЦ—^‚·‚й kn-title=Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=May Wathone Oo en-aut-sei=May Wathone Oo en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=5 article-no= start-page=605 end-page=608 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=Surgical Resection for Local and Lateral Lymph Node Recurrence of MSI-high Cecal Cancer with the BRAF V600E Mutation en-subtitle= kn-subtitle= en-abstract= kn-abstract=An 84-year-old female underwent open right hemicolectomy with D3 lymph node dissection for cecal cancer, pathologically identified as pT4aN2M0 Stage IIIc and BRAF mutation-positive. Due to early recurrence of abdominal wall and right lateral lymph nodes, the patient was treated with FOLFOXIRI+Bevacizumab. Imaging after 5 courses of chemotherapy found tumor shrinkage and no new metastases. The patient did not tolerate chemotherapy well, and tumor resection was performed. Microsatellite instability (MSI) testing using multiplex polymerase chain reaction (PCR) fragment analysis revealed MSI-high status. The patient is currently recurrence-free without chemotherapy at 1 year postoperatively. BRAF-mutated colorectal cancer has a poor prognosis, and may require resection of the metastatic or recurrent tumor after comprehensive evaluation. en-copyright= kn-copyright= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JikuharaAtsushi en-aut-sei=Jikuhara en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgawaRyunosuke en-aut-sei=Ogawa en-aut-mei=Ryunosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Department of Surgery, Fukuyama Daiichi Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Fukuyama Daiichi Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Fukuyama Daiichi Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=BRAF V600E mutation kn-keyword=BRAF V600E mutation en-keyword=cecal cancer, MSI-high kn-keyword=cecal cancer, MSI-high END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=9 article-no= start-page=1805 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rice Nudix Hydrolase OsNUDX2 Sanitizes Oxidized Nucleotides en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nudix hydrolase (NUDX) hydrolyzes 8-oxo-(d)GTP to reduce the levels of oxidized nucleotides in the cells. 8-oxo-(d)GTP produced by reactive oxygen species (ROS) is incorporated into DNA/RNA and mispaired with adenine, causing replicational and transcriptional errors. Here, we identified a rice OsNUDX2 gene, whose expression level was increased 15-fold under UV-C irradiation. The open reading frame of the OsNUDX2 gene, which encodes 776 amino acid residues, was cloned into Escherichia coli cells to produce the protein of 100 kDa. The recombinant protein hydrolyzed 8-oxo-dGTP, in addition to dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP), as did Arabidopsis AtNUDX1; whereas the amino acid sequence of OsNUDX2 had 18% identity with AtNUDX1. OsNUDX2 had 14% identity with barley HvNUDX12, which hydrolyzes 8-oxo-dGTP and diadenosine tetraphosphates. Suppression of the lacZ amber mutation caused by the incorporation of 8-oxo-GTP into mRNA was prevented to a significant degree when the OsNUDX2 gene was expressed in mutT-deficient E. coli cells. These results suggest that the different substrate specificity and identity among plant 8-oxo-dGTP-hydrolyzing NUDXs and OsNUDX2 reduces UV stress by sanitizing the oxidized nucleotides. en-copyright= kn-copyright= en-aut-name=KondoYuki en-aut-sei=Kondo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RikiishiKazuhide en-aut-sei=Rikiishi en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugimotoManabu en-aut-sei=Sugimoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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= en-keyword=8-oxo-dGTP kn-keyword=8-oxo-dGTP en-keyword=nudix hydrolase kn-keyword=nudix hydrolase en-keyword=Oryza sativa kn-keyword=Oryza sativa en-keyword=transcriptional error kn-keyword=transcriptional error en-keyword=UV-C kn-keyword=UV-C END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=60 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exosomal Wnt7a from a low metastatic subclone promotes lung metastasis of a highly metastatic subclone in the murine 4t1 breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Patients with triple-negative breast cancer (TNBC) often have poorer prognosis than those with other subtypes because of its aggressive behaviors. Cancer cells are heterogeneous, and only a few highly metastatic subclones metastasize. Although the majority of subclones may not metastasize, they could contribute by releasing factors that increase the capacity of highly metastatic cells and/or provide a favorable tumor microenvironment (TME). Here, we analyzed the interclonal communication in TNBC which leads to efficient cancer progression, particularly lung metastasis, using the polyclonal murine 4T1 BC model. Methods We isolated two 4T1 subclones, LM.4T1 and HM.4T1 cells with a low and a high metastatic potential, respectively, and examined the effects of LM.4T1 cells on the behaviors of HM.4T1 cells using the cell scratch assay, sphere-forming assay, sphere invasion assay, RT-qPCR, and western blotting in vitro. We also examined the contribution of LM.4T1 cells to the lung metastasis of HM.4T1 cells and TME in vivo. To identify a critical factor which may be responsible for the effects by LM.4T1 cells, we analyzed the data obtained from the GEO database. Results Co-injection of LM.4T1 cells significantly augmented lung metastases by HM.4T1 cells. LM.4T1-derived exosomes promoted the migration and invasion of HM.4T1 cells in vitro, and blocking the secretion of exosome abrogated their effects on HM.4T1 cells. Analyses of data obtained from the GEO database suggested that Wnt7a might be a critical factor responsible for the enhancing effects. In fact, a higher level of Wnt7a was detected in LM.4T1 cells, especially in exosomes, than in HM.4T1 cells, and deletion of Wnt7a in LM.4T1 cells significantly decreased the lung metastasis of HM.4T1 cells. Further, treatment with Wnt7a increased the spheroid formation by HM.4T1 cells via activation of the PI3K/Akt/mTOR signaling pathway. Finally, infiltration of alpha SMA-positive fibroblasts and angiogenesis was more prominent in tumors of LM.4T1 cells and deletion of Wnt7a in LM.4T1 cells markedly reduced angiogenesis. Conclusions We demonstrated, for the first time, that a low metastatic subclone can enhance lung metastasis of highly metastatic subclone via exosomal Wnt7a and propose Wnt7a as a molecular target to treat TNBC patients. en-copyright= kn-copyright= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning 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=TianMiao en-aut-sei=Tian en-aut-mei=Miao 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=KondoTakamasa en-aut-sei=Kondo en-aut-mei=Takamasa 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=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=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=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo 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 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= affil-num=9 en-affil=Department of Cell Biology, 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=Breast cancer kn-keyword=Breast cancer en-keyword=Metastasis kn-keyword=Metastasis en-keyword=Exosomes kn-keyword=Exosomes en-keyword=Epithelial mesenchymal transition kn-keyword=Epithelial mesenchymal transition en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ѓ}ѓEѓX”x‹•ЊЊЌДџу—¬ЏбЉQ‚Й‚Ё‚Ї‚йЌRHM G B‚PЌR‘М‚М•ЫЊм“IЊш‰К kn-title=Protective effects of anti-HMGB1 monoclonal antibody on lung ischemia reperfusion injury in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name=’†“cЊ›‘ѕY kn-aut-sei=’†“c kn-aut-mei=Њ›‘ѕY aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=PolyI:C‚НЃAA549ЌЧ–EЉ”‚Й‚Ё‚ў‚ДЃATGF-ѓА1‚Є‘Јђi‚·‚йAkt‚МѓЉѓ“Ћ_‰»‹y‚С€Ъ“®”\‚Мґђi‚р—}ђ§‚·‚й kn-title=PolyI:C suppresses TGF-ѓА1-induced Akt phosphorylation and reduces the motility of A549 lung carcinoma cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YamaguchiTakahiro en-aut-sei=Yamaguchi en-aut-mei=Takahiro kn-aut-name=ЋRЊы—ІњA kn-aut-sei=ЋRЊы kn-aut-mei=—ІњA aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue= article-no= start-page=249 end-page=261 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220616 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Modulation of p53 expression in cancer-associated fibroblasts prevents peritoneal metastasis of cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are associated with the establishment and progression of peritoneal metastasis. This study investigated the efficacy of replicative oncolytic adenovirus-mediated p53 gene therapy (OBP-702) against CAFs and peritoneal metastasis of gastric cancer (GC). Higher CAF expression in the primary tumor was associated with poor prognosis of GC, and higher CAF expression was also observed with peritoneal metastasis in immunohistochemical analysis of clinical samples. And, we found transcriptional alteration of p53 in CAFs relative to normal gastric fibroblasts (NGFs). CAFs increased the secretion of cancer-promoting cytokines, including interleukin-6, and gained resistance to chemotherapy relative to NGFs. OBP-702 showed cytotoxicity to both GC cells and CAFs but not to NGFs. Overexpression of wild-type p53 by OBP-702 infection caused apoptosis and autophagy of CAFs and decreased the secretion of cancer-promoting cytokines by CAFs. Combination therapy using intraperitoneal administration of OBP-702 and paclitaxel synergistically inhibited the tumor growth of peritoneal metastases and decreased CAFs in peritoneal metastases. OBP-702, a replicative oncolytic adenovirus-mediated p53 gene therapy, offers a promising biological therapeutic strategy for peritoneal metastasis, modulating CAFs in addition to achieving tumor lysis. en-copyright= kn-copyright= en-aut-name=OgawaToshihiro en-aut-sei=Ogawa en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Oncolys BioPharma kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=203 end-page=215 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-ѓА-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-ѓА (TGF-ѓА) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-ѓА-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-ѓА-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression. en-copyright= kn-copyright= en-aut-name=MasudaTomoya en-aut-sei=Masuda en-aut-mei=Tomoya 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=IedaTakeshi en-aut-sei=Ieda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 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=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= 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=Oncolys BioPharma Inc. 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= en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=EMT kn-keyword=EMT en-keyword=TGF-ѓА kn-keyword=TGF-ѓА en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=E1A kn-keyword=E1A END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=155 end-page=165 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinicopathological Features and Surgical Outcomes of Small Bowel Metastasis from Renal Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Small bowel metastasis from renal cell carcinoma (RCC) is rare, and its clinicopathological characteristics are unclear; thus, we revisited the concept of this tumor and reviewed its diagnostic and treatment modalities. We filtered MEDLINE searches of articles published in English between 1950 and 2019, and identified 100 patients who had undergone treatment, including 1 patient from our clinic. We extracted patient characteristics, treatment, and prognostic data, resulting in clinicopathological data on 100 patients (83 men, 17 women). Mean age was 63 years (range, 16-86 years). Tumor sites were duodenum, jejunum, ileum, and multiple sites in 30, 37, 25, and 7 patients, respectively. The 1-, 3-, and 5-year overall survival rates after diagnosis were 53.0%, 36.0%, and 36.0%. Curative resection patients showed 62.1% 5-year survival after surgery, vs. 27.5% in noncurative surgical management cases. Good prognoses can be expected if these tumors are identified early for complete removal. Surgery is the only curative option. To determine the best management strategy and improve prognostic accuracy, we continue to collect and analyze epidemiological and pathological data. Although this condition is rare, surgery should be considered if curative resection is expected. Prognosis after curative resection is not poor, but recurrence is not unlikely. en-copyright= kn-copyright= en-aut-name=KimuraJiro en-aut-sei=Kimura en-aut-mei=Jiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuiKenta en-aut-sei=Sui en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HataYasuhiro en-aut-sei=Hata en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IiyamaTatsuo en-aut-sei=Iiyama en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OnoNoriaki en-aut-sei=Ono en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, National Center for Global Health and Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, National Center for Global Health and Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, National Center for Global Health and Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, National Center for Global Health and Medicine kn-affil= affil-num=5 en-affil=Department of Diagnostic Pathology, National Center for Global Health and Medicine kn-affil= affil-num=6 en-affil=Department of Radiology, National Center for Global Health and Medicine kn-affil= affil-num=7 en-affil=Department of Biostatistics, National Center for Global Health and Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Kochi Health Sciences Center kn-affil= en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=small bowel metastasis kn-keyword=small bowel metastasis en-keyword=intestine kn-keyword=intestine en-keyword=tumor kn-keyword=tumor END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=4819 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220321 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Under normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of beta-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS. en-copyright= kn-copyright= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=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=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= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=1 article-no= start-page=29 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. Here, we demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo.
Methods Three different pancreatic cancer line cells, BxPC3, PANC1, and PK8 cells were mixed with miPSCs and subcutaneously injected into immunodeficient mice. Tumors were evaluated by histological analysis and cells derived from iPSCs were isolated and selected from tumors. The isolated cells were characterized for cancer stem cell characters in vitro and in vivo as well as their responses to anticancer drugs. The impact of co-injection of iPSCs with cancer cells on transcriptome and signaling pathways of iPSCs was investigated.
Results The injection of miPSCs mixed with human pancreatic cancer cells into immunodeficient mice maintained the stemness of miPSCs and changed their phenotype. The miPSCs acquired CSC characteristics of tumorigenicity and self-renewal. The drug responses and the metastatic ability of CSCs converted from miPSCs varied depending on the microenvironment of cancer cells. Interestingly, transcriptome profiles of these cells indicated that the pathways related with aggressiveness and energy production were upregulated from the levels of miPSCs.
Conclusions
Our result suggests that cancer-inducing microenvironment in vivo could rewire the cell signaling and metabolic pathways to convert normal stem cells into CSCs. 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=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=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumonKazuki en-aut-sei=Kumon en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= en-aut-name=Al KadiMohamad en-aut-sei=Al Kadi en-aut-mei=Mohamad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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 Pathology and Experimental Medicine, Medical School, 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= affil-num=5 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=8 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Mouse genetics program, Center for Cancer Research, National Cancer Institute kn-affil= affil-num=10 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Cancer stem cells kn-keyword=Cancer stem cells en-keyword=iPSCs kn-keyword=iPSCs en-keyword=Conversion kn-keyword=Conversion en-keyword=Plasticity kn-keyword=Plasticity en-keyword=Tumorigenesis kn-keyword=Tumorigenesis en-keyword=Pancreatic cancer microenvironments kn-keyword=Pancreatic cancer microenvironments END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=‹Я“ЎдЭ‘ѕYЋыЏWЋнЋqѓfЃ[ѓ^ѓxЃ[ѓX kn-title=Kondo Seed Collection en-subtitle= kn-subtitle= en-abstract=‘еЊґЏ§”_‰п”_‹ЖЊ¤‹†ЏЉ (Њ»ЃE‰ЄЋR‘еЉwЋ‘Њ№ђA•Ё‰ИЉwЊ¤‹†ЏЉ)Џ‰‘гЏЉ’· ‹Я“ЎдЭ‘ѕY”ЋЋm‚Й‚ж‚иЋыЏW‚і‚к‚ЅЋнЋq‚М•W–{‚М–Ъ^‚Е‚·ЃB•W–{•r‚вЋЋЊ±ЉЗ‚Мѓ‰ѓxѓ‹‚М‹LЌЪ‚р‚а‚Ж‚ЙЌмђ¬‚µ‚Ѕ‚а‚М‚Е‚·ЃBЋыЏW“ъЃAa–јЃAЉw–јЃA“ьЋиђж‚МЏо•с‚р‰{——‚Е‚«‚Ь‚·ЃB kn-abstract=This is a catalogue of seed specimens collected by Dr Mantaro Kondo, the first director of the Ohara Shonokai Agricultural Research Institute(now Institute of Plant Science and Resources, Okayama University). It is based on the description on the label of the specimen bottle or test tube. You can view information on collection dates, Japanese names, scientific names and sources. en-copyright= kn-copyright= en-aut-name=Group of Wild Plant Science, Institute of Plant Science and Resources, Okayama University en-aut-sei=Group of Wild Plant Science, Institute of Plant Science and Resources, Okayama University en-aut-mei= kn-aut-name=‰ЄЋR‘еЉw Ћ‘Њ№ђA•Ё‰ИЉwЊ¤‹†ЏЉ –мђ¶ђA•ЁѓOѓ‹Ѓ[ѓv kn-aut-sei=‰ЄЋR‘еЉw Ћ‘Њ№ђA•Ё‰ИЉwЊ¤‹†ЏЉ –мђ¶ђA•ЁѓOѓ‹Ѓ[ѓv kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=e148960 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Accumulating evidence has shown that cancer stroma and BM-derived cells (BMDCs) in the tumor microenvironment (TME) play vital roles in tumor progression. However, the mechanism by which oral cancer stroma recruits any particular subset of BMDCs remains largely unknown. Here, we sought to identify the subset of BMDCs that is recruited by cancer stroma. We established a sequential transplantation model in BALB/c nude mice, including (a) BM transplantation of GFP-expressing cells and (b) coxenografting of patient-derived stroma (PDS; 2 cases, designated PDS1 and PDS2) with oral cancer cells (HSC-2). As controls, xenografting was performed with HSC-2 alone or in combination with normal human dermal fibroblasts (HDF). PDS1, PDS2, and HDF all promoted BMDC migration in vitro and recruitment in vivo. Multicolor immunofluorescence revealed that the PDS coxenografts recruited Arginase-1(+)CD11b(+)GR1(+)GFP(+) cells, which are myeloid-derived suppressor cells (MDSCs), to the TME, whereas the HDF coxenograft did not. Screening using microarrays revealed that PDS1 and PDS2 expressed CCL2 mRNA (encoding C-C motif chemokine ligand 2) at higher levels than did HDF. Indeed, PDS xenografts contained significantly higher proportions of CCL2(+) stromal cells and CCR2(+)Arginase-1(+)CD11b(+)GR1(+) MDSCs (as receiver cells) than the HDF coxenograft. Consistently, a CCL2 synthesis inhibitor and a CCR2 antagonist significantly inhibited the PDS-driven migration of BM cells in vitro. Furthermore, i.p. injection of the CCR2 antagonist to the PDS xenograft models significantly reduced the CCR2(+)Arginase-1(+)CD11b(+)GR1(+) MDSC infiltration to the TME. In conclusion, oral cancer stroma-secreted CCL2 is a key signal for recruiting CCR2(+) MDSCs from BM to the TME. 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=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=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=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=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=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 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=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= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=Center for Comprehensive Genomic Medicine, Okayama University Hospital 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=Department of Oral and Maxillofacial 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=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 Oral Pathology and Medicine, 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= affil-num=13 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue= article-no= start-page=71 end-page=86 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spred2 controls the severity of Concanavalin A-induced liver damage by limiting interferon-gamma production by CD4(+) and CD8(+) T cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Mitogen-activated protein kinases (MAPKs) are involved in T cell-mediated liver damage. However, the inhibitory mechanism(s) that controls T cell-mediated liver damage remains unknown. Objectives: We investigated whether Spred2 (Sprouty-related, EVH1 domain-containing protein 2) that negatively regulates ERK-MAPK pathway has a biological impact on T cell-mediated liver damage by using a murine model. Methods: We induced hepatotoxicity in genetically engineered mice by intravenously injecting Concanavalin A (Con A) and analyzed the mechanisms using serum chemistry, histology, ELISA, qRT-PCR, Western blotting and flow cytometry. Results: Spred2-deficient mice (Spred2(-/-)) developed more sever liver damage than wild-type (WT) mice with increased interferon-gamma (IFNy) production. Hepatic ERK phosphorylation was enhanced in Spred2(-/-) mice, and pretreatment of Spred2(-/-) mice with the MAPK/ERK inhibitor U0126 markedly inhibited the liver damage and reduced IFN gamma production. Neutralization of IFNy abolished the damage with decreased hepatic Stat1 activation in Spred2(-/-) mice. IFN gamma was mainly produced from CD4(+) and CD8(+) T cells, and their depletion decreased liver damage and IFN gamma production. Transplantation of CD4(+) and/or CD8(+) T cells from Spred2(-/-) mice into RAG1(-/-) mice deficient in both T and B cells caused more severe liver damage than those from WT mice. Hepatic expression of T cell attractants, CXCL9 and CXCL10, was augmented in Spred2(-/-) mice as compared to WT mice. Conversely, liver damage, IFN gamma production and the recruitment of CD4(+) and CD8(+) T cells in livers after Con A challenge were lower in Spred2 transgenic mice, and Spred2-overexpressing CD4(+) and CD8(+) T cells produced lower levels of IFN gamma than WT cells upon stimulation with Con A in vitro. Conclusion: We demonstrated, for the first time, that Spred2 functions as an endogenous regulator of T cell IFNy production and Spred2-mediated inhibition of ERK-MAPK pathway may be an effective remedy for T cell-dependent liver damage. 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=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=LiuQiuying en-aut-sei=Liu en-aut-mei=Qiuying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CaoChen en-aut-sei=Cao en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=KunkelSteven L. en-aut-sei=Kunkel en-aut-mei=Steven L. 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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology, University of Michigan Medical School 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=Liver damage kn-keyword=Liver damage en-keyword=MAPK kn-keyword=MAPK en-keyword=Signal transduction and regulation kn-keyword=Signal transduction and regulation en-keyword=Gene-modified mice kn-keyword=Gene-modified mice en-keyword=Spred2 kn-keyword=Spred2 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Nanog‚НђH“№‚Є‚с‚Й‚Ё‚Ї‚й‰»Љw—Г–@‘Пђ«‚Мѓ}Ѓ[ѓJЃ[‚Е‚ ‚иЃA“SѓLѓЊЃ[ѓgЌЬ‚М—L—p‚ИЋЎ—Г•W“I‚Е‚ ‚й kn-title=Nanog is a promising chemoresistant stemness marker and therapeutic target by iron chelators for esophageal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NarusakaToru en-aut-sei=Narusaka en-aut-mei=Toru kn-aut-name=–ВЌв“O kn-aut-sei=–ВЌв kn-aut-mei=“O aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=10 article-no= start-page=2006 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification and Characterization of Rice OsHKT1;3 Variants en-subtitle= kn-subtitle= en-abstract= kn-abstract=In rice, the high-affinity K+ transporter, OsHKT1;3, functions as a Na+-selective transporter. mRNA variants of OsHKT1;3 have been reported previously, but their functions remain unknown. In this study, five OsHKT1;3 variants (V1-V5) were identified from japonica rice (Nipponbare) in addition to OsHKT1;3_FL. Absolute quantification qPCR analyses revealed that the transcript level of OsHKT1;3_FL was significantly higher than other variants in both the roots and shoots. Expression levels of OsHKT1;3_FL, and some variants, increased after 24 h of salt stress. Two electrode voltage clamp experiments in a heterologous expression system using Xenopus laevis oocytes revealed that oocytes expressing OsHKT1;3_FL and all of its variants exhibited smaller Na+ currents. The presented data, together with previous data, provide insights to understanding how OsHKT family members are involved in the mechanisms of ion homeostasis and salt tolerance in rice.

en-copyright= kn-copyright= en-aut-name=ImranShahin en-aut-sei=Imran en-aut-mei=Shahin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsuchiyaYoshiyuki en-aut-sei=Tsuchiya en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TranSen Thi Huong en-aut-sei=Tran en-aut-mei=Sen Thi Huong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Na+ transport kn-keyword=Na+ transport en-keyword=rice kn-keyword=rice en-keyword=OsHKT1 kn-keyword=OsHKT1 en-keyword=3 kn-keyword=3 en-keyword=mRNA variants kn-keyword=mRNA variants en-keyword=TEVC kn-keyword=TEVC END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=1 article-no= start-page=10 end-page=14 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Attempt of thyX gene silencing and construction of a thyX deleted clone in a Mycobacterium bovis BCG en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mycobacterium tuberculosis, the causative agent of tuberculosis, possess flavin-dependent thymidylate synthase, ThyX. Since thyX is absent in humans and was shown to be essential for M. tuberculosis normal growth, ThyX is thought to be an attractive novel TB drug target. This study assessed thyX essentiality in Mycobacterium bovis BCG strains using CRISPR interference based gene silencing and found that thyX is not essential in an M. bovis BCG Tokyo derivative strain. A thyX deletion mutant strain was successfully constructed from that strain, which reinforces the non-essentiality of thyX under a certain genetic background. en-copyright= kn-copyright= en-aut-name=ArimuraYuki en-aut-sei=Arimura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MinatoYusuke en-aut-sei=Minato en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaTakayuki en-aut-sei=Wada en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RyumonAyako en-aut-sei=Ryumon en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirataNao en-aut-sei=Hirata en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakajimaChie en-aut-sei=Nakajima en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuzukiYasuhiko en-aut-sei=Suzuki en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AtoManabu en-aut-sei=Ato en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KobayashiKazuo en-aut-sei=Kobayashi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OharaNaoko en-aut-sei=Ohara en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Microbiology, Fujita Health University School of Medicine kn-affil= affil-num=3 en-affil=Department of Microbiology, Graduate School of Human Life Science, Osaka City University kn-affil= affil-num=4 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Microbiology, Fujita Health University School of Medicine kn-affil= affil-num=7 en-affil=Division of Bioresources, Hokkaido University International Institute for Zoonosis Control kn-affil= affil-num=8 en-affil=Division of Bioresources, Hokkaido University International Institute for Zoonosis Control kn-affil= affil-num=9 en-affil=Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases kn-affil= affil-num=10 en-affil=Department of Immunology, National Institute of Infectious Diseases kn-affil= affil-num=11 en-affil=Department of Operative Dentistry, Okayama University Hospital, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=thymidylate synthase kn-keyword=thymidylate synthase en-keyword=ThyX kn-keyword=ThyX en-keyword=Mycobacterium kn-keyword=Mycobacterium en-keyword=BCG kn-keyword=BCG END start-ver=1.4 cd-journal=joma no-vol=95 cd-vols= no-issue=17 article-no= start-page=e00467-21 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021810 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Proof of Concept of the Yadokari Nature: a Capsidless Replicase-Encoding but Replication-Dependent Positive-Sense Single-Stranded RNA Virus Hosted by an Unrelated Double-Stranded RNA Virus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Viruses typically encode their own capsids that encase their genomes. However, a capsidless positive-sense single stranded RNA [(+)ssRNA] virus, YkV1, depends on an unrelated double-stranded RNA (dsRNA) virus, YnV1, for encapsidation and replication. en-copyright= kn-copyright= en-aut-name=DasSubha en-aut-sei=Das en-aut-mei=Subha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AlamMd Mahfuz en-aut-sei=Alam en-aut-mei=Md Mahfuz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhangRui en-aut-sei=Zhang en-aut-mei=Rui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HisanoSakae en-aut-sei=Hisano en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=6 article-no= start-page=755 end-page=758 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=Left Hemihepatectomy for Hepatocellular Carcinoma Following Esophagectomy with Retrosternal Gastric Tube Reconstruction for Esophageal Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Approximately 4% of patients with esophageal cancer develop a second primary malignancy in the upper gastrointestinal trunk. However, hepatectomy following esophagectomy for esophageal cancer has rarely been reported. We report the case of a 70-year-old man who underwent an esophagectomy for esophageal cancer with retrosternal gastric tube reconstruction. Nine years later, he developed hepatocellular carcinoma with tumor thrombus involving the left portal vein, and was successfully treated with left hemihepatectomy. Special attention should be paid to avoiding incidental injury of the gastric tube as well as the right gastroepiploic artery during the hepatectomy. en-copyright= kn-copyright= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuiseTakashi en-aut-sei=Kuise en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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= en-keyword=liver resection, kn-keyword=liver resection, en-keyword=esophagectomy, kn-keyword=esophagectomy, en-keyword=retrosternal gastric tube reconstruction kn-keyword=retrosternal gastric tube reconstruction END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=4 article-no= start-page=539 end-page=542 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=An Elderly Male with Primary Sj?grenЃfs Syndrome Presenting Pleuritis as the Initial Manifestation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary Sj?grenЃfs syndrome (SS) is an autoimmune disease that usually affects the exocrine glands in mid-dle-aged women. Fifteen percent of SS patients experience severe systemic extraglandular complications, and pleuritis is one of the rare complications of SS. We report the case of an elderly Japanese man who initially pre-sented with a prolonged fever and chest pain and was finally diagnosed with primary SS-associated pleuritis. Of the nine reported cases of primary SS that initially presented with pleuritis, up to six cases were elderly males. This case highlights the complication of pleuritis among elderly males with primary SS. en-copyright= kn-copyright= en-aut-name=YamamotoYukichika en-aut-sei=Yamamoto en-aut-mei=Yukichika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OkaKosuke en-aut-sei=Oka en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HasegawaKou en-aut-sei=Hasegawa en-aut-mei=Kou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Sj?grenЃfs syndrome kn-keyword=Sj?grenЃfs syndrome en-keyword=pleuritis kn-keyword=pleuritis en-keyword=elderly male kn-keyword=elderly male 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-ѓА1-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)-ѓА 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-ѓА-treated A549 human LC cells.
Methods and results: By in vitro cell proliferation assay, polyI:C showed no effect on the growth of A549 cells treated with TGF-ѓА1 at the concentration range up to 10 ѓКg/ml; however, it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-ѓА1-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 Ѓecadherin switchingЃf. The Akt inhibitor perifosine inhibited TGF-ѓА1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C.
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=71 cd-vols= no-issue=2 article-no= start-page=155 end-page=166 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transcriptomic analysis of developing seeds in a wheat (Triticum aestivum L.) mutant RSD32 with reduced seed dormancy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Seed dormancy, a major factor regulating pre-harvest sprouting, can severely hinder wheat cultivation. Reduced Seed Dormancy 32 (RSD32), a wheat (Triticum aestivum L.) mutant with reduced seed dormancy, is derived from the pre-harvest sprouting tolerant cultivar, 'Norin61'. RSD32 is regulated by a single recessive gene and mutant phenotype expressed in a seed-specific manner. Gene expressions in embryos of 'Norin61' and RSD32 were compared using RNA sequencing (RNA-seq) analysis at different developmental stages of 20, 30, and 40 days after pollination (DAP). Numbers of up-regulated genes in RSD32 are equivalent in all developmental stages. However, down-regulated genes in RSD32 are more numerous on DAP20 and DAP30 than on DAP40. In central components affecting the circadian clock, homologues to the morning-expressed genes are expressed at lower levels in RSD32. However, higher expressions of homologues acting as evening-expressed genes are observed in RSD32. Homologues of Ca2+ signaling pathway related genes are specifically expressed on DAP20 in 'Norin61'. Lower expression is shown in RSD32. These results suggest that RSD32 mutation expresses on DAP20 and earlier seed developmental stages and suggest that circadian clock regulation and Ca2+ signaling pathway are involved in the regulation of wheat seed dormancy. en-copyright= kn-copyright= en-aut-name=RikiishiKazuhide en-aut-sei=Rikiishi en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugimotoManabu en-aut-sei=Sugimoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaekawaMasahiko en-aut-sei=Maekawa en-aut-mei=Masahiko 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=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= en-keyword=mutant kn-keyword=mutant en-keyword=seed development kn-keyword=seed development en-keyword=seed dormancy kn-keyword=seed dormancy en-keyword=transcriptome kn-keyword=transcriptome en-keyword=wheat kn-keyword=wheat END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=1876 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Assessment of Demineralization Inhibition Effects of Dentin Desensitizers Using Swept-Source Optical Coherence Tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of this study was to evaluate the mechanism of action and the inhibiting effects of two types of desensitizers against dentin demineralization using pre-demineralized hypersensitivity tooth model in vitro. In this study, we confirmed that a hypersensitivity tooth model from our preliminary experiment could be prepared by immersing dentin discs in an acetic acid-based solution with pH 5.0 for three days. Dentin discs with three days of demineralization were prepared and applied by one of the desensitizers containing calcium fluoro-alumino-silicate glass (Nanoseal, NS) or fluoro-zinc-silicate glass (Caredyne Shield, CS), followed by an additional three days of demineralization. Dentin discs for three days of demineralization (de3) and six days of demineralization (de6) without the desensitizers were also prepared. The dentin discs after the experimental protocol were scanned using swept-source optical coherence tomography (SS-OCT) to image the cross-sectional (2D) view of the samples and evaluate the SS-OCT signal. The signal intensity profiles of SS-OCT from the region of interest of 300, 500, and 700 mu m in depth were obtained to calculate the integrated signal intensity and signal attenuation coefficient. The morphological differences and remaining chemical elements of the dentin discs were also analyzed using scanning electron microscopy and energy-dispersive X-ray spectroscopy. SS-OCT images of CS and NS groups showed no obvious differences between the groups. However, SS-OCT signal profiles for both the CS and NS groups showed smaller attenuation coefficients and larger integrated signal intensities than those of the de6 group. Reactional deposits of the desensitizers even after the additional three days of demineralization were observed on the dentin surface in NS group, whereas remnants containing Zn were detected within the dentinal tubules in CS group. Consequently, both CS and NS groups showed inhibition effects against the additional three days of demineralization in this study. Our findings demonstrate that SS-OCT signal analysis can be used to monitor the dentin demineralization and inhibition effects of desensitizers against dentin demineralization in vitro. en-copyright= kn-copyright= en-aut-name=MatsuzakiKumiko en-aut-sei=Matsuzaki en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimadaYasushi en-aut-sei=Shimada en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinnoYasuo en-aut-sei=Shinno en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoSerina en-aut-sei=Ono en-aut-mei=Serina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamajiKozo en-aut-sei=Yamaji en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OharaNaoko en-aut-sei=Ohara en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SadrAlireza en-aut-sei=Sadr en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SumiYasunori en-aut-sei=Sumi en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TagamiJunji en-aut-sei=Tagami en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshiyamaMasahiro en-aut-sei=Yoshiyama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Operative Dentistry, Field of Study of Biofunctional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Operative Dentistry, Field of Study of Biofunctional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Operative Dentistry, Field of Study of Biofunctional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Operative Dentistry, Field of Study of Biofunctional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Operative Dentistry, Field of Study of Biofunctional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Operative Dentistry, Field of Study of Biofunctional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Biomimetics Biomaterials Biophotonics Biomechanics & Technology Laboratory, Department of Restorative Dentistry, University of Washington kn-affil= affil-num=8 en-affil=Center of Advanced Medicine for Dental and Oral Diseases, Department for Advanced Dental Research, National Center for Geriatrics and Ger Ontology kn-affil= affil-num=9 en-affil=Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=10 en-affil=Department of Operative Dentistry, Field of Study of Biofunctional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=SS-OCT kn-keyword=SS-OCT en-keyword=dentin desensitizer kn-keyword=dentin desensitizer en-keyword=dentin demineralization kn-keyword=dentin demineralization 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=MatsumotoЃ]NakanoMichiyo en-aut-sei=MatsumotoЃ]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=16 cd-vols= no-issue=1 article-no= start-page=380 end-page=388 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A comparison of colorimetric and visual methods for the assessment of masticatory performance with color-changeable chewing gum in older persons en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/purpose
Color-changeable chewing gum is used for the evaluation of masticatory performance. However, it is currently unclear whether colorimetric and visual assessment methods yield consistent results. This study aimed to clarify the consistency between colorimetric and visual methods used for the evaluation of color changes in color-changeable chewing gum.
Materials and methods
The sample comprised 644 older persons (mean age, 75.4?Ѓ}?6.4 years). The chewing gum was masticated 60 times at the participant's own chewing rate and then expectorated. The color of the chewing gum was evaluated with the ѓўE values and a? values, measured using a colorimeter, and the 10 Color Shades (10CSh) and 5 Color Scales (5CSc), using visual evaluation. Spearman's correlation analysis was performed to examine the correlation between the results obtained by the four methods. The significance level was set at ѓї?=?0.05.
Results
The ѓўE values, a? values, 10CSh scores, and 5CSc scores were all significantly correlated. The highest correlation coefficient (0.979) was between the ѓўE values and a? values. The lowest correlation coefficient (0.847) was between the a? values and 5CSc scores. Decreased masticatory performance was observed with increased age.
Conclusion
Significant correlations were found for all four methods used in the assessment of masticatory performance with color-changeable chewing gum. While visually based assessments are valid, colorimetric methods are more sensitive to smaller changes in masticatory performance. en-copyright= kn-copyright= en-aut-name=KugimiyaYoshihiro en-aut-sei=Kugimiya en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeYutaka en-aut-sei=Watanabe en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShirobeMaki en-aut-sei=Shirobe en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MotohashiYoshiko en-aut-sei=Motohashi en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MotokawaKeiko en-aut-sei=Motokawa en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EdahiroAyako en-aut-sei=Edahiro en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaYuki en-aut-sei=Ohara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RyuMasahiro en-aut-sei=Ryu en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IgarashiKentaro en-aut-sei=Igarashi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoshinoDaichi en-aut-sei=Hoshino en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakajimaJunko en-aut-sei=Nakajima en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UedaTakayuki en-aut-sei=Ueda en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TaniguchiYu en-aut-sei=Taniguchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OgawaToru en-aut-sei=Ogawa en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaekawaKenji en-aut-sei=Maekawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TamakiKatsushi en-aut-sei=Tamaki en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=KitamuraAkihiko en-aut-sei=Kitamura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShinkaiShoji en-aut-sei=Shinkai en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HiranoHirohiko en-aut-sei=Hirano en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Removable Prosthodontics and Gerodontology, Tokyo Dental College kn-affil= affil-num=2 en-affil=Gerodontology, Department of Oral Health Science, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=3 en-affil=The Tokyo Metropolitan Support Center for Preventative Long-term and Frail Elderly Care kn-affil= affil-num=4 en-affil=Research Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=5 en-affil=Research Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=6 en-affil=Research Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=7 en-affil=Research Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=8 en-affil=Department of Removable Prosthodontics and Gerodontology, Tokyo Dental College kn-affil= affil-num=9 en-affil=Removable Prosthodontics, Nihon University School of Dentistry at Matsudo kn-affil= affil-num=10 en-affil=Special Needs Dentistry, Division of Community Based Comprehensive Dentistry, School of Dentistry, Showa University kn-affil= affil-num=11 en-affil=Department of Oral Medicine and Hospital Dentistry, Tokyo Dental College kn-affil= affil-num=12 en-affil=Department of Removable Prosthodontics and Gerodontology, Tokyo Dental College kn-affil= affil-num=13 en-affil=Center for Health and Environmental Risk Research, National Institute for Environmental Studies kn-affil= affil-num=14 en-affil=Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry kn-affil= affil-num=15 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Critical Care Medicine and Dentistry, Division of Prosthodontic Dentistry for Function of TMJ and Occlusion, Graduate School of Dentistry, Kanagawa Dental University kn-affil= affil-num=17 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Research Team for Social Participation and Health Promotion, Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=19 en-affil=Social Sciences and Human Care, Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=20 en-affil=Research Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of Gerontology kn-affil= en-keyword=Aged kn-keyword=Aged en-keyword=Chewing gum kn-keyword=Chewing gum en-keyword=Colorimetry kn-keyword=Colorimetry en-keyword=Color kn-keyword=Color en-keyword=Mastication kn-keyword=Mastication END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=8 article-no= start-page=1831 end-page=1839 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial intelligence supported anemia control system (AISACS) to prevent anemia in maintenance hemodialysis patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anemia, for which erythropoiesis-stimulating agents (ESAs) and iron supplements (ISs) are used as preventive measures, presents important difficulties for hemodialysis patients. Nevertheless, the number of physicians able to manage such medications appropriately is not keeping pace with the rapid increase of hemodialysis patients. Moreover, the high cost of ESAs imposes heavy burdens on medical insurance systems. An artificial-intelligence-supported anemia control system (AISACS) trained using administration direction data from experienced physicians has been developed by the authors. For the system, appropriate data selection and rectification techniques play important roles. Decision making related to ESAs poses a multi-class classification problem for which a two-step classification technique is introduced. Several validations have demonstrated that AISACS exhibits high performance with correct classification rates of 72%-87% and clinically appropriate classification rates of 92%-98%. en-copyright= kn-copyright= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaHiroshi en-aut-sei=Ikeda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugitaniYoshiki en-aut-sei=Sugitani en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuitoHiroshi en-aut-sei=Suito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HuynhViet Quang Huy en-aut-sei=Huynh en-aut-mei=Viet Quang Huy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KinomuraMasaru en-aut-sei=Kinomura en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Pathology & Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Shigei Medical Research Hospital kn-affil= affil-num=3 en-affil=Advanced Institute for Materials Research, Tohoku University kn-affil= affil-num=4 en-affil=Advanced Institute for Materials Research, Tohoku University kn-affil= affil-num=5 en-affil=Advanced Institute for Materials Research, Tohoku University kn-affil= affil-num=6 en-affil=Division of Hemodialysis and Apheresis, Okayama University Hospital kn-affil= affil-num=7 en-affil=Kobayashi Medicine Clinic kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anemia kn-keyword=anemia en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=erythropoiesis-stimulating agents kn-keyword=erythropoiesis-stimulating agents en-keyword=hemodialysis kn-keyword=hemodialysis en-keyword=iron kn-keyword=iron END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=1693 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy. en-copyright= kn-copyright= en-aut-name=KatsubeRyoichi en-aut-sei=Katsube en-aut-mei=Ryoichi 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=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=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KomotoSatoshi en-aut-sei=Komoto en-aut-mei=Satoshi 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=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KobayashiHisataka en-aut-sei=Kobayashi en-aut-mei=Hisataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=6 article-no= start-page=607 end-page=614 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200614 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Number of functional teeth more strongly predicts allЃ]cause mortality than number of present teeth in Japanese older adults en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim
Previous studies on the association between intraoral conditions and mortality in communityЃ]dwelling older individuals reported that fewer present teeth (PT) are significant risk factors for mortality. However, how the number of PT relative to the number of functional teeth (FT), including both present and rehabilitated teeth, influences mortality has not been investigated fully. This study examined the impact of the number of FT on mortality among communityЃ]dwelling Japanese older adults.
Methods
This study was a retrospective, observational and populationЃ]based followЃ]up study, which examined 1188 older individuals who participated in an annual geriatric health examination from 2009 to 2015. The average followЃ]up period was 1697.0?Ѓ}?774.5?days. The primary outcome was allЃ]cause mortality at followЃ]up. The numbers of PT and FT of each participant were counted during an oral examination. In addition, demographics, clinical variables, blood nutrient markers, physical functions and perceived masticatory function were measured.
Results
Kaplan?Meier analysis, followed by a logЃ]rank test, revealed that fewer PT (P? Conclusions
Current results suggest that the number of FT more strongly predicts allЃ]cause mortality than the number of PT among communityЃ]dwelling older adults. Further studies are necessary to consider the confounding of socioeconomic status and disability status. en-copyright= kn-copyright= en-aut-name=MaekawaKenji en-aut-sei=Maekawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkeuchiTomoko en-aut-sei=Ikeuchi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinkaiShoji en-aut-sei=Shinkai en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiranoHirohiko en-aut-sei=Hirano en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RyuMasahiro en-aut-sei=Ryu en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TamakiKatsushi en-aut-sei=Tamaki en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YataniHirofumi en-aut-sei=Yatani en-aut-mei=Hirofumi 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=Kusatsu ISLE Study Working Group Collaborators en-aut-sei=Kusatsu ISLE Study Working Group Collaborators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KimuraЃ]Ono Aya en-aut-sei=KimuraЃ]Ono en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KikutanTakeshi en-aut-sei=Kikutan en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuganumaTakashi en-aut-sei=Suganuma en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AyukawaYasunori en-aut-sei=Ayukawa en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=GondaTomoya en-aut-sei=Gonda en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OgawaToru en-aut-sei=Ogawa en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujisawaMasanori en-aut-sei=Fujisawa en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Ishigaki Shoichi en-aut-sei=Ishigaki en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=WatanabeYutaka en-aut-sei=Watanabe en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KitamuraAkihiko en-aut-sei=Kitamura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Taniguchi Yu en-aut-sei=Taniguchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FujiwaraYoshinori en-aut-sei=Fujiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=EdahiroAyako en-aut-sei=Edahiro en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=Ohara Yuki en-aut-sei=Ohara en-aut-mei= Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FuruyaJunichi en-aut-sei=Furuya en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NakajimaJunko en-aut-sei=Nakajima en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=UmekiKento en-aut-sei=Umeki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=IgarashiKentaro en-aut-sei=Igarashi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=Horibeasuhiro en-aut-sei=Horibe en-aut-mei=asuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KugimiyaYoshihiro en-aut-sei=Kugimiya en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=KawaiYasuhiko en-aut-sei=Kawai en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MatsumuraHideo en-aut-sei=Matsumura en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=IchikawaTetsuo en-aut-sei=Ichikawa en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=Ohkawa Shuji en-aut-sei=Ohkawa en-aut-mei= Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= affil-num=1 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=3 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=4 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=5 en-affil=Research Planning and Promotion Committee kn-affil= affil-num=6 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=7 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=8 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil= kn-affil= affil-num=10 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=11 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=12 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=13 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=14 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=15 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=16 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=17 en-affil=Research Planning and Promotion Committee, Japan Prosthodontic Society kn-affil= affil-num=18 en-affil=Hokkaido University Faculty of Dental Medicine kn-affil= affil-num=19 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=20 en-affil=National Institute for Environmental Studies kn-affil= affil-num=21 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=22 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=23 en-affil=Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=24 en-affil=Tokyo Medical and Dental University kn-affil= affil-num=25 en-affil=Tokyo Dental College kn-affil= affil-num=26 en-affil=Nihon University School of Dentistry at Matsudo kn-affil= affil-num=27 en-affil=Nihon University School of Dentistry at Matsudo kn-affil= affil-num=28 en-affil=Tokyo Dental College kn-affil= affil-num=29 en-affil=Tokyo Dental College kn-affil= affil-num=30 en-affil=Nihon University School of Dentistry at Matsudo kn-affil= affil-num=31 en-affil=Nihon University School of Dentistry kn-affil= affil-num=32 en-affil=Tokushima University Graduate School, Institute of Biomedical Sciences kn-affil= affil-num=33 en-affil=Meikai University School of Dentistry kn-affil= en-keyword=functional teeth kn-keyword=functional teeth en-keyword=mortality kn-keyword=mortality en-keyword=present teeth kn-keyword=present teeth en-keyword=risk factor kn-keyword=risk factor END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=6 article-no= start-page=557 end-page=562 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Japanese Patient with Gastric Cancer and Dihydropyrimidine Dehydrogenase Deficiency Presenting with DPYD Variants en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 63-year-old Japanese male with stomach adenocarcinoma received oral 5-fluorouracil derivative, cisplatin and trastuzumab chemotherapy. On day 8, severe diarrhea and mucositis developed; chemotherapy was stopped. On day 14, the patient developed renal dysfunction and febrile neutropenia. He also suffered from pneumonia due to Candida albicans. Systemic symptoms improved after intensive conservative treatment. Best supportive care was continued until the patient died from gastric cancer. The dihydropyrimidine dehydroge-nase protein level was low at 3.18 U/mg protein. The result of DPYD genotyping revealed three variants at posi-tions 1615 (G > A), 1627 (A > G), and 1896 (T > C) in exons 13, 13, and 14, respectively. en-copyright= kn-copyright= en-aut-name=IshiguroMikako en-aut-sei=Ishiguro en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakenakaRyuta en-aut-sei=Takenaka en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OguraKenichiro en-aut-sei=Ogura en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiratsukaAkira en-aut-sei=Hiratsuka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakedaHiromasa en-aut-sei=Takeda en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaiDaisuke en-aut-sei=Kawai en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsugenoHirofumi en-aut-sei=Tsugeno en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujikiShigeatsu en-aut-sei=Fujiki en-aut-mei=Shigeatsu 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 Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=3 en-affil=Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences kn-affil= affil-num=4 en-affil=Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=5-fluorouracil kn-keyword=5-fluorouracil en-keyword=dihydropyrimidine dehydrogenase deficiency kn-keyword=dihydropyrimidine dehydrogenase deficiency en-keyword=DPYD variant kn-keyword=DPYD variant en-keyword=gastric cancer kn-keyword=gastric cancer END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=6 article-no= start-page=475 end-page=481 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis by Endoscopic Pancreatic Stenting after Insertion of Self-Expandable Metal Stent for Malignant Distal Biliary Stricture en-subtitle= kn-subtitle= en-abstract= kn-abstract=The insertion of a self-expandable metal stent (SEMS) for nonpancreatic cancer is a factor predicting the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We evaluated the efficacy of endo-scopic pancreatic stenting (EPS) to prevent PEP after SEMS insertion in patients with malignant distal biliary stricture and without main pancreatic duct (MPD) obstruction. We performed a single-center, retrospective, historically controlled investigation to assess the outcomes of 33 consecutive patients who underwent SEMS insertion. From March 2013 to June 2015, 13 patients did not undergo EPS (Non-EPS group). The other 20 patients underwent EPS (EPS group) between July 2015 and August 2018. The background data demonstrated no signi?cant differences. Except for one patient in the Non-EPS group, all patients underwent biliary sphinc-terotomy. The EPS groupЃfs PEP incidence was signi?cantly lower (n = 1, 5%) than that of the Non-EPS group (n = 4, 31%) (p = 0.04). The median serum amylase and lipase levels after the procedure were signi?cantly lower in the EPS group than in the Non-EPS group (amylase: 104 vs. 262 U/L; p < 0.01, lipase: 102 vs. 666 U/L; p = 0.01). The use of EPS decreased the incidence of PEP after SEMS insertion in individuals with malignant distal biliary stricture and without MPD obstruction. en-copyright= kn-copyright= en-aut-name=HaradaRyo en-aut-sei=Harada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsutsuiTomoaki en-aut-sei=Tsutsui en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HattoriNao en-aut-sei=Hattori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueMasafumi en-aut-sei=Inoue en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobashiHaruhiko en-aut-sei=Kobashi en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Japanese Red Cross Okayama Hospital kn-affil= en-keyword=post-endoscopic retrograde cholangiopancreatography pancreatitis kn-keyword=post-endoscopic retrograde cholangiopancreatography pancreatitis en-keyword=endoscopic pancreatic stent kn-keyword=endoscopic pancreatic stent en-keyword=main pancreatic duct obstruction kn-keyword=main pancreatic duct obstruction en-keyword=self-expandable metal stent kn-keyword=self-expandable metal stent en-keyword=distal biliary stricture kn-keyword=distal biliary stricture END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=4 article-no= start-page=322 end-page=326 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Construction and characterization of the PGN_0296 mutant of Porphyromonas gingivalis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The periodontal pathogen Porphyromonas gingivalis produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in the organism's virulence, and pigmentation. We previously showed that deletion of the PGN_0297 and PGN_0300 genes reduced the proteolytic activity of gingipains. The role of the PGN_0296 gene, consisting of an operon with the PGN_0297 and PGN_0300 genes, is unclear. Herein, we examined the effect of PGN_0296 gene deletion on the proteolytic activity. Although the proteolytic activity of the gingipains did not decrease in the culture supernatant of a PGN_0296 gene deletion mutant (ѓўPGN_0296), the growth was delayed. en-copyright= kn-copyright= en-aut-name=ShahriarAbu Saleh Muhammad en-aut-sei=Shahriar en-aut-mei=Abu Saleh Muhammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoShintaro en-aut-sei=Ono en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaNaoko en-aut-sei=Ohara en-aut-mei=Naoko 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= affil-num=1 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Periodontal Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Operative Dentistry, Okayama University Hospital, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=Periodontal diseases kn-keyword=Periodontal diseases en-keyword=Gingipain kn-keyword=Gingipain en-keyword=Bacterial secretion system kn-keyword=Bacterial secretion system END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=6 article-no= start-page=505 end-page=511 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=New Vascular-Access Intervention Assistance Plate Provides Good Operability and Safety by Preventing Accidental Falls: First Experience of 1,872 Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vascular-access interventions are necessary for the continuation of hemodialysis, and they are performed under X-ray guidance. During interventions, patientsЃf accidental falls from the bed are a serious problem, and spe-cialized fixation systems for hemodialysis patients to prevent their falls from the bed have been lacking. We developed a new fixation plate made of polypropylene homopolymer and tested its ability to prevent such falls retrospectively. This plate, which we named the Ѓevascular-access intervention assistance plate,Ѓf offers functional features such as the concurrent fixation of the body and either arm and an arm space with serrations for fixing a forearm strap. We performed computer simulations to examine the strength of the plate, and we evaluated the efficacy of fall prevention by reviewing patientsЃf medical records. The results demonstrated that the functional design of the plate provides good operability via accurate concurrent fixations of the body and arm. The com-puter simulation analysis results indicated the plateЃfs sufficient strength. The medical records analysis revealed three accidental falls before the plateЃfs introduction (401 patients, 1,437 interventions), and none after plate introduction (683 patients, 1,872 interventions). Accidental falls were significantly prevented by use of the plate (p < 0.05). The dementia rate and type of procedure were not significantly different between the patients who fell and those who did not. This vascular-access intervention assisted plate provides good operability and safety by preventing accidental falls among hemodialysis patients. en-copyright= kn-copyright= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HiramatsuSatoshi en-aut-sei=Hiramatsu en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Pathology & Experimental Medicine, 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 Dialysis Access Center, Shigei Medical Research Hospital kn-affil= en-keyword=hemodialysis kn-keyword=hemodialysis en-keyword=fall accident kn-keyword=fall accident en-keyword=incident kn-keyword=incident en-keyword=vascular access kn-keyword=vascular access END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=5 article-no= start-page=449 end-page=453 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Seronegative Oligoarthritis Preceding Psoriasis by 9.5 Years en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a case of psoriatic arthritis where oligoarthritis preceded the skin lesions. A 57-year-old man complained of left third-finger pain. Laboratory examinations were negative for anti-cyclic citrullinated peptide antibodies and rheumatoid factor; he was treated for suspected rheumatoid arthritis. Six years later, X-ray revealed enthesitis of his fingers and wrist joint. At 9.5 years after the initial visit, skin lesions appeared in the left auricular region and buttock and dermatopathology findings indicated psoriasis vulgaris. The final diagnosis was psoriatic arthritis. In cases of seronegative oligoarthritis, psoriatic arthritis must be considered because some patients demonstrate osteoarticular lesions preceding skin lesions. en-copyright= kn-copyright= en-aut-name=TsuchiyaJunpei en-aut-sei=Tsuchiya en-aut-mei=Junpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoNaoki en-aut-sei=Kondo en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujimotoAtsushi en-aut-sei=Fujimoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoRie en-aut-sei=Kondo en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaMasahiko en-aut-sei=Yamada en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuraishiTatsuya en-aut-sei=Kuraishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YodaTakuya en-aut-sei=Yoda en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AbeRiichiro en-aut-sei=Abe en-aut-mei=Riichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EndoNaoto en-aut-sei=Endo en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Division of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=8 en-affil=Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=9 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=enthesitis kn-keyword=enthesitis en-keyword=psoriatic arthritis kn-keyword=psoriatic arthritis en-keyword=seronegative oligoarthritis kn-keyword=seronegative oligoarthritis en-keyword=classification criteria for psoriatic arthritis kn-keyword=classification criteria for psoriatic arthritis 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=68 cd-vols= no-issue=1 article-no= start-page=57 end-page=62 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prolonged warm ischemia exacerbated acute rejection after lung transplantation from donation after cardiac death in a mouse en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: In lung transplantation (LTx) from donation after cardiac death (DCD), the donor lungs are inevitably exposed to warm ischemic time (WIT) between the cardiac arrest and the initiation of cold preservation. We conducted this study to examine the effect of prolonged WIT on lung allograft rejection in a murine model of LTx from DCD.
Methods: Allogeneic BALB/c ЃЁ B6 LTx from DCD was performed with a WIT of 15 min (WIT15 group, n = 5) or 60 min (WIT60 group, n = 5). Recipients were immunosuppressed by perioperative costimulatory blockade. The lung allografts were analyzed by histology and flow cytometry on day 7 after the LTx.
Results: Histologically, the rejection grade in the WIT60 group was significantly higher than that in the WIT15 group (3.4 Ѓ} 0.4 vs. 2.2 Ѓ} 0.2, P = 0.0278). Moreover, the intragraft CD8+ to CD4+ T cell ratio in the WIT60 group was significantly higher than that in the WIT15 group (2.3 Ѓ} 0.12 vs. 1.2 Ѓ} 0.11, P < 0.0001).
Conclusions: Prolonged WIT could exacerbate the severity of lung allograft rejection after LTx from DCD. Minimization of the WIT could improve the outcomes after LTx from DCD. en-copyright= kn-copyright= en-aut-name=HiranoYutaka en-aut-sei=Hirano en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoSumiharu en-aut-sei=Yamamoto en-aut-mei=Sumiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaMasanori en-aut-sei=Okada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtaniShinji en-aut-sei=Otani en-aut-mei=Shinji 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=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi 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= en-aut-name=OtoTakahiro en-aut-sei=Oto en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=Department of General Thoracic 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=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 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=8 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=10 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=Brain dead donor kn-keyword=Brain dead donor en-keyword=Donation after cardiac death kn-keyword=Donation after cardiac death en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=Organ preservation kn-keyword=Organ preservation en-keyword=Rejection kn-keyword=Rejection END start-ver=1.4 cd-journal=joma no-vol=131 cd-vols= no-issue=3 article-no= start-page=127 end-page=130 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2018 Incentive Award of the Okayama Medical Association in Cancer Research (2018 Hayashibara Prize and Yamada Prize) kn-title=•Ѕђ¬30”N“x‰ЄЋR€гЉw‰пЏЬ ‚Є‚сЊ¤‹†Џ§—гЏЬЃi—СЊґЏЬЃEЋR“cЏЬЃj en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KatoTakuya en-aut-sei=Kato en-aut-mei=Takuya kn-aut-name=‰Б“Ў‘м–з kn-aut-sei=‰Б“Ў kn-aut-mei=‘м–з aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰ИЃ@ЏБ‰»ЉнЉO‰ИЉw END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=1 end-page=6 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Promising New Anti-Cancer Strategy: Iron Chelators Targeting CSCs en-subtitle= kn-subtitle= en-abstract= kn-abstract= Iron is a trace but vital element in the human body and is necessary for a multitude of crucial processes in life. However, iron overload is known to induce carcinogenesis via oxidative stress. Cancer cells require large amounts of iron for their rapid division and cell growth. Iron was recently found to play a role in cancer stem cells (CSCs); it maintains stemness during development. Iron also plays an important role in stemness by moderating reactive oxygen species. Thus, iron metabolism in CSCs is a promising therapeutic target. In this review, we summarize the roles of iron in cancer cells and CSCs. We also summarize anti-cancer therapeutic studies with iron chelators and describe our expectation of a new therapeutic strategy for CSCs on the basis of our findings. 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=XingBoyi en-aut-sei=Xing en-aut-mei=Boyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QiJiping en-aut-sei=Qi en-aut-mei=Jiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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, 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= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, the First Affiliated Hospital of Harbin Medical University 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 Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cancer stem cell kn-keyword=cancer stem cell en-keyword=stemness kn-keyword=stemness en-keyword=iron kn-keyword=iron en-keyword=chelation kn-keyword=chelation en-keyword=chemotherapy kn-keyword=chemotherapy END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page=2756 end-page=2762 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer stem cell induction from mouse embryonic stem cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= Although cancers are often removed by surgery and treated by chemotherapy and/or radiation therapies, they often reoccur following treatment due to the presence of resistant residual cells such as cancer stem cells (CSCs). CSCs are characterized by their self-renewal, pluripotency, and tumorigenicity properties, and are promising therapeutic targets for the complete therapy of cancers; however, the number of CSCs in cancer tissue is typically too small to investigate fully. We have previously reported that CSCs could be established from induced pluripotent stem cells (iPSCs) using a conditioned medium during cancer cell culture. In the present study, mouse embryonic stem cells (mESCs) were observed to be converted to CSCs (mES-CSCs). This demonstrated that CSC induction does not exclusively occur following gene editing in somatic cells, and that conditioned medium from cancer cells may contain factors that can induce CSCs. Therefore, not only iPSCs but also mESCs, were demonstrated to be able to produce CSCs as one of the potentials of pluripotency of stem cells, suggesting that the conversion to CSCs is not specific to iPSCs. The resultant mES-CSCs would be also useful to generate tissue specific cancers and these naturally occurring cancers can contribute to drug screenings, but also undergo further investigation in order to reveal cancer mechanisms. en-copyright= kn-copyright= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiChikae en-aut-sei=Murakami en-aut-mei=Chikae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=El?AaragBishoy en-aut-sei=El?Aarag en-aut-mei=Bishoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki 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=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, 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=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Health Service Center, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= en-keyword=cancer stem cell kn-keyword=cancer stem cell en-keyword=conditioned medium kn-keyword=conditioned medium en-keyword=mouse embryonic stem cells kn-keyword=mouse embryonic stem cells END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=1 article-no= start-page=100 end-page=118 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rescue from Stx2-Producing E.?coli-Associated Encephalopathy by Intravenous Injection of Muse Cells in NOD-SCID Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis, hemolytic uremic syndrome, and acute encephalopathies that may lead to sudden death or severe neurologic sequelae. Current treatments, including immunoglobulin G (IgG) immunoadsorption, plasma exchange, steroid pulse therapy, and the monoclonal antibody eculizumab, have limited effects against the severe neurologic sequelae. Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative non-tumorigenic stem cells that naturally reside in the body and are currently under clinical trials for regenerative medicine. When administered intravenously, Musecells accumulate to the damaged tissue, where they exert anti-inflammatory, anti-apoptotic, anti-fibrotic, and immunomodulatory effects, and replace damaged cells by differentiating into tissue-constituent cells. Here, severely immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice orally inoculated with 9 Ѓ~ 109 colony-forming units of STEC O111 and treated 48 h later with intravenous injection of 5 Ѓ~ 104 Muse cells exhibited 100% survival and no severe after-effects of infection. Suppression of granulocyte-colony-stimulating factor (G-CSF) by RNAi abolished the beneficial effects of Muse cells, leading to a 40% death and significant body weight loss, suggesting the involvement of G-CSF in the beneficial effects of Muse cells in STEC-infected mice. Thus, intravenous administration of Muse cells could be a candidate therapeutic approach for preventing fatal encephalopathy after STEC infection. en-copyright= kn-copyright= en-aut-name=OzuruRyo en-aut-sei=Ozuru en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakaoShohei en-aut-sei=Wakao en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiTakahiro en-aut-sei=Tsuji en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MatsubaTakashi en-aut-sei=Matsuba en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AmuranMuhammad Y. en-aut-sei=Amuran en-aut-mei=Muhammad Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IsobeJunko en-aut-sei=Isobe en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IinoMorio en-aut-sei=Iino en-aut-mei=Morio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishidaNaoki en-aut-sei=Nishida en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoSari en-aut-sei=Matsumoto en-aut-mei=Sari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwadateKimiharu en-aut-sei=Iwadate en-aut-mei=Kimiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KonishiNoriko en-aut-sei=Konishi en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasudaKaori en-aut-sei=Yasuda en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TashiroKosuke en-aut-sei=Tashiro en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HidaMisato en-aut-sei=Hida en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YadoiwaArisato en-aut-sei=Yadoiwa en-aut-mei=Arisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatoShinsuke en-aut-sei=Kato en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamashitaEijiro en-aut-sei=Yamashita en-aut-mei=Eijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MatsumotoSohkichi en-aut-sei=Matsumoto en-aut-mei=Sohkichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KurozawaYoichi en-aut-sei=Kurozawa en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=DezawaMari en-aut-sei=Dezawa en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FujiiJun en-aut-sei=Fujii en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Division of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University kn-affil= affil-num=2 en-affil=Department of Stem Cell Biology and Histology, Graduate School of Medicine, Tohoku University kn-affil= affil-num=3 en-affil=Division of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University kn-affil= affil-num=4 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University kn-affil= affil-num=6 en-affil=Department of Neurology, Hasanuddin University Faculty of Medicine kn-affil= affil-num=7 en-affil=Department of Bacteriology, Toyama Institute of Health kn-affil= affil-num=8 en-affil=Division of Legal Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=9 en-affil=Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama kn-affil= affil-num=10 en-affil=Department of Forensic Medicine, The Jikei University School of Medicine kn-affil= affil-num=11 en-affil=Department of Forensic Medicine, The Jikei University School of Medicine kn-affil= affil-num=12 en-affil=Department of Food Microbiology, Tokyo Metropolitan Institute of Public kn-affil= affil-num=13 en-affil=Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University kn-affil= affil-num=14 en-affil=Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University kn-affil= affil-num=15 en-affil=Division of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University kn-affil= affil-num=16 en-affil=Division of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University kn-affil= affil-num=17 en-affil=Division of Neuropathology, Department of Brain and Neuroscience, Faculty of Medicine, School of Medicine, Tottori University Faculty of Medicine kn-affil= affil-num=18 en-affil=Division of Clinical Radiology, Tottori University Hospital kn-affil= affil-num=19 en-affil=Department of Bacteriology, Niigata University School of Medicine kn-affil= affil-num=20 en-affil=Division of Health Administration and Promotion, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=21 en-affil=Department of Stem Cell Biology and Histology, Graduate School of Medicine, Tohoku University kn-affil= affil-num=22 en-affil=Division of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University kn-affil= en-keyword=Muse cells kn-keyword=Muse cells en-keyword=Shiga toxin-producing Escherichia coli kn-keyword=Shiga toxin-producing Escherichia coli en-keyword=acute encephalopathy kn-keyword=acute encephalopathy END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=1 article-no= start-page=1 end-page=25 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A representation for algebraic K-theory of quasi-coherent modules over affine spectral schemes en-subtitle= kn-subtitle= en-abstract= kn-abstract= In this paper, we study K-theory of spectral schemes by using locally free sheaves. Let us regard the K-theory as a functor K on affine spectral schemes. Then, we prove that the group completion ?B^G(B^GGL) represents the sheafification of K with respect to Zariski (resp. Nisnevich) topology G, where B^GGL is a classifying space of a colimit of affine spectral schemes GLn. en-copyright= kn-copyright= en-aut-name=OharaMariko en-aut-sei=Ohara en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Mathematical Sciences Shinshu University kn-affil= en-keyword=Infinity category kn-keyword=Infinity category en-keyword=Derived algebraic geometry kn-keyword=Derived algebraic geometry en-keyword= K-theory kn-keyword= K-theory END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue= article-no= start-page=16378 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=2019118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment-colorectal cancer network en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epithelial-mesenchymal transition (EMT) is a biological process by which epithelial cells acquire mesenchymal characteristics. In malignant tumors, EMT is crucial for acquisition of a mesenchymal phenotype with invasive and metastatic properties, leading to tumor progression. An inflammatory microenvironment is thought to be responsible for the development and progression of colorectal cancer (CRC); however, the precise role of inflammatory microenvironments in EMT-related CRC progression remains unclear. Here, we show the spatiotemporal visualization of CRC cells undergoing EMT using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drives red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-alpha, IL-1 beta, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. In vivo experiments further demonstrated the distribution of RFP-positive CRC cells in rectal and metastatic tumors. Our data suggest that the EMT imaging system described here is a powerful tool for monitoring EMT in inflammatory microenvironment-CRC networks. en-copyright= kn-copyright= en-aut-name=IedaTakeshi en-aut-sei=Ieda en-aut-mei=Takeshi 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=OkabayashiHiroki en-aut-sei=Okabayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=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=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=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=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=SaitouTakashi en-aut-sei=Saitou en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ImamuraTakeshi en-aut-sei=Imamura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=6 article-no= start-page=927 end-page=933 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Methotrexate-associated lymphoproliferative disorder with multiple pulmonary nodules and bilateral cervical lymphadenopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract= As has been well recognized, methotrexate (MTX) leads to a state of immunosuppression and can provide a basis for the development of lymphoproliferative disorders (LPDs). MTX-associated LPDs can affect nodal sites as well as extranodal sites, though the manifestation of an LPD in the form of multiple pulmonary nodules is rare. Here, we report two cases of MTX-associated LPD with multiple bilateral pulmonary nodules, which was a finding suggestive of lung cancer, and bilateral cervical lymphadenopathy. After withdrawal of MTX, the multiple bilateral pulmonary nodules and bilateral cervical lymphadenopathy disappeared without chemotherapy in both cases. From these results, patients with pulmonary nodules and cervical lymphadenopathy should be examined for head and neck malignant tumors. Also, physicians should carefully check the administration of MTX. In patients with an MTX-associated LPD, we need to make an early diagnosis and consider discontinuing the administration of MTX as soon as possible. en-copyright= kn-copyright= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KariyaShin en-aut-sei=Kariya en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Noujima-HaradaMai en-aut-sei=Noujima-Harada en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=NaitoTomoyuki en-aut-sei=Naito en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoJunya en-aut-sei=Matsumoto en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NodaYohei en-aut-sei=Noda en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkanoMitsuhiro en-aut-sei=Okano en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=NishizakiKazunori en-aut-sei=Nishizaki en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, kn-affil= affil-num=4 en-affil=Department of Pathology, Kagawa Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Otolaryngology, International University of Health and Welfare School of Medicine kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, kn-affil= affil-num=10 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=MTX-associated LPD kn-keyword=MTX-associated LPD en-keyword=Methotrexate kn-keyword=Methotrexate en-keyword=Pulmonary nodules kn-keyword=Pulmonary nodules END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=17 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spred2 Regulates High Fat Diet-Induced Adipose Tissue Inflammation, and Metabolic Abnormalities in Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract= Chronic low-grade inflammation in visceral adipose tissues triggers the development of obesity-related insulin resistance, leading to the metabolic syndrome, a serious health condition with higher risk of cardiovascular disease, diabetes, and stroke. In the present study, we investigated whether Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, plays a role in the development of high fat diet (HFD)-induced obesity, adipose tissue inflammation, metabolic abnormalities, and insulin resistance. Spred2 knockout (KO) mice, fed with HFD, exhibited an augmented body weight gain, which was associated with enhanced adipocyte hypertrophy in mesenteric white adipose tissue (mWAT) and deteriorated dyslipidemia, compared with wild-type (WT) controls. The number of infiltrating macrophages with a M1 phenotype, and the crown-like structures, composed of macrophages surrounding dead or dying adipocytes, were more abundant in Spred2 KO-mWAT compared to in WT-mWAT. Exacerbated adipose tissue inflammation in Spred2 KO mice led to aggravated insulin resistance and fatty liver disease. To analyze the mechanism(s) that caused adipose tissue inflammation, cytokine response in mWAT was investigated. Stromal vascular fraction that contained macrophages from Spred2 KO-mWAT showed elevated levels of tumor necrosis factor ѓї (TNFѓї) and monocyte chemoattractant protein-1 (MCP-1/CCL2) compared with those from WT-mWAT. Upon stimulation with palmitate acid (PA), bone marrow-derived macrophages (BMDMs) derived from Spred2 KO mice secreted higher levels of TNFѓї and MCP-1 than those from WT mice with enhanced ERK activation. U0126, a MEK inhibitor, reduced the PA-induced cytokine response. Taken together, these results suggested that Spred2, in macrophages, negatively regulates high fat diet-induced obesity, adipose tissue inflammation, metabolic abnormalities, and insulin resistance by inhibiting the ERK/MAPK pathway. Thus, Spred2 represents a potential therapeutic tool for the prevention of insulin resistance and resultant metabolic syndrome. en-copyright= kn-copyright= en-aut-name=OhkuraTakahiro en-aut-sei=Ohkura 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=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=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MarutaniRie en-aut-sei=Marutani en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UsamiKaya en-aut-sei=Usami en-aut-mei=Kaya 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, 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= affil-num=3 en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Ras/Raf/ERK/MAPK kn-keyword=Ras/Raf/ERK/MAPK en-keyword=Spred2 kn-keyword=Spred2 en-keyword=adipocyte kn-keyword=adipocyte en-keyword=inflammation kn-keyword=inflammation en-keyword=macrophage kn-keyword=macrophage en-keyword=obesity kn-keyword=obesity END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=2 article-no= start-page=177 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness en-subtitle= kn-subtitle= en-abstract= kn-abstract= Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy. en-copyright= kn-copyright= en-aut-name=KatsuraYuki en-aut-sei=Katsura en-aut-mei=Yuki 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=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaTakayuki en-aut-sei=Ninomiya en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=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=KomotoSatoshi en-aut-sei=Komoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= en-aut-name=XingBoyi en-aut-sei=Xing en-aut-mei=Boyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=Kasai Tomonari en-aut-sei=Kasai en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 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=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= 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 Pathology and Experimental MedicineOkayama 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= Shigei Medical Research Institute kn-affil= affil-num=11 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=School of Bioscience and Biotechnology, Tokyo University of Technology kn-affil= affil-num=17 en-affil= Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=18 en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=combination therapy kn-keyword=combination therapy en-keyword=iron kn-keyword=iron en-keyword=stemness kn-keyword=stemness END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=11 article-no= start-page=1019 end-page=1028 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The relationship between the PD-L1 expression of surgically resected and fine-needle aspiration specimens for patients with pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND:
Recently, therapeutic antibodies against programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) have shown promising clinical results for several solid tumors, including pancreatic cancer. In this study, we evaluated the relationship between the PD-L1 expression of surgical resected and fine-needle aspiration (FNA) specimens for patients with pancreatic cancer.
METHODS:
Of 121 patients who underwent endoscopic ultrasound-guided (EUS)-FNA before surgery for pancreatic cancer in an academic center, the 94 (78%) with adequate FNA specimens for a histological evaluation were retrospectively analyzed. All the patients had undergone upfront surgery without any chemotherapy or radiotherapy. We performed immunohistochemistry (IHC) staining to investigate the PD-L1 expression in both resected and FNA specimens. The positive-stained cells were counted, and their percentage was used for the investigation.
RESULTS:
Of the 94 patients, 16 (17%) and 11 (10%) were defined as positive on resected cancer specimens using cutoff points of 5% and 10% positively stained cancer cell counts, respectively. The concordance rates for the positive frequency of PD-L1 expression between resected and FNA specimens were 44% (7/16) and 55% (6/11) when the positivity was set to???5% and???10%, respectively. The concordance rates for the negative frequency of PD-L1 expression between two specimens were 97% (76/78) and 99% (82/83) when the positivity was set to???5% and???10%, respectively.
CONCLUSIONS:
Approximately, half of the patients with PD-L1 expression positive and almost all the patients with PD-L1 expression negative could be diagnosed on FNA specimens. en-copyright= kn-copyright= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki 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=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=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaNoriyuki en-aut-sei=Tanaka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=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=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FushimiSoichiro en-aut-sei=Fushimi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 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=14 ORCID= affil-num=1 en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of PathologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Transplant and Surgical OncologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Transplant and Surgical OncologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of PathologyHimeji Red Cross Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Transplant and Surgical OncologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry en-keyword=PD-L1 kn-keyword=PD-L1 en-keyword=Pancreatic cancer kn-keyword=Pancreatic cancer END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=4 article-no= start-page=315 end-page=323 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=Construction and Characterization of a PGN_0297 Mutant of Porphyromonas gingivalis: Evidence of the Contribution of PGN_0297 to Gingipain Activity en-subtitle= kn-subtitle= en-abstract= kn-abstract=The periodontal pathogen Porphyromonas gingivalis shows colonial pigmentation on blood agar and produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in an organismЃfs virulence and pigmentation. We showed previously that deletion of the PGN_0300 gene abolished the pigmentation activity and reduced the proteolytic activity of gingipains. The role of the PGN_0297 gene, which consists of an operon with the PGN_0300 gene, is unclear. Herein we examined the effect of PGN_0297 gene deletion on the pigmentation and proteolytic activities and transcriptional levels of gingipains. A PGN_0297 gene deletion mutant (ѓўPGN_0297) did not exhibit the pigmentation. The proteolytic activity of the gingipains was decreased in the culture supernatant and on the cell surface of ѓўPGN_0297. The mutant ѓўPGN_0297 failed to attenuate Akt phosphorylation at Thr308 and Ser473, but both phosphorylations were attenuated in the wild-type and its complementation strain. The deletion of PGN_0297 gene did not substantially affect the transcriptional levels of the gingipain genes kgp, rgpA, and rgpB. Taken together, these results indicate that PGN_0297 is closely involved in the secretion and maturation of gingipains. en-copyright= kn-copyright= en-aut-name=OnoShintaro en-aut-sei=Ono en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TachibanaMasato en-aut-sei=Tachibana en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Abu Saleh Muhammad Shahriar en-aut-sei=Abu Saleh Muhammad Shahriar en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HelingWang en-aut-sei=Heling en-aut-mei=Wang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=periodontitis kn-keyword=periodontitis en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=gingipain kn-keyword=gingipain en-keyword=C-terminal domain kn-keyword=C-terminal domain en-keyword=secretion system kn-keyword=secretion system END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=3 article-no= start-page=263 end-page=267 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sudden, Sharp Turn in an AIDS PatientЃfs Course Following the Onset of Fulminant Type 1 Diabetes en-subtitle= kn-subtitle= en-abstract= kn-abstract= A previously healthy 40-year-old Japanese male was urgently admitted with a 2-month history of dysphagia, 30-kg weight loss, and fever. Human immunodeficiency virus (HIV) antibodies and cytomegalovirus antigenemia were positive. Pneumocystis pneumonia and cytomegalovirus pneumonia were suspected. The patient was diagnosed with acquired immune deficiency syndrome (AIDS). Cytomegalovirus antigenemia became negative 20 days after the positive result. On hospital day 41, he experienced cardiopulmonary arrest. The clinical diagnosis was fulminant type 1 diabetes mellitus. He later developed hypoglycemia and was diagnosed with adrenal insufficiency accompanied by septic shock. He died of multiple organ failure 29 h post-admission to our ICU. en-copyright= kn-copyright= en-aut-name=ShimoyamaYuichiro en-aut-sei=Shimoyama en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UmegakiOsamu en-aut-sei=Umegaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OoiYukimasa en-aut-sei=Ooi en-aut-mei=Yukimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShigemotoSho en-aut-sei=Shigemoto en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AguiTomoyuki en-aut-sei=Agui en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KadonoNoriko en-aut-sei=Kadono en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MinamiToshiaki en-aut-sei=Minami en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Intensive Care Unit, Osaka Medical College Hospital kn-affil= affil-num=2 en-affil=Department of Intensive Care Unit, Osaka Medical College Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Osaka Medical College Hospital kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Osaka Medical College Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Osaka Medical College Hospital kn-affil= affil-num=6 en-affil=Department of Intensive Care Unit, Osaka Medical College Hospital kn-affil= affil-num=7 en-affil=Department ofAnesthesiology, Osaka Medical College Hospital kn-affil= en-keyword=fulminant type 1 diabetes mellitus kn-keyword=fulminant type 1 diabetes mellitus en-keyword=human immunodeficiency virus kn-keyword=human immunodeficiency virus en-keyword=cytomegalovirus kn-keyword=cytomegalovirus en-keyword=hypoglycemia kn-keyword=hypoglycemia 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 patientЃfs 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=18 cd-vols= no-issue=6 article-no= start-page=1617 end-page=1621 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20170625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular Subtypes of Breast Cancers from Myanmar Women: A Study of 91 Cases at Two Pathology Centers en-subtitle= kn-subtitle= en-abstract= kn-abstract= BACKGROUND: Breast cancer is the most common cancer in Myanmar women. Revealing the hormonal receptor status, human epidermal growth factor receptor 2 (HER2) and Ki-67 expression is useful for estimating patient prognosis as well as determination of treatment strategy. However, immunohistochemical features and classification of molecular subtypes in breast cancers from Myanmar remain unknown. METHODS: The clinicopathological features of 91 breast cancers from Myanmar women were examined. Immunohistochemistry was performed on tissue specimens with antibodies to estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki-67, cytokeratin (CK)5/6 and CK14. Immunohistochemistry-based molecular subtyping was conducted. RESULTS: Breast cancers in Myanmar women were relatively large, high grade with frequent metastatic lymph nodes. Of the 91 patients, tumors with ER positive, PgR positive, and HER2 positive were 57.1%, 37.4%, and 28.6%, respectively. The most prevalent subtype was luminal B (HER2-) (39.6%), followed by HER2 (22.0%), triple negative (TN)-basal-like (12.1%), luminal A (11.0%), TN-null (8.8%) and luminal B (HER2+) (6.6%). The mean Ki-67 expression of 91 cases was 33.9% (33.9% Ѓ} 19.2%) and the median was 28% (range; 4%-90%). The mean Ki-67 expression of luminal A, luminal B, HER2 and TN-basal-like/ null was 7%, 30%, 40%, and 57%/43%, respectively. A higher Ki-67 expression significantly correlated with a higher grade, larger size and higher stage of malignancy. CONCLUSIONS: We, for the first time, investigated the histopathological features of breast cancers from Myanmar women. Myanmar breast cancers appeared to be aggressive in nature, as evidenced by high frequency of poor-prognosis subtypes with high level of Ki-67 expression. en-copyright= kn-copyright= en-aut-name=Thar Htet San en-aut-sei=Thar Htet San en-aut-mei= 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=FushimiSoichiro en-aut-sei=Fushimi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SoeLamin en-aut-sei=Soe en-aut-mei=Lamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Ngu Wah Min en-aut-sei=Ngu Wah Min en-aut-mei= 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=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=Myint Myint Yee en-aut-sei=Myint Myint Yee en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OdaShinsuke en-aut-sei=Oda en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Matsukawa Akihiro 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, Myeik General Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Sakura Specialist Hospital 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, Central Women Hospital 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=Breast cancer kn-keyword=Breast cancer en-keyword=molecular subtypes kn-keyword=molecular subtypes en-keyword=Ki-67 expression kn-keyword=Ki-67 expression en-keyword=Myanmar kn-keyword=Myanmar END start-ver=1.4 cd-journal=joma no-vol=129 cd-vols= no-issue=1 article-no= start-page=41 end-page=44 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20170403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Thoracoscopic esophagectomy was effective in a case of lower esophageal stenosis due to recurrence of achalasia after myotomy 40 years previously kn-title=40”NЊo‰Я‚µ‚ЅђH“№ѓAѓJѓ‰ѓVѓAЏpЊг‚МђH“№Љg’ЈЃE‰є•”ђH“№‹·ЌуЏЗ‚Й ‘О‚µ‚Д‹№Ќo‹ѕ‰єђH“№€џ‘S“E‚Є’Њш‚µ‚Ѕ1—б en-subtitle= kn-subtitle= en-abstract= kn-abstract= When planning surgery for achalasia, it is important to plan for adequate myotomy and prevention of reflux. However, achalasia may recur if the procedure was inadequate or in patients with a long-term course. The present case is a 68-year-old woman who underwent myotomy of the lower esophageal sphincter 40 years ago, but recently reported difficulty in swallowing. Dilatation of the thoracic esophagus and stenosis of the abdominal esophagus were identified by examination, and the patient was diagnosed with recurrence of achalasia. After percutaneous endoscopic gastrostomy was performed to recover nutritional status, thoracoscopic esophagectomy was carried out. The patient'spost-operative course was uneventful and oral intake was enabled. At the time of writing, there has been no re-recurrence. There is no standard therapy for post-operative recurrence of achalasia. We believe that thoracoscopic esophagectomy for the recurrence of achalasia is a safe and minimally invasive alternative to conventional surgery. en-copyright= kn-copyright= en-aut-name=KatsuraYuki en-aut-sei=Katsura en-aut-mei=Yuki kn-aut-name=Њj—C‹M kn-aut-sei=Њj kn-aut-mei=—C‹M aut-affil-num=1 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name=”’ђм–х”Ћ kn-aut-sei=”’ђм kn-aut-mei=–х”Ћ aut-affil-num=2 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name=“cзІЏr‰о kn-aut-sei=“cзІ kn-aut-mei=Џr‰о aut-affil-num=3 ORCID= en-aut-name=MaedaNaomi en-aut-sei=Maeda en-aut-mei=Naomi kn-aut-name=‘O“c’јЊ© kn-aut-sei=‘O“c kn-aut-mei=’јЊ© aut-affil-num=4 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name=–мЉФaЌL kn-aut-sei=–мЉФ kn-aut-mei=aЌL aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name=“ЎЊґЏr‹` kn-aut-sei=“ЎЊґ kn-aut-mei=Џr‹` aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И en-keyword=ђH“№ѓAѓJѓ‰ѓVѓA (achalasia) kn-keyword=ђH“№ѓAѓJѓ‰ѓVѓA (achalasia) en-keyword=ЌДЋиЏp (reoperation) kn-keyword=ЌДЋиЏp (reoperation) en-keyword=ђH“№€џ‘S“E (esophagectomy) kn-keyword=ђH“№€џ‘S“E (esophagectomy) END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=2 article-no= start-page=111 end-page=116 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=Magnified observation of spontaneous morphological changes of duodenal follicular lymphoma kn-title=Љg‘е“аЋ‹‹ѕЊџЌё‚Й‚ДЊ`‘Ф•П‰»‚рЉПЋ@‚µ‚¦‚ЅЏ\“сЋw’°аh–Eђ«ѓЉѓ“ѓpЋо‚М1—б en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ѓ@A 63-year-old Japanese woman was diagnosed with duodenal follicular lymphoma. The initial esophagogastroduodenoscopic examination with magnifying observation revealed opaque white spots and enlarged whitish villi. Nine months later, esophagogastroduodenoscopy showed that the size of the lymphoma lesion decreased, and only opaque white spots were visible. The histological analysis of biopsy samples obtained during the initial endoscopy examination showed both neoplastic follicles and an inter-follicular infiltration of lymphoma cells, whereas the biopsy samples obtained at the endoscopy performed 9 months later showed only neoplastic follicle formation. These results suggest that the magnifying endoscopic features may reflect the underlying pathological mechanisms : enlarged whitish villi are probably due to lymphoma cell infiltration in the inter-follicular area, and opaque white spots are probably caused by neoplastic follicle formation. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name=ЉвЋє‰л–з kn-aut-sei=ЉвЋє kn-aut-mei=‰л–з aut-affil-num=1 ORCID= en-aut-name=TakataKatsuyoshi en-aut-sei=Takata en-aut-mei=Katsuyoshi kn-aut-name=Ќ‚“cЏ®—З kn-aut-sei=Ќ‚“c kn-aut-mei=Џ®—З aut-affil-num=2 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name=ђм–мђЅЋi kn-aut-sei=ђм–м kn-aut-mei=ђЅЋi aut-affil-num=3 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name=‰НЊґЏЛN kn-aut-sei=‰НЊґ kn-aut-mei=ЏЛN aut-affil-num=4 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name=‹g–мђі kn-aut-sei=‹g–м kn-aut-mei=ђі aut-affil-num=5 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name=‰Є“c—T”V kn-aut-sei=‰Є“c kn-aut-mei=—T”V aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰ИЃ@ЏБ‰»ЉнЃEЉМ‘џ“а‰ИЉw affil-num=2 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И •a—ќЉwЃiЋоб‡•a—ќЃj affil-num=3 en-affil=Department of Endoscopy, Okayama University Hospital kn-affil=‰ЄЋR‘еЉw•a‰@ ЊхЉw€г—Гђf—Г•” affil-num=4 en-affil=Department of Endoscopy, Okayama University Hospital kn-affil=‰ЄЋR‘еЉw•a‰@ ЊхЉw€г—Гђf—Г•” affil-num=5 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И •a—ќЉwЃiЋоб‡•a—ќЃj affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰ИЃ@ЏБ‰»ЉнЃEЉМ‘џ“а‰ИЉw en-keyword=ЏБ‰»ЉЗЊґ”аh–Eђ«ѓЉѓ“ѓpЋоЃiprimary gastrointestinal follicular lymphomaЃj kn-keyword=ЏБ‰»ЉЗЊґ”аh–Eђ«ѓЉѓ“ѓpЋоЃiprimary gastrointestinal follicular lymphomaЃj en-keyword=€«ђ«ѓЉѓ“ѓpЋоЃimalignant lymphomaЃj kn-keyword=€«ђ«ѓЉѓ“ѓpЋоЃimalignant lymphomaЃj en-keyword=Љg‘е“аЋ‹‹ѕЊџЌёЃimagnifying endoscopyЃj kn-keyword=Љg‘е“аЋ‹‹ѕЊџЌёЃimagnifying endoscopyЃj END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=3 article-no= start-page=213 end-page=216 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recurrence after Endoscopic Curative Resection of Mucosal Gastric Cancer Associated with an Adjacent Neoplastic Precursor Lesion en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 69-year-old man underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) at the lesser curvature in the angle of stomach. Histological examination revealed tub1, pM, ly0, v0, pLM(-), pVM(-), and the resection was considered curative. The scar after ESD was followed by esophagogastroduodenoscopy (EGD) and biopsy. Twenty months later, EGD showed an ulcerative lesion in the vicinity of the ESD scar, and histological examination of the biopsy specimen showed adenocarcinoma. A distal gastrectomy with lymph node dissection was then performed. Postoperative pathology showed tub1, pM, pN0, ly0, v0, and Stage 1A. Skip lesions were seen in the specimen resected by ESD, and the histological review confirmed so-called Ѓgdysplasia-like atypiaЃh (DLA) between the lesions. It has been reported recently that in DLA, the dysplasia-like change involves only the bases of the pits, without upper pit or surface epithelium involvement, and it is said that the rate of DLA is higher in gastric cancer patients. We speculated that a precancerous lesion close to the resected cancer developed into a local recurrence. en-copyright= kn-copyright= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=KubotaTetsushi en-aut-sei=Kubota en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuwadaKazuya en-aut-sei=Kuwada en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KagawaTetsuya en-aut-sei=Kagawa en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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= affil-num=1 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=dysplasia-like atypia kn-keyword=dysplasia-like atypia en-keyword=early gastric cancer kn-keyword=early gastric cancer en-keyword=endoscopic submucosal dissection kn-keyword=endoscopic submucosal dissection en-keyword=local recurrence kn-keyword=local recurrence END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=1 article-no= start-page=13 end-page=19 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Current state of and views regarding clinical approarches to Helicobacter pylori infection kn-title=Helicobacter pylori Љґђхђf—Г‚МЊ»‹µ‚Ж“W–] en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name=‰Є“c—T”V kn-aut-sei=‰Є“c kn-aut-mei=—T”V aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И ЏБ‰»ЉнЃEЉМ‘џ“а‰ИЉw en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori en-keyword=Џњ‹Ы—Г–@ kn-keyword=Џњ‹Ы—Г–@ en-keyword=€ЭЉа kn-keyword=€ЭЉа en-keyword=€Э‰Љ kn-keyword=€Э‰Љ en-keyword=MALT ѓЉѓ“ѓpЋо kn-keyword=MALT ѓЉѓ“ѓpЋо 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= dt-pub= dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ЊЊ‰t“§ђН—pѓJѓeЃ[ѓeѓ‹—Ї’u€К’u‚МЋ–‘OђЭ’иЉн‹п‚МЉJ” en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ѓ@ЊЊ‰t“§ђН•Є–м‚Е‚НђlЊы‚МЌ‚—о‰»‚Й”є‚ўѓJѓeЃ[ѓeѓ‹‚р—p‚ў‚Ѕ“§ђН‚МѓjЃ[ѓY‚ЄЌ‚‚Ь‚Б‚Д‚ў‚Ь‚·ЃB€А‘S‚ЕЊш—¦‚ж‚“§ђН‚рЌs‚¤‚Ѕ‚Я‚МђіЉm‚ИѓJѓeЃ[ѓeѓ‹—Ї’u‚Й‚НЃA€гЋt‚Мђк–е“I‚И’mЋЇЃE‹ZЏp‚Є•K—v‚Е‚·ЃBђіЉm‚И€К’u‚Й—Ї’u‚Е‚«‚И‚Ї‚к‚ОЃAђі‚µ‚ЊЊ‰t“§ђН‚рЌs‚¤Ћ–‚Є‚Е‚«‚И‚ў‚ѕ‚Ї‚Н‚И‚ЃA€г—ГЋ–ЊМ‚р€ш‚«‹N‚±‚µ‚Ѕ‚иЃAЌД—Ї’uЋћ‚М“§Ћ‹‘•’u‚МЋg—p‚Й‚ж‚йЉіЋТ‚і‚с‚Ц‚М”н”љ‚р‘ќ‘е‚і‚№‚Ѕ‚иЃAЌ‚‰ї‚И“§ђН—pѓJѓeЃ[ѓeѓ‹”pЉь‚Й‚ж‚й€г—Г”п‚М–і‘К‚Єђ¶‚¶‚Ь‚·ЃB ‚±‚М–в‘и‚р‰рЊ€‚·‚й‚Ѕ‚Я‚ЙЃAЋ„’B‚НѓJѓeЃ[ѓeѓ‹‚М—Ї’u€К’uЋ–‘OђЭ’иЉн‹п‚рЌl€Д‚µ“Б‹–ђ\ђї‚µЃAѓЃѓfѓBѓJѓ‹ѓeѓNѓm‚Ё‚©‚в‚Ь‚М‹¦—Н‚р“ѕ‚ДЃAѓPѓCЃEѓeѓNѓmЋР‚ЕѓvѓЌѓgѓ^ѓCѓv‚рЉ®ђ¬‚і‚№‚Ь‚µ‚ЅЃB‚±‚М“xЃAЏd€д€гЉwЊ¤‹†ЏЉ•Ќ‘®•a‰@‚Е—ХЏ°Њ¤‹†‚рЌs‚ўЃA€А‘Sђ«‚Й–в‘и‚И‚ЃA—ЗЌD‚И—Ї’uђ¬ђС‚р“ѕ‚йЋ–‚Є‚Е‚«‚Ь‚µ‚ЅЃBЌЎЊг‚Нђ¬‰К‚рЉw‰пЃA_•¶‚Е”•\‚·‚й‚Ж‹¤‚ЙЃA“§ђН€ИЉO‚МѓJѓeЃ[ѓeѓ‹‚Ц‚М‰ћ—p‚вЉCЉO“WЉJ‚аЋ‹–м‚ЙЋ–‹Ж‰»‚рђi‚Я‚Д‚ў‚—\’и‚Е‚·ЃB en-copyright= kn-copyright= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name=‘еЊґ—ЏН kn-aut-sei=‘еЊґ kn-aut-mei=—ЏН aut-affil-num=1 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=џNЉФ‹і•¶ kn-aut-sei=џNЉФ kn-aut-mei=‹і•¶ aut-affil-num=2 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=“‚€д—Џ№ kn-aut-sei=“‚€д kn-aut-mei=—Џ№ aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰ИЃi€гЃj –Ж‰u•a—ќЉw affil-num=2 en-affil= kn-affil= affil-num=3 en-affil= kn-affil= en-keyword=ђlЊы“§ђН kn-keyword=ђlЊы“§ђН en-keyword=ѓJѓeЃ[ѓeѓ‹ kn-keyword=ѓJѓeЃ[ѓeѓ‹ en-keyword=—Ї’uЉн‹п kn-keyword=—Ї’uЉн‹п en-keyword=“њ”A•a kn-keyword=“њ”A•a en-keyword=Ћи‹Z kn-keyword=Ћи‹Z END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=4 article-no= start-page=227 end-page=235 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=201508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reactivity of CA19-9 and CA125 in Histological Subtypes of Epithelial Ovarian Tumors and Ovarian Endometriosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Previous reports have shown that some ovarian endometrioid adenocarcinomas and ovarian clear cell adenocarcinomas derive from ovarian endometriosis (OE), and that endocervical-like mucinous borderline ovarian tumors are associated with OE. We examined the relationship between the staging and histological subtypes of OE or epithelial ovarian tumors (EOT) and the serum levels of carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125) to evaluate the potential of these markers for preoperative diagnosis. First, we analyzed the preoperative serum levels of CA19-9 and CA125 in 195 patients who were histopathologically diagnosed with OE or EOT. We then performed a case-control study in which 308 women were enrolled, the 195 women described above and 113 healthy women as control subjects. Serum CA19-9 and CA125 levels were found to be useful in differentiating between OE and serous adenocarcinoma, but not between OE and other EOT. Moreover, serum CA19-9 levels were useful for preoperative assessment between OE and stage I mucinous borderline ovarian tumors, with or without the interstitial infiltration. In addition, considering that the serum CA19-9 levels in stage I mucinous borderline ovarian tumors were elevated via the interstitial infiltration of leukocytes and that precancerous lesions are associated with a cancerous glycosylation disorder in the process of inflammatory carcinogenesis, the CA19-9 level may be considered a suitable biomarker for estimating drug susceptibility. en-copyright= kn-copyright= en-aut-name=NakagawaNaohisa en-aut-sei=Nakagawa en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KodaHiromi en-aut-sei=Koda en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NittaNoriko en-aut-sei=Nitta en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaharaYukie en-aut-sei=Nakahara en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UnoJiro en-aut-sei=Uno en-aut-mei=Jiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=NakahoriTakashi en-aut-sei=Nakahori en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaMasaaki en-aut-sei=Hasegawa en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KataokaMikio en-aut-sei=Kataoka en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Field of Medical Technology, Graduate School of Health Sciences, Okayama University affil-num=2 en-affil= kn-affil=Department of Clinical Laboratory, Kurashiki Central Hospital Ohara HealthCare Foundation affil-num=3 en-affil= kn-affil=Department of Clinical Laboratory, Kurashiki Central Hospital Ohara HealthCare Foundation affil-num=4 en-affil= kn-affil=Department of Clinical Laboratory, Kurashiki Central Hospital Ohara HealthCare Foundation affil-num=5 en-affil= kn-affil=Department of Clinical Laboratory, Kurashiki Central Hospital Ohara HealthCare Foundation affil-num=6 en-affil= kn-affil=Department of Clinical Laboratory, Kurashiki Central Hospital Ohara HealthCare Foundation affil-num=7 en-affil= kn-affil=Department of Obstetrics and Gynecology, Kurashiki Central Hospital Ohara HealthCare Foundation affil-num=8 en-affil= kn-affil=Department of Obstetrics and Gynecology, Kurashiki Central Hospital Ohara HealthCare Foundation affil-num=9 en-affil= kn-affil=Field of Medical Technology, Graduate School of Health Sciences, Okayama University en-keyword=ovarian endometriosis kn-keyword=ovarian endometriosis en-keyword=epithelial ovarian tumors kn-keyword=epithelial ovarian tumors en-keyword=histological subtype kn-keyword=histological subtype en-keyword=carbohydrate antigen 19-9 kn-keyword=carbohydrate antigen 19-9 en-keyword=carbohydrate antigen 125 kn-keyword=carbohydrate antigen 125 END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=3 article-no= start-page=173 end-page=176 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=201506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prone-Position Thoracoscopic Ligation of the Thoracic Duct for Chyle Leak Following Radical Neck Dissection in a Patient with a Right Aortic Arch en-subtitle= kn-subtitle= en-abstract= kn-abstract=A chyle leak can occur as a complication after neck or chest surgery. Such a leak prolongs the hospital stay and is sometimes life-threatening. The treatment options are conservative management, interventional radiologic embolization, and surgery. Thoracoscopic ligation of the thoracic duct has emerged as a promising and definitive treatment. The case of a 65-year-old Japanese male patient with a rare congenital right aortic arch (type‡VB1 of Edward?s classification) and a severe chyle leak that occurred after a total pharyngolaryngo-esophagectomy (TPLE) is described. The chyle leak was successfully managed by thoracoscopic ligation of the thoracic duct via a left-side approach with the patient in the prone position. en-copyright= kn-copyright= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro 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=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=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=chyle leak kn-keyword=chyle leak en-keyword=thoracic duct kn-keyword=thoracic duct en-keyword=thoracoscopy kn-keyword=thoracoscopy en-keyword=prone position kn-keyword=prone position END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=2 article-no= start-page=93 end-page=94 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2013 Incentive Award of the Okayama Medical Association in Cancer Research (2013 Hayashibara Prize and Yamada Prize) kn-title=•Ѕђ¬25”N“x‰ЄЋR€гЉw‰пЏЬ ‚Є‚сЊ¤‹†Џ§—гЏЬЃi—СЊґЏЬЃEЋR“cЏЬЃj en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name=‘еЊґ—ЏН kn-aut-sei=‘еЊґ kn-aut-mei=—ЏН aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•Љw‘ЌЌ‡Њ¤‹†‰ИЃ@ЏБ‰»ЉнЉO‰ИЉw END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=2 article-no= start-page=111 end-page=117 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=Assistant-Based Standardization of Prone Position Thoracoscopic Esophagectomy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thoracoscopic esophagectomy in the prone position (TEPP) might enable solo-surgery in cases requiring resection of the esophagus and the surrounding lymph nodes due to the associated advantages of good exposure of the surgical field and ergonomic considerations for the surgeon. However, no one approach can be for all patients requiring extensive lymphadenectomy. We recently developed an assistant-based procedure to standardize exposure of the surgical field. Patients were divided into 1 of 2 groups:a pre-standardization group (nЃЃ37) and a post-standardization group (nЃЃ28). The thoracoscopic operative time was significantly shorter (pЃЃ0.0037) in the post-standardization group (nЃЃ28; 267Ѓ}31min) than in the pre-standardization group (nЃЃ37;301Ѓ}53min). Further, learning curve analysis using the moving average method showed stabilization of the thoracoscopic operative time after the standardization. No significant differences were found in the number of mediastinal lymph nodes dissected or intraoperative blood loss between the 2 groups. There were also no significant differences in the complication rate. Assistant-based surgery and standardization of the procedure resulted in a well-exposed and safe surgical field. TEPP decreased the operative time, even in patients requiring extensive lymphadenectomy. en-copyright= kn-copyright= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro 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=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsubeRyoichi en-aut-sei=Katsube en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=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=SakuramaKazufumi en-aut-sei=Sakurama en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=thoracoscopic esophagectomy kn-keyword=thoracoscopic esophagectomy en-keyword=prone position kn-keyword=prone position en-keyword=standardization kn-keyword=standardization END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=1 article-no= start-page=45 end-page=48 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 patient with primary malignant melanoma of the esophagus who underwent esophagectomy kn-title=ђH“№Њґ”€«ђ«Ќ•ђFЋо‚М‚PђШЏњ—б en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ѓ@We report the case of a 61-old-man with a primary malignant melanoma of the esophagus, an extremely rare and highly aggressive malignancy. He presented with dysphagia, and we performed an upper gastrointestinal endoscopy that detected a tumor in the thoracic part of the esophagus. The biopsy showed malignant melanoma. PET/CT, endoscopy and an esophagogram showed that a 70-mm scaled type 2+1 tumor in the thoracic esophagus and no metastases. We diagnosed a cT3cN0cM0 cStage II tumor. We then performed a subtotal esophagectomy with two-field lymph node dissection and esophagogastrostomy via a retrosternal route. The pathological examination of the resected specimens confirmed that the type 2+1 tumor was PMME (pT2N0M0 pStage II). We administered six courses of postoperative adjuvant chemotherapy with dacarbazine, and the patient has had no recurrence for 17 months after the surgery. en-copyright= kn-copyright= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name=‘O“c’јЊ© kn-aut-sei=‘O“c kn-aut-mei=’јЊ© aut-affil-num=1 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name=”’ђм–х”Ћ kn-aut-sei=”’ђм kn-aut-mei=–х”Ћ aut-affil-num=2 ORCID= en-aut-name=KoujimaTakeshi en-aut-sei=Koujima en-aut-mei=Takeshi kn-aut-name=љ •{“‡Њ’ kn-aut-sei=љ •{“‡ kn-aut-mei=Њ’ aut-affil-num=3 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name=‘еЊґ—ЏН kn-aut-sei=‘еЊґ kn-aut-mei=—ЏН aut-affil-num=4 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name=“cзІЏr•г kn-aut-sei=“cзІ kn-aut-mei=Џr•г aut-affil-num=5 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name=–мЉФaЌL kn-aut-sei=–мЉФ kn-aut-mei=aЌL aut-affil-num=6 ORCID= en-aut-name=SakuramaKazuhumi en-aut-sei=Sakurama en-aut-mei=Kazuhumi kn-aut-name=џNЉФ‹і•¶ kn-aut-sei=џNЉФ kn-aut-mei=‹і•¶ aut-affil-num=7 ORCID= en-aut-name=FujiwaraToshiyosi en-aut-sei=Fujiwara en-aut-mei=Toshiyosi kn-aut-name=“ЎЊґЏr‹` kn-aut-sei=“ЎЊґ kn-aut-mei=Џr‹` aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=2 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=3 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=4 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=5 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=6 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=7 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=8 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И en-keyword=ђH“№ЃiesophagusЃj kn-keyword=ђH“№ЃiesophagusЃj en-keyword=€«ђ«Ќ•ђFЋоЃimalignant melanomaЃj kn-keyword=€«ђ«Ќ•ђFЋоЃimalignant melanomaЃj END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=1 article-no= start-page=39 end-page=43 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=Complete response of primary esophageal endocrine cell carcinoma resected after neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil kn-title=Џp‘ODCF—Г–@‚Є’Њш‚µ‚ЅђH“№Њґ”“а•Є”еЌЧ–EЉа‚М‚PђШЏњ—б en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ѓ@Esophageal endocrine cell carcinoma is extremely rare. We report a case of esophageal endocrine cell carcinoma showing histological complete response to neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (DCF). A 66-year-old man had been experiencing epigastralgia, and a type 2 tumor in the thoracic part of esophagus was detected by upper endoscopy. The biopsy showed endocrine cell carcinoma. PET/CT, endoscopy and an esophagogram showed that the patient had a 70-mm scaled type 2 tumor in the middle thoracic esophagus, and they also revealed lymph node metastases (no. 106recR). We diagnosed a cT3cN1cM0 cStage III tumor. With two courses of DCF treatment, both the primary tumor and lymph node metastases showed a partial response. We performed a subtotal esophagectomy with three-field lymph node dissection. The pathological examination of the resected specimens revealed no malignant cells in the esophagus or lymph nodes, and we concluded that the pathological effect of the DCF treatment was Grade 3. en-copyright= kn-copyright= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name=‘O“c’јЊ© kn-aut-sei=‘O“c kn-aut-mei=’јЊ© aut-affil-num=1 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name=”’ђм–х”Ћ kn-aut-sei=”’ђм kn-aut-mei=–х”Ћ aut-affil-num=2 ORCID= en-aut-name=KoujimaTakeshi en-aut-sei=Koujima en-aut-mei=Takeshi kn-aut-name=љ •{“‡Њ’ kn-aut-sei=љ •{“‡ kn-aut-mei=Њ’ aut-affil-num=3 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name=‘еЊґ—ЏН kn-aut-sei=‘еЊґ kn-aut-mei=—ЏН aut-affil-num=4 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name=“cзІЏr•г kn-aut-sei=“cзІ kn-aut-mei=Џr•г aut-affil-num=5 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name=–мЉФaЌL kn-aut-sei=–мЉФ kn-aut-mei=aЌL aut-affil-num=6 ORCID= en-aut-name=SakuramaKazuhumi en-aut-sei=Sakurama en-aut-mei=Kazuhumi kn-aut-name=џNЉФ‹і•¶ kn-aut-sei=џNЉФ kn-aut-mei=‹і•¶ aut-affil-num=7 ORCID= en-aut-name=FujiwaraToshiyosi en-aut-sei=Fujiwara en-aut-mei=Toshiyosi kn-aut-name=“ЎЊґЏr‹` kn-aut-sei=“ЎЊґ kn-aut-mei=Џr‹` aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=2 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=3 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=4 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=5 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=6 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=7 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И affil-num=8 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЏБ‰»ЉЗЉO‰И en-keyword=ђH“№ЉаЃiesophageal cancerЃj kn-keyword=ђH“№ЉаЃiesophageal cancerЃj en-keyword=“а•Є”еЌЧ–EЉаЃiendocrine cell carcinomaЃj kn-keyword=“а•Є”еЌЧ–EЉаЃiendocrine cell carcinomaЃj en-keyword=DCF—Г–@ЃiDCF treatmentЃj kn-keyword=DCF—Г–@ЃiDCF treatmentЃj END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=27 end-page=41 dt-received= dt-revised= dt-accepted= dt-pub-year=1991 dt-pub=199103 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A BASIC STUDY FOR DEVELOPMENT OF FARM ON ЃgMurramЃh AREA IN KENYA en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MoritaNobuharu en-aut-sei=Morita en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritsuguMasumi en-aut-sei=Moritsugu en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaUeru en-aut-sei=Tanaka en-aut-mei=Ueru 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=19 end-page=26 dt-received= dt-revised= dt-accepted= dt-pub-year=1991 dt-pub=199103 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RAPID DETECTION OF CUCUMBER MOSAIC VIRUS BY A SIMPLIFIED F(ab')2 ELISA USING PEG en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MaedaTakanori en-aut-sei=Maeda en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InouyeNarinobu en-aut-sei=Inouye en-aut-mei=Narinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=11 end-page=18 dt-received= dt-revised= dt-accepted= dt-pub-year=1991 dt-pub=199103 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CHANGES IN CONCENTRATION OFC ADMIUM, ZINC AND IRON IN GLUTINOUS AND NON-GLUTINOUS RICE FOR 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dt-pub-year=1983 dt-pub=198303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=EFFECT OF NITROGEN SOURCE ON GROWTH AND MINERAL UPTAKE IN PLANTS UNDER CONSTANT pH AND CONVENTIONAL CULTURE CONDITIONS en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MoritsuguMasumi en-aut-sei=Moritsugu en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiTakao en-aut-sei=Suzuki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawasakiToshio en-aut-sei=Kawasaki en-aut-mei=Toshio 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page=115 end-page=123 dt-received= dt-revised= dt-accepted= dt-pub-year=1983 dt-pub=198303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CHANGES IN SOME ENZYME ACTIVITIES OF RICE AND CHINESE CABBAGE DUE TO NITROGEN STATUS en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsumotoHideaki en-aut-sei=Matsumoto en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhnoSeishi en-aut-sei=Ohno en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamayaTomoyuki en-aut-sei=Yamaya en-aut-mei=Tomoyuki 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=55 end-page=64 dt-received= dt-revised= dt-accepted= dt-pub-year=1980 dt-pub=198001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=EFFECT OF CALCIUM ON MAGNESIUM UPTAKE IN PLANTS (Part 1) The Apparent Accelerative 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en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A NEW SYSTEM OF AUTOMATIC pH REGULATION IN SOLUTION CULTURE en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MoritsuguMasumi en-aut-sei=Moritsugu en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawasakiToshio en-aut-sei=Kawasaki en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=259 end-page=316 dt-received= dt-revised= dt-accepted= dt-pub-year= dt-pub= dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=List of Literature on Barley. (I) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakahashiRyuhei en-aut-sei=Takahashi en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=252 end-page=258 dt-received= dt-revised= dt-accepted= dt-pub-year=1943 dt-pub=19430615 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Illustrations and Descriptions of Fungi Injurious to the Culture of Siitake Mushroom. II. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MihasiT. en-aut-sei=Mihasi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaT. en-aut-sei=Nakayama en-aut-mei=T. 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=238 end-page=251 dt-received= dt-revised= dt-accepted= dt-pub-year=1943 dt-pub=19430524 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=On Two Alternaria Species Injurious to Cotton Fibers in Bolls. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraK. en-aut-sei=Kimura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyawakiY. en-aut-sei=Miyawaki en-aut-mei=Y. 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=230 end-page=237 dt-received= dt-revised= dt-accepted= dt-pub-year=1943 dt-pub=19430228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=On the Relation of Temperature and Light to the Development of Sporophores in Cortinellus Berkeleyanus. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyawakiY. en-aut-sei=Miyawaki en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=214 end-page=229 dt-received= dt-revised= dt-accepted= dt-pub-year=1943 dt-pub=19430208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Disinfection of Rice Seeds Affected by Helminthosporium Oryzae, with Special Reference to the Hot-Water Treatments. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakayamaT. en-aut-sei=Nakayama en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=208 end-page=213 dt-received= dt-revised= dt-accepted= dt-pub-year=1943 dt-pub=19430109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Notes on the Pathological Anatomy of Rice Grains Affected by Helminthosporium Oryzae. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakayamaT. en-aut-sei=Nakayama en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=191 end-page=207 dt-received= dt-revised= dt-accepted= dt-pub-year=1943 dt-pub=19430322 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experimental Studies on the Resistance of the Rice Weevil, Calandra oryzae L., to Heat. II. Lethal Effects of Heat upon the Larvae and Pupae. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TsuchiyaT. en-aut-sei=Tsuchiya en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KosakaK. en-aut-sei=Kosaka en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=170 end-page=190 dt-received= dt-revised= dt-accepted= dt-pub-year=1943 dt-pub=19430110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experimental Studies on the Resistance of the Rice Weevil, Calandra oryzae L., to Heat. I. Resistance of Adult Weevil to Heat. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TsuchiyaTakashi en-aut-sei=Tsuchiya en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=156 end-page=169 dt-received= dt-revised= dt-accepted= dt-pub-year=1943 dt-pub=19430115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Untersuchungen der verschiedenen Reiskörner geringerer Qualitat. VI. Die Reiskörner der durch die Dürre stark beschädigten Missernten. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TerasakaY. en-aut-sei=Terasaka en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UnoM. en-aut-sei=Uno en-aut-mei=M. 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=151 end-page=155 dt-received= dt-revised= dt-accepted= dt-pub-year=1943 dt-pub=19430107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feststellung der Sortenechtheit des Weizensaatgutes durch Tyrosinfärbung. Vergleich mit Phenolfärbung. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=141 end-page=150 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19421227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alkaliprüfung der polierten Weissreiskörner. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=134 end-page=140 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19421219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feststellung der Sortenechtheit von enthülsten Reiskörnern. IV. Alkaliprüfung und Schluss. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=129 end-page=133 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19421211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feststellung der Sortenechtheit von enthülsten Reiskörnern. III. Jodjodkalifärbung. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=121 end-page=128 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19421204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feststellung der Sortenechtheit von enthülsten Reiskörnern. II. Phenol-und Paracresolfärbung. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=117 end-page=120 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19421125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feststellung der Sortenechtheit von enthülsten Reiskörnern. I. Phenolfuchsinfärbung. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=91 end-page=115 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19420430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on the Fluorescence of Cereal Grains. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OkaHikoichi en-aut-sei=Oka en-aut-mei=Hikoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=71 end-page=90 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19420421 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on the Classification and the Geographical Distribution of the Japanese Barley Varieties. I. Significance of the Bimodal Curve of the Coleoptile Length. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakahashiRyuhei en-aut-sei=Takahashi en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=61 end-page=70 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19420701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Illustrations and Descriptions of Fungi Injurious to the Culture of Siitake Mushroom. I. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MihasiT. en-aut-sei=Mihasi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaT. en-aut-sei=Nakayama en-aut-mei=T. 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=39 end-page=60 dt-received= dt-revised= dt-accepted= dt-pub-year=1941 dt-pub=19411110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on the Effect of Kinds of Tree in Culture Medium upon the Growth of Cortinellus Berkeleyanus. I. The Mycelial Growth in Pure Culture on the Sawdust Medium prepared of Various Kinds of Tree. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraK. en-aut-sei=Kimura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyawakiY. en-aut-sei=Miyawaki en-aut-mei=Y. 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=29 end-page=38 dt-received= dt-revised= dt-accepted= dt-pub-year=1941 dt-pub=19411110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Principles of Artificial Propagation of Tricholoma comglobatum (Vitt.) Sacc. I. Germination of the Spores and the Cultural Characters of the Fungous Mycelium. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraK. en-aut-sei=Kimura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=22 end-page=28 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19420315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Untersuchungen über die Keimung der Unkrautsamen Japans. II. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KondoM. en-aut-sei=Kondo en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=14 end-page=21 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19420311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Untersuchungen über die Keimung der Unkrautsamen Japans. I. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KondoM. en-aut-sei=Kondo en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=1 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=1942 dt-pub=19420120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Untersuchungen der Unkrautsamen Japans VIII. Leguminosae (I). en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KondoM. en-aut-sei=Kondo en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=489 end-page=505 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Literatur-Verzeichnis über Reis und Reiskultur. III. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KondōM. en-aut-sei=Kondō en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkaH. en-aut-sei=Oka en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=477 end-page=488 dt-received= dt-revised= dt-accepted= dt-pub-year=1939 dt-pub=19391225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=On the Heterothallism of Phytopathogenic Fungi. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=465 end-page=476 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19401215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Heat as a Means of Controlling the Angoumois Grain-Moth. III. Resistance to High Temperature of the Angoumois Grain-Moth. (2) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HarukawaChukichi en-aut-sei=Harukawa en-aut-mei=Chukichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KumashiroSaburô en-aut-sei=Kumashiro en-aut-mei=Saburô kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=455 end-page=464 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19401102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Heat as a Means of Controlling Angoumois Grain-Moth. II. Velocity of the Rise of Wheat Temperature during Heating. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HarukawaChukichi en-aut-sei=Harukawa en-aut-mei=Chukichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=443 end-page=453 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on the Principles of Growing Japanese Matutake Artificially. II. On the Isolation of the Mycelium in Pure Culture. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraK. en-aut-sei=Kimura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyawakiY. en-aut-sei=Miyawaki en-aut-mei=Y. 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=427 end-page=442 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=On a Phytophthora Rot of Fig. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirataK. en-aut-sei=Hirata en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraK. en-aut-sei=Kimura en-aut-mei=K. 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=421 end-page=426 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Contribution to Pathological Anatomy of Rice Plants Affected by Gibberella Fujikuroi (Saw.) Wollenweber. I. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoY. en-aut-sei=Nisikado en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraK. en-aut-sei=Kimura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=409 end-page=420 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Untersuchungen über Unkrautsamen Japans. VII. Polygonaceae (I). en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=389 end-page=408 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400424 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Untersuchungen über Unkrautsamen Japans. VI. Compositae (I). en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=371 end-page=387 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400413 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Untersuchungen über Unkrautsamen Japans. V. Gramineae (3). en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=349 end-page=370 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400406 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Untersuchung und Bewertung von Gerste, Weizen, Sojabohnen und Rapssamen. Zweite Mitteilung. Zusatz: Reis und Mais. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=325 end-page=347 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ursache der Phenolfärbung von Weizen-und Gerstenkörnern. Anhang: Behandlung mit Paracresol, Benzidin usw. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=317 end-page=324 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feststellung der Sortenechtheit des Saatgutes der Gerste durch Phenolfärbung. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=305 end-page=315 dt-received= dt-revised= dt-accepted= dt-pub-year=1940 dt-pub=19400303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feststellung der Sortenechtheit des Saatgutes des Weizens durch Phenolfarbung. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?M. en-aut-sei=Kond? en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaY. en-aut-sei=Kasahara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=1 article-no= start-page=147 end-page=151 dt-received= dt-revised= dt-accepted= dt-pub-year=1925 dt-pub=19251007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Über die Erhaltung der Keimkraft von Sämereien und über Trocknungsmittel. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?Mantar? en-aut-sei=Kond? en-aut-mei=Mantar? kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=1 article-no= start-page=135 end-page=146 dt-received= dt-revised= dt-accepted= dt-pub-year=1925 dt-pub=19250530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Über die Einwirkung des Kalks auf die Erhaltung der Keimkraft von Sämereien. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kond?Mantar? en-aut-sei=Kond? en-aut-mei=Mantar? kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=1 article-no= start-page=127 end-page=133 dt-received= dt-revised= dt-accepted= dt-pub-year=1925 dt-pub=19250910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Über die Dauer der Erhaltung der Keimkraft bei verschiedenen Samenarten in Japan. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KondōMantarō en-aut-sei=Kondō en-aut-mei=Mantarō kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=1 article-no= start-page=1 end-page=126 dt-received= dt-revised= dt-accepted= dt-pub-year=1925 dt-pub=19250412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Kreuzungsuntersuchungen an Reispflanzen. I Genetische Analyse der Granne, der Spelzenfarbe und der Endospermbeschaffenheit bei einigen Sorten des Reises. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YamaguchiYasuke en-aut-sei=Yamaguchi en-aut-mei=Yasuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=5 article-no= start-page=597 end-page=612 dt-received= dt-revised= dt-accepted= dt-pub-year=1925 dt-pub=19250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Über ein neues Helminthosporium auf Panicum Crus-Galli L. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NisikadoYosikazu en-aut-sei=Nisikado en-aut-mei=Yosikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyakeChūichi en-aut-sei=Miyake en-aut-mei=Chūichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=5 article-no= start-page=559 end-page=595 dt-received= dt-revised= dt-accepted= dt-pub-year=1925 dt-pub=19250530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Über die in der Landwirtschaft Japans gebrauchten Samen. (Fünfte Mitteilung.) Besonders über Malvacesamen. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KondōMantarō en-aut-sei=Kondō en-aut-mei=Mantarō kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=5 article-no= start-page=547 end-page=558 dt-received= dt-revised= dt-accepted= dt-pub-year=1925 dt-pub=19250326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fusarium Aspidioti Sawada, it s Culture and Morphology. with Plate XXXIV. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KasaiMikio en-aut-sei=Kasai en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=5 article-no= start-page=521 end-page=545 dt-received= dt-revised= dt-accepted= dt-pub-year=1925 dt-pub=19250301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on the Rush Saw-Fly, Tomostethus juncivorus Rohwer. en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HarukawaChukichi en-aut-sei=Harukawa en-aut-mei=Chukichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= 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=125 cd-vols= no-issue=2 article-no= start-page=103 end-page=107 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B cell characteristics kn-title=Џ\“сЋw’°аh–Eђ«ѓЉѓ“ѓpЋо‚НAID‚М”Њ»‚рЊ‡‚‚ЄBACH2‚М”Њ»‚р—L‚µmemoryBЌЧ–E‚Ж‚µ‚Д‚Мђ«Ћї‚р—L‚·‚й en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakataKatsuyoshi en-aut-sei=Takata en-aut-mei=Katsuyoshi kn-aut-name=Ќ‚“cЏ®—З kn-aut-sei=Ќ‚“c kn-aut-mei=Џ®—З aut-affil-num=1 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato 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en-aut-mei=Hideo kn-aut-name=’Ј‘ЦЏG—Y kn-aut-sei=’Ј‘Ц kn-aut-mei=ЏG—Y aut-affil-num=9 ORCID= en-aut-name=KatoSeiichi en-aut-sei=Kato en-aut-mei=Seiichi kn-aut-name=‰Б“ЎЏИ€к kn-aut-sei=‰Б“Ў kn-aut-mei=ЏИ€к aut-affil-num=10 ORCID= en-aut-name=HayashiEiko en-aut-sei=Hayashi en-aut-mei=Eiko kn-aut-name=—С‰rЋq kn-aut-sei=—С kn-aut-mei=‰rЋq aut-affil-num=11 ORCID= en-aut-name=OkaTakashi en-aut-sei=Oka en-aut-mei=Takashi kn-aut-name=‰ЄЌ„Ћj kn-aut-sei=‰Є kn-aut-mei=Ќ„Ћj aut-affil-num=12 ORCID= en-aut-name=HoshiiYoshinobu en-aut-sei=Hoshii en-aut-mei=Yoshinobu kn-aut-name=ђЇ€д‰ГђM kn-aut-sei=ђЇ€д kn-aut-mei=‰ГђM aut-affil-num=13 ORCID= en-aut-name=TariAkira en-aut-sei=Tari en-aut-mei=Akira kn-aut-name=“c—Џ» kn-aut-sei=“c— kn-aut-mei=Џ» aut-affil-num=14 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name=‰Є“c—T”V kn-aut-sei=‰Є“c kn-aut-mei=—T”V aut-affil-num=15 ORCID= en-aut-name=MohamadoABD Alkader Lamia en-aut-sei=Mohamado en-aut-mei=ABD Alkader Lamia kn-aut-name= 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kn-affil=“ЊЉC‘еЉw€гЉw•”Ѓ@•a—ќђf’fЉwЌuЌА affil-num=7 en-affil= kn-affil=“Њ–k‘еЉw‘еЉw‰@€гЉwЊnЊ¤‹†‰И ђ¶•Ё‰»Љw•Є–м affil-num=8 en-affil= kn-affil=ЌO‘O‘еЉw€гЉw•”Ѓ@Џ¬Ћ™‰ИЉw affil-num=9 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И ЊЊ‰tЃE–Ж‰u•aЉw•Є–м affil-num=10 en-affil= kn-affil=–јЊГ‰®‘еЉw•a‰@Ѓ@•a—ќ•” affil-num=11 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И •a—ќЉwЃiЋоб‡•a—ќЃj affil-num=12 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И •a—ќЉwЃiЋоб‡•a—ќЃj affil-num=13 en-affil= kn-affil=ЋRЊы‘еЉw€гЉw•”Ѓ@•a—ќЉw affil-num=14 en-affil= kn-affil=ЌL“‡ђФЏ\ЋљЃEЊґ”љ•a‰@Ѓ@ЏБ‰»Љн“а‰И affil-num=15 en-affil= kn-affil=‰ЄЋR‘еЉw•a‰@Ѓ@ЊхЉwђf—Г•” affil-num=16 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И •a—ќЉwЃiЋоб‡•a—ќЃj affil-num=17 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰ИЊЊ‰tЃEЋоб‡ЃEЊД‹zЉн“а‰ИЉw affil-num=18 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰ИЊЊ‰tЃEЋоб‡ЃEЊД‹zЉн“а‰ИЉw affil-num=19 en-affil= kn-affil=€¤’m‚Є‚сѓZѓ“ѓ^Ѓ[Ѓ@ЊЊ‰tЌЧ–E—Г–@•” affil-num=20 en-affil= kn-affil=‰ЄЋR‘еЉw‘еЉw‰@€гЋ•–тЉw‘ЌЌ‡Њ¤‹†‰И •a—ќЉwЃiЋоб‡•a—ќЃj en-keyword=follicular lymphoma kn-keyword=follicular lymphoma en-keyword=gastrointestinal tract kn-keyword=gastrointestinal tract en-keyword=BACH2 kn-keyword=BACH2 en-keyword=memory B cell kn-keyword=memory B cell END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=4 article-no= start-page=205 end-page=213 dt-received= dt-revised= dt-accepted= dt-pub-year=1989 dt-pub=1989 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A STUDY OF ECOLOGICAL DIFFERENCES BETWEEN JAPANESE AND CHINESE VERY EARLY CULTIVARS OF BARLEY I. Responses to Day-length under Alternating Temperatures during Day and Night en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YasudaShozo en-aut-sei=Yasuda en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiJiro en-aut-sei=Hayashi en-aut-mei=Jiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=4 article-no= start-page=199 end-page=204 dt-received= dt-revised= dt-accepted= dt-pub-year=1989 dt-pub=1989 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=EFFECT OF GRAMINE ON THE FECUNDITYЃCLONGEVITY AND PROBING BEHAVIOUR OF THE GREENBUG, SCHIZAPHIS GRAMINUM (RONDANI) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KawadaKazuo en-aut-sei=Kawada en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LoharMohamed Khan en-aut-sei=Lohar en-aut-mei=Mohamed Khan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=4 article-no= start-page=189 end-page=198 dt-received= dt-revised= dt-accepted= dt-pub-year=1989 dt-pub=1989 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=BIOSYSTEMATIC STUDIES ON THE HORDEUM MURINUM AGGREGATE en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KonishiT. en-aut-sei=Konishi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=4 article-no= start-page=181 end-page=188 dt-received= dt-revised= dt-accepted= dt-pub-year=1989 dt-pub=1989 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ACCUMULATION OF ASPARAGINE IN NaCl-STRESSED BARLEY SEEDLINGS en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YamayaTomoyuki en-aut-sei=Yamaya en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoHideaki en-aut-sei=Matsumoto en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=4 article-no= start-page=169 end-page=180 dt-received= dt-revised= dt-accepted= dt-pub-year=1989 dt-pub=1989 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ANTIFEEDING RESPONSE OF SPARROW TO THE CONSTITUENTS OF INSECT SECRETORY DEFENSIVE SUBSTANCES AND RELATIVES en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KanehisaKatsuo en-aut-sei=Kanehisa en-aut-mei=Katsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiragaTakashi en-aut-sei=Shiraga en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsumukiHisaaki en-aut-sei=Tsumuki en-aut-mei=Hisaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatabeNaohisa en-aut-sei=Watabe en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=4 article-no= start-page=159 end-page=167 dt-received= dt-revised= dt-accepted= dt-pub-year=1989 dt-pub=1989 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CHANGES OF MEMBRANE ASSOCIATED ATPASE ACTIVITY OF CORN ROOT DUE TO SALT STRESS en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsumotoHideaki en-aut-sei=Matsumoto en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkibaTomokazu en-aut-sei=Akiba en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawasakiToshio en-aut-sei=Kawasaki en-aut-mei=Toshio 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=149 end-page=157 dt-received= dt-revised= dt-accepted= dt-pub-year=1987 dt-pub=1987 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=DIFFERENTIATION OF TWO SEROTYPES OF CUCUMBER MOSAIC VIRUS IN JAPAN BY F(ab')2 ELISA WITH CROSS-ABSORBED ANTIBODIES* en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MaedaTakanori en-aut-sei=Maeda en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InouyeNarinobu en-aut-sei=Inouye en-aut-mei=Narinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=145 end-page=148 dt-received= dt-revised= dt-accepted= dt-pub-year=1987 dt-pub=1987 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A STUDY ON THE FOLIAGE ARRANGEMENT OF BARNYARDGRASS AND RICE PLANT en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NishiKatsuhisa en-aut-sei=Nishi en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=137 end-page=144 dt-received= dt-revised= dt-accepted= dt-pub-year=1987 dt-pub=1987 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PROBING BEHAVIOUR OF THE APHID, SCHIZAPHIS GRAMINUM (RONDANI), RHOPALOSIPHUM MAIDIS (FITCH) AND LONGIUNGUIS SACCHARI (ZEHNTNER) ON RESISTANT AND SUSCEPTIBLE SORGHUM PLANTS en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LoharMohamad Khan en-aut-sei=Lohar en-aut-mei=Mohamad Khan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawadaKazuo en-aut-sei=Kawada en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=131 end-page=136 dt-received= dt-revised= dt-accepted= dt-pub-year=1987 dt-pub=1987 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ECOLOGICAL STUDIES ON THE GOLDENROD GALL FLY, EUROSTA SOLlDAGINIS (FITCH) (DIPTERA: TEPHRITIDAE)* en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TsumukiHisaaki en-aut-sei=Tsumuki en-aut-mei=Hisaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=G.BaustJohn en-aut-sei=G.Baust en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=101 end-page=129 dt-received= dt-revised= dt-accepted= dt-pub-year=1987 dt-pub=1987 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on chromosome elimination in the hybrids between Hordeum bulbosum and H. vulgare* en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FukuyamaToshinori en-aut-sei=Fukuyama en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=91 end-page=100 dt-received= dt-revised= dt-accepted= dt-pub-year=1986 dt-pub=1986 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ESTIMATION OF THE DRY MATTER WEIGHT OF THE BARNYARDGRASS AT MATURITY EARLY IN ITS GROWING STAGE en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NishiKatsuhisa en-aut-sei=Nishi en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=77 end-page=89 dt-received= dt-revised= dt-accepted= dt-pub-year=1986 dt-pub=1986 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=UPTAKE OF NITROGEN AND PHOSPHATE, AND WATER PURIFICATION CAPACITY BY WATER HYACINTH (Eichhornia crassipes (Mart.) 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kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=57 end-page=61 dt-received= dt-revised= dt-accepted= dt-pub-year=1986 dt-pub=1986 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A PROTECTIVE EFFECT OF ѓБ-GLOBULIN ON ѓї-GLUCOSIDASES FROM SPINACH SEEDS en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UchidaKei en-aut-sei=Uchida en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiYukio en-aut-sei=Suzuki en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=49 end-page=56 dt-received= dt-revised= dt-accepted= dt-pub-year=1986 dt-pub=1986 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RAPID FLOTATION SEPARATION AND ATOMIC ABSORPTION SPECTROMETRIC DETERMINATION OF ARSENIC IN NATURAL WATERS* en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NakashimaSusumu en-aut-sei=Nakashima en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YagiMasakazu en-aut-sei=Yagi en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=35 end-page=48 dt-received= dt-revised= dt-accepted= dt-pub-year=1985 dt-pub=1985 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=EFFECT OF CALCIUM ON MAGNESIUM UPTAKE IN PLANTS (Part 2) The Effect of Macro-Nutrients on the Apparent Acceleration of Magnesium Uptake by Calcium* en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MoritsuguMasumi en-aut-sei=Moritsugu en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawasakiToshio en-aut-sei=Kawasaki en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=25 end-page=34 dt-received= dt-revised= dt-accepted= dt-pub-year=1985 dt-pub=1985 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A PRELIMINARY INVESTIGATION ON CHEMICAL QUALITY OF INLAND WATERS IN KENYA en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MoritsuguMasumi en-aut-sei=Moritsugu en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=11 end-page=23 dt-received= dt-revised= dt-accepted= dt-pub-year=1985 dt-pub=1985 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ATMOSPHERIC CO, CONCENTRATION AT A SUBURBAN LOCATION, KURASHIKI, DURING 1976/1977 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SeoTakuro en-aut-sei=Seo en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaitaniToshihiko en-aut-sei=Maitani en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraokaNaoko en-aut-sei=Hiraoka en-aut-mei=Naoko 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=1 end-page=10 dt-received= dt-revised= dt-accepted= dt-pub-year=1985 dt-pub=1985 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CYTOMORPHOLOGICAL STUDY OF EU-, HYPO- AND HYPER-TRIPLOIDS IN BARLEY 1) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=PrasadGanesh en-aut-sei=Prasad en-aut-mei=Ganesh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiRyuhei en-aut-sei=Takahashi en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasudaShozo en-aut-sei=Yasuda en-aut-mei=Shozo 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= kn-affil= affil-num=3 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=4 article-no= start-page=251 end-page=264 dt-received= dt-revised= dt-accepted= dt-pub-year=1984 dt-pub=1984 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=INHERITANCE AND LlNKAGE STUDIES IN BARLEY VII. Location of Six New Mutant Genes on Chromosome 3 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KonishiTakeo en-aut-sei=Konishi en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiJiro en-aut-sei=Hayashi en-aut-mei=Jiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyaIsamu en-aut-sei=Moriya en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiRyuhei en-aut-sei=Takahashi en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=4 article-no= start-page=227 end-page=250 dt-received= dt-revised= dt-accepted= dt-pub-year=1984 dt-pub=1984 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=INHERITANCE AND LlNKAGE STUDIES IN BARLEY VI. Ten Mutant Genes Located on Chromosomes 1 to 7, Except 3 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HayashiJiro en-aut-sei=Hayashi en-aut-mei=Jiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KonishiTakeo en-aut-sei=Konishi en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyaIsamu en-aut-sei=Moriya en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiRyuhei en-aut-sei=Takahashi en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=4 article-no= start-page=211 end-page=225 dt-received= dt-revised= dt-accepted= dt-pub-year=1984 dt-pub=1984 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=COMPARATIVE STUDIES ON THE DEVELOPMENT OF SPIKE PRIMORDIA BETWEEN CULTIVARS OF COMMON WHEAT AND BARLEY en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YasudaShozo en-aut-sei=Yasuda en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END