start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=
article-no=
start-page=243
end-page=252
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190614
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We recently demonstrated the generation of mouse induced tissue-specific stem (iTS) cells through transient overexpression of reprogramming factors combined with tissue-specific selection. Here we induced expandable tissue-specific progenitor (iTP) cells from human pancreatic tissue through transient expression of genes encoding the reprogramming factors OCT4 (octamer-binding transcription factor 4), p53 small hairpin RNA (shRNA), SOX2 (sex-determining region Y-box 2), KLF4 (Kruppel-like factor 4), L-MYC, and LIN28. Transfection of episomal plasmid vectors into human pancreatic tissue efficiently generated iTP cells expressing genetic markers of endoderm and pancreatic progenitors. The iTP cells differentiated into insulin-producing cells more efficiently than human induced pluripotent stem cells (iPSCs). iTP cells continued to proliferate faster than pancreatic tissue cells until days 100?120 (passages 15?20). iTP cells subcutaneously inoculated into immunodeficient mice did not form teratomas. Genomic bisulfite nucleotide sequence analysis demonstrated that the OCT4 and NANOG promoters remained partially methylated in iTP cells. We compared the global gene expression profiles of iPSCs, iTP cells, and pancreatic cells (islets >80%). Microarray analyses revealed that the gene expression profiles of iTP cells were similar, but not identical, to those of iPSCs but different from those of pancreatic cells. The generation of human iTP cells may have important implications for the clinical application of stem/progenitor cells.
en-copyright=
kn-copyright=

en-aut-name=NoguchiHirofumi
en-aut-sei=Noguchi
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=Miyagi-ShiohiraChika
en-aut-sei=Miyagi-Shiohira
en-aut-mei=Chika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakashimaYoshiki
en-aut-sei=Nakashima
en-aut-mei=Yoshiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KinjoTakao
en-aut-sei=Kinjo
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KobayashiNaoya
en-aut-sei=Kobayashi
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SaitohIssei
en-aut-sei=Saitoh
en-aut-mei=Issei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=WatanabeMasami
en-aut-sei=Watanabe
en-aut-mei=Masami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ShapiroA. M. James
en-aut-sei=Shapiro
en-aut-mei=A. M. James
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KinTatsuya
en-aut-sei=Kin
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus
kn-affil=

affil-num=2
en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus
kn-affil=

affil-num=3
en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus
kn-affil=

affil-num=4
en-affil=Department of Basic Laboratory Sciences, School of Health Sciences in Faculty of Medicine, University of the Ryukyus
kn-affil=

affil-num=5
en-affil=Okayama Saidaiji Hospital
kn-affil=

affil-num=6
en-affil=Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University
kn-affil=

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

affil-num=8
en-affil=Clinical Islet Transplant Program and Department of Surgery, University of Alberta
kn-affil=

affil-num=9
en-affil=Clinical Islet Transplant Program and Department of Surgery, University of Alberta
kn-affil=
en-keyword=induced tissue-specific progenitor cells
kn-keyword=induced tissue-specific progenitor cells
en-keyword=iTP
kn-keyword=iTP
en-keyword=induced tissue-specific stem cells
kn-keyword=induced tissue-specific stem cells
en-keyword=iTS
kn-keyword=iTS
en-keyword=induced pluripotent stem cells
kn-keyword=induced pluripotent stem cells
en-keyword=iPSCs
kn-keyword=iPSCs
en-keyword=reprogramming factors
kn-keyword=reprogramming factors
en-keyword=pancreas
kn-keyword=pancreas
END

start-ver=1.4
cd-journal=joma
no-vol=28
cd-vols=
no-issue=5
article-no=
start-page=1362
end-page=1369
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190730
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Genome-Edited Triple-Recessive Mutation AltersSeed Dormancy in Wheat
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=1Common wheat has three sets of sub-genomes, making mutations difficult to observe, especially for traits controlled by recessive genes. Here, we produced hexaploid wheat lines with loss of function of homeoalleles of Qsd1, which controls seed dormancy in barley, by Agrobacterium-mediated CRISPR/Cas9. Of the eight transformed wheat events produced, three independent events carrying multiple mutations in wheat Qsd1 homeoalleles were obtained. Notably, one line had mutations in every homeoallele. We crossed this plant with wild-type cultivar Fielder to generate a transgene-free triple-recessive mutant, as revealed by Mendelian segregation. The mutant showed a significantly longer seed dormancy period than wild-type, which may result in reduced pre-harvest sprouting of grains on spikes. PCR, southern blotting, and whole-genome shotgun sequencing revealed that this segregant lacked transgenes in its genomic sequence. This technique serves as a model for trait improvement in wheat, particularly for genetically recessive traits, based on locus information from diploid barley.
en-copyright=
kn-copyright=

en-aut-name=AbeFumitaka
en-aut-sei=Abe
en-aut-mei=Fumitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HaqueEmdadul
en-aut-sei=Haque
en-aut-mei=Emdadul
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=TanakaTsuyoshi
en-aut-sei=Tanaka
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KamiyaYoko
en-aut-sei=Kamiya
en-aut-mei=Yoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MikamiMasafumi
en-aut-sei=Mikami
en-aut-mei=Masafumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KawauraKanako
en-aut-sei=Kawaura
en-aut-mei=Kanako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=EndoMasaki
en-aut-sei=Endo
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OnishiKazumitsu
en-aut-sei=Onishi
en-aut-mei=Kazumitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HayashiTakeshi
en-aut-sei=Hayashi
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
ORCID=

affil-num=1
en-affil=Division of Wheat and Barley Research, Institute of Crop Science, NARO
kn-affil=

affil-num=2
en-affil=Division of Wheat and Barley Research, Institute of Crop Science, NARO
kn-affil=

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

affil-num=4
en-affil=Division of Basic Research, Institute of Crop Science, NARO
kn-affil=

affil-num=5
en-affil=Kihara Institute for Biological Research, Yokohama City University
kn-affil=

affil-num=6
en-affil=Graduate School of Nanobioscience, Yokohama City University
kn-affil=

affil-num=7
en-affil=Kihara Institute for Biological Research, Yokohama City University
kn-affil=

affil-num=8
en-affil=Division of Applied Genetics, Institute of Agrobiological Sciences, NARO
kn-affil=

affil-num=9
en-affil=Department of Agro-Environmental Science, Obihiro University of Agriculture and Veterinary Medicine
kn-affil=

affil-num=10
en-affil=Division of Basic Research, Institute of Crop Science, NARO
kn-affil=

affil-num=11
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=
en-keyword=CRISPR/Cas9
kn-keyword=CRISPR/Cas9
en-keyword=Qsd1
kn-keyword=Qsd1
en-keyword=multiple mutation
kn-keyword=multiple mutation
en-keyword=seed dormancy
kn-keyword=seed dormancy
en-keyword=wheat
kn-keyword=wheat
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=2
article-no=
start-page=100850
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200118
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PLOD2 is essential to functional activation of integrin β1 for invasion/metastasis in head and neck squamous cell carcinomas.
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Identifying the specific functional regulator of integrin family molecules in cancer cells is critical because they are directly involved in tumor invasion and metastasis. Here we report high expression of PLOD2 in oropharyngeal squamous cell carcinomas (SCCs) and its critical role as a stabilizer of integrin β1, enabling integrin β1 to initiate tumor invasion/metastasis. Integrin β1 stabilized by PLOD2-mediated hydroxylation was recruited to the plasma membrane, its functional site, and accelerated tumor cell motility, leading to tumor metastasis in vivo, whereas loss of PLOD2 expression abrogated it. In accordance with molecular analysis, examination of oropharyngeal SCC tissues from patients corroborated PLOD2 expression associated with integrin β1 at the invasive front of tumor nests. PLOD2 is thus implicated as the key regulator of integrin β1 that prominently regulates tumor invasion and metastasis, and it provides important clues engendering novel therapeutics for these intractable cancers.
en-copyright=
kn-copyright=

en-aut-name=UekiYushi
en-aut-sei=Ueki
en-aut-mei=Yushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SaitoKen
en-aut-sei=Saito
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IiokaHidekazu
en-aut-sei=Iioka
en-aut-mei=Hidekazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SakamotoIzumi
en-aut-sei=Sakamoto
en-aut-mei=Izumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KandaYasuhiro
en-aut-sei=Kanda
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=HoriiArata
en-aut-sei=Horii
en-aut-mei=Arata
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KondoEisaku
en-aut-sei=Kondo
en-aut-mei=Eisaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

affil-num=2
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

affil-num=3
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

affil-num=4
en-affil=ACROSCALE Inc.
kn-affil=

affil-num=5
en-affil=Department of Immunology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

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

affil-num=7
en-affil=Department of Otolaryngology, Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

affil-num=8
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=
en-keyword=Cancer
kn-keyword=Cancer
en-keyword=Molecular Biology
kn-keyword=Molecular Biology
END

start-ver=1.4
cd-journal=joma
no-vol=28
cd-vols=
no-issue=3
article-no=
start-page=794
end-page=804
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs.
en-copyright=
kn-copyright=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KumonKento
en-aut-sei=Kumon
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TsumuraTomoko
en-aut-sei=Tsumura
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MorihiroToshiaki
en-aut-sei=Morihiro
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=

en-aut-name=AoyamaKatsuyuki
en-aut-sei=Aoyama
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=俊
kn-aut-sei=
kn-aut-mei=俊
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=MizuguchiHiroyuki
en-aut-sei=Mizuguchi
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
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=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=Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University
kn-affil=

affil-num=15
en-affil=Oncolys BioPharma
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=immune checkpoint
kn-keyword=immune checkpoint
en-keyword=programmed death-1
kn-keyword=programmed death-1
en-keyword=oncolytic adenovirus
kn-keyword=oncolytic adenovirus
en-keyword=combined immunotherapy
kn-keyword=combined immunotherapy
en-keyword=immunogenic cell death
kn-keyword=immunogenic cell death
en-keyword=tumor infiltrating lymphocytes
kn-keyword=tumor infiltrating lymphocytes
en-keyword=CD8
kn-keyword=CD8
en-keyword=abscopal effect
kn-keyword=abscopal effect
END

start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=
article-no=
start-page=42
end-page=56
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191122
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=2-Methylthio Conversion of N6-Isopentenyladenosine in Mitochondrial tRNAs by CDK5RAP1 Promotes the Maintenance of Glioma-Initiating Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=2-Methylthio-N-6-isopentenyl modification of adenosine (ms(2)i(6)A) is an evolutionally conserved modification found in mitochondrial (mt)-tRNAs. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) specifically converts N6-isopentenyladenosine (i(6)A) to ms(2)i(6)A at position A37 of four mt-DNA-encoded tRNAs, and the modification regulates efficient mitochondrial translation and energy metabolism in mammals. Here, we report that the ms 2 conversion mediated by CDK5RAP1 in mt-tRNAs is required to sustain glioma-initiating cell (GIC)-related traits. CDK5RAP1 maintained the self-renewal capacity, undifferentiated state, and tumorigenic potential of GICs. This regulation was not related to the translational control of mt-proteins. CDK5RAP1 abrogated the antitumor effect of i(6)A by converting i(6)A to ms (2)i(6) A and protected GICs from excessive autophagy triggered by i(6)A. The elevated activity of CDK5RAP1 contributed to the amelioration of the tumor-suppressive effect of i(6)A and promoted GIC maintenance. This work demonstrates that CDK5RAP1 is crucial for the detoxification of endogenous i(6)A and that GICs readily utilize this mechanism for survival.
en-copyright=
kn-copyright=

en-aut-name=YamamotoTakahiro
en-aut-sei=Yamamoto
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FujimuraAtsushi
en-aut-sei=Fujimura
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WeiFan-Yan
en-aut-sei=Wei
en-aut-mei=Fan-Yan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ShinojimaNaoki
en-aut-sei=Shinojima
en-aut-mei=Naoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KurodaJun-Ichiro
en-aut-sei=Kuroda
en-aut-mei=Jun-Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MukasaAkitake
en-aut-sei=Mukasa
en-aut-mei=Akitake
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TomizawaKazuhito
en-aut-sei=Tomizawa
en-aut-mei=Kazuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University
kn-affil=

affil-num=2
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University
kn-affil=

affil-num=4
en-affil=Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University
kn-affil=

affil-num=5
en-affil=Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University
kn-affil=

affil-num=6
en-affil=Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University
kn-affil=

affil-num=7
en-affil=Neutron Therapy Research Center, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=
article-no=
start-page=1167
end-page=1177
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200513
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Hair cell transduction efficiency of single- and dual-AAV serotypes in adult murine cochleae
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Gene delivery is a key component for the treatment of genetic hearing loss. To date, a myriad of adeno-associated virus (AAV) serotypes and surgical approaches have been employed to deliver transgenes to cochlear hair cells, but the efficacy of dual transduction remains unclear. Herein, we investigated cellular tropism of single injections of AAV serotype 1 (AAV1), AAV2, AAV8, AAV9, and Anc80L65, and quantitated dual-vector co-transduction rates following co-injection of AAV2 and AAV9 vectors in adult murine cochlea. We used the combined round window membrane and canal fenestration (RWM+CF) injection technique for vector delivery. Single AAV2 injections were most robust and transduced 96.7% ± 1.1% of inner hair cells (IHCs) and 83.9% ± 2.0% of outer hair cells (OHCs) throughout the cochlea without causing hearing impairment or hair cell loss. Dual AAV2 injection co-transduced 96.9% ± 1.7% of IHCs and 65.6% ± 8.95% of OHCs. Together, RWM+CF-injected single or dual AAV2 provides the highest auditory hair cell transduction efficiency of the AAV serotypes we studied. These findings broaden the application of cochlear gene therapy targeting hair cells. 
en-copyright=
kn-copyright=

en-aut-name=OmichiRyotaro
en-aut-sei=Omichi
en-aut-mei=Ryotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YoshimuraHidekane
en-aut-sei=Yoshimura
en-aut-mei=Hidekane
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ShibataSeiji B.
en-aut-sei=Shibata
en-aut-mei=Seiji B.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=VandenbergheLuk H.
en-aut-sei=Vandenberghe
en-aut-mei=Luk H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SmithRichard J.H.
en-aut-sei=Smith
en-aut-mei=Richard J.H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

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

affil-num=2
en-affil= Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa
kn-affil=

affil-num=3
en-affil= Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa
kn-affil=

affil-num=4
en-affil=Grousbeck Gene Therapy Center, Ocular Genomics Institute, Schepens Eye Research Institute and Mass Eye and Ear
kn-affil=

affil-num=5
en-affil=Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa
kn-affil=
en-keyword=AAV2
kn-keyword=AAV2
en-keyword=adeno-associated virus
kn-keyword=adeno-associated virus
en-keyword=deafness
kn-keyword=deafness
en-keyword=dual vectors
kn-keyword=dual vectors
en-keyword=gene therapy
kn-keyword=gene therapy
en-keyword=hair cells
kn-keyword=hair cells
en-keyword=hearing loss
kn-keyword=hearing loss
en-keyword=injection
kn-keyword=injection
en-keyword=tropism
kn-keyword=tropism
en-keyword=viral vectors
kn-keyword=viral vectors
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=4
article-no=
start-page=100998
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200424
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from T cells and succeeded in regenerating CTLs specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. In this study, we extended our strategy to solid tumors. The regenerated WT1-specific CTLs had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma (RCC) cell line. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/β genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of RCC, demonstrating the feasibility of our strategy against solid tumors. 
en-copyright=
kn-copyright=

en-aut-name=KashimaSoki
en-aut-sei=Kashima
en-aut-mei=Soki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MaedaTakuya
en-aut-sei=Maeda
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MasudaKyoko
en-aut-sei=Masuda
en-aut-mei=Kyoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NaganoSeiji
en-aut-sei=Nagano
en-aut-mei=Seiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=InoueTakamitsu
en-aut-sei=Inoue
en-aut-mei=Takamitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakedaMasashi
en-aut-sei=Takeda
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KonoYuka
en-aut-sei=Kono
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KobayashiTakashi
en-aut-sei=Kobayashi
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SaitoShigeyoshi
en-aut-sei=Saito
en-aut-mei=Shigeyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=Ichise Hiroshi
en-aut-sei=Ichise
en-aut-mei= Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KobayashiYuka
en-aut-sei=Kobayashi
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=IwaisakoKeiko
en-aut-sei=Iwaisako
en-aut-mei=Keiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=TeradaKoji
en-aut-sei=Terada
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=AgataYasutoshi
en-aut-sei=Agata
en-aut-mei=Yasutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=NumakuraKazuyuki
en-aut-sei=Numakura
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=SaitoMitsuru
en-aut-sei=Saito
en-aut-mei=Mitsuru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=NaritaShintaro
en-aut-sei=Narita
en-aut-mei=Shintaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=YasukawaMasaki
en-aut-sei=Yasukawa
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=OgawaOsamu
en-aut-sei=Ogawa
en-aut-mei=Osamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=HabuchiTomonori
en-aut-sei=Habuchi
en-aut-mei=Tomonori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=KawamotoHiroshi
en-aut-sei=Kawamoto
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

affil-num=1
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=2
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=3
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=4
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=5
en-affil= Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Urology, Kyoto University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil= Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=8
en-affil=Department of Urology, Kyoto University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University
kn-affil=

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

affil-num=11
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=12
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=13
en-affil=Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University
kn-affil=

affil-num=14
en-affil=Department of Biochemistry and Molecular Biology, Shiga University of Medical School
kn-affil=

affil-num=15
en-affil=Department of Biochemistry and Molecular Biology, Shiga University of Medical School
kn-affil=

affil-num=16
en-affil=Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=17
en-affil=Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=18
en-affil=Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=19
en-affil=Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University
kn-affil=

affil-num=20
en-affil=Department of Urology, Kyoto University Graduate School of Medicine
kn-affil=

affil-num=21
en-affil=Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=22
en-affil= Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=
en-keyword=Cancer
kn-keyword=Cancer
en-keyword=Cellular Therapy
kn-keyword=Cellular Therapy
en-keyword=Immunological Methods
kn-keyword=Immunological Methods
END

start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=
article-no=
start-page=107
end-page=117
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=Oncolytic Virus-Mediated Targeting of the ERK Signaling Pathway Inhibits Invasive Propensity in Human Pancreatic Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pancreatic ductal adenocarcinoma (PDAC) cells have an exceptional ability to invade nerves through pronounced crosstalk between nerves and cancer cells; however, the mechanism of PDAC cell invasion remains to be elucidated. Here, we demonstrate the therapeutic potential of telomerase-specific oncolytic adenoviruses, OBP -301 and tumor suppressor p53-armed OBP-702, against human PDAC cells. Highly invasive PDAC cells exhibited higher levels of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) expression independent of KRAS expression; ERK1/2 inhibitor or small interfering RNA (siRNA) treatment significantly reduced the migration and invasion of PDAC cells, suggesting that the ERK signaling pathway is associated with the invasiveness of PDAC cells. OBP-702 infection suppressed ERK signaling and inhibited PDAC cell migration and invasion more efficiently than OBP-301. OBP-702 also effectively inhibited PDAC cell invasion even when invasiveness was enhanced by administration of motility stimulators, such as nerve and neurosecretory factors. Moreover, noninvasive whole-body imaging analyses showed that OBP-702 significantly suppressed tumor growth in an orthotopic PDAC xenograft model, although both viruses were equally effective against subcutaneous tumors, suggesting that OBP-702 can influence the orthotopic tumor microenvironment. Our data suggest that oncolytic virus-mediated disruption of ERK signaling is a promising antitumor strategy for attenuating the invasiveness of PDAC cells.
en-copyright=
kn-copyright=

en-aut-name=KoujimaTakeshi
en-aut-sei=Koujima
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=IedaTakeshi
en-aut-sei=Ieda
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ArakiHiroyuki
en-aut-sei=Araki
en-aut-mei=Hiroyuki
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=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=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=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=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=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
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=MizuguchiHiroyuki
en-aut-sei=Mizuguchi
en-aut-mei=Hiroyuki
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
kn-affil=

affil-num=13
en-affil=Laboratory of Biochemistry and Molecular Biology, Graduate School of 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=
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=6
article-no=
start-page=101180
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=Histidine-Rich Glycoprotein Inhibits High-Mobility Group Box-1-Mediated Pathways in Vascular Endothelial Cells through CLEC-1A
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=High-mobility group box-1 (HMGB1) protein has been postulated to play a pathogenic role in severe sepsis. Histidine-rich glycoprotein (HRG), a 75 kDa plasma protein, was demonstrated to improve the survival rate of septic mice through the regulation of neutrophils and endothelium barrier function. As the relalionship of HRG and HMGB1 remains poorly understood, we investigated the effects of HRG on HMGB1-mediated pathway in endothelial cells, focusing on the involvement of specific receptors for HRG. HRC potently inhibited the HMGB1 mobilization and effectively suppressed rHMGB1-induced inflammatory responses and expression of all three HMGB1 receptors in endothelial cells. Moreover, we first clarified that these protective effects of HRG on endothelial cells were mediated through C-type lectin domain family 1 member A (CLEC-1A) receptor. Thus, current study elueiates protective effects of HRG on vascular endothelial cells through inhintion of HMGB1-mediated pathways may contribute to the therapeutic effects of HRG on severe sepsis.
en-copyright=
kn-copyright=

en-aut-name=GaoShangze
en-aut-sei=Gao
en-aut-mei=Shangze
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=WangDengli
en-aut-sei=Wang
en-aut-mei=Dengli
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakahashiYouhei
en-aut-sei=Takahashi
en-aut-mei=Youhei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TeshigawaraKiyoshi
en-aut-sei=Teshigawara
en-aut-mei=Kiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ZhongHui
en-aut-sei=Zhong
en-aut-mei=Hui
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MoriShuji
en-aut-sei=Mori
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TakahashiHideo
en-aut-sei=Takahashi
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

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

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

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

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

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

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

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

affil-num=8
en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University
kn-affil=

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

affil-num=10
en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University
kn-affil=

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

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=6
article-no=
start-page=101146
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=Genetic Factors Associated with Heading Responses Revealed by Field Evaluation of 274 Barley Accessions for 20 Seasons
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Heading time is a key trait in cereals affecting the maturation period for optimal grain filling before harvest. Here, we aimed to understand the factors controlling heading time in barley (Hordeum vulgare). We characterized a set of 274 barley accessions collected worldwide by planting them for 20 seasons under different environmental conditions at the same location in Kurashiki, Japan. We examined interactions among accessions, known genetic factors, and an environmental factor to determine the factors controlling heading response. Locally adapted accessions have been selected for genetic factors that stabilize heading responses appropriate for barley cultivation, and these accessions show stable heading responses even under varying environmental conditions. We identified vernalization requirement and PPD-H1 haplotype as major stabilizing mechanisms of the heading response for regional adaptation in Kurashiki.
en-copyright=
kn-copyright=

en-aut-name=SatoKazuhiro
en-aut-sei=Sato
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IshiiMakoto
en-aut-sei=Ishii
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakahagiKotaro
en-aut-sei=Takahagi
en-aut-mei=Kotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InoueKomaki
en-aut-sei=Inoue
en-aut-mei=Komaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShimizuMinami
en-aut-sei=Shimizu
en-aut-mei=Minami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=Uehara-YamaguchiYukiko
en-aut-sei=Uehara-Yamaguchi
en-aut-mei=Yukiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NishiiRyuei
en-aut-sei=Nishii
en-aut-mei=Ryuei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MochidaKeiichi
en-aut-sei=Mochida
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=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=RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=4
en-affil=RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=5
en-affil=RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=6
en-affil=RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=7
en-affil=School of Information and Data Sciences, Nagasaki 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=23
cd-vols=
no-issue=6
article-no=
start-page=101248
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=BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Elucidating fine architectures and functions of cellular and synaptic connections requires development of new flexible methods. Here, we created a concept called the “battle of transgenes,” based on which we generated strategies using genetically engineered battles of multiple recombinases. The strategies enabled split-tunable allocation of multiple transgenes. We demonstrated the versatility of these strategies and technologies in inducing strong and multi-sparse allocations of multiple transgenes. Furthermore, the combination of our transgenic strategy and expansion microscopy enabled three-dimensional high-resolution imaging of whole synaptic structures in the hippocampus with simultaneous visualizations of endogenous synaptic proteins. These strategies and technologies based on the battle of genes may accelerate the analysis of whole synaptic and cellular connections in diverse life science fields.
en-copyright=
kn-copyright=

en-aut-name=KoharaKeigo
en-aut-sei=Kohara
en-aut-mei=Keigo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=InoueAkitoshi
en-aut-sei=Inoue
en-aut-mei=Akitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakanoYousuke
en-aut-sei=Nakano
en-aut-mei=Yousuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HiraiHirokazu
en-aut-sei=Hirai
en-aut-mei=Hirokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KobayashiTakuya
en-aut-sei=Kobayashi
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MaruyamaMasato
en-aut-sei=Maruyama
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=BabaRyosuke
en-aut-sei=Baba
en-aut-mei=Ryosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KawashimaChiho
en-aut-sei=Kawashima
en-aut-mei=Chiho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Cellular and Functional Biology, Institute of Biomedical Science, Kansai Medical University
kn-affil=

affil-num=2
en-affil=Department of Medical Chemistry, Kansai Medical University, Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Anatomy, Kansai Medical University, Graduate School of Medicine
kn-affil=

affil-num=4
en-affil=Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Medical Chemistry, Kansai Medical University, Graduate School of Medicine, Hirakata
kn-affil=

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

affil-num=7
en-affil=Department of Cellular and Functional Biology, Institute of Biomedical Science, Kansai Medical University
kn-affil=

affil-num=8
en-affil=Department of Cellular and Functional Biology, Institute of Biomedical Science, Kansai Medical University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=1
cd-vols=
no-issue=1
article-no=
start-page=100023
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200619
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Highly Efficient CRISPR-Associated Protein 9 Ribonucleoprotein-Based Genome Editing in Euglena gracilis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Euglena gracilis, a unicellular phytoflagellate microalga, is a promising biomaterial for foods, feeds, and biofuels. However, targeted mutagenesis in this species has been a long-standing challenge. We recently developed a transgene-free, highly efficient, genome editing method for E.?gracilis using CRISPR/Cas9 ribonucleoproteins (RNPs). Our method achieved mutagenesis rates of approximately 80% or more through an electroporation-based direct delivery of Cas9 RNPs. Therefore, this method is suitable for basic research and industrial applications, such as the breeding of Euglena. For complete details on the use and execution of this protocol, please refer to Nomura et?al. (2019).
en-copyright=
kn-copyright=

en-aut-name=NomuraToshihisa
en-aut-sei=Nomura
en-aut-mei=Toshihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YoshikawaMizuki
en-aut-sei=Yoshikawa
en-aut-mei=Mizuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SuzukiKengo
en-aut-sei=Suzuki
en-aut-mei=Kengo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MochidaKeiichi
en-aut-sei=Mochida
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=RIKEN Center for Sustainable Resource Science
kn-affil=

affil-num=2
en-affil=RIKEN Baton Zone Program
kn-affil=

affil-num=3
en-affil=RIKEN Baton Zone Program
kn-affil=

affil-num=4
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=1
cd-vols=
no-issue=2
article-no=
start-page=100053
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200613
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Protocol for Genome Editing to Produce Multiple Mutants in Wheat
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Here, we describe a protocol for producing multiple recessive mutants via genome editing in hexaploid wheat (Triticum aestivum) cv. Fielder. Using Agrobacterium-delivered CRISPR/Cas9 and three sub-genome-specific primer sets, all possible combinations of single, double, and triple transgene-free mutants can be generated. The technique for acceleration of generation advancement with embryo culture reduces time for mutant production. The mutants produced by this protocol can be used for the analysis of gene function and crop improvement. For complete details on the use and execution of this protocol, please refer to Abe et?al. (2019).
en-copyright=
kn-copyright=

en-aut-name=AbeFumitaka
en-aut-sei=Abe
en-aut-mei=Fumitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IshidaYuji
en-aut-sei=Ishida
en-aut-mei=Yuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=

en-aut-name=EndoMasaki
en-aut-sei=Endo
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KomariToshihiko
en-aut-sei=Komari
en-aut-mei=Toshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TokiSeiichi
en-aut-sei=Toki
en-aut-mei=Seiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

affil-num=1
en-affil=Division of Basic Research, Institute of Crop Science, NARO
kn-affil=

affil-num=2
en-affil=Plant Innovation Center, Japan Tobacco Inc.
kn-affil=

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

affil-num=4
en-affil=Division of Applied Genetics, Institute of Agrobiological Sciences, NARO
kn-affil=

affil-num=5
en-affil=Plant Innovation Center, Japan Tobacco Inc.
kn-affil=

affil-num=6
en-affil=Division of Applied Genetics, Institute of Agrobiological Sciences, NARO
kn-affil=

affil-num=7
en-affil=Institute of Plant Science and Resources, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=10
article-no=
start-page=101648
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201023
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER.
en-copyright=
kn-copyright=

en-aut-name=MiyataTakashi
en-aut-sei=Miyata
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HagiwaraDaisuke
en-aut-sei=Hagiwara
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HodaiYuichi
en-aut-sei=Hodai
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MiwataTsutomu
en-aut-sei=Miwata
en-aut-mei=Tsutomu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KawaguchiYohei
en-aut-sei=Kawaguchi
en-aut-mei=Yohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KurimotoJunki
en-aut-sei=Kurimoto
en-aut-mei=Junki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OzakiHajime
en-aut-sei=Ozaki
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MitsumotoKazuki
en-aut-sei=Mitsumoto
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TakagiHiroshi
en-aut-sei=Takagi
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SugaHidetaka
en-aut-sei=Suga
en-aut-mei=Hidetaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KobayashiTomoko
en-aut-sei=Kobayashi
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SugiyamaMariko
en-aut-sei=Sugiyama
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OnoueTakeshi
en-aut-sei=Onoue
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=ItoYoshihiro
en-aut-sei=Ito
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=IwamaShintaro
en-aut-sei=Iwama
en-aut-mei=Shintaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=BannoRyoichi
en-aut-sei=Banno
en-aut-mei=Ryoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=MatsumotoMami
en-aut-sei=Matsumoto
en-aut-mei=Mami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=KawakamiNatsuko
en-aut-sei=Kawakami
en-aut-mei=Natsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=OhnoNobuhiko
en-aut-sei=Ohno
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=SakamotoHirotaka
en-aut-sei=Sakamoto
en-aut-mei=Hirotaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=ArimaHiroshi
en-aut-sei=Arima
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

affil-num=1
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=4
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=8
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=10
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=13
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=14
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=15
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=16
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=

affil-num=17
en-affil=Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences
kn-affil=

affil-num=18
en-affil=Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences
kn-affil=

affil-num=19
en-affil=Department of Anatomy, Division of Histology and Cell Biology, Jichi Medical University, School of Medicine
kn-affil=

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

affil-num=21
en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=38
cd-vols=
no-issue=5
article-no=
start-page=110331
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (T-ex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the T-ex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the T-ex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such T-ex clonotypes, mainly from TDLNs.
en-copyright=
kn-copyright=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=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=SaxNicolas
en-aut-sei=Sax
en-aut-mei=Nicolas
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AriyasuRyo
en-aut-sei=Ariyasu
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=IshikawaMasakazu
en-aut-sei=Ishikawa
en-aut-mei=Masakazu
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=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UenoToshihide
en-aut-sei=Ueno
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IrieTakuma
en-aut-sei=Irie
en-aut-mei=Takuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TanjiEtsuko
en-aut-sei=Tanji
en-aut-mei=Etsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MorinagaTakao
en-aut-sei=Morinaga
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=HonobeAkiko
en-aut-sei=Honobe
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
ORCID=

en-aut-name=YoshinoMitsuru
en-aut-sei=Yoshino
en-aut-mei=Mitsuru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=IwataTakekazu
en-aut-sei=Iwata
en-aut-mei=Takekazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KawaseKatsushige
en-aut-sei=Kawase
en-aut-mei=Katsushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=SasakiKeita
en-aut-sei=Sasaki
en-aut-mei=Keita
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=HanazawaToyoyuki
en-aut-sei=Hanazawa
en-aut-mei=Toyoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=KochinVitaly
en-aut-sei=Kochin
en-aut-mei=Vitaly
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
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=20
ORCID=

en-aut-name=MatsueHiroyuki
en-aut-sei=Matsue
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=HinoMasayuki
en-aut-sei=Hino
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
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=23
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=24
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=25
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=26
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=KOTAI Biotechnologies, Inc.
kn-affil=

affil-num=4
en-affil=Division of Cancer Immunology, National Cancer Center, Research Institute, Exploratory Oncology Research and Clinical Trial Center (EPOC)
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=Division of Cellular Signaling, National Cancer Center, Research Institute
kn-affil=

affil-num=8
en-affil=Division of Cellular Signaling, National Cancer Center, Research Institute
kn-affil=

affil-num=9
en-affil=Division of Cancer Immunology, National Cancer Center, Research Institute, Exploratory Oncology Research and Clinical Trial Center (EPOC)
kn-affil=

affil-num=10
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=11
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=12
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=13
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=

affil-num=14
en-affil=Department of Thoracic Surgery, Chiba Cancer Center
kn-affil=

affil-num=15
en-affil=Department of Thoracic Surgery, Chiba Cancer Center
kn-affil=

affil-num=16
en-affil=Chiba Cancer Center, Research Institute
kn-affil=

affil-num=17
en-affil=Department of Head and Neck Surgery, Chiba Cancer Center
kn-affil=

affil-num=18
en-affil=Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine
kn-affil=

affil-num=19
en-affil=Department of Immunology, Nagoya University Graduate School of Medicine
kn-affil=

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

affil-num=21
en-affil=Department of Dermatology, Chiba University Graduate School of Medicine
kn-affil=

affil-num=22
en-affil=Department of Hematology, Graduate School of Medicine, Osaka City University
kn-affil=

affil-num=23
en-affil=Division of Cellular Signaling, National Cancer Center, Research Institute
kn-affil=

affil-num=24
en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
kn-affil=

affil-num=25
en-affil=Division of Cancer Immunology, National Cancer Center, Research Institute, Exploratory Oncology Research and Clinical Trial Center (EPOC)
kn-affil=

affil-num=26
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=25
cd-vols=
no-issue=3
article-no=
start-page=103869
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220318
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Lipid flippase dysfunction as a therapeutic target for endosomal anomalies in Alzheimer's disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Endosomal anomalies because of vesicular traffic impairment have been indicated as an early pathology of Alzheimer'vertical bar disease (AD). However, the mechanisms and therapeutic targets remain unclear. We previously reported thatbCTF, one of the pathogenic metabolites of APP, interacts with TMEM30A. TMEM30A constitutes a lipid flippase with P4-ATPase and regulates vesicular trafficking through the asymmetric distribution of phospholipids. Therefore, the alteration of lipid flippase activity in AD pathology has got attention. Herein, we showed that the interaction between beta CTF and TMEM30A suppresses the physiological formation and activity of lipid flippase in AD model cells, A7, and App(NLG-F/NLG-F) model mice. Furthermore, the T-RAP peptide derived from the beta CTF binding site of TMEM30A improved endosomal anomalies, which could be a result of the restored lipid flippase activity. Our results provide insights into the mechanisms of vesicular traffic impairment and suggest a therapeutic target for AD.
en-copyright=
kn-copyright=

en-aut-name=KaneshiroNanaka
en-aut-sei=Kaneshiro
en-aut-mei=Nanaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KomaiMasato
en-aut-sei=Komai
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ImaokaRyosuke
en-aut-sei=Imaoka
en-aut-mei=Ryosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IkedaAtsuya
en-aut-sei=Ikeda
en-aut-mei=Atsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KamikuboYuji
en-aut-sei=Kamikubo
en-aut-mei=Yuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SaitoTakashi
en-aut-sei=Saito
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SaidoTakaomi C.
en-aut-sei=Saido
en-aut-mei=Takaomi C.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TomitaTaisuke
en-aut-sei=Tomita
en-aut-mei=Taisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HashimotoTadafumi
en-aut-sei=Hashimoto
en-aut-mei=Tadafumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=IwatsuboTakeshi
en-aut-sei=Iwatsubo
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=SakuraiTakashi
en-aut-sei=Sakurai
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=UeharaTakashi
en-aut-sei=Uehara
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=TakasugiNobumasa
en-aut-sei=Takasugi
en-aut-mei=Nobumasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

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

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

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

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

affil-num=5
en-affil=Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Neurocognitive Science, Nagoya City University Graduate School of Medical Sciences
kn-affil=

affil-num=7
en-affil=Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science
kn-affil=

affil-num=8
en-affil=Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo
kn-affil=

affil-num=9
en-affil=Department of Neuropathology, Graduate School of Medicine, The University of Tokyo
kn-affil=

affil-num=10
en-affil=Department of Neuropathology, Graduate School of Medicine, The University of Tokyo
kn-affil=

affil-num=11
en-affil=Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine
kn-affil=

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

affil-num=13
en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=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=18
cd-vols=
no-issue=
article-no=
start-page=262
end-page=271
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Boosting Replication and Penetration of Oncolytic Adenovirus by Paclitaxel Eradicate Peritoneal Metastasis of Gastric Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Peritoneal metastasis is the most frequent form of distant metastasis and recurrence in gastric cancer, and the prognosis is extremely poor due to the resistance of systemic chemotherapy. Here, we demonstrate that intraperitoneal (i.p.) administration of a green fluorescence protein (GFP)-expressing attenuated adenovirus with oncolytic potency (OBP-401) synergistically suppressed the peritoneal metastasis of gastric cancer in combination with paclitaxel (PTX). OBP-401 synergistically suppressed the viability of human gastric cancer cells in combination with PTX. PTX enhanced the antitumor effect of OBP-401 due to enhanced viral replication in cancer cells. The combination therapy increased induction of mitotic catastrophe, resulting in accelerated autophagy and apoptosis. Peritoneally disseminated nodules were selectively visualized as GFP-positive spots by i.p. administration of OBP-401 in an orthotopic human gastric cancer peritoneal dissemination model. PTX enhanced the deep penetration of OBP-401 into the disseminated nodules. Moreover, a non-invasive in vivo imaging system demonstrated that the combination therapy of i.p. OBP-401 administration with PTX significantly inhibited growth of peritoneal metastatic tumors and the amount of malignant ascites. i.p. virotherapy with PTX may be a promising treatment strategy for the peritoneal metastasis of gastric cancer.
en-copyright=
kn-copyright=

en-aut-name=IshikawaWataru
en-aut-sei=Ishikawa
en-aut-mei=Wataru
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=OgawaToshihiro
en-aut-sei=Ogawa
en-aut-mei=Toshihiro
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=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
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=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
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=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=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=Oncolys BioPharma, Inc.
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=peritoneal metastasis
kn-keyword=peritoneal metastasis
en-keyword=adenovirus
kn-keyword=adenovirus
en-keyword=gastric cancer
kn-keyword=gastric cancer
en-keyword=intraperitoneal chemotherapy
kn-keyword=intraperitoneal chemotherapy
en-keyword=paclitaxel
kn-keyword=paclitaxel
en-keyword=oncolytic virus
kn-keyword=oncolytic virus
END

start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=
article-no=
start-page=14
end-page=23
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Elimination of MYCN-Amplified Neuroblastoma Cells by Telomerase-Targeted Oncolytic Virus via MYCN Suppression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. High-risk NB is characterized by MYCN amplification and human telomerase reverse transcriptase (hTERT) rearrangement, contributing to hTERT activation and a poor outcome. For targeting hTERT-activated tumors, we developed two oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in which the hTERT promoter drives expression of the viral E1 gene for tumor-specific virus replication. In this study, we demonstrate the therapeutic potential of the hTERT-driven oncolytic adenoviruses OBP-301 and OBP-702 using four human MYCN-amplified NB cell lines (IMR-32, CHP-134, NB-1, LA-N-5) exhibiting high hTERT expression. OBP-301 and OBP-702 exhibited a strong antitumor effect in association with autophagy in NB cells. Virus-mediated activation of E2F1 protein suppressed MYCN expression. OBP-301 and OBP-702 significantly suppressed the growth of subcutaneous CHP-134 tumors. Thus, these hTERT-driven oncolytic adenoviruses are promising antitumor agents for eliminating MYCN-amplified NB cells via E2F1-mediated suppression of MYCN protein.
en-copyright=
kn-copyright=

en-aut-name=TanimotoTerutaka
en-aut-sei=Tanimoto
en-aut-mei=Terutaka
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=IedaTakeshi
en-aut-sei=Ieda
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NousoHiroshi
en-aut-sei=Nouso
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TaniMorimichi
en-aut-sei=Tani
en-aut-mei=Morimichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OyamaTakanori
en-aut-sei=Oyama
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
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=8
ORCID=

en-aut-name=NodaTakuo
en-aut-sei=Noda
en-aut-mei=Takuo
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 Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

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

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

affil-num=7
en-affil=Oncolys BioPharma, Inc.
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 Pediatric 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=neuroblastoma
kn-keyword=neuroblastoma
en-keyword=MYCN
kn-keyword=MYCN
en-keyword=hTERT
kn-keyword=hTERT
en-keyword=adenovirus
kn-keyword=adenovirus
en-keyword=E2F1
kn-keyword=E2F1
END

start-ver=1.4
cd-journal=joma
no-vol=27
cd-vols=
no-issue=
article-no=
start-page=3
end-page=13
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221215
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) antibody, provide improved clinical outcome in certain cancers. However, pancreatic ductal adeno-carcinoma (PDAC) is refractory to PD-1 blockade therapy due to poor immune response. Oncolytic virotherapy is a novel approach for inducing immunogenic cell death (ICD). We demonstrated the therapeutic potential of p53-expressing telo-merase-specific oncolytic adenovirus OBP-702 to induce ICD and anti-tumor immune responses in human PDAC cells with different p53 status (Capan-2, PK-59, PK-45H, Capan-1, MIA PaCa-2, BxPC-3) and murine PDAC cells (PAN02). OBP-702 significantly enhanced ICD with secretion of extracel-lular adenosine triphosphate and high-mobility group box pro-tein B1 by inducing p53-mediated apoptosis and autophagy. OBP-702 significantly promoted the tumor infiltration of CD8+ T cells and the anti-tumor efficacy of PD-1 blockade in a subcutaneous PAN02 syngeneic tumor model. Our results suggest that oncolytic adenovirus-mediated p53 overexpres-sion augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade.
en-copyright=
kn-copyright=

en-aut-name=ArakiHiroyuki
en-aut-sei=Araki
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

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

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KajiwaraYoshinori
en-aut-sei=Kajiwara
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamadaMotohiko
en-aut-sei=Yamada
en-aut-mei=Motohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

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

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

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

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

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

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

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

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

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

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

affil-num=11
en-affil=Oncolys BioPharma, Inc.
kn-affil=

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

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

start-ver=1.4
cd-journal=joma
no-vol=26
cd-vols=
no-issue=3
article-no=
start-page=106133
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230317
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The forebrain cholinergic system promotes higher brain function in part by signaling through the M1 muscarinic acetylcholine receptor (mAChR). Long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmis-sion in the hippocampus are also induced by mAChR. An AMPA receptor (AMPAR) trafficking model for hippocampal neurons has been proposed to simulate N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the early phase. In this study, we demonstrated the validity of the hypothesis that the mAChR-dependent LTP/LTD shares a common AMPAR trafficking pathway associated with NMDAR-dependent LTP/LTD. However, unlike NMDAR, Ca2+ influx into the spine cytosol occurs owing to the Ca2+ stored inside the ER and is induced via the activation of inositol 1,4,5-trisphosphate (IP3) receptors during M1 mAChR activation. Moreover, the AMPAR trafficking model implies that alterations in LTP and LTD observed in Alzheimer's disease could be attributed to age-dependent reductions in AMPAR expression levels.
en-copyright=
kn-copyright=

en-aut-name=SumiTomonari
en-aut-sei=Sumi
en-aut-mei=Tomonari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HaradaKouji
en-aut-sei=Harada
en-aut-mei=Kouji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Research Institute for Interdisciplinary Science, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Computer Science and Engineering, Toyohashi University of Technology
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=7
article-no=
start-page=e18241
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202307
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Expression and clinicopathological characteristics of PDX1, PTF1A, and SALL4 in large and small ducts of ectopic pancreas located in gastro-duodenum and jejunum
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=An ectopic pancreas is defined as pancreatic tissue outside its normal location, anatomically separated from the pancreas.<br>
　The transcription factor pancreas/duodenum homeobox protein 1 (PDX1) is involved in maintaining the pancreas and functions in early pancreatic development, beta cell differentiation, and endocrine non beta cells. Pancreatic transcription factor 1 subunit alpha (PTF1A) affects exocrine cell formation and regulation of acinar cell identity, and is expressed in exocrine cells as a transcription factor. The depletion of SALL4 disrupts self-renewal and induces differentiation.<br>
　To clarify which of PDX1, PTF1A, or SALL4 determines the difference in Heinrich's classification, we examined the localization and number of positive cells. We analyzed the differential expression of PDX1, PTF1A, and SALL4 in large and small ducts in ectopic pancreas by immunohistochemistry. Results showed that the number of PTF1A-positive cells in large ducts was more widespread in type I than in type II in the gastro-duodenum, and more SALL4-positive cells were noticed in large ducts than in small ducts in the gastro-duodenum of type II. Our results revealed that PTF1A might promote exocrine differentiation in developing the pancreatic tissues, and that those with widespread expression differentiate into exocrine cells.
en-copyright=
kn-copyright=

en-aut-name=ChenMengxi
en-aut-sei=Chen
en-aut-mei=Mengxi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IgawaTakuro
en-aut-sei=Igawa
en-aut-mei=Takuro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HanYanyan
en-aut-sei=Han
en-aut-mei=Yanyan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=PengFangli
en-aut-sei=Peng
en-aut-mei=Fangli
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=JinZaishun
en-aut-sei=Jin
en-aut-mei=Zaishun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

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

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

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

affil-num=6
en-affil=Department of Pathology, Mudanjiang Medical University
kn-affil=

affil-num=7
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=PDX1
kn-keyword=PDX1
en-keyword=PTF1A
kn-keyword=PTF1A
en-keyword=SALL4
kn-keyword=SALL4
en-keyword=Ectopic pancreas
kn-keyword=Ectopic pancreas
en-keyword=Gastro-duodenum
kn-keyword=Gastro-duodenum
en-keyword=Jejunum
kn-keyword=Jejunum
END

start-ver=1.4
cd-journal=joma
no-vol=3
cd-vols=
no-issue=1
article-no=
start-page=101046
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220318
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Expression of microbial rhodopsins in Escherichia coli and their extraction and purification using styrene-maleic acid copolymers
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Microbial rhodopsins are photoreceptive membrane proteins showing various light-dependent biological activities. Styrene-maleic acid (SMA) copolymers spontaneously form nanoscale lipid particles containing membrane proteins and associated lipids without detergent, and can be used to characterize membrane molecules. Here, we provide a protocol to functionally express a thermally stable rhodopsin, Rubrobacter xylanophilus rhodopsin, and an unstable rhodopsin, Halobacterium salinarum sensory rhodopsin I, in Escherichia coli. We then describe the preparation of SMA and the extraction and purification of rhodopsin molecules using SMA. <br>
For complete details on the use and execution of this protocol, please refer to Ueta et al. (2020).
en-copyright=
kn-copyright=

en-aut-name=KojimaKeiichi
en-aut-sei=Kojima
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SudoYuki
en-aut-sei=Sudo
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

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

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

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=8
article-no=
start-page=e19038
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202308
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Bayesian statistical modeling to predict observer-specific optimal windowing parameters in magnetic resonance imaging
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Magnetic resonance (MR) images require a process known as windowing for optimizing the display conditions. However, the conventional windowing process often fails to achieve the preferred display conditions for observers due to various factors. This study proposes a novel framework for predicting the preferred windowing parameters for each observer using Bayesian statistical modeling. MR images obtained from 1000 patients were divided into training and test sets at a 7:3 ratio. The image intensity and windowing parameters were standardized using previously reported methods. Bayesian statistical modeling was utilized to predict the windowing parameters preferred by three MR imaging (MRI) operators. The performance of the proposed framework was evaluated by assessing the mean relative error (MRE), mean absolute error (MAE), and Pearson's correlation coefficient (ρ) of the test set. In addition, the naive method, which presumes that the average value of the windowing parameters for each acquisition sequence and body region in the training set is optimal, was also used for comparison. Three MRI operators and three radiologists conducted visual assessments. The mean MRE, MAE, and ρ values for the window level and width (WL/WW) in the proposed framework were 12.6 and 13.9, 42.9 and 85.4, and 0.98 and 0.98, respectively. These results outperformed those obtained using the naive method. The visual assessments revealed no significant differences between the original and predicted display conditions, indicating that the proposed framework accurately predicts individualized windowing parameters with the additional advantages of robustness and ease of use. Thus, the proposed framework can effectively predict the windowing parameters preferred by each observer.
en-copyright=
kn-copyright=

en-aut-name=SugimotoKohei
en-aut-sei=Sugimoto
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OitaMasataka
en-aut-sei=Oita
en-aut-mei=Masataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KurodaMasahiro
en-aut-sei=Kuroda
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

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

affil-num=2
en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University
kn-affil=
en-keyword=MR image
kn-keyword=MR image
en-keyword=Image intensity standardization
kn-keyword=Image intensity standardization
en-keyword=Windowing
kn-keyword=Windowing
en-keyword=Prediction
kn-keyword=Prediction
en-keyword=Bayesian statistical modeling
kn-keyword=Bayesian statistical modeling
END

start-ver=1.4
cd-journal=joma
no-vol=3
cd-vols=
no-issue=4
article-no=
start-page=101786
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221216
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A protocol to induce expandable limb-bud mesenchymal cells from human pluripotent stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Here, we present a protocol for the selective differentiation of human pluripotent stem cells mimicking human developmental processes into expandable PRRX1+ limb-bud mesenchymal (ExpLBM) cells. This approach enables expansion through serial passage while maintaining capacity for chondrogenic differentiation. For complete details on the use and execution of this protocol, please refer to Yamada et al. (2021, 2022).
en-copyright=
kn-copyright=

en-aut-name=TakaoTomoka
en-aut-sei=Takao
en-aut-mei=Tomoka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YamadaDaisuke
en-aut-sei=Yamada
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakaradaTakeshi
en-aut-sei=Takarada
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

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

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

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

start-ver=1.4
cd-journal=joma
no-vol=42
cd-vols=
no-issue=12
article-no=
start-page=113569
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231226
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mechanistic dissection of premature translation termination induced by acidic residues-enriched nascent peptide
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Ribosomes polymerize nascent peptides through repeated inter-subunit rearrangements between the classic and hybrid states. The peptidyl-tRNA, the intermediate species during translation elongation, stabi-lizes the translating ribosome to ensure robust continuity of elongation. However, the translation of acidic residue-rich sequences destabilizes the ribosome, leading to a stochastic premature translation cessation termed intrinsic ribosome destabilization (IRD), which is still ill-defined. Here, we dissect the molecular mechanisms underlying IRD in Escherichia coli. Reconstitution of the IRD event reveals that (1) the prolonged ribosome stalling enhances IRD-mediated translation discontinuation, (2) IRD depends on temperature, (3) the destabilized 70S ribosome complex is not necessarily split, and (4) the destabilized ribosome is subjected to peptidyl-tRNA hydrolase-mediated hydrolysis of the peptidyl-tRNA without subunit splitting or recycling factors-mediated subunit splitting. Collectively, our data indicate that the translation of acidic-rich sequences alters the conformation of the 70S ribosome to an aberrant state that allows the noncanonical pre-mature termination.
en-copyright=
kn-copyright=

en-aut-name=ChadaniYuhei
en-aut-sei=Chadani
en-aut-mei=Yuhei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KanamoriTakashi
en-aut-sei=Kanamori
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NiwaTatsuya
en-aut-sei=Niwa
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IchiharaKazuya
en-aut-sei=Ichihara
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NakayamaKeiichi I.
en-aut-sei=Nakayama
en-aut-mei=Keiichi I.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MatsumotoAkinobu
en-aut-sei=Matsumoto
en-aut-mei=Akinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TaguchiHideki
en-aut-sei=Taguchi
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=GeneFrontier Corporation
kn-affil=

affil-num=3
en-affil=Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology
kn-affil=

affil-num=4
en-affil=Division of Biological Science, Graduate School of Science, Nagoya University
kn-affil=

affil-num=5
en-affil=Anticancer Strategies Laboratory, TMDU Advanced Research Institute, Tokyo Medical and Dental University
kn-affil=

affil-num=6
en-affil=Division of Biological Science, Graduate School of Science, Nagoya University
kn-affil=

affil-num=7
en-affil=Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology
kn-affil=
END

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

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

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

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

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

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

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

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

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

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

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

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

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

en-aut-name=OkadaHiroyuki
en-aut-sei=Okada
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=OtsukaMotoyuki
en-aut-sei=Otsuka
en-aut-mei=Motoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

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

affil-num=2
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

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

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

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

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

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

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

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

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

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

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

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