start-ver=1.4
cd-journal=joma
no-vol=19
cd-vols=
no-issue=5
article-no=
start-page=e0300644
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240517
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PAI-1 mediates acquired resistance to MET-targeted therapy in non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we investigated the possible mechanisms acquired for crizotinib in MET-amplified lung carcinoma cell lines. Two MET-amplified lung cancer cell lines, EBC-1 and H1993, were established for acquired resistance to MET-TKI crizotinib and were functionally elucidated. Genomic and transcriptomic data were used to assess the factors contributing to the resistance mechanism, and the alterations hypothesized to confer resistance were validated. Multiple mechanisms underlie acquired resistance to crizotinib in MET-amplified lung cancer cell lines. In EBC-1-derived resistant cells, the overexpression of SERPINE1, the gene encoding plasminogen activator inhibitor-1 (PAI-1), mediated the drug resistance mechanism. Crizotinib resistance was addressed by combination therapy with a PAI-1 inhibitor and PAI-1 knockdown. Another mechanism of resistance in different subline cells of EBC-1 was evaluated as epithelial-to-mesenchymal transition with the upregulation of antiapoptotic proteins. In H1993-derived resistant cells, MEK inhibitors could be a potential therapeutic strategy for overcoming resistance with downstream mitogen-activated protein kinase pathway activation. In this study, we revealed the different mechanisms of acquired resistance to the MET inhibitor crizotinib with potential therapeutic application in patients with MET-amplified lung carcinoma.
en-copyright=
kn-copyright=
en-aut-name=ThuYin Min
en-aut-sei=Thu
en-aut-mei=Yin Min
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OchiKosuke
en-aut-sei=Ochi
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TsudakaShimpei
en-aut-sei=Tsudaka
en-aut-mei=Shimpei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TakatsuFumiaki
en-aut-sei=Takatsu
en-aut-mei=Fumiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=DateKeiichi
en-aut-sei=Date
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MatsudaNaoki
en-aut-sei=Matsuda
en-aut-mei=Naoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=IwataKazuma
en-aut-sei=Iwata
en-aut-mei=Kazuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NakataKentaro
en-aut-sei=Nakata
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=OkazakiMikio
en-aut-sei=Okazaki
en-aut-mei=Mikio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine
kn-affil=
affil-num=11
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=73
cd-vols=
no-issue=2
article-no=
start-page=323
end-page=331
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Topical application of activator protein-1 inhibitor T-5224 suppresses inflammation and improves skin barrier function in a murine atopic dermatitis-like dermatitis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders.
Methods: Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the in vivo study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice. Baricitinib, a conventional therapeutic agent Janus kinase (JAK) inhibitor, was also topically applied. In the in vitro study, human epidermal keratinocytes were treated with T-5224 and stimulated with AD-related cytokines.
Results: AP-1/c-Jun was phosphorylated at skin lesions in AD patients. In vivo, topical T-5224 application inhibited ear swelling (P < 0.001), restored filaggrin (Flg) expression (P < 0.01), and generally suppressed immune-related pathways. T-5224 significantly suppressed Il17a and l17f expression, whereas baricitinib did not.Baricitinib suppressed Il4, Il19, Il33 and Ifnb expression, whereas T-5224 did not. Il1a, Il1b, Il23a, Ifna, S100a8, and S100a9 expression was cooperatively downregulated following the combined use of T5224 and baricitinib. In vitro, T-5224 restored the expression of FLG and loricrin (LOR) (P < 0.05) and suppressed IL33 expression (P < 0.05) without affecting cell viability and cytotoxicity.
Conclusions: Topical T-5224 ameliorates clinical manifestations of AD-like dermatitis in mice. The effect of this inhibitor is amplified via combined use with JAK inhibitors.
en-copyright=
kn-copyright=
en-aut-name=SasakuraMinori
en-aut-sei=Sasakura
en-aut-mei=Minori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=UrakamiHitoshi
en-aut-sei=Urakami
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TachibanaKota
en-aut-sei=Tachibana
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IkedaKenta
en-aut-sei=Ikeda
en-aut-mei=Kenta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HasuiKen-Ichi
en-aut-sei=Hasui
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MatsudaYoshihiro
en-aut-sei=Matsuda
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SunagawaKo
en-aut-sei=Sunagawa
en-aut-mei=Ko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=EnnishiDaisuke
en-aut-sei=Ennishi
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MorizaneShin
en-aut-sei=Morizane
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=AP-1 inhibitor
kn-keyword=AP-1 inhibitor
en-keyword=Atopic dermatitis
kn-keyword=Atopic dermatitis
en-keyword=Baricitinib
kn-keyword=Baricitinib
en-keyword=T-5224
kn-keyword=T-5224
en-keyword=Topical application
kn-keyword=Topical application
END
start-ver=1.4
cd-journal=joma
no-vol=7
cd-vols=
no-issue=24
article-no=
start-page=7459
end-page=7470
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231214
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell–like (GCB) DLBCL, activated B-cell–like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.
en-copyright=
kn-copyright=
en-aut-name=UrataTomohiro
en-aut-sei=Urata
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NaoiYusuke
en-aut-sei=Naoi
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=JiangAixiang
en-aut-sei=Jiang
en-aut-mei=Aixiang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=BoyleMerrill
en-aut-sei=Boyle
en-aut-mei=Merrill
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=SunamiKazutaka
en-aut-sei=Sunami
en-aut-mei=Kazutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=ImaiToshi
en-aut-sei=Imai
en-aut-mei=Toshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NawaYuichiro
en-aut-sei=Nawa
en-aut-mei=Yuichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=HiramatsuYasushi
en-aut-sei=Hiramatsu
en-aut-mei=Yasushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=YamamotoKazuhiko
en-aut-sei=Yamamoto
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=FujiiSoichiro
en-aut-sei=Fujii
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YoshidaIsao
en-aut-sei=Yoshida
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=YanoTomofumi
en-aut-sei=Yano
en-aut-mei=Tomofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=ChijimatsuRyota
en-aut-sei=Chijimatsu
en-aut-mei=Ryota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MurakamiHiroyuki
en-aut-sei=Murakami
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=IkeuchiKazuhiro
en-aut-sei=Ikeuchi
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=KobayashiHiroki
en-aut-sei=Kobayashi
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=TaniKatsuma
en-aut-sei=Tani
en-aut-mei=Katsuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=UjiieHideki
en-aut-sei=Ujiie
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=InoueHirofumi
en-aut-sei=Inoue
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=YamamotoAkira
en-aut-sei=Yamamoto
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=KondoTakumi
en-aut-sei=Kondo
en-aut-mei=Takumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
en-aut-name=FujiwaraHideaki
en-aut-sei=Fujiwara
en-aut-mei=Hideaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=
en-aut-name=AsadaNoboru
en-aut-sei=Asada
en-aut-mei=Noboru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=
en-aut-name=NishimoriHisakazu
en-aut-sei=Nishimori
en-aut-mei=Hisakazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=
en-aut-name=FujiiKeiko
en-aut-sei=Fujii
en-aut-mei=Keiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=
en-aut-name=FujiiNobuharu
en-aut-sei=Fujii
en-aut-mei=Nobuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
ORCID=
en-aut-name=MatsuokaKen-ichi
en-aut-sei=Matsuoka
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=28
ORCID=
en-aut-name=SawadaKeisuke
en-aut-sei=Sawada
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=29
ORCID=
en-aut-name=MomoseShuji
en-aut-sei=Momose
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=30
ORCID=
en-aut-name=TamaruJun-ichi
en-aut-sei=Tamaru
en-aut-mei=Jun-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=31
ORCID=
en-aut-name=NishikoriAsami
en-aut-sei=Nishikori
en-aut-mei=Asami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=32
ORCID=
en-aut-name=SatoYasuharu
en-aut-sei=Sato
en-aut-mei=Yasuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=33
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=34
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=35
ORCID=
en-aut-name=ScottDavid W.
en-aut-sei=Scott
en-aut-mei=David W.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=36
ORCID=
en-aut-name=EnnishiDaisuke
en-aut-sei=Ennishi
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=37
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=British Columbia Cancer, Centre for Lymphoid Cancer
kn-affil=
affil-num=4
en-affil=British Columbia Cancer, Centre for Lymphoid Cancer
kn-affil=
affil-num=5
en-affil=Department of Hematology, NHO Okayama Medical Center
kn-affil=
affil-num=6
en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center
kn-affil=
affil-num=7
en-affil=Division of Hematology, Ehime Prefectural Central Hospital
kn-affil=
affil-num=8
en-affil=Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital
kn-affil=
affil-num=9
en-affil=Department of Hematology and Oncology, Okayama City Hospital
kn-affil=
affil-num=10
en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital
kn-affil=
affil-num=11
en-affil=Department of Hematologic Oncology, NHO Shikoku Cancer Center
kn-affil=
affil-num=12
en-affil=Department of Internal Medicine, Okayama Rosai Hospital
kn-affil=
affil-num=13
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=17
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
kn-affil=
affil-num=20
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=21
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=22
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=23
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=24
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=25
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=26
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=27
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=28
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=29
en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University
kn-affil=
affil-num=30
en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University
kn-affil=
affil-num=31
en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University
kn-affil=
affil-num=32
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=
affil-num=33
en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
kn-affil=
affil-num=34
en-affil=Department of Pathology, Okayama University
kn-affil=
affil-num=35
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=36
en-affil=British Columbia Cancer, Centre for Lymphoid Cancer
kn-affil=
affil-num=37
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=1
article-no=
start-page=8912
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230601
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Identification of genetic loci associated with renal dysfunction after lung transplantation using an ethnic-specific single-nucleotide polymorphism array
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Renal dysfunction is a long-term complication associated with an increased mortality after lung transplantation (LT). We investigated the association of single-nucleotide polymorphisms (SNPs) with the development of renal dysfunction after LT using a Japanese-specific SNP array. First, eligible samples of 34 LT recipients were genotyped using the SNP array and divided into two groups, according to the presence of homozygous and heterozygous combinations of mutant alleles of the 162 renal-related SNPs. To identify candidate SNPs, the renal function tests were compared between the two groups for each SNP. Next, we investigated the association between the candidate SNPs and the time course of changes of the estimated glomerular filtration rate (eGFR) in the 99 recipients until 10 years after the LT. Delta eGFR was defined as the difference between the postoperative and preoperative eGFR values. Eight SNPs were identified as the candidate SNPs in the 34 recipients. Validation analysis of these 8 candidate SNPs in all the 99 recipients showed that three SNPs, namely, rs10277115, rs4690095, and rs792064, were associated with significant changes of the Delta eGFR. Pre-transplant identification of high-risk patients for the development of renal dysfunction after LT based on the presence of these SNPs might contribute to providing personalized medicine.
en-copyright=
kn-copyright=
en-aut-name=TomiokaYasuaki
en-aut-sei=Tomioka
en-aut-mei=Yasuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=YamamotoHaruchika
en-aut-sei=Yamamoto
en-aut-mei=Haruchika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=ShiotaniToshio
en-aut-sei=Shiotani
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TanakaShin
en-aut-sei=Tanaka
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=MiyoshiKentaroh
en-aut-sei=Miyoshi
en-aut-mei=Kentaroh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OtaniShinji
en-aut-sei=Otani
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=OkazakiMikio
en-aut-sei=Okazaki
en-aut-mei=Mikio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=YamaneMasaomi
en-aut-sei=Yamane
en-aut-mei=Masaomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=3
article-no=
start-page=323
end-page=330
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202306
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.
en-copyright=
kn-copyright=
en-aut-name=MakinoKeigo
en-aut-sei=Makino
en-aut-mei=Keigo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OtaniYoshihiro
en-aut-sei=Otani
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujiiKentaro
en-aut-sei=Fujii
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IshidaJoji
en-aut-sei=Ishida
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HiranoShuichiro
en-aut-sei=Hirano
en-aut-mei=Shuichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SurugaYasuki
en-aut-sei=Suruga
en-aut-mei=Yasuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=WashioKana
en-aut-sei=Washio
en-aut-mei=Kana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NishidaKenji
en-aut-sei=Nishida
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=YanaiHiroyuki
en-aut-sei=Yanai
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=EnnishiDaisuke
en-aut-sei=Ennishi
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=DateIsao
en-aut-sei=Date
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
affil-num=1
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Departments of Pediatrics, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Departments of Pathology, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Departments of Pathology, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=comprehensive genomic profiling
kn-keyword=comprehensive genomic profiling
en-keyword=pediatric brain tumor
kn-keyword=pediatric brain tumor
en-keyword=genome-wide DNA methylation
kn-keyword=genome-wide DNA methylation
en-keyword=MYCN
kn-keyword=MYCN
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=
article-no=
start-page=1187479
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230518
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Etiology of recurrent cystitis in postmenopausal women based on vaginal microbiota and the role of Lactobacillus vaginal suppository
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: The vaginal microbiota can be altered by uropathogenic bacteria associated with recurrent cystitis (RC), and the vaginal administration of Lactobacillus have suggested certain effects to prevent RC. The relationship between vaginal microbiota and the development of RC has not been elucidated. We aimed to clarify the etiology of RC from vaginal microbiota and importance of vaginal Lactobacillus.
Methods: Vaginal samples obtained from 39 postmenopausal women were classified into four groups: healthy controls; uncomplicated cystitis; RC; and prevention (prevented RC by Lactobacillus crispatus-containing vaginal suppositories). Principal coordinate analysis and beta-diversity analysis was used to assess 16S rRNA gene sequencing data from the vaginal microbiome.
Results: Cluster analysis divided the vaginal bacterial communities among 129 vaginal samples into three clusters (A, B, and C). Fourteen of 14 (100%) samples from the RC group and 51 of 53 (96%) samples from the prevention group were in clusters B and C, while 29 of 38 (76%) samples from the healthy group and 14 of 24 (58%) samples from the uncomplicated cystitis group were in cluster A. The principal coordinate analysis showed that plots in the uncomplicated cystitis group were similar to the healthy group, indicating a large separation between the RC group and the uncomplicated cystitis group. On beta-diversity analysis, there were significant differences between the healthy group and the uncomplicated cystitis group (p = 0.045), and between the RC group and the uncomplicated cystitis group or the healthy group (p = 0.001, p = 0.001, respectively). There were no significant differences between the RC group and the prevention group (p = 0.446). The top six taxa were as follows: Prevotella, Lactobacillus, Streptococcus, Enterobacteriaceae, Anaerococcus, and Bifidobacterium. Among patients with RC, Lactobacillus was undetectable before administration of suppositories, while the median relative abundance of Lactobacillus was 19% during administration of suppositories (p = 0.0211), reducing the average cystitis episodes per year (6.3 vs. 2.4, p = 0.0015).
Conclusion: The vaginal microbiota of postmenopausal women with RC is differed from healthy controls and uncomplicated cystitis in terms of lack of Lactobacillus and relatively dominant of Enterobacteriaceae. Vaginal administration of Lactobacillus-containing suppositories can prevent RC by stabilizing vaginal dysbiosis and causing a loss of pathogenic bacteria virulence.
en-copyright=
kn-copyright=
en-aut-name=SekitoTakanori
en-aut-sei=Sekito
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=WadaKoichiro
en-aut-sei=Wada
en-aut-mei=Koichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=IshiiAyano
en-aut-sei=Ishii
en-aut-mei=Ayano
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IwataTakehiro
en-aut-sei=Iwata
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MatsubaraTakehiro
en-aut-sei=Matsubara
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=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=ArakiMotoo
en-aut-sei=Araki
en-aut-mei=Motoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SadahiraTakuya
en-aut-sei=Sadahira
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=2
en-affil=Department of Urology, Shimane University Faculty of Medicine
kn-affil=
affil-num=3
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=4
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=5
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=8
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=9
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
en-keyword=cystitis
kn-keyword=cystitis
en-keyword=vagina
kn-keyword=vagina
en-keyword=microbiota
kn-keyword=microbiota
en-keyword=Lactobacillus
kn-keyword=Lactobacillus
en-keyword=urinary tract infection
kn-keyword=urinary tract infection
END
start-ver=1.4
cd-journal=joma
no-vol=2022
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220724
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction.
en-copyright=
kn-copyright=
en-aut-name=OchiKosuke
en-aut-sei=Ochi
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=ThuYin Min
en-aut-sei=Thu
en-aut-mei=Yin Min
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakatsuFumiaki
en-aut-sei=Takatsu
en-aut-mei=Fumiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TsudakaShimpei
en-aut-sei=Tsudaka
en-aut-mei=Shimpei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=ZhuYidan
en-aut-sei=Zhu
en-aut-mei=Yidan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NakataKentaro
en-aut-sei=Nakata
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TakedaTatsuaki
en-aut-sei=Takeda
en-aut-mei=Tatsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=OkazakiMikio
en-aut-sei=Okazaki
en-aut-mei=Mikio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=ShienTadahiko
en-aut-sei=Shien
en-aut-mei=Tadahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=OkamotoYoshiharu
en-aut-sei=Okamoto
en-aut-mei=Yoshiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
affil-num=1
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Departments of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University
kn-affil=
affil-num=15
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cancer-associated fibroblast
kn-keyword=cancer-associated fibroblast
en-keyword=drug resistance
kn-keyword=drug resistance
en-keyword=tranilast
kn-keyword=tranilast
END
start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=7297
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220504
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=One-step nucleic acid amplification for intraoperative diagnosis of lymph node metastasis in lung cancer patients: a single-center prospective study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer.
en-copyright=
kn-copyright=
en-aut-name=NambaKei
en-aut-sei=Namba
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MiuraAkihiro
en-aut-sei=Miura
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TakahashiYuta
en-aut-sei=Takahashi
en-aut-mei=Yuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MiyauchiShunsaku
en-aut-sei=Miyauchi
en-aut-mei=Shunsaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=ArakiKota
en-aut-sei=Araki
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NakataKentaro
en-aut-sei=Nakata
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=TanakaShin
en-aut-sei=Tanaka
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=MiyoshiKentaroh
en-aut-sei=Miyoshi
en-aut-mei=Kentaroh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=OtaniShinji
en-aut-sei=Otani
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=OkazakiMikio
en-aut-sei=Okazaki
en-aut-mei=Mikio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=YamaneMasaomi
en-aut-sei=Yamane
en-aut-mei=Masaomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of Pathology, Memorial Sloan Kettering Cancer Center
kn-affil=
affil-num=2
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=17
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=1
article-no=
start-page=20
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220207
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Identification of targetable kinases in idiopathic pulmonary fibrosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). Methods Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). Results Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. Conclusions We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF.
en-copyright=
kn-copyright=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SenooSatoru
en-aut-sei=Senoo
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=5
en-affil=Department of Thoracic Surgery, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Organ Transplant Center, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=12
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=17
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=18
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=19
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=Idiopathic pulmonary fibrosis
kn-keyword=Idiopathic pulmonary fibrosis
en-keyword=RNA sequencing
kn-keyword=RNA sequencing
en-keyword=Molecular therapeutic target
kn-keyword=Molecular therapeutic target
en-keyword=Personalized therapy
kn-keyword=Personalized therapy
END
start-ver=1.4
cd-journal=joma
no-vol=7
cd-vols=
no-issue=1
article-no=
start-page=e148960
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220111
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Accumulating evidence has shown that cancer stroma and BM-derived cells (BMDCs) in the tumor microenvironment (TME) play vital roles in tumor progression. However, the mechanism by which oral cancer stroma recruits any particular subset of BMDCs remains largely unknown. Here, we sought to identify the subset of BMDCs that is recruited by cancer stroma. We established a sequential transplantation model in BALB/c nude mice, including (a) BM transplantation of GFP-expressing cells and (b) coxenografting of patient-derived stroma (PDS; 2 cases, designated PDS1 and PDS2) with oral cancer cells (HSC-2). As controls, xenografting was performed with HSC-2 alone or in combination with normal human dermal fibroblasts (HDF). PDS1, PDS2, and HDF all promoted BMDC migration in vitro and recruitment in vivo. Multicolor immunofluorescence revealed that the PDS coxenografts recruited Arginase-1(+)CD11b(+)GR1(+)GFP(+) cells, which are myeloid-derived suppressor cells (MDSCs), to the TME, whereas the HDF coxenograft did not. Screening using microarrays revealed that PDS1 and PDS2 expressed CCL2 mRNA (encoding C-C motif chemokine ligand 2) at higher levels than did HDF. Indeed, PDS xenografts contained significantly higher proportions of CCL2(+) stromal cells and CCR2(+)Arginase-1(+)CD11b(+)GR1(+) MDSCs (as receiver cells) than the HDF coxenograft. Consistently, a CCL2 synthesis inhibitor and a CCR2 antagonist significantly inhibited the PDS-driven migration of BM cells in vitro. Furthermore, i.p. injection of the CCR2 antagonist to the PDS xenograft models significantly reduced the CCR2(+)Arginase-1(+)CD11b(+)GR1(+) MDSC infiltration to the TME. In conclusion, oral cancer stroma-secreted CCL2 is a key signal for recruiting CCR2(+) MDSCs from BM to the TME.
en-copyright=
kn-copyright=
en-aut-name=OoMay Wathone
en-aut-sei=Oo
en-aut-mei=May Wathone
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KawaiHotaka
en-aut-sei=Kawai
en-aut-mei=Hotaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TakabatakeKiyofumi
en-aut-sei=Takabatake
en-aut-mei=Kiyofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=EguchiTakanori
en-aut-sei=Eguchi
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=OnoKisho
en-aut-sei=Ono
en-aut-mei=Kisho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=ShanQiusheng
en-aut-sei=Shan
en-aut-mei=Qiusheng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=YoshidaSaori
en-aut-sei=Yoshida
en-aut-mei=Saori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OmoriHaruka
en-aut-sei=Omori
en-aut-mei=Haruka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=SukegawaShintaro
en-aut-sei=Sukegawa
en-aut-mei=Shintaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NakanoKeisuke
en-aut-sei=Nakano
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=OkamotoKuniaki
en-aut-sei=Okamoto
en-aut-mei=Kuniaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=SasakiAkira
en-aut-sei=Sasaki
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=NagatsukaHitoshi
en-aut-sei=Nagatsuka
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=11
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=12
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=13
en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=14
en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=15
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=1
article-no=
start-page=13125
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210623
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Reduced dose of PTCy followed by adjuvant alpha-galactosylceramide enhances GVL effect without sacrificing GVHD suppression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient's condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by alpha -galactosylceramide (alpha -GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of alpha -GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4(+)Foxp3(+) regulatory T cells. These studies indicate that alpha -GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk.
en-copyright=
kn-copyright=
en-aut-name=NakamuraMakoto
en-aut-sei=Nakamura
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MeguriYusuke
en-aut-sei=Meguri
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=IkegawaShuntaro
en-aut-sei=Ikegawa
en-aut-mei=Shuntaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KondoTakumi
en-aut-sei=Kondo
en-aut-mei=Takumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=SumiiYuichi
en-aut-sei=Sumii
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=FukumiTakuya
en-aut-sei=Fukumi
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=IwamotoMiki
en-aut-sei=Iwamoto
en-aut-mei=Miki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=SandoYasuhisa
en-aut-sei=Sando
en-aut-mei=Yasuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SugiuraHiroyuki
en-aut-sei=Sugiura
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=AsadaNoboru
en-aut-sei=Asada
en-aut-mei=Noboru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=EnnishiDaisuke
en-aut-sei=Ennishi
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=Fukuda-KawaguchiEmi
en-aut-sei=Fukuda-Kawaguchi
en-aut-mei=Emi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=IshiiYasuyuki
en-aut-sei=Ishii
en-aut-mei=Yasuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=MatsuokaKen-Ichi
en-aut-sei=Matsuoka
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
affil-num=1
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=REGiMMUNE Corporation
kn-affil=
affil-num=14
en-affil=REGiMMUNE Corporation
kn-affil=
affil-num=15
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=71
cd-vols=
no-issue=
article-no=
start-page=360
end-page=364
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210303
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Best practices for the extraction of genomic DNA from formalin‐fixed paraffin‐embedded tumor tissue for cancer genomic profiling tests
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Recently, two cancer genomic profiling tests have been approved in Japan and implemented in routine clinical practice: the FDA‐approved FoundationOne CDx test, and the OncoGuide NCC Oncopanel test. The quality and quantity of DNA significantly affects the sequencing results; therefore, preparing a sufficient amount of high‐quality DNA for clinical cancer genomic profiling tests is important. We examined the best practices for the extraction of cancer genomic DNA from formalin‐fixed paraffin‐embedded (FFPE) tumor tissues of pancreatic, lung and colon cancer specimens. We found that the quality of cancer genomic DNA extracted from 10‐μm‐thick FFPE samples improved significantly, compared with that from 4‐μm‐thick FFPE samples, suggesting that 10‐μm‐thick FFPE samples are preferable for clinical cancer genomic profiling tests. For convenience, we created a quick reference table for calculating the required number of FFPE slides.
en-copyright=
kn-copyright=
en-aut-name=InoueHirofumi
en-aut-sei=Inoue
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
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=4
ORCID=
en-aut-name=MatsuokaHiromi
en-aut-sei=Matsuoka
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SanehiraEtsuko
en-aut-sei=Sanehira
en-aut-mei=Etsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MatsuokaMasashi
en-aut-sei=Matsuoka
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=YanaiHiroyuki
en-aut-sei=Yanai
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=HirasawaAkira
en-aut-sei=Hirasawa
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
kn-affil=
affil-num=2
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
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 Pathology, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
kn-affil=
affil-num=10
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
kn-affil=
en-keyword=cancer genomic profiling tests
kn-keyword=cancer genomic profiling tests
en-keyword=formalin‐fixed paraffin‐embedded (FFPE) tumor tissue
kn-keyword=formalin‐fixed paraffin‐embedded (FFPE) tumor tissue
en-keyword= genomic DNA extraction
kn-keyword= genomic DNA extraction
END
start-ver=1.4
cd-journal=joma
no-vol=140
cd-vols=
no-issue=5
article-no=
start-page=657
end-page=661
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200501
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=ゲノム医療におけるデータサイエンティストの役割と育成
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The development of specialized training programs for medical personnel, particularly nurses, clinical laboratory technicians, and pharmacists, is considered critical for the promotion of genomic medicine throughout Japan. Specifically, medical personnel skilled at analyzing and understanding high-throughput genomic data are in high demand. In this symposium, we will introduce the basic knowledge and skills necessary for processing genomic data.
en-copyright=
kn-copyright=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=冨田秀太
kn-aut-sei=冨田
kn-aut-mei=秀太
aut-affil-num=1
ORCID=
en-aut-name=MoritaMizuki
en-aut-sei=Morita
en-aut-mei=Mizuki
kn-aut-name=森田瑞樹
kn-aut-sei=森田
kn-aut-mei=瑞樹
aut-affil-num=2
ORCID=
en-aut-name=YamashitaNoriyuki
en-aut-sei=Yamashita
en-aut-mei=Noriyuki
kn-aut-name=山下範之
kn-aut-sei=山下
kn-aut-mei=範之
aut-affil-num=3
ORCID=
en-aut-name=HirasawaAkira
en-aut-sei=Hirasawa
en-aut-mei=Akira
kn-aut-name=平沢晃
kn-aut-sei=平沢
kn-aut-mei=晃
aut-affil-num=4
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=豊岡伸一
kn-aut-sei=豊岡
kn-aut-mei=伸一
aut-affil-num=5
ORCID=
affil-num=1
en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科
affil-num=2
en-affil=Department of Biorepository Research and Networking, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科クリニカルバイオバンクネットワーキング事業化研究講座
affil-num=3
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=岡山大学病院新医療研究開発センター
affil-num=4
en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科臨床遺伝子診療科
affil-num=5
en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科呼吸器・乳腺内分泌外科
en-keyword=genomic medicine
kn-keyword=genomic medicine
en-keyword=tumor mutation burden
kn-keyword=tumor mutation burden
en-keyword=biomedical data science
kn-keyword=biomedical data science
en-keyword=bioinformatics
kn-keyword=bioinformatics
END
start-ver=1.4
cd-journal=joma
no-vol=20
cd-vols=
no-issue=6
article-no=
start-page=393
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202012
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Detection of epidermal growth factor receptor mutations in exhaled breath condensate using droplet digital polymerase chain reaction
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The detection of certain oncogenic driver mutations, including those of epidermal growth factor receptor (EGFR), is essential for determining treatment strategies for advanced non‑small cell lung cancer (NSCLC). The current study assessed the feasibility of testing exhaled breath condensate (EBC) for EGFR mutations by droplet digital PCR (ddPCR). Samples were collected from 12 patients with NSCLC harboring EGFR mutations that were admitted to Okayama University Hospital between June 1, 2014 and December 31, 2017. A total of 21 EBC samples were collected using the RTube™ method and EGFR mutations (L858R, exon 19 deletions or T790M) were assessed through ddPCR analysis (EBC‑ddPCR). A total of 3 healthy volunteer samples were also tested to determine a threshold value for each mutation. Various patient characteristics were determined, including sex (3 males and 9 females), age (range 54‑81 years; median, 66 years), smoking history (10 had never smoked; 2 were former smokers), histology (12 patients exhibited adenocarcinoma), clinical stage (9 patients were stage IV; 3 exhibited post‑operative recurrence) and EGFR mutation type (4 had L858R; 8 had exon 19 deletions; 8 had T790M). EBC‑ddPCR demonstrated positive droplets in 8 of the 12 patients. The sensitivity and specificity of each mutation was as follows: 27.3 and 80.0% for EGFR L858R, 30.0 and 90.9% for EGFR Ex19del, and 22.2 and 100% for EGFR T790M. EBC‑ddPCR analysis of EGFR mutations exhibited modest sensitivity and acceptable specificity. EBC‑ddPCR is a minimally invasive and replicable procedure and may be a complementary method for EGFR testing in patients where blood or tissue sampling proves difficult.
en-copyright=
kn-copyright=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TamuraTomoki
en-aut-sei=Tamura
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MatsubaraTakehiro
en-aut-sei=Matsubara
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SenooSatoru
en-aut-sei=Senoo
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=NinomiyaTakashi
en-aut-sei=Ninomiya
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Okayama University Hospital Biobank
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Okayama University Hospital Biobank
kn-affil=
affil-num=17
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=18
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=20
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=21
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=non-small cell lung cancer
kn-keyword=non-small cell lung cancer
en-keyword=epidermal growth factor receptor mutations
kn-keyword=epidermal growth factor receptor mutations
en-keyword=droplet digital PCR
kn-keyword=droplet digital PCR
en-keyword=exhaled breath condensate
kn-keyword=exhaled breath condensate
en-keyword=EGFR-TKIs
kn-keyword=EGFR-TKIs
END
start-ver=1.4
cd-journal=joma
no-vol=529
cd-vols=
no-issue=3
article-no=
start-page=760
end-page=765
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200827
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background
The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors.
Materials and methods
A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed.
Results
TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor.
Conclusion
Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance.
en-copyright=
kn-copyright=
en-aut-name=OchiKosuke
en-aut-sei=Ochi
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TakanoJui
en-aut-sei=Takano
en-aut-mei=Jui
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MiyauchiShunsaku
en-aut-sei=Miyauchi
en-aut-mei=Shunsaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TakedaTatsuaki
en-aut-sei=Takeda
en-aut-mei=Tatsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MiuraAkihiro
en-aut-sei=Miura
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=ArakiKota
en-aut-sei=Araki
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NakataKentaro
en-aut-sei=Nakata
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=OkazakiMikio
en-aut-sei=Okazaki
en-aut-mei=Mikio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=ShienTadahiko
en-aut-sei=Shien
en-aut-mei=Tadahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=YamaneMasaomi
en-aut-sei=Yamane
en-aut-mei=Masaomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=AzumaKazuo
en-aut-sei=Azuma
en-aut-mei=Kazuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=OkamotoYoshiharu
en-aut-sei=Okamoto
en-aut-mei=Yoshiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University
kn-affil=
affil-num=17
en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University
kn-affil=
affil-num=18
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Monensin
kn-keyword=Monensin
en-keyword=Epithelial-mesenchymal transition
kn-keyword=Epithelial-mesenchymal transition
en-keyword=Non-small cell lung cancer
kn-keyword=Non-small cell lung cancer
en-keyword=Drug repositioning
kn-keyword=Drug repositioning
en-keyword=Drug resistance
kn-keyword=Drug resistance
END
start-ver=1.4
cd-journal=joma
no-vol=109
cd-vols=
no-issue=
article-no=
start-page=239
end-page=249
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200519
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques (APs). We investigated the general and oral conditions from each patient and performed next-generation sequencing (NGS) analysis for all bacterial samples. There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the tongue surface were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. These results suggested that oral bacteria did not affect the formation of atheromatous plaques directly.
en-copyright=
kn-copyright=
en-aut-name=IsoshimaDaichi
en-aut-sei=Isoshima
en-aut-mei=Daichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=YamashiroKeisuke
en-aut-sei=Yamashiro
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MatsunagaKazuyuki
en-aut-sei=Matsunaga
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TaniguchiMakoto
en-aut-sei=Taniguchi
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MatsubaraTakehiro
en-aut-sei=Matsubara
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=OtaShinzo
en-aut-sei=Ota
en-aut-mei=Shinzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=SatoMichiyoshi
en-aut-sei=Sato
en-aut-mei=Michiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=ShimoeYutaka
en-aut-sei=Shimoe
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KohriyamaTatsuo
en-aut-sei=Kohriyama
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=AriasZulema
en-aut-sei=Arias
en-aut-mei=Zulema
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=OmoriKazuhiro
en-aut-sei=Omori
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=YamamotoTadashi
en-aut-sei=Yamamoto
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=TakashibaShogo
en-aut-sei=Takashiba
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Oral Microbiome Center, Taniguchi Dental Clinic
kn-affil=
affil-num=5
en-affil=Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Neurology, Brain Attack Center Ota Memorial Hospital
kn-affil=
affil-num=8
en-affil=Department of Neurology, Brain Attack Center Ota Memorial Hospital
kn-affil=
affil-num=9
en-affil=Department of Neurology, Brain Attack Center Ota Memorial Hospital
kn-affil=
affil-num=10
en-affil=Department of Neurology, Brain Attack Center Ota Memorial Hospital
kn-affil=
affil-num=11
en-affil= Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Microbiome
kn-keyword=Microbiome
en-keyword=Atherosclerosis
kn-keyword=Atherosclerosis
en-keyword=Periodontitis
kn-keyword=Periodontitis
en-keyword=Next-generating sequencing
kn-keyword=Next-generating sequencing
en-keyword=Oral bacteria
kn-keyword=Oral bacteria
END
start-ver=1.4
cd-journal=joma
no-vol=2020
cd-vols=
no-issue=
article-no=
start-page=9349132
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200227
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=DV200 Index for Assessing RNA Integrity in Next-Generation Sequencing
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Poor quality of biological samples will result in an inaccurate analysis of next-generation sequencing (NGS). Therefore, methods to accurately evaluate sample integrity are needed. Among methods for evaluating RNA quality, the RNA integrity number equivalent (RINe) is widely used, whereas the DV200, which evaluates the percentage of fragments of >200 nucleotides, is also used as a quality assessment standard. In this study, we compared the RINe and DV200 RNA quality indexes to determine the most suitable RNA index for the NGS analysis. Seventy-one RNA samples were extracted from formalin-fixed paraffin-embedded tissue samples (n=30), fresh-frozen samples (n=25), or cell lines (n=16). After assessing RNA quality using the RINe and DV200, we prepared two kinds of stranded mRNA sequencing libraries. Finally, we calculated the correlation between each RNA quality index and the amount of library product (1(st) PCR product per input RNA). The DV200 measure showed stronger correlation with the amount of library product than the RINe (R2=0.8208 for the DV200 versus 0.6927 for the RINe). Receiver operating characteristic curve analyses revealed that the DV200 was the better marker for predicting efficient library production than the RINe using a threshold of >10 ng/ng for the amount of the 1(st) PCR product per input RNA (cutoff value for the RINe and DV200, 2.3 and 66.1%; area under the curve, 0.99 and 0.91; sensitivity, 82% and 92%; and specificity, 93% and 100%, respectively). Our results indicate that NGS libraries prepared using RNA samples with the DV200 value>66.1% exhibit greater sensitivity and specificity than those prepared with the RINe values>2.3. These findings suggest that the DV200 is superior to the RINe, especially for low-quality RNA, because it is a more consistent assessment of the amount of the 1(st) NGS library product per input.
en-copyright=
kn-copyright=
en-aut-name=MatsubaraTakehiro
en-aut-sei=Matsubara
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MoritaMizuki
en-aut-sei=Morita
en-aut-mei=Mizuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=UwaboTakahiro
en-aut-sei=Uwabo
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=
en-aut-name=KanazawaSusumu
en-aut-sei=Kanazawa
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=HirasawaAkira
en-aut-sei=Hirasawa
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine
kn-affil=
affil-num=3
en-affil=Department of Biomedical Informatics,Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems
kn-affil=
affil-num=4
en-affil=Department of Biomedical Informatics,Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems
kn-affil=
affil-num=5
en-affil=Department of Biobank, 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 Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=111
cd-vols=
no-issue=3
article-no=
start-page=849
end-page=856
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191219
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=YES1 activation induces acquired resistance to neratinib in HER2-amplified breast and lung cancers
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Molecular-targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2-positive breast cancer. However, acquired resistance of various cancers to molecular-targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib-resistant cell lines from HER2-amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib-resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1-amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2-targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome.
en-copyright=
kn-copyright=
en-aut-name=TakedaTatsuaki
en-aut-sei=Takeda
en-aut-mei=Tatsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MiyauchiShunsaku
en-aut-sei=Miyauchi
en-aut-mei=Shunsaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=ArakiKota
en-aut-sei=Araki
en-aut-mei=Kota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NakataKentaro
en-aut-sei=Nakata
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MiuraAkihiro
en-aut-sei=Miura
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NambaKei
en-aut-sei=Namba
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=\
kn-aut-sei=
kn-aut-mei=\
aut-affil-num=10
ORCID=
en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=ShienTadahiko
en-aut-sei=Shien
en-aut-mei=Tadahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KitamuraYoshihisa
en-aut-sei=Kitamura
en-aut-mei=Yoshihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=SendoToshiaki
en-aut-sei=Sendo
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=breast cancer
kn-keyword=breast cancer
en-keyword=drug resistance
kn-keyword=drug resistance
en-keyword=lung cancer
kn-keyword=lung cancer
en-keyword=neratinib
kn-keyword=neratinib
en-keyword=YES1
kn-keyword=YES1
END
start-ver=1.4
cd-journal=joma
no-vol=110
cd-vols=
no-issue=8
article-no=
start-page=2549
end-page=2557
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190604
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Acquired resistance mechanisms to afatinib in HER2-amplified gastric cancer cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer treatment, especially that for breast and lung cancer, has entered a new era and continues to evolve, with the development of genome analysis technology and the advent of molecular targeted drugs including tyrosine kinase inhibitors. Nevertheless, acquired drug resistance to molecular targeted drugs is unavoidable, creating a clinically challenging problem. We recently reported the antitumor effect of a pan-HER inhibitor, afatinib, against human epidermal growth factor receptor 2 (HER2)-amplified gastric cancer cells. The purpose of the present study was to identify the mechanisms of acquired afatinib resistance and to investigate the treatment strategies for HER2-amplified gastric cancer cells. Two afatinib-resistant gastric cancer cell lines were established from 2 HER2-amplified cell lines, N87 and SNU216. Subsequently, we investigated the molecular profiles of resistant cells. The activation of the HER2 pathway was downregulated in N87-derived resistant cells, whereas it was upregulated in SNU216-derived resistant cells. In the N87-derived cell line, both MET and AXL were activated, and combination treatment with afatinib and cabozantinib, a multikinase inhibitor that inhibits MET and AXL, suppressed the cell growth of cells with acquired resistance both in vitro and in vivo. In the SNU216-derived cell line, YES1, which is a member of the Src family, was remarkably activated, and dasatinib, a Src inhibitor, exerted a strong antitumor effect in these cells. In conclusion, we identified MET and AXL activation in addition to YES1 activation as novel mechanisms of afatinib resistance in HER2-driven gastric cancer. Our results also indicated that treatment strategies targeting individual mechanisms of resistance are key to overcoming such resistance.
en-copyright=
kn-copyright=
en-aut-name=YoshiokaTakahiro
en-aut-sei=Yoshioka
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TakedaTatsuaki
en-aut-sei=Takeda
en-aut-mei=Tatsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakahashiYuta
en-aut-sei=Takahashi
en-aut-mei=Yuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KuriharaEisuke
en-aut-sei=Kurihara
en-aut-mei=Eisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=OgoshiYusuke
en-aut-sei=Ogoshi
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NambaKei
en-aut-sei=Namba
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TorigoeHidejiro
en-aut-sei=Torigoe
en-aut-mei=Hidejiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SatoHiroki
en-aut-sei=Sato
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=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=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Bioinformatics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=afatinib
kn-keyword=afatinib
en-keyword=gastric cancer
kn-keyword=gastric cancer
en-keyword=HER2
kn-keyword=HER2
en-keyword=MET
kn-keyword=MET
en-keyword=YES1
kn-keyword=YES1
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=11
article-no=
start-page=2009
end-page=2018
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=Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction
The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples.
Methods
Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction.
Results
ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes.
Conclusions
High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy.
en-copyright=
kn-copyright=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MatsubaraTakehiro
en-aut-sei=Matsubara
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KayataniHiroe
en-aut-sei=Kayatani
en-aut-mei=Hiroe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SatoAkiko
en-aut-sei=Sato
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NinomiyaTakashi
en-aut-sei=Ninomiya
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=TakataMinoru
en-aut-sei=Takata
en-aut-mei=Minoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Center of Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=18
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Graduate School of Biostudies, Radiation Biology Center, Kyoto University
kn-affil=
affil-num=20
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=21
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=ALK G1202R
kn-keyword=ALK G1202R
en-keyword=Alectinib
kn-keyword=Alectinib
en-keyword=Amphiregulin
kn-keyword=Amphiregulin
en-keyword=MET
kn-keyword=MET
en-keyword=NSCLC
kn-keyword=NSCLC
END
start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=7
article-no=
start-page=627
end-page=640
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=201907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes.
en-copyright=
kn-copyright=
en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SumardikaI Wayan
en-aut-sei=Sumardika
en-aut-mei=I Wayan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=InoueYusuke
en-aut-sei=Inoue
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=IiokaHidekazu
en-aut-sei=Iioka
en-aut-mei=Hidekazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MitsuiYosuke
en-aut-sei=Mitsui
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=
en-aut-name=RumaI Made Winarsa
en-aut-sei=Ruma
en-aut-mei=I Made Winarsa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=SatoHiroki
en-aut-sei=Sato
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YamauchiAkira
en-aut-sei=Yamauchi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=YamamotoKen-ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=KuboMiyoko
en-aut-sei=Kubo
en-aut-mei=Miyoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=PutrantoEndy Widya
en-aut-sei=Putranto
en-aut-mei=Endy Widya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=MurakamiTakashi
en-aut-sei=Murakami
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=LiuMing
en-aut-sei=Liu
en-aut-mei=Ming
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
en-aut-name=HibinoToshihiko
en-aut-sei=Hibino
en-aut-mei=Toshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
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=24
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=25
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
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=27
ORCID=
affil-num=1
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=
affil-num=6
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=
affil-num=7
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=
affil-num=9
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=
affil-num=12
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=17
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=19
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=20
en-affil=Department of Pediatrics, Dr. Sardjito Hospital/Faculty of Medicine, Universitas Gadjah Mada
kn-affil=
affil-num=21
en-affil=Department of Microbiology, Faculty of Medicine, Saitama Medical University
kn-affil=
affil-num=22
en-affil=Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University
kn-affil=
affil-num=23
en-affil=Department of Dermatology, Tokyo Medical University
kn-affil=
affil-num=24
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=25
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=
affil-num=26
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=27
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END