JaLCDOI 10.18926/AMO/52785
FullText URL 68_4_191.pdf
Author Shien, Kazuhiko| Yamamoto, Hiromasa| Soh, Junichi| Miyoshi, Shinichiro| Toyooka, Shinichi|
Abstract Non-small cell lung cancer (NSCLC) harboring an activating mutation within the epidermal growth factor receptor (EGFR) was defined as a clinically distinct molecular group. These lesions show oncogene addiction to EGFR and dramatic responses to the EGFR tyrosine kinase inhibitors (TKIs). Several large Phase III trials have shown that EGFR-TKIs improved the progression-free survival of patients with EGFR mutant NSCLC compared to conventional chemotherapy. However, the long-term effectiveness of EGFR-TKIs is usually limited because of acquired drug resistance. To overcome this resistance to EGFR-TKIs, it will be essential to identify the specific mechanisms underlying the resistance. Many investigators have attempted to identify the mechanisms using preclinical models and drug-resistant clinical samples. As a result, several mechanisms have been showed to be responsible for the resistance, but not all of the relevant mechanisms have been uncovered. In this review, we provide an overview of mechanisms underlying drug-resistance to EGFR-TKIs, focusing on results obtained with preclinical models, and we present some possible strategies to overcome the EGFR-TKI resistance.
Keywords non-small cell lung cancer EGFR mutation tyrosine-kinase inhibitor drug resistance cancer stem cell
Amo Type Review
Published Date 2014-08
Publication Title Acta Medica Okayama
Volume volume68
Issue issue4
Publisher Okayama University Medical School
Start Page 191
End Page 200
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 25145405
Web of Science KeyUT 000340687500001
JaLCDOI 10.18926/AMO/52140
FullText URL 68_1_23.pdf
Author Ueno, Tsuyoshi| Toyooka, Shinichi| Fukazawa, Takuya| Kubo, Takafumi| Soh, Junichi| Asano, Hiroaki| Muraoka, Takayuki| Tanaka, Norimitsu| Maki, Yuho| Shien, Kazuhiko| Furukawa, Masashi| Sakaguchi, Masakiyo| Yamamoto, Hiromasa| Tsukuda, Kazunori| Miyoshi, Shinichiro|
Abstract The microRNA-34s (miR-34s) have p53 response elements in their 5ʼ-flanking regions and demonstrate tumor-suppressive functions. In malignant pleural mesothelioma (MPM), we previously reported that expression of miR-34b and miR-34c (miR-34b/c) was frequently downregulated by methylation in MPM cell lines and primary tumors. The forced overexpression of miR-34b/c showed significant antitumor effects with the induction of apoptosis in MPM cells. In this study, we examined the in vivo antitumor effects of miR-34b/c using adenovirus vector on MPM. We subcutaneously transplanted NCI-H290, a human MPM cell line, into BALB/C mice and injected adenovirus vector expressing miR-34b/c, luciferase driven by the cytomegalovirus promoter (Ad-miR-34b/c or Ad-Luc), or PBS control into tumors over 5mm in diameter. A statistically significant growth inhibition of the tumor volume was observed in the Ad-miR-34b/c group from day 6 onward compared to the Ad-Luc group. The inhibition rate of Ad-miR-34b/c, compared to the tumor volume treated with Ad-Luc, was 58.6% on day 10 and 54.7% on day13. Our results indicate that adenovirus-mediated miR-34b/c gene therapy could be useful for the clinical treatment of MPM.
Keywords mesothelioma microRNA microRNA-34b/c p53
Amo Type Original Article
Published Date 2014-02
Publication Title Acta Medica Okayama
Volume volume68
Issue issue1
Publisher Okayama University Medical School
Start Page 23
End Page 26
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 24553485
Web of Sience KeyUT 000331592800004
Title Alternative The 69th Annual Scientific Meeting of the Japanese Association for Thoracic Surgery
Author Miyoshi, Shinichiro|
Publication Title Journal of Okayama Medical Association
Published Date 2017-04-03
Volume volume129
Issue issue1
Start Page 63
End Page 64
ISSN 0030-1558
language 日本語
Copyright Holders Copyright (c) 2017 岡山医学会
File Version publisher
DOI 10.4044/joma.129.63
Author Muraoka, Takayuki| Soh, Junichi| Toyooka, Shinichi| Aoe, Keisuke| Fujimoto, Nobukazu| Hashida, Shinsuke| Maki, Yuho| Tanaka, Norimitsu| Shien, Kazuhiko| Furukawa, Masashi| Yamamoto, Hiromasa| Asano, Hiroaki| Tsukuda, Kazunori| Kishimoto, Takumi| Otsuki, Takemi| Miyoshi, Shinichiro|
Published Date 2013-12
Publication Title Lung Cancer
Volume volume82
Issue issue3
Content Type Journal Article
Author Maki, Yuho| Soh, Junichi| Ichimura, Kouichi| Shien, Kazuhiko| Furukawa, Masashi| Muraoka, Takayuki| Tanaka, Norimitsu| Ueno, Tsuyoshi| Yamamoto, Hiromasa| Asano, Hiroaki| Tsukuda, Kazunori| Toyooka, Shinichi| Miyoshi, Shinichiro|
Published Date 2013-01
Publication Title Oncology Reports
Volume volume29
Issue issue1
Content Type Journal Article
Author Miyoshi, Shinichiro|
Published Date 2009-12-01
Publication Title 岡山医学会雑誌
Volume volume121
Issue issue3
Content Type Journal Article