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
JaLCDOI 10.18926/AMO/46629
FullText URL 65_3_179.pdf
Author Teramen, Hirotake| Tsukuda, Kazunori| Tanaka, Norimitsu| Ueno, Tsuyoshi| Kubo, Takafumi| Ando, Midori| Soh, Junichi| Asano, Hiroaki| Pass, Harvery I.| Toyooka, Shinichi| Miyoshi, Shinichiro|
Abstract Suppression of p21 has been implicated in the genesis and progression of many human malignancies. DNA methylation is an important mechanism of gene silencing in human malignancies. In this study, we examined the expression status and aberrant methylaion of p21 in lung cancers and malignant pleural mesotheliomas (MPM). We used 12 small cell lung cancer (SCLC) cell lines, 13 non-small cell lung cancer (NSCLC) cell lines, 50 primary NSCLCs, 6 MPM cell lines and 10 primary MPMs. The expression and methylation of p21 was examined by reverse transcription-PCR (RT-PCR), Western blotting and methylation-specific PCR (MSP) assay. Loss of p21 protein expression was observed in 7 SCLC cell lines (58.3%), 5 NSCLC cell lines (38.5%) and 3 MPM cell lines (50%) while mRNA expression was lost in 2 SCLC cell lines (16.7%), 2 NSCLC cell lines (15.4%) and none of the MPM cell lines. Aberrant methylation of p21 was found in 8.3% of SCLC cell lines, 30.2% of NSCLCs and 6.3% of MPMs. Among primary NSCLCs, methylation in adenocarcinomas was significantly more frequent than in squamous cell carcinomas. Loss of p21 expression was frequently observed in lung cancers and MPMs and aberrant methylation was one of the mechanisms of suppression of p21, especially in NSCLCs.
Keywords p21 methylation lung cancer mesothelioma
Amo Type Original Article
Published Date 2011-06
Publication Title Acta Medica Okayama
Volume volume65
Issue issue3
Publisher Okayama University Medical School
Start Page 179
End Page 184
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2011 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 21709715
Web of Science KeyUT 000292017500004
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
Title Alternative The 69th Annual Scientific Meeting of the Japanese Association for Thoracic Surgery
FullText URL 129_63.pdf
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
NAID 130005632076
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