著者 Putranto, Endy Widya| Murata, Hitoshi| Yamamoto, Ken-Ichi| Kataoka, Ken| Yamada, Hidenori| Futami, Jun-Ichiro| Sakaguchi, Masakiyo| Huh, Nam-Ho|
発行日 2013-10
出版物タイトル International Journal of Molecular Medicine
32巻
4号
資料タイプ 学術雑誌論文
JaLCDOI 10.18926/AMO/52140
フルテキストURL 68_1_23.pdf
著者 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|
抄録 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.
キーワード mesothelioma microRNA microRNA-34b/c p53
Amo Type Original Article
発行日 2014-02
出版物タイトル Acta Medica Okayama
68巻
1号
出版者 Okayama University Medical School
開始ページ 23
終了ページ 26
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
著作権者 CopyrightⒸ 2014 by Okayama University Medical School
論文のバージョン publisher
査読 有り
Submission Path amo/vol68/iss1/4
PubMed ID 24553485
Web of Sience KeyUT 000331592800004
著者 Tanimoto, Ryuta| Sakaguchi, Masakiyo| Abarzua, Fernando| Kataoka, Ken| Kurose, Kaoru| Murata, Hitoshi| Nasu, Yasutomo| Kumon, Hiromi| Huh, Nam-Ho|
発行日 2010-04-01
出版物タイトル International Journal of Cancer
126巻
7号
資料タイプ 学術雑誌論文
著者 Sakaguchi, Masakiyo| Kataoka, Ken| Abarzua, Fernando| Tanimoto, Ryuta| Watanabe, Masami| Murata, Hitoshi| Than, Swe Swe| Kurose, Kaoru| Kashiwakura, Yuji| Ochiai, Kazuhiko| Nasu, Yasutomo| Kumon, Hiromi| Huh, Nam-ho|
発行日 2009-05-22
出版物タイトル The Journal of Biological Chemistry
284巻
21号
資料タイプ 学術雑誌論文
JaLCDOI 10.18926/AMO/48076
フルテキストURL 66_1_7.pdf
著者 Kawauchi, Keiichiro| Watanabe, Masami| Kaku, Haruki| Huang, Peng| Sasaki, Kasumi| Sakaguchi, Masakiyo| Ochiai, Kazuhiko| Huh, Nam-ho| Nasu, Yasutomo| Kumon, Hiromi|
抄録 The preclinical safety and therapeutic efficacy of adenoviral vectors that express the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) was examined for use in prostate cancer gene therapy. The Ad-human (h) and mouse (m) REIC were previously demonstrated to induce strong anti-cancer effects in vitro and in vivo, and we herein report the results of two in vivo studies. First, intra-tumor Ad-hREIC administration was examined for toxicity and therapeutic effects in a subcutaneous tumor model using the PC3 prostate cancer cell line. Second, intra-prostatic Ad-mREIC administration was tested for toxicity in normal mice. The whole-body and spleen weights, hematological and serum chemistry parameters, and histological evaluation of tissues from throughout the body were analyzed. Both experiments indicated that there was no significant difference in the examined parameters between the Ad-REIC-treated group and the control (PBS- or Ad-LacZ-treated) group. In the in vitro analysis using PC3 cells, a significant apoptotic effect was observed after Ad-hREIC treatment. Confirming this observation, the robust anti-tumor efficacy of Ad-hREIC was demonstrated in the in vivo subcutaneous prostate cancer model. Based on the results of these preclinical experiments, we consider the adenovirus-mediated REIC/Dkk-3 in situ gene therapy to be safe and useful for the clinical treatment of prostate cancer.
キーワード REIC Dickkopf-3 gene therapy prostate cancer preclinical study
Amo Type Original Article
発行日 2012-02
出版物タイトル Acta Medica Okayama
66巻
1号
出版者 Okayama University Medical School
開始ページ 7
終了ページ 16
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
著作権者 CopyrightⒸ 2012 by Okayama University Medical School
論文のバージョン publisher
査読 有り
Submission Path amo/vol66/iss1/2
PubMed ID 22358134
Web of Sience KeyUT 000300800700002
著者 Ochiai, Kazuhiko| Watanabe, Masami| Ueki, Hideo| Huang, Peng| Fujii, Yasuyuki| Nasu, Yasutomo| Noguchi, Hirofumi| Hirata, Takeshi| Sakaguchi, Masakiyo| Huh, Nam-ho| Kashiwakura, Yuji| Kaku, Haruki| Kumon, Hiromi|
発行日 2011-08-26
出版物タイトル Biochemical and Biophysical Research Communications
412巻
2号
資料タイプ 学術雑誌論文
著者 Kondo, Asami| Sakaguchi, Masakiyo| Makino, Eiichi| Namba, Masayoshi| Okada, Shigeru| Huh, Nam-ho|
発行日 2002-02
出版物タイトル Acta Medica Okayama
56巻
1号
資料タイプ 学術雑誌論文
JaLCDOI 10.18926/AMO/30945
フルテキストURL fulltext.pdf
著者 Kobayashi, Tomoko| Sakaguchi, Masakiyo| Tanimoto, Ryuta| Abarzua, Fernando| Takaishi, Mikiro| Kaku, Haruki| Kataoka, Ken| Saika, Takashi| Nasu, Yasutomo| Miyazaki, Masahiro| Kumon, Hiromi| Huh, Nam-ho|
抄録 <p>We have recently shown that a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC) is effective against various human cancers, including those of prostate, testis and breast origins. The aim of the present study was to examine the sensitivity of bladder cancers to Ad-REIC and to clarify the molecular mechanisms that determine sensitivity/resistance. We found that 2 human bladder cancer cell lines, T24 and J82, are resistant to Ad-REIC. In T24 and J82 cells, the ER stress response and activation of JNK were observed in a manner similar to that in the sensitive PC3 cells. Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells. Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines. Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis. The results indicate that some human bladder cancers are resistant to apoptosis induced by overexpression of REIC/Dkk-3, which is at least in part due to up-regulation of Bcl-2. These results provide a basis for possible use of Bcl-2 as a marker of sensitive cancers and to try to sensitize resistant cancers to Ad-REIC by down-regulation of Bcl-2.</p>
キーワード REIC/Dkk-3 bladder cancer apoptosis Bcl-2
Amo Type Original Article
発行日 2008-12
出版物タイトル Acta Medica Okayama
62巻
6号
出版者 Okayama University Medical School
開始ページ 393
終了ページ 401
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
論文のバージョン publisher
査読 有り
Submission Path amo/vol62/iss6/6
Web of Sience KeyUT 000262025000006
著者 阪口 政清|
発行日 2001-03-25
出版物タイトル
資料タイプ 学位論文