Author Putranto, Endy Widya| Murata, Hitoshi| Yamamoto, Ken-Ichi| Kataoka, Ken| Yamada, Hidenori| Futami, Jun-Ichiro| Sakaguchi, Masakiyo| Huh, Nam-Ho|
Published Date 2013-10
Publication Title International Journal of Molecular Medicine
Volume volume32
Issue issue4
Content Type Journal Article
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
Author Tanimoto, Ryuta| Sakaguchi, Masakiyo| Abarzua, Fernando| Kataoka, Ken| Kurose, Kaoru| Murata, Hitoshi| Nasu, Yasutomo| Kumon, Hiromi| Huh, Nam-Ho|
Published Date 2010-04-01
Publication Title International Journal of Cancer
Volume volume126
Issue issue7
Content Type Journal Article
Author 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|
Published Date 2009-05-22
Publication Title The Journal of Biological Chemistry
Volume volume284
Issue issue21
Content Type Journal Article
JaLCDOI 10.18926/AMO/48076
FullText URL 66_1_7.pdf
Author Kawauchi, Keiichiro| Watanabe, Masami| Kaku, Haruki| Huang, Peng| Sasaki, Kasumi| Sakaguchi, Masakiyo| Ochiai, Kazuhiko| Huh, Nam-ho| Nasu, Yasutomo| Kumon, Hiromi|
Abstract 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.
Keywords REIC Dickkopf-3 gene therapy prostate cancer preclinical study
Amo Type Original Article
Published Date 2012-02
Publication Title Acta Medica Okayama
Volume volume66
Issue issue1
Publisher Okayama University Medical School
Start Page 7
End Page 16
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2012 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 22358134
Web of Sience KeyUT 000300800700002
Author 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|
Published Date 2011-08-26
Publication Title Biochemical and Biophysical Research Communications
Volume volume412
Issue issue2
Content Type Journal Article
JaLCDOI 10.18926/AMO/31719
FullText URL fulltext.pdf
Author Kondo, Asami| Sakaguchi, Masakiyo| Makino, Eiichi| Namba, Masayoshi| Okada, Shigeru| Huh, Nam-ho|
Abstract <p>Using 2-dimensional gel electrophoresis, we previously demonstrated that the S100C protein remarkably decreased after immortalization of normal human fibroblasts, and that this protein caused growth inhibition of human tumor cells when forcibly expressed in these cells, suggesting that S100C plays a significant role in tumor suppression. The present study was carried out to determine what type of human tissues express S100C protein, and, subsequently, whether the S100C content in these tissues changes after normal cells have been transformed into cancer cells. We found that ductal cells in various tissues were positively stained with the S100C protein. In comparison, epithelial cells in digestive organs such as the stomach, small intestine, and colon were not stained as strongly. When 14 pairs of human normal and cancerous tissues were stained with the antibody, decreases in the staining levels of S100C were observed in 6 kinds of cancerous tissues--from the bronchus, mammary duct, renal tubule, prostate, uterus, and testis--in comparison with staining in their normal counterparts. These results suggest that S100C is a new tumor marker protein, the expression of which significantly decreases after malignant transformation of human tissues.</p>
Keywords S100C-antibody human tissues immunostaining
Amo Type Article
Published Date 2002-02
Publication Title Acta Medica Okayama
Volume volume56
Issue issue1
Publisher Okayama University Medical School
Start Page 31
End Page 34
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 11873942
Web of Sience KeyUT 000174031300006
JaLCDOI 10.18926/AMO/30945
FullText URL fulltext.pdf
Author 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|
Abstract <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>
Keywords REIC/Dkk-3 bladder cancer apoptosis Bcl-2
Amo Type Original Article
Published Date 2008-12
Publication Title Acta Medica Okayama
Volume volume62
Issue issue6
Publisher Okayama University Medical School
Start Page 393
End Page 401
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
Web of Sience KeyUT 000262025000006
Author 阪口 政清|
Published Date 2001-03-25
Publication Title
Content Type Thesis or Dissertation