Faculty Profiles - KAGAWA Shunsuke

Papers - KAGAWA Shunsuke

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テロメアーゼ特異的制限増殖型アデノウイルスによる末梢血中ヒトがん細胞検出方法の開発(A three-step simple imaging method to detect viable human circulating tumor cells in the peripheral blood)

橋本悠里, 児島亨, 渡邉雄一, 黒田新士, 宇野太, 香川俊輔, 水口裕之, 浦田泰生, 田中紀章, 藤原俊義

日本癌学会総会記事 67回 486 - 486 2008.9

食道癌化学療法中にウェルニッケ脳症を発症した1例

藤原康宏, 猶本良夫, 田辺俊介, 近藤喜太, 河本洋伸, 元木崇之, 宇野太, 香川俊輔, 白川靖博, 山辻知樹, 小林直哉, 藤原俊義, 松原長秀, 松岡順治, 田中紀章

岡山医学会雑誌 120 ( 2 ) 241 - 241 2008.8

EUS-FNA後の出血により緊急手術を行った胃GISTの1例

藤智和, 猶本良夫, 田邊俊介, 近藤喜太, 藤原康宏, 吉田亮介, 野間和広, 櫻間一史, 宇野太, 香川俊輔, 白川靖博, 山辻知樹, 小林直哉, 藤原俊義, 松原長秀, 松岡順治, 田中紀章

岡山医学会雑誌 120 ( 2 ) 249 - 250 2008.8

当科における食道類基底細胞癌切除症例の検討

田辺俊介, 猶本良夫, 近藤喜太, 河本洋伸, 藤原康宏, 櫻間一史, 宇野太, 高岡宗徳, 香川俊輔, 白川靖博, 山辻知樹, 小林直哉, 藤原俊義, 松原長秀, 羽井佐実, 松岡順治, 田中紀章

岡山医学会雑誌 120 ( 2 ) 241 - 241 2008.8

Combination of oncolytic adenovirotherapy and Bax gene therapy in human cancer xenografted models. Potential merits and hurdles for combination therapy

Masayoshi Hioki, Shunsuke Kagawa, Toshiya Fujiwara, Ryo Sakai, Turn Kojima, Yuichi Watanabe, Yuuri Hashimoto, Futoshi Uno, Norialki Tanaka, Toshiyoshi Fujiwara

INTERNATIONAL JOURNAL OF CANCER 122 ( 11 ) 2628 - 2633 2008.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-LISS

Cancer gene therapy and oncolytic virotherapy have been studied extensively. However, their clinical application is hampered by their weak anticancer activity. We previously constructed a replicating adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase (hTERT) promoter drives expression of the adenoviral El genes, and causes selective lysis of human cancer cells. We hypothesized that combination adenoviral therapy containing OBP-301 and a nonreplicating adenovirus expressing the proapoptotic Bax gene could overcome the weakness and augment the anticancer efficacy of each modality. Combination treatment resulted in marked Bax protein expression and enhanced efficacy in in vitro cell viability assay, when compared with either single treatment. However, combination treatment was not as effective in suppressing both subcutaneous and pleural disseminated tumors compared with OBP-301 treatment alone. Further investigation revealed that combination treatment resulted in suppressed EIA protein expression associated with reduced viral replication. Our results suggest that Bax gene therapy in combination with oncolytic adenovirotherapy potentially augments their antitumor activity, but further improvements may be required to maximize the combinatorial effect in vivo, for the Bax gene expression to avoid interference with production of the oncolytic virus. (c) 2008 Wiley-Liss, Inc.

DOI： 10.1002/ijc.23438

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Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation

Y. Endo, R. Sakai, M. Ouchi, H. Onimatsu, M. Hioki, S. Kagawa, F. Uno, Y. Watanabe, Y. Urata, N. Tanaka, T. Fujiwara

ONCOGENE 27 ( 17 ) 2375 - 2381 2008.4

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Dendritic cells ( DCs) are the most potent antigen-presenting cells and acquire cellular antigens and danger signals from dying cells to initiate antitumor immune responses via direct cell- to- cell interaction and cytokine production. The optimal forms of tumor cell death for priming DCs for the release of danger signals are not fully understood. OBP- 301 ( Telomelysin) is a telomerase-specific replication- competent adenovirus that induces selective E1 expression and exclusively kills human cancer cells. Here, we show that OBP- 301 replication produced the endogenous danger signaling molecule, uric acid, in infected human tumor cells, which in turn stimulated DCs to produce interferon-gamma ( IFN-gamma) and interleukin 12 ( IL- 12). Subsequently, IFN-gamma release upregulated the endogenous expression of the proteasome activator PA28 in tumor cells and resulted in the induction of cytotoxic T- lymphocytes. Our data suggest that virus- mediated oncolysis might be the effective stimulus for immature DCs to induce specific activity against human cancer cells.

DOI： 10.1038/sj.onc.1210884

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Establishment of biological and pharmacokinetic assays of telomerase-specific replication-selective adenovirus

Yuuri Hashimoto, Yuichi Watanabe, Yoshiko Shirakiya, Futoshi Uno, Shunsuke Kagawa, Hitoshi Kawamura, Katsuyuki Nagai, Noriaki Tanaka, Horomi Kumon, Yasuo Urata, Toshiyoshi Fujiwara

CANCER SCIENCE 99 ( 2 ) 385 - 390 2008.2

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL PUBLISHING

The use of replication-selective tumor-specific viruses represents a novel approach for the treatment of neoplastic disease. We constructed an attenuated adenovirus, telomerase-specific replication-selective adenovirus (TRAD), in which the human telomerase reverse transcriptase promoter element drives the expression of the E1A and E1B genes linked with an internal ribosome entry site (IRES). Forty-eight hours after TRAD infection at a multiplicity of infection of 1.0, the cell viability of H1299 human lung cancer cells was consistently less than 50% and therefore this procedure could be used as a potency assay to assess the biological activity of TRAD. We also established a quantitative real-time polymerase chain reaction (PCR) analysis with consensus primers for either the adenovirus E1A or IRES sequence. The linear ranges of quantitation with E1A and IRES primers were 10(3)-10(8) and 10(2)-10(8) plaque-forming units/mL in the plasma, respectively. The PCR analysis demonstrated that the levels of E1A in normal tissues were more than 10(3) lower than in the tumors of A549 human lung tumor xenografts in nu/n mu mice at 28 days after intratumoral injection. Our results suggest that the cell-killing assay against H1299 cells and real-time PCR can be used to assess the biological activity and biodistribution of TRAD in clinical trials.

DOI： 10.1111/j.1349-7006.2007.00665.x

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In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus

KISHIMOTO Hiroyuki, KOJIMA Toru, WATANABE Yuichi, KAGAWA Shunsuke, FUJIWARA Toshiya, UNO Futoshi, TERAISHI Fuminori, KYO Satoru, MIZUGUCHI Hiroyuki, HASHIMOTO Yuuri, URATA Yasuo, TANAKA Noriaki, FUJIWARA Toshiyoshi

120 ( 1 ) 13 - 21 2008

腫瘍融解ウイルスによる細胞死であるオンコライシスは細胞内にdanger signalを発生させ、プロテアソームアクチベーター（PA28）発現を増強することで細胞障害性Tリンパ球による免疫応答を活性化する.

遠藤芳克, 酒井亮, 大内正明, 鬼松秀樹, 日置勝義, 香川俊輔, 宇野太, 渡邉雄一, 浦田泰生, 田中紀章, 藤原俊義

岡山医学会雑誌 120 ( 3 ) 259 - 264 2008

Adenomyoma of the stomach presenting as localized peritonitis

Shunsuke Kagawa, Toshiyoshi Fujiwara, Masahiko Nishizaki, Yoshio Naomoto, Isozaki Hiroshi, Noriaki Tanaka

DIGESTIVE DISEASES AND SCIENCES 52 ( 11 ) 3184 - 3187 2007.11

リンパ節微小転移を標的としたテロメラーゼ依存性腫瘍融解ウイルス療法(Telomerase-specific virotherapy targeting lymph node micrometastasis of human cancer)

児島亨, 渡辺雄一, 橋本悠里, 黒田新士, 宇野太, 香川俊輔, 浦田泰生, 田中紀章, 藤原俊義

日本癌学会総会記事 66回 91 - 91 2007.8

テロメラーゼ依存性腫瘍融解ウイルス療法と放射線療法の相互増感作用(Mutual sensitization with telomerase-specific oncolytic virotherapy and ionizing radiation in antitumor activity)

黒田新士, 藤原俊哉, 児島亨, 渡邊雄一, 橋本悠里, 宇野太, 香川俊輔, 浦田泰生, 田中紀章, 藤原俊義

日本癌学会総会記事 66回 385 - 385 2007.8

Advanced gastric adenocarcinoma mimicking a submucosal tumor

F. Teraishi, F. Uno, S. Kagawa, T. Fujiwara, A. Gouchi, N. Tanaka

ENDOSCOPY 39 ( Suppl 1 ) E191 - E192 2007.2

Cisplatin/Docetaxel+同時性放射線照射が奏効し根治手術を施行し得たstage IIIA非小細胞肺癌の1例

寺石文則, 香川俊輔, 宇野太, 武田洋正, 瀧川奈義夫, 藤原俊義, 田中紀章

癌と化学療法 34 ( 9 ) 1493 - 1495 2007

A case of nodular silicosis mimicking metastatic lung tumors

62 ( 9 ) 1269 - 1271 2007

Telomerase-specific replication-selective virotherapy for prostate cancer Reviewed

Kaku Haruki, Nasu Yasutomo, Huang Peng, Saika Takashi, Kagawa Shunsuke, Fujiwara Toshiyoshi, Kumon Hiromi, Urata Yasuo

JOURNAL OF GENE MEDICINE 8 ( 12 ) 1454 2006.12

JNK2 deficient cells acquire high adenoviral infectivity and adenovirus-mediated transgene expression

Fuminori Teraishi, Shunsuke Kagawa, Toshiyoshi Fujiwara, Noriaki Tanaka

JOURNAL OF GENE MEDICINE 8 ( 12 ) 1466 - 1466 2006.12

In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus

Hiroyuki Kishimoto, Toru Kojima, Yuichi Watanabe, Shunsuke Kagawa, Toshiya Fujiwara, Futoshi Uno, Fuminori Teraishi, Satoru Kyo, Hiroyuki Mizuguchi, Yuuri Hashimoto, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara

NATURE MEDICINE 12 ( 10 ) 1213 - 1219 2006.10

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Currently available methods for detection of tumors in vivo such as computed tomography and magnetic resonance imaging are not specific for tumors. Here we describe a new approach for visualizing tumors whose fluorescence can be detected using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401). OBP-401 contains the replication cassette, in which the human telomerase reverse transcriptase (hTERT) promoter drives expression of E1 genes, and the GFP gene for monitoring viral replication. When OBP-401 was intratumorally injected into HT29 tumors orthotopically implanted into the rectum in BALB/c nu/nu mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. Our results indicate that OBP-401 causes viral spread into the regional lymphatic area and selectively replicates in neoplastic lesions, resulting in GFP expression in metastatic lymph nodes. This technology is adaptable to detect lymph node metastasis in vivo as a preclinical model of surgical navigation.

DOI： 10.1038/nm1404

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テロメラーゼ特異的GFP発現ナノバイオ・ウイルス製剤(OBP-401)を用いた微小癌組織のin vivoイメージング・システム

児島亨, 藤原俊義, 岸本浩行, 橋本悠里, 香川俊輔, 宇野太, 浦田泰生, 田中紀章

日本癌学会総会記事 65回 258 - 258 2006.9

Enhanced antitumor efficacy of telomerase-selective oncolytic adenoviral agent OBP-401 with docetaxel: Preclinical evaluation of chemovirotherapy

Toshiya Fujiwara, Shunsuke Kagawa, Hiroyuki Kishimoto, Yoshikatsu Endo, Masayoshi Hioki, Yoshihiro Ikeda, Ryo Sakai, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara

INTERNATIONAL JOURNAL OF CANCER 119 ( 2 ) 432 - 440 2006.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Oncolytic adenoviruses are being developed as novel anticancer therapeutics and currently undergoing clinical trials. We previously demonstrated that telomerase-specific replication-competent adenovirus (Telomelysin: OBP-301), in which the human telomerase reverse transcriptase (hTERT) promoter regulates viral replication, efficiently killed human tumor cells. We further constructed OBP-401 (Telomelysin-GFP) that expresses the green fluorescent protein (GFP) reporter gene under the control of the cytomegalovirus promoter in the E3 region to monitor viral distribution. Here, we examined the feasibility of a single-agent therapy with OBP-401 as well as of combining OBP-401 with chemotherapeutic agents. Infection of OBP-401 alone or followed by the treatment of a chemotherapeutic drug, docetaxel (Taxotere), resulted in a profound in vitro cytotoxicity and GFP expression in various human cancer cell lines originating from different organs (lung, colon, esophagus, stomach, liver and prostate), although the magnitude of antitumor effect varied among the cell types. Other chemotherapeutic drugs such as vinorelbine (Navelbine) and SN38 (the potent active metabolite of irinotecan) combined with OBP-401 also inhibited the growth of human cancer cells. Quantitative real-time PCR analysis demonstrated that docetaxel did not affect viral replication. For in vivo evaluation, nu/nu mice xenografted with H1299 human lung tumor received intratumoral injection of OBP-401 and intraperitoneal administration of docetaxel. Analysis of growth of implanted tumors showed a significant, therapeutic synergism, although OBP-401 alone and docetaxel alone showed modest inhibition of tumor growth. Thus, OBP-401 in combination with docetaxel efficiently enhances the antitumor efficacy both in vitro and in vivo, and the outcome has important implications for tumor-specific oncolytic chemovirotherapies for human cancers. (c) 2006 Wiley-Liss, Inc.

DOI： 10.1002/ijc.21846

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