研究者詳細 - 香川　俊輔

論文 - 香川　俊輔

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In Vivo Biological Purging for Lymph Node Metastasis of Human Colorectal Cancer by Telomerase-Specific Oncolytic Virotherapy

Toru Kojima, Yuichi Watanabe, Yuuri Hashimoto, Shinji Kuroda, Yasumoto Yamasaki, Shuya Yano, Masaaki Ouchi, Hiroshi Tazawa, Futoshi Uno, Shunsuke Kagawa, Satoru Kyo, Hiroyuki Mizuguchi, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara

ANNALS OF SURGERY 251 ( 6 ) 1079 - 1086 2010年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Background/Objective: The aim of this study was to develop a less invasive way of targeting lymph node metastasis for the treatment of human gastrointestinal cancer. Lymphatic invasion is a major route for cancer cell dissemination, and adequate treatment of locoregional lymph nodes is required for curative treatment in patients with malignancies.
Methods: Human telomerase reverse transcription (hTERT) is the catalytic subunit of telomerase, which is highly active in cancer cells but quiescent in most normal somatic cells. OBP-301 (Telomelysin) is an attenuated adenovirus with oncolytic potency that contains the hTERT promoter element to regulate viral replication. We examined whether OBP-301 injected into the primary tumor might be useful for purging micrometastasis from regional lymph nodes in an orthotopic colorectal cancer model.
Results: OBP-301 was intratumorally injected into HT29 tumors orthotopically implanted into the rectum in BALB/c nu/nu mice. By using a highly sensitive quantitative PCR analysis that targets the human-specific Alu sequence, we showed that OBP-301 caused viral spread into the regional lymphatic area and selectively replicated in neoplastic lesions, resulting in tumor-cell-specific death in metastatic lymph nodes. Moreover, although the surgical removal of primary tumors increased the tendency of lymph node metastasis, preoperative intratumoral injection of virus significantly reduced lymph node metastasis.
Conclusions: Our results indicate that intratumoral injection of OBP-301 mediates effective in vivo purging of metastatic tumor cells from regional lymph nodes, which may help optimize treatment of human cancer, especially gastrointestinal malignancies.

DOI： 10.1097/SLA.0b013e3181deb69d

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A novel translational approach for human malignant pleural mesothelioma: heparanase-assisted dual virotherapy

Y. Watanabe, T. Kojima, S. Kagawa, F. Uno, Y. Hashimoto, S. Kyo, H. Mizuguchi, N. Tanaka, H. Kawamura, D. Ichimaru, Y. Urata, T. Fujiwara

ONCOGENE 29 ( 8 ) 1145 - 1154 2010年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that is related to asbestos exposure. MPM is characterized by rapid and diffuse local growth in the thoracic cavity, and it has a poor prognosis because it is often refractory to conventional therapy. Although MPM is an extraordinarily challenging disease to treat, locoregional virotherapy may be useful against this aggressive disease because of the accessibility by intrapleural virus delivery. In this study, we show that telomerase-specific, replication-selective adenovirus OBP-301 can efficiently infect and kill human mesothelioma cells by viral replication. Intrathoracic administration of virus significantly reduced the number and size of human mesothelioma tumors intrathoracically implanted into nu/nu mice. A high-definition, fluorescence optical imaging system with an ultra-thin, flexible fibered microprobe clearly detected intracellular replication of green fluorescent protein-expressing oncolytic virus in intrathoracically established mesothelioma tumors. As the extracellular matrix (ECM) may contribute to the physiological resistance of a solid tumor by preventing the penetration of therapeutic agents (including oncolytic viruses), we also examined whether the co-expression of heparanase, an endoglucuronidase capable of specifically degrading heparan sulfate, that influences the physiological barrier to macromolecule penetration, can modify the permeability of the ECM, resulting in profound therapeutic efficacy. Co-injection of OBP-301 and a replication-defective adenovirus (Ad-S/hep)-expressing heparanase resulted in more profound antitumor effects without apparent toxicity in an orthotopic pleural dissemination model. Our results suggest that intrathoracic dual virotherapy with telomerase-specific oncolytic adenovirus in combination with heparanase-expressing adenovirus may be efficacious in the prevention and treatment of pleural dissemination of human malignant mesothelioma. Oncogene (2010) 29, 1145-1154; doi: 10.1038/onc.2009.415; published online 23 November 2009

DOI： 10.1038/onc.2009.415

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当院における内視鏡的胃瘻造設の現況

田辺俊介, 白川靖博, 近藤喜太, 藤原康宏, 野間和広, 宇野太, 永坂岳司, 香川俊輔, 山辻知樹, 小林直哉, 藤原俊義, 内藤稔, 猶本良夫

岡山医学会雑誌 121 ( 3 ) 230 - 231 2009年12月

腹腔鏡補助下胃切除術における術野展開の工夫

香川俊輔, 宇野太, 合地明, 小林直哉, 山辻知樹, 白川靖博, 永坂岳司, 野間和広, 藤原康宏, 田辺俊介, 近藤喜太, 猶本良夫, 藤原俊義

日本内視鏡外科学会雑誌 14 ( 7 ) 562 - 562 2009年12月

A simple biological imaging system for detecting viable human circulating tumor cells

Toru Kojima, Yuuri Hashimoto, Yuichi Watanabe, Shunsuke Kagawa, Futoshi Uno, Shinji Kuroda, Hiroshi Tazawa, Satoru Kyo, Hiroyuki Mizuguchi, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara

JOURNAL OF CLINICAL INVESTIGATION 119 ( 10 ) 3172 - 3181 2009年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC CLINICAL INVESTIGATION INC

The presence of circulating tumor cells (CTCs) in the peripheral blood is associated with short survival, making the detection of CTCs clinically useful as a prognostic factor of disease outcome and/or a surrogate marker of treatment response. Recent technical advances in immunocytometric analysis and quantitative real-time PCR have made it possible to detect a few CTCs in the blood; however, there is no sensitive assay to specifically detect viable CTCs. Here, we report what we believe to be a new approach to visually detect live human CTCs among millions of peripheral blood leukocytes, using a telomerase-specific replication-selective adenovirus expressing GFP. First, we constructed a GFP-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication (OBP-401; TelomeScan). We then used OBP-401 to establish a simple ex vivo method that was able to detect viable human CTCs in the peripheral blood. The detection method involved a 3-step procedure, including the lysis of rbc, the subsequent addition of OBP-401 to the cell pellets, and an automated scan using fluorescence microscopy. OBP-401 infection increased the signal-to-background ratio as a tumor-specific probe, because the fluorescent signal was amplified only in viable, infected human tumor cells, by viral replication. This GFP-expressing virus-based method is remarkably simple and allows precise enumeration of CTCs.

DOI： 10.1172/JCI38609

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進行再発大腸癌に対するセツキシマブの治療経験

藤原康宏, 猶本良夫, 近藤喜太, 田辺俊介, 桜間一史, 野間和広, 高岡宗徳, 宇野太, 永坂岳司, 香川俊輔, 白川靖博, 山辻知樹, 小林直哉, 藤原俊義, 松岡順治, 田中紀章, 羽井佐実

岡山医学会雑誌 121 ( 2 ) 133 - 133 2009年8月

テロメラーゼ依存的制限増殖型GFP発現アデノウイルスによる末梢血中ヒト循環がん細胞の検出(A simple biological imaging method for detection of viable human circulating tumor cells in the blood)

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

日本癌学会総会記事 68回 244 - 244 2009年8月

当科におけるバレット食道癌症例の検討

野間和広, 猶本良夫, 田辺俊介, 近藤喜太, 藤原康宏, 櫻間一史, 高岡宗徳, 宇野太, 永坂岳司, 香川俊輔, 白川靖博, 山辻知樹, 小林直哉, 藤原俊義, 松岡順治, 田中紀章, 羽井佐実

岡山医学会雑誌 121 ( 2 ) 133 - 133 2009年8月

食道原発小細胞癌の一治療例の報告

田辺俊介, 猶本良夫, 近藤喜太, 藤原康宏, 野間和広, 櫻間一史, 高岡宗徳, 宇野太, 永坂岳司, 香川俊輔, 白川靖博, 山辻知樹, 小林直哉, 藤原俊義, 松岡順治, 田中紀章, 羽井佐実

岡山医学会雑誌 121 ( 2 ) 132 - 132 2009年8月

ゲノム研究が切り開く肺がんの新たな予防・治療戦略肺癌に対する遺伝子およびベクターを用いた分子治療(Novel therapeutic and preventive strategies blazed by genome research on lung cancer Gene and Vector-based Molecular Therapy for Lung Cancer)

香川俊輔, 黒田新士, 宇野太, 田澤大, 浦田泰生, 藤原俊義

日本癌学会総会記事 68回 56 - 56 2009年8月

分子標的薬治療中のOncologic emergencyに対する対応

山辻知樹, 猶本良夫, 西谷正史, 田辺俊介, 近藤喜太, 藤原康宏, 野間和広, 櫻間一史, 高岡宗徳, 宇野太, 香川俊輔, 白川靖博, 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 121 ( 1 ) 65 - 65 2009年4月

イマチニブ抵抗性GISTに対するスニチニブの使用経験

藤原康宏, 田辺俊介, 猶本良夫, 西谷正史, 近藤喜太, 野間和広, 櫻間一史, 高岡宗徳, 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 121 ( 1 ) 64 - 64 2009年4月

当科における胃機能温存食道切除再建術の工夫

野間和広, 藤原康宏, 田辺俊介, 猶本良夫, 西谷正史, 近藤喜太, 櫻間一史, 高岡宗徳, 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, 羽井佐実, 松岡順治, 田中紀章

岡山医学会雑誌 121 ( 1 ) 66 - 66 2009年4月

オーバーチューブによる頸部食道穿孔に対して手術を施行した2症例の検討

田辺俊介, 猶本良夫, 西谷正史, 近藤喜太, 藤原康宏, 野間和広, 櫻間一史, 高岡宗徳, 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, 羽井佐実, 松岡順治, 田中紀章

岡山医学会雑誌 121 ( 1 ) 65 - 66 2009年4月

A Novel Antiangiogenic Effect for Telomerase-Specific Virotherapy through Host Immune System 査読

Yoshihiro Ikeda, Toru Kojima, Shinji Kuroda, Yoshikatsu Endo, Ryo Sakai, Masayoshi Hioki, Hiroyuki Kishimoto, Futoshi Uno, Shunsuke Kagawa, Yuichi Watanabe, Yuuri Hashimoto, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara

JOURNAL OF IMMUNOLOGY 182 ( 3 ) 1763 - 1769 2009年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC IMMUNOLOGISTS

Soluble factors in the tumor microenvironment may influence the process of angiogenesis; a process essential for the growth and progression of malignant tumors. In this study, we describe a novel antiangiogenic effect of conditional replication-selective adenovirus through the stimulation of host immune reaction. An attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase promoter element drives expression of El genes, could replicate in and cause selective lysis of cancer cells. Mixed lymphocyte-tumor cell culture demonstrated that OBP-301-infected cancer cells stimulated PBMC to produce IFN-gamma into the supernatants. When the supernatants were subjected to the assay of in vitro angiogenesis, the tube formation of HUVECs was inhibited more efficiently than recombinant IFN-gamma. Moreover, in vivo angiogenic assay using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice showed that tumor cell-induced neovascularization was markedly reduced when the chambers contained the mixed lymphocyte-tumor cell culture supernatants. The growth of s.c. murine colon tumors in syngenic mice was significantly inhibited due to the reduced vascularity by intratumoral injection of OBP-301. The antitumor as well as antiangiogenic effects, however, were less apparent in SCID mice due to the lack of host immune responses. Our data suggest that OBP-301 seems to have antiangiogenic properties through the stimulation of host immune cells to produce endogenous antiangiogenic factors such as IFN-gamma. The Journal of Immunology, 2009, 182: 1763-1769.

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早期胃癌に対する腹腔鏡補助下胃切除術―導入初期18例の検討

香川俊輔, 宇野太, 合地明, 藤原康宏, 田辺俊介, 近藤喜太, 楳田祐三, 小林直哉, 猶本良夫, 田中紀章

日本外科系連合学会雑誌 34 ( 2 ) 151 - 156 2009年

記述言語：日本語出版者・発行元：日本外科系連合学会

目的:2006年より導入した腹腔鏡補助下胃切除術(laparoscope-assisted gastrectomy:LAG)と開腹下胃切除術(open gastrectomy:OG)との比較により,われわれのLAGの妥当性を検討した.方法:胃中下部の早期胃癌を適応とし,2006年3月より2008年8月まで18例に対して腹腔鏡補助下に幽門保存胃切除術(pylorus preserving gastrectomy:PPG),幽門側胃切除術(distal gastrectomy:DG),分節胃切除術(segmental gastrectomy:SEG)を行ったが,これらの術後成績をOG 50例と比較した.結果:LADGを7例,LAPPGを10例,LASEGを1例に行い,OG症例より手術時間はLAGで80分長く,出血量は約200ml少なかった.排ガス,および解熱までの日数は約1日早かった.経口摂取時期,在院日数に有意差はなかった.結語:LAGは安全に施行でき,今後推進していくに足るものと考えられる.(著者抄録)

DOI： 10.4030/jjcs.34.151

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J01066&link_issn=&doc_id=20090609200004&doc_link_id=10.4030%2Fjjcs.34.151&url=https%3A%2F%2Fdoi.org%2F10.4030%2Fjjcs.34.151&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

腹腔鏡補助下手術を施行した大腸内視鏡検査で発見された回腸カルチノイド腫瘍の一例

小林直哉, 香川俊輔, 近藤喜太, 楳田祐三, 西谷正史, 山辻知樹, 白川靖博, 田辺俊介, 藤原康宏, 宇野太, 猶本良夫, 田中紀章, 堀井城一朗, 川野誠司, 浦岡俊夫, 平岡佐規子, 加藤順, 岡田裕之, 山本和秀, 大原信哉, 市村浩一, 大森昌子, 森谷行利

外科治療 100 ( 2 ) 212 - 215 2009年

記述言語：日本語出版者・発行元：(株)永井書店

症例は61歳男性で検診にて便潜血反応を指摘され、精検の大腸内視鏡では大腸に特記すべき所見は認めなかったが、回腸終末部(バウヒン弁から3cm口側)に10mm大の粘膜下腫瘍様突起を認め、生検所見から回腸カルチノイド腫瘍と診断された。入院時、血液・生化学試験は正常範囲で、腹部CTでは造影にて回腸末端部位に造影効果を有する10mm大の腫瘍像を認め、小腸内視鏡では多発病変は認めなかった。治療は腹腔鏡補助下に第2群リンパ節郭清D2+回盲部切除術を施行、切除標本は10×10mm大で漿膜への露出は認めず、術後経過良好で10日目に退院となった。病理組織学的所見では腫瘍は粘膜下層を主座に増生し、表層は一部粘膜内、深部は固有筋層から一部漿膜下層への浸潤を認め、深達度SSで第1群リンパ節転移陽性、脈管侵襲陽性(ly1・v1)であった。主体は異型を伴うカルチノイド腫瘍像で、最近の分類では高分化神経内分泌癌(well differentiated neuroendocrine carcinoma、G2、T3、N1、Stage IIIBに相当した。

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テロメラーゼ依存性腫瘍融解アデノウイルスによる放射線感受性増強 E1B55kDaによるATMリン酸化阻害(Radiosensitization by telomerase-specific oncolytic adenovirus via E1B 55kDa-mediated inhibition of ATM phosphorylation)

黒田新士, 藤原俊哉, 矢野修也, 山崎泰源, 児島亨, 宇野太, 香川俊輔, 田澤大, 橋本悠里, 大内正明, 浦田泰生, 田中紀章, 藤原俊義

日本癌学会総会記事 67回 90 - 90 2008年9月

胃癌幹細胞に対する新規治療テロメラーゼ特異的腫瘍融解ウイルス治療(A Novel Telomerase-Specific Oncolytic Virotherapy Targeting Human Gastric Cancer Stem Cells)

矢野修也, 橋本悠里, 山崎泰源, 黒田新士, 児島亨, 田澤大, 宇野太, 香川俊輔, 大内正明, 浦田泰生, 田中紀章, 藤原俊義

日本癌学会総会記事 67回 73 - 74 2008年9月

当院における早期胃癌に対する腹腔鏡補助下胃切除術と開腹胃切除術との比較検討

香川俊輔, 宇野太, 合地明, 松原長秀, 小林直哉, 山辻知樹, 白川靖博, 藤原康宏, 近藤喜太, 田辺俊介, 猶本良夫, 藤原俊義, 田中紀章

日本内視鏡外科学会雑誌 13 ( 7 ) 232 - 232 2008年9月

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