Faculty Profiles - KAGAWA Shunsuke

Papers - KAGAWA Shunsuke

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腹腔鏡下胃切除術におけるリンパ節郭清のコツ da Vinci手術からLADGへのfeedback 幽門下リンパ節郭清

西崎正彦, 香川俊輔, 宇野太, 石田道拡, 黒田新士, 岸本浩行, 白川靖博, 藤原俊義

日本胃癌学会総会記事 85回 202 - 202 2013.2

A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus.

Sasaki T, Tazawa H, Hasei J, Osaki S, Kunisada T, Yoshida A, Hashimoto Y, Yano S, Yoshida R, Kagawa S, Uno F, Urata Y, Ozaki T, Fujiwara T

Gene Ther 2013

我々の目指すチーム内視鏡外科当科における腹臥位胸腔鏡下食道亜全摘における術者助手のコラボレーション Reviewed

野間和広, 白川靖博, 青山克幸, 前田直見, 大原利章, 田辺俊介, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 17 ( 7 ) 604 - 604 2012.12

Robotic Surgeryによる胃切除 Double bipolar techniqueによる術野展開の工夫と郭清手技

西崎正彦, 石田道拡, 黒田新士, 岸本浩行, 宇野太, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 17 ( 7 ) 296 - 296 2012.12

Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells

Ryosuke Yoshida, Hiroshi Tazawa, Yuuri Hashimoto, Shuya Yano, Teppei Onishi, Tsuyoshi Sasaki, Yasuhiro Shirakawa, Hiroyuki Kishimoto, Futoshi Uno, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

CANCER IMMUNOLOGY IMMUNOTHERAPY 61 ( 11 ) 1905 - 1916 2012.11

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

Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive breast and gastric cancers; however, acquired resistance presents a formidable obstacle to long-term tumor responses in the majority of patients. Here, we show the mechanism of resistance to trastuzumab in HER2-positive human cancer cells and explore the molecular sensitization by exogenous expression of HER2-extracellular domain (ECD) in HER2-negative or trastuzumab-resistant human cancer cells. We found that long-term exposure to trastuzumab induced resistance in HER2-positive cancer cells; HER2 expression was downregulated, and antibody-dependent cellular cytotoxicity (ADCC) activity was impaired. We next examined the hypothesis that trastuzumab-resistant cells could be re-sensitized by the transfer of non-functional HER2-ECD. Exogenous HER2-ECD expression induced by the stable transfection of a plasmid vector or infection with a replication-deficient adenovirus vector had no apparent effect on the signaling pathway, but strongly enhanced ADCC activity in low HER2-expressing or trastuzumab-resistant human cancer cells. Our data indicate that restoration of HER2-ECD expression sensitizes HER2-negative or HER2-downregulated human cancer cells to trastuzumab-mediated ADCC, an outcome that has important implications for the treatment of human cancers.

DOI： 10.1007/s00262-012-1249-x

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[A case of transverse myelopathy due to spinal bone metastasis of gastric cancer].

Aiko Kono, Shunsuke Kagawa, Hiroyuki Kishimoto, Futoshi Uno, Masahiko Nishizaki, Masahiko Oiwa, Toshiyoshi Fujiwara

Gan to kagaku ryoho. Cancer & chemotherapy 39 ( 12 ) 2357 - 9 2012.11

Language：Japanese Publishing type：Research paper (scientific journal)

We report a case of gastric cancer that presented as transverse myelopathy due to spinal bone metastasis. A 45-year- old man with advanced gastric cancer underwent distal gastrectomy and lymph node dissection for curative intent. However, pathological examination of the specimen revealed positive cytological findings in the peritoneal lavage fluid in addition to serosal invasion and lymph node metastasis(pT4aN3bCY1, stage IV). Three months after the operation, during the second course of chemotherapy with S-1, he began to complain of back pain, and positron emission tomography-computed tomography revealed spinal bone metastasis. Despite immediate radiotherapy for the bone metastasis, he soon suffered from paraplegia in the lower extremities followed by disturbances of bladder and bowel function. We created a sigmoid colostomy, which enabled self-care for defecation, and resumed radiotherapy and chemotherapy. Bone metastasis of gastric cancer is rare but the prognosis is very poor. Because of a rapidly deteriorating clinical course, early diagnosis and multidisciplinary approaches are important for gastric cancer patients with spinal metastasis.

PubMed

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[Stent placement using a double-balloon endoscope for malignant duodenal obstruction with Roux-en-Y Anastomosis-a case report].

Masahiko Oiwa, Shunsuke Kagawa, Hiroyuki Kishimoto, Futoshi Uno, Masahiko Nishizaki, Aiko Kono, Toshiyoshi Fujiwara

Gan to kagaku ryoho. Cancer & chemotherapy 39 ( 12 ) 2372 - 4 2012.11

Language：Japanese Publishing type：Research paper (scientific journal)

A 79-year-old man who had previously undergone partial resection of the remnant stomach and Roux-en-Y reconstruction was diagnosed as having peritoneal recurrence near the ligament of Treitz. In the course of chemotherapy for recurrent gastric cancer, he complained of colic pain. CT examination revealed a marked dilation of the duodenum suggesting the presence of a distal duodenal stricture resulting from the known recurrent tumor. To palliate this intestinal obstruction, we successfully placed an expandable metal stent(EMS) using a double-balloon enteroscope(DBE), which achieved immediate relief of the obstruction and enabled the resumption of oral intake and chemotherapy. While the endoscopic placement of an EMS is available for malignant gastro-intestinal obstruction, it is considerably more difficult to approach the duodenum with Roux-en-Y anastomosis. A DBE has made it possible to place an EMS deep in the small intestine. In the present case, this minimally invasive procedure avoided the need for surgery and greatly contributed to palliation. Thus, EMS placement using a DBE is a possible palliative treatment for malignant small bowel obstruction.

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当科における食道胃接合部癌に対する再建法の工夫胸腔内観音開き法吻合の経験 Reviewed

野間和広, 白川靖博, 青山克幸, 前田直見, 大原利章, 田辺俊介, 西崎正彦, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 73 ( 増刊 ) 525 - 525 2012.10

出血性ショックをきたした回腸静脈瘤破裂に対しバルーン下逆行性経静脈的塞栓術(BRTO)が奏功した1例

濱田侑紀, 竹原裕子, 竹原清人, 大原利章, 近藤喜太, 永坂岳司, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 73 ( 増刊 ) 1084 - 1084 2012.10

腹腔鏡下胃全摘術・噴門切除術とその再建術式腹腔鏡補助下噴門側胃切除術のための「観音開き法」食道残胃吻合の工夫

西崎正彦, 石田道拡, 黒田新士, 岸本浩行, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 73 ( 増刊 ) 372 - 372 2012.10

コンポジットメッシュと非吸収性タックを用い腹腔鏡下にて修復した腹壁瘢痕ヘルニアの一例

石田道拡, 香川俊輔, 岸本浩行, 黒田新士, 西崎正彦, 藤原俊義

日本臨床外科学会雑誌 73 ( 増刊 ) 947 - 947 2012.10

A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression

Yasumoto Yamasaki, Hiroshi Tazawa, Yuuri Hashimoto, Toru Kojima, Shinji Kuroda, Shuya Yano, Ryosuke Yoshida, Futoshi Uno, Hiroyuki Mizuguchi, Akira Ohtsuru, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

EUROPEAN JOURNAL OF CANCER 48 ( 14 ) 2282 - 2291 2012.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Oncolytic viruses engineered to replicate in tumour cells but not in normal cells could be used as tumour-specific vectors carrying the therapeutic genes. We previously developed a telomerase-specific oncolytic adenovirus, OBP-301, that causes cell death in human cancer cells with telomerase activities. Here, we further modified OBP-301 to express the wild-type p53 tumour suppressor gene (OBP-702), and investigated whether OBP-702 induces stronger antitumour activity than OBP-301. The antitumour effect of OBP-702 was compared to that of OBP-301 on OBP-301-sensitive (H358 and H460) and OBP-301-resistant (T.Tn and HSC4) human cancer cells. OBP-702 suppressed the viability of both OBP-301-sensitive and OBP-301-resistant cancer cells more efficiently than OBP-301. OBP-702 caused increased apoptosis compared to OBP-301 or a replication-deficient adenovirus expressing the p53 gene (Ad-p53) in H358 and T.Tn cells. Adenovirus E1A-mediated p21 and MDM2 downregulation was involved in the apoptosis caused by OBP-702. Moreover, OBP-702 significantly suppressed tumour growth in subcutaneous tumour xenograft models compared to monotherapy with OBP-301 or Ad-p53. Our data demonstrated that OBP-702 infection expressed adenovirus E1A and then inhibited p21 and MDM2 expression, which in turn efficiently induced apoptotic cell death. This novel apoptotic mechanism suggests that the p53-expressing OBP-702 is a promising antitumour reagent for human cancer and could improve the clinical outcome. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejca.2011.12.020

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腫瘍特異的制限増殖型アデノウイルスを用いた血液循環腫瘍細胞の遺伝子解析技術の開発(Development of genetic analysis of circulating tumor cells using a telomerase-specific replication-competent adenovirus) Reviewed

重安邦俊, 橋本悠里, 宇野太, 永坂岳司, 田澤大, 香川俊輔, 水口裕之, 浦田泰生, 藤原俊義

日本癌学会総会記事 71回 50 - 50 2012.8

テロメラーゼ依存性増殖型アデノウイルス製剤を用いた早期大腸癌の低侵襲治療の開発(Less invasive therapeutic intervention for early colorectal cancers using telomerase-dependent replicating adenovirus)

菊地覚次, 岸本浩行, 田澤大, 橋本悠里, 宇野太, 西崎正彦, 香川俊輔, 浦田泰生, ロバート・ホフマン, 藤原俊義

日本癌学会総会記事 71回 202 - 202 2012.8

耐術能を有する超高齢者は胃癌に対する手術の意義が示唆される Reviewed

香川俊輔, 宇野太, 岸本浩行, 西崎正彦, 白川靖博, 永坂岳司, 野間和広, 田辺俊介, 近藤喜太, 大原利章

日本消化器外科学会総会 67回 3 - 3 2012.7

がん特異的増殖アデノウイルス製剤OBP-401を用いた生体内癌組織蛍光イメージング

岸本浩行, 菊地覚次, 橋本悠里, 宇野太, 田澤大, 西崎正彦, 香川俊輔, 藤原俊義

日本消化器外科学会総会 67回 1 - 1 2012.7

ロボット支援下胃切除術の術野展開と郭清手技

西崎正彦, 香川俊輔, 宇野太, 岸本浩行, 藤原俊義

日本消化器外科学会総会 67回 1 - 1 2012.7

The hTERT Promoter Enhances the Antitumor Activity of an Oncolytic Adenovirus under a Hypoxic Microenvironment

Yuuri Hashimoto, Hiroshi Tazawa, Fuminori Teraishi, Toru Kojima, Yuichi Watanabe, Futoshi Uno, Shuya Yano, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

PLOS ONE 7 ( 6 ) 2012.6

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin), in which the human telomerase reverse transcriptase (hTERT) promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5). In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen) or a hypoxic (1% oxygen) condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1 alpha and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells.

DOI： 10.1371/journal.pone.0039292

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ロボット支援下幽門側胃切除術の安全な導入 Reviewed

西崎正彦, 香川俊輔, 宇野太, 岸本浩行, 近藤喜太, 田邊俊介, 大原利章, 野間和広, 永坂岳志, 白川靖博, 藤原俊義

日本外科学会雑誌 113 ( 臨増2 ) 490 - 490 2012.3

消化管間質腫瘍における血中浮遊腫瘍細胞検出の試み Reviewed

宇野太, 重安邦俊, 永坂岳司, 香川俊輔, 西崎正彦, 岸本浩行, 藤原俊義

日本外科学会雑誌 113 ( 臨増2 ) 369 - 369 2012.3

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Papers - KAGAWA Shunsuke