The mechanism of acquisition of cancer metastatic capacity in peritoneal free cancer cells disseminated by cancer surgery and development of treatment for these cancer cells

• Project/Area Number: 15K10096
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Murata Satoshi 滋賀医科大学, 医学部, 講師 (90239525)
• Co-Investigator(Kenkyū-buntansha): 山本 寛 滋賀医科大学, 医学部, 非常勤講師 (00283557) ; 山口 剛 滋賀医科大学, 医学部, 助教 (10510290) ; 谷 眞至 滋賀医科大学, 医学部, 教授 (60236677) ; 清水 智治 滋賀医科大学, 医学部, 准教授 (70402708) ; 三宅 亨 滋賀医科大学, 医学部, 助教 (70581924)
• Research Collaborator: KODAMA Hirokazu ; TAKEBAYASHI Katsushi ; ARIKAWA Ikuko ; YAMAMOTO Miho
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 腹膜転移 / 腹腔内遊離癌細胞 / 癌幹細胞 / 腹腔内治療 / 腹腔内がん細胞 / 腹腔内癌細胞 / 上皮間葉転換 / 手術侵襲

Outline of Final Research Achievements

The purpose of the study was to elucidate the mechanism of peritoneal recurrences after curative gastric cancer (GC) surgery, and also to develop an effective therapy for source of cancer recurrence. Viable cancer cells that could cause peritoneal recurrence existed in the invasive serosa surface, lymphatic or blood vessels, and also in the residual gastric lumen after gastrectomy. These cancer cells contained cancer stem-like cells expressing CD44, and cancer recurrence occurred only in cases where cancer cells were detected in the intraperitoneal lavage fluid during GC surgery. Hyperthermic intraperitoneal chemotherapy (HIPEC) targeting intraoperatively spilled cancer cells significantly inhibited postoperative recurrence. GC surgery disseminated cancer cells including cancer stem-like cells into the peritoneal cavity, and these spilled cancer cells have been the source of cancer recurrence. We found that this source of cancer recurrence can be effectively treated by HIPEC.

Research Products

• [Journal Article] Feasibility and safety of hyperthermic intraperitoneal chemotherapy using 5-fluorouracil combined with cisplatin and mitomycin C in patients undergoing gastrectomy for advanced gastric cancer (2017)
  • Author(s): Murata Satoshi、Yamamoto Hiroshi、Naitoh Hiroyuki、Yamaguchi Tsuyoshi、Kaida Sachiko、Shimizu Tomoharu、Shiomi Hisanori、Naka Shigeyuki、Tani Tohru、Tani Masaji
  • Journal Title: Journal of Surgical Oncology Volume: 116 Issue: 8 Pages: 1159-1165
  • DOI: 10.1002/jso.24771
  • Peer Reviewed
• [Journal Article] 5-fluorouracil combined with cisplatin and mitomycin C as an optimized regimen for hyperthermic intraperitoneal chemotherapy in gastric cancer (2017)
  • Author(s): Murata Satoshi、Yamamoto Hiroshi、Shimizu Tomoharu、Naitoh Hiroyuki、Yamaguchi Tsuyoshi、Kaida Sachiko、Takebayashi Katsushi、Miyake Toru、Tani Tohru、Tani Masaji
  • Journal Title: Journal of Surgical Oncology Volume: 117 Issue: 4 Pages: 671-677
  • DOI: 10.1002/jso.24906
  • Peer Reviewed
• [Journal Article] 腹腔内遊離癌細胞の検出 (2017)
  • Author(s): 村田聡、谷眞至
  • Journal Title: 外科 Volume: 79 Pages: 907-914
• [Journal Article] Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer. (2017)
  • Author(s): Kodama H, Murata S, Ishida M, Yamamoto H, Yamaguchi T, Kaida S, Miyake T, Takebayashi K, Kushima R, Tani M.
  • Journal Title: Br J Cancer Volume: 116 Issue: 2 Pages: 186-194
  • DOI: 10.1038/bjc.2016.401
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Viable cancer cells in the remnant stomach are a potential source of peritoneal metastasis after curative distal gastrectomy for gastric cancer (2016)
  • Author(s): Satoshi Murata, Hiroshi Yamamoto, Tsuyoshi Yamaguchi, Sachiko Kaida, Mitsuaki Ishida, Tomoharu Shimizu, Toru Miyake, Tohru Tani, Ryoji Kushima, Masaji Tani.
  • Journal Title: Ann Surg Oncol Volume: 未 Issue: 9 Pages: 2920-2927
  • DOI: 10.1245/s10434-016-5219-y
  • Peer Reviewed
• [Presentation] Peritoneal liquid biopsy used to predict cancer recurrence after gastrointestinal cancer surgery. (2018)
  • Author(s): Satoshi Murata, Katsushi Takebayashi, Tsuyoshi Yamaguchi, Sachiko Kaida, Hirokazu Kodama, Hiroya Akabori, Hiroya Iida, Naomi Kitamura, Hiromitsu Maehira, Haruki Mori, Toru Miyake, Yuki Kawai, Tsuyoshi Mori, Tomoyuki Ueki, Hiromichi Sonoda, Soichiro Tani, Yoshitaka Terada, Tomoharu Shimizu, Yataro Daigo, Masaji Tani
  • Organizer: ASCO annual meeting 2018
  • Int'l Joint Research
• [Presentation] A source of cancer stem-like cells that cause peritoneal metastasis after gastric cancer surgery (2018)
  • Author(s): 村田 聡,竹林 克士,児玉 泰一,山口 剛,貝田 佐知子,石田 光明,三宅 亨,北村 直美,植木 智之,飯田 洋也,前平 博允,園田 寛道,生田 大二,清水 智治,九嶋 亮治,谷 眞至
  • Organizer: 第90回日本胃癌学会総会
• [Presentation] Pathophysiology and therapeutic strategy for peritoneal recurrence after gastric cancer surgery (2017)
  • Author(s): Satoshi Murata, Katsushi Takebayashi, Hiroshi Yamamoto, Tsuyoshi Yamaguchi, Sachiko Kaida, Hirokazu Kodama, Reiko Ohtake, Tomoharu Shimizu, Tsuyoshi Mori, Yuki Kawai, Naomi Kitamura, Toru Miyake, Hiroya Akabori, Hiroya Iida, Tomoyuki Ueki, Hiromichi Sonoda, Haruki Mori, Nobuhito Nitta, Shigeyuki Naka, Masaji Tani
  • Organizer: ASCO annual meeting 2017
  • Int'l Joint Research
• [Presentation] 胃癌切除後腹腔内がん細胞検出による再発リスク予測と、術中腹腔内治療による再発予防 (2017)
  • Author(s): 村田 聡、竹林克士、山口 剛、貝田佐知子、児玉泰一、山本 寛、河合由紀、森 毅、飯田洋也、北村直美、前平博充、三宅 亨、植木智之、清水智治、谷 眞至
  • Organizer: 第55回日本癌治療学会学術集会
• [Presentation] Intraoperative adjuvant HIPEC prevents hepatic recurrence as well as peritoneal recurrence after curative gastrectomy for an advanced gastric cancer. (2016)
  • Author(s): Satoshi Murata, Sachiko Kaida, Hirokazu Kodama, Tsuyoshi Yamaguchi, Katsushi Takebayashi, Reiko Ohtake, Hiroshi Yamamoto, Masaji Tani
  • Organizer: The 10th International Congress on Peritoneal Surface Malignancies
  • Place of Presentation: Washington, DC.
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Prevents Hepatic Recurrence after Curative Gastrectomy for Advanced Gastric Cancer (2016)
  • Author(s): Satoshi Murata, Tsuyoshi Yamaguchi, Sachiko Kaida, Katsushi Takebayashi, Hiroya Akabori, Hiroya Iida, Hiromichi Sonoda, Toru Miyake, Tomoharu Shimizu, Hiroshi Yamamoto, Masaji Tani
  • Organizer: 40th World Congress of the International College of Surgeons
  • Place of Presentation: Kyoto
  • Year and Date: 2016-10-23
  • Int'l Joint Research
• [Presentation] 胃癌浸潤最深部におけるCD44陽性癌幹細胞の存在と臨床的意義 (2016)
  • Author(s): 児玉泰一 村田聡 石田光明 Pham Minh Ngoc 三宅亨 梅田朋子 北村直美 河合由紀 山口剛 貝田佐知子 竹林克士 山本寛 谷眞至
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] A propensity-matched analysis comparing hepatic recurrence after curative gastrectomy followed by adjuvant HIPEC to surgery alone for advanced gastric cancer. (2016)
  • Author(s): Satoshi Murata, Sachiko Kaida, Hirokazu Kodama, Hiroshi Yamamoto, Tsuyoshi Yamaguchi, Reiko Ohtake, Masaji Tani
  • Organizer: 2016 ASCO Annual Meeting
  • Place of Presentation: Chicago
  • Year and Date: 2016-06-02
  • Int'l Joint Research
• [Presentation] 消化器癌治癒手術後の再発メカニズムと再発予防に関する研究 (2016)
  • Author(s): 村田 聡，山本 寛，山口 剛，貝田 佐知子，仲 成幸，赤堀 浩也，村上 耕一郞，北村 直美，三宅 亨，児玉 泰一，油木 純一，新田 信人，清水 智治，園田 寛道，太田 裕之，植木 智之，梅田 朋子，森 毅，河合 由紀，竹林 克士，谷 眞至
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-04-14
• [Presentation] 胃癌手術時の消化管再建における腹腔内癌細胞散布の危険性について (2015)
  • Author(s): 村田 聡，山本 寛，山口 剛，貝田 佐知子，石田 光明，竹林 克士，塩見 尚礼，仲 成幸，清水 智治，園田 寛道，太田 裕之，目片 英治，九嶋 亮治，谷 徹，谷 眞至
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2015-10-29
• [Patent(Industrial Property Rights)] 胃癌患者の予後の検査方法 (2016)
  • Inventor(s): 村田 聡、谷 眞至
  • Industrial Property Rights Holder: 村田 聡、谷 眞至
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-234200
  • Filing Date: 2016-12-01