Therapeutic effect of suppresion of lymphatic invasion by regulating epithelial-mesenchymal transition in gastric cancer

• Project/Area Number: 25462037
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Keio University
• Principal Investigator: Wada Norihito 慶應義塾大学, 医学部, 講師 (40256087)
• Co-Investigator(Kenkyū-buntansha): HAYASHIDA Tetsu 慶應義塾大学, 医学部, 専任講師 (80327543)
• Co-Investigator(Renkei-kenkyūsha): KATO Fumihiko 慶應義塾大学, 医学部, 助教 (90573428)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 胃癌 / リンパ節転移 / リンパ管新生 / ＨＯＸＢ９ / 上皮間葉移行 / 浸潤能 / 幹細胞性 / リンパ管密度

Outline of Final Research Achievements

In this study, we investigated the therapeutic effect of suppression of lymphatic invasion by regulating epithelial-mesenchymal transition (EMT) in gastric cancer. Clinicopathological study using gastric cancer specimen revealed that patients with HOXB9 expression have higher node metastasis and vascular/lymphovascular infiltration. HOXB9 positive group had worse overall survival, as well. We established a gastric cancer cell line TMK-1 with HOXB9 gene and showed higher level of lymphangiogenic factors using RT-PCR. HOXB9 would be a promising molecule which could suppress the gastric cancer progression in the aspect of lymphatic invasion.

Research Products

• [Journal Article] Sentinel lymph node mapping for 385 gastric cancer patients. (2016)
  • Author(s): Niihara M, Takeuchi H, Nakahara T, Saikawa Y, Takahashi T, Wada N, Mukai M, Kitagawa Y.
  • Journal Title: J Surg Res Volume: 200 Issue: 1 Pages: 73-81
  • DOI: 10.1016/j.jss.2015.06.064
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Auxiliary diagnosis of lymph node metastasis in early gastric cancer using quantitative evaluation of sentinel node radioactivity. (2016)
  • Author(s): Kamiya S, Takeuchi H, Nakahara T, Niihara M, Nakamura R, Takahashi T, Wada N, Kawakubo H, Saikawa Y, Omori T, Murakami K, Kitagawa Y.
  • Journal Title: Gastric Cancer Volume: 印刷中
  • NAID: 40020959230
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical significance of the anterosuperior lymph nodes along the common hepatic artery identified by sentinel node mapping in patients with gastric cancer. (2016)
  • Author(s): Shimada A, Takeuchi H, Kamiya S, Fukuda K, Nakamura R, Takahashi T, Wada N, Kawakubo H, Saikawa Y, Omori T, Nakahara T, Jinzaki M, Murakami K, Kitagawa Y.
  • Journal Title: Gastric Cancer Volume: 印刷中
  • NAID: 40020959245
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Surgical Resection of Remnant Gastric Cancer Following Distal Gastrectomy: A Retrospective Clinicopathological Study. (2016)
  • Author(s): Takahashi M, Takeuchi H, Tsuwano S, Nakamura R, Takahashi T, Wada N, Kawakubo H, Saikawa Y, Kitagawa Y.
  • Journal Title: Ann Surg Oncol Volume: 23 Issue: 2 Pages: 511-521
  • DOI: 10.1245/s10434-015-4678-x
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phase I study of S-1 plus fractional cisplatin as adjuvant chemotherapy for advanced gastric cancer in an outpatient setting (KOGC-03). (2015)
  • Author(s): Takahashi T, Saikawa Y, Fukuda K, Nakamura R, Wada N, Kawakubo H, Takeuchi H, Takaishi H, Kitagawa Y.
  • Journal Title: Anticancer Res Volume: 35 Pages: 467-471
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] (Pro)renin receptor blocker improves survival of rats with sepsis. (2014)
  • Author(s): Hirano Y, Takeuchi H, Suda K, Hagiwara T, Miyasho T, Kawamura Y, Yamada S, Oyama T, Takahashi T, Wada N, Saikawa Y, Ichihara A, Kitagawa Y.
  • Journal Title: J Surg Res Volume: 186 Issue: 1 Pages: 269-277
  • DOI: 10.1016/j.jss.2013.08.004
  • Peer Reviewed
• [Journal Article] The neutrophil elastase inhibitor sivelestat suppresses accelerated gastrointestinal tumor growth via peritonitis after cecal ligation and puncture. (2013)
  • Author(s): Kumagai K, Saikawa Y, Takeuchi H, Suda K, Fukuda K, Nakamura R, Takahashi T, Kawakubo H, Wada N, Miyasho T, Kitagawa Y.
  • Journal Title: Anticancer Res Volume: 33 Pages: 3653-3659
  • Peer Reviewed
• [Journal Article] Clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma (2013)
  • Author(s): Ogura M, Takeuchi H, Kawakubo H, Nishi T, Fukuda K, Nakamura R, Takahashi T, Wada N, Saikawa Y, Omori T, Miyasho T, Yamada S, and Kitagawa Y
  • Journal Title: Surgery Volume: 154 Issue: 3 Pages: 512-520
  • DOI: 10.1016/j.surg.2013.06.013
  • Peer Reviewed
• [Journal Article] Clinical utility of preoperative evaluation of bronchial arteries by three-dimensional computed tomographic angiography for esophageal cancer surgery. (2013)
  • Author(s): Wada T, Takeuchi H, Kawakubo H, Nakamura R, Oyama T, Takahashi T, Wada N, Saikawa Y, Omori T, Jinzaki M, Kuribayashi S, Kitagawa Y.
  • Journal Title: Dis Esophagus Volume: 26 Issue: 6 Pages: 616-622
  • DOI: 10.1111/dote.12012
  • Peer Reviewed
• [Journal Article] Establishment and characterization of novel cell lines and xenografts from patients with gastrointestinal stromal tumors. (2013)
  • Author(s): Fukuda K, Saikawa Y, Sako H, Yoshimura Y, Takahashi T, Wada N, Kawakubo H, Takeuchi H, Ohmori T, Kitagawa Y.
  • Journal Title: Oncol Rep Volume: 30 Issue: 1 Pages: 71-78
  • DOI: 10.3892/or.2013.2425
  • Peer Reviewed
• [Presentation] Reduced port approach for laparoscopic repair of abdominal wall hernia (2016)
  • Author(s): Norihito Wada
  • Organizer: Society of American Gastrointestinal and Endoscopic Surgeons
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-03-18
  • Int'l Joint Research / Invited
• [Presentation] Feasibility and outcomes of hernia repair in patients over 80 years old (2015)
  • Author(s): Wada N, Furukawa T, Kitagawa Y
  • Organizer: International Society of Surgery
  • Place of Presentation: Bangkok,Thailand
  • Year and Date: 2015-08-27
  • Int'l Joint Research
• [Presentation] Clinical results of single incision laparoscopic totally extraperitoneal inguinal hernia repair under local anesthesia with overnight stay (2015)
  • Author(s): Wada N, Furukawa T, Kitagawa Y
  • Organizer: International Association for Ambulatory Surgery
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-05-11
  • Int'l Joint Research
• [Presentation] Clinical results of a single-institution experience in single-port laparoscopic totally extraperitoneal inguinal hernia repair under local anesthesia with conscious sedation (2015)
  • Author(s): Wada N, Furukawa T, Kitagawa Y
  • Organizer: 1st World Conference on Abdominal Wall Hernia Surgery
  • Place of Presentation: Milan, Italy
  • Year and Date: 2015-04-27
  • Int'l Joint Research
• [Presentation] Single Port TEP without Balloon and Tacks Performed Under Local Anesthesia (2014)
  • Author(s): Wada N, Furukawa T, Kitagawa Y
  • Organizer: American Hernia Society
  • Place of Presentation: Las Vegas, USA
• [Presentation] Feasibility of single incision endoscopic totally extraperitoneal hernia surgery under local anesthesia (2013)
  • Author(s): Wada N, Furukawa T, Kitagawa Y
  • Organizer: International Society of Surgery
  • Place of Presentation: Helsinki, Finland
• [Presentation] HOXB9 expression and gastric cancer progression (2013)
  • Author(s): Fumihiko Kato, Norihito Wada, Tetsu Hayashida, Yuji Kikuchi, Kazumasa Fukuda, Rieko Nakamura, Tsunehiro Takahashi, Hirofumi Kawakubo, Hiroya Takeuchi, Yoshiro Saikawa, Yuko Kitagawa
  • Organizer: The 4th JCA-AACR Special Joint Conference: The Latest Advances in Gastric Cancer Research: From Basic Science to Therapeutics
  • Place of Presentation: Maihama, Chiba, Japan
• [Presentation] Functional evaluation of postoperative stomach using double-contrast (2013)
  • Author(s): N. Wada, M. Tsutsui, S. Mayanagi,
  • Organizer: International Gastric Cancer Congress
  • Place of Presentation: Verona, Italy
• [Presentation] Development and Expansion of Ambulatory Surgery in Japan (2013)
  • Author(s): Norihito Wada
  • Organizer: International Association for Ambulatory Surgery
  • Place of Presentation: Budapest, Hungary
  • Invited
• [Book] 今日の治療指針2014年版 (2014)
  • Author(s): 和田則仁、古川俊治
  • Total Pages: 5
  • Publisher: 医学書院
• [Remarks] 慶應義塾大学医学部一般・消化器外科
  • URL: http://keiosurg.umin.jp/ggs/
• [Remarks] 和田則仁ホームページ
  • URL: http://plaza.umin.ac.jp/~nori/
• [Patent(Industrial Property Rights)] 処置具挿入補助具 (2014)
  • Inventor(s): 和田則仁
  • Industrial Property Rights Holder: 学校法人慶應義塾、株式会社トップ
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-01-15