Clinical significance of Laminin-332 and its potential as a therapeutic target

• Project/Area Number: 20591572
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: MIYANARI Nobutomo Kumamoto University, 医学部附属病院, 非常勤診療講師 (90336230)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Naoko 熊本大学, 医学部附属病院, 非常勤診療医師 (20452899) ; BABA Hideo 熊本大学, 大学院・生命科学研究部, 教授 (20240905) ; YOSHIDA Naoya 熊本大学, 医学部附属病院, 非常勤診療医師 (60467983)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 食道外科学 / mTOR / RAD001 / ラミミン-332 / 食道癌 / 消化器癌

Research Abstract

Inactivation of the AKT pathway by laminin-332 blocking antibody suppressed the invasiveness of esophageal cancer cell line. The addition of the purified laminin-332 activated the AKT pathway and increased the invasiveness of cell line. These results indicate that Laminin-332 could contribute to the malignant behavior of esophageal cancer through AKT pathway. mTOR is a key molecule in the AKT pathway and is increasingly important as a potential target for anticancer therapy. Thus, we focused on revealing clinical usefulness of mTOR inhibitor in esophageal cancer. p-mTOR overexpression was independently associated with poor prognosis in ESCC, supporting the potential for mTOR as a therapeutic target for ESCC. We are currently performing further in vitro and in vivo study to clarify the antitumor effect of RAD001 (mTOR inhibitor) on ESCC.

Research Products

• [Journal Article] Clinical Significance of Wntinduced Secreted Protein-1 (WISP -1/CCN4) in Esophageal Squamous Cell Carcinoma. (2011)
  • Author(s): Nagai Y, Watanabe M, Ishikawa S, Karashima R, Kurashige J, Iwagami S, Iwatsuki M, Baba Y, Imamura Y, Hayashi N, Baba H.
  • Journal Title: Anticancer Res. 31(3) Pages: 991-997
  • Peer Reviewed
• [Journal Article] Induction chemotherapy with docetaxel/cisplatin/5-fluorouracil for patients with node-positive esophageal cancer. (2011)
  • Author(s): Watanabe M, Nagai Y, Kinoshita K, Saito S, Kurashige J, Karashima R, Hirashima K, Sato N, Imamura Y, Hiyoshi Y, Baba Y, Iwagami S, Miyamoto Y, Iwatsuki M, Hayashi N, Baba H.
  • Journal Title: Digestion. 83(3) Pages: 146-152
  • Peer Reviewed
• [Journal Article] Extensive lymphatic spread of cancer cells in patients with thoracic esophageal squamous cell carcinoma : detection of CEA-mRNA in the three-field lymph nodes. (2010)
  • Author(s): Imamura Y, Hayashi N, Sato N, Kinoshita K, Kurashige J, Saito S, Hirashima K, Karashima R, Hiyoshi Y, Nagai Y, Watanabe M, Baba H.
  • Journal Title: J Surg Oncol. 102(5) Pages: 509-515
  • Peer Reviewed
• [Journal Article] Phosphorylated mTOR expression is associated with poor prognosis for patients with esophageal squamous cell carcinoma. (2010)
  • Author(s): Hirashima K, Baba Y, Watanabe M, Karashima R, Sato N, Imamura Y, Hiyoshi Y, Nagai Y, Hayashi N, Iyama K, Baba H.
  • Journal Title: Ann Surg Oncol. 17(9) Pages: 2486-2493
  • Peer Reviewed
• [Journal Article] p12CDK2-AP1 is associated with tumor progression and a poor prognosis in esophageal squamous cell carcinoma. (2009)
  • Author(s): Hiyoshi Y, Watanabe M, Hirashima K, Karashima R, Sato N, Imamura Y, Nagai Y, Yoshida N, Toyama E, Hayashi N, Baba H.
  • Journal Title: Oncol Rep. 22(1) Pages: 35-39
  • Peer Reviewed
• [Journal Article] Transcervical superior mediastinal lymph node dissection combined with transhiatal lower esophageal dissection before transthoracic esophagectomy : a safe approach for salvage esophagectomy. (2009)
  • Author(s): Watanabe M, Yoshida N, Karashima R, Sato N, Hirashima K, Imamura Y, Hiyoshi Y, Nagai Y, Iwagami S, Toyama E, Hayashi N, Baba H.
  • Journal Title: J Am Coll Surg. 208(4)
  • Peer Reviewed
• [Journal Article] MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. (2009)
  • Author(s): Hiyoshi Y, Kamohara H, Karashima R, Sato N, Imamura Y, Nagai Y, Yoshida N, Toyama E, Hayashi N, Watanabe M, Baba H.
  • Journal Title: Clin Cancer Res. 15(6) Pages: 1915-1922
  • Peer Reviewed
• [Journal Article] The relationship between the glucose transporter type 1 expression and F-fluorodeoxyglucose uptake in esophageal squamous cell carcinoma. (2009)
  • Author(s): Hiyoshi Y, Watanabe M, Imamura Y, Nagai Y, Baba Y, Yoshida N, Toyama E, Hayashi N, Baba H.
  • Journal Title: Oncology. 76(4) Pages: 286-292
  • Peer Reviewed
• [Journal Article] Pattern of Lymph Node Involvement in Proximal Gastric Cancer (2009)
  • Author(s): Ishikawa S
  • Journal Title: World J Surg 33 8 Pages: 1687-1692
  • Peer Reviewed
• [Journal Article] Submucosal tumour in a young girl (2009)
  • Author(s): Hayashi N
  • Journal Title: Gut 58 8 Pages: 1040-1090
  • Peer Reviewed
• [Journal Article] Multiple and metachronous esophageal intramural metastases from a gastric adenocarcinoma. (2008)
  • Author(s): Ikeda O, Toh Y, Aoki Y, Harimoto N, Taomoto J, Masuda T, Ohga T, Adachi E, Sakaguchi Y, Okamura T, Hirahashi M, Nishiyama K, Baba H.
  • Journal Title: Gastric Cancer. 11(2) Pages: 19-22
  • Peer Reviewed
• [Journal Article] The expression of type IV collagen alpha6 chain is related to the prognosis in patients with esophageal squamous cell carcinoma. (2008)
  • Author(s): Yoshifumi Baba
  • Journal Title: Ann Surg Oncol. 15(2) Pages: 555-65
  • Peer Reviewed
• [Journal Article] Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation. (2008)
  • Author(s): Yoshifumi Baba
  • Journal Title: Br J Cancer. 98(5) Pages: 974-80
  • Peer Reviewed
• [Presentation] 食道扁平上皮癌におけるmTOR阻害薬(RAD001)の可能性の検討 (2010)
  • Author(s): 平島浩太郎、渡邊雅之、斉藤誠哉、蔵重淳二、木下浩一、佐藤伸隆、辛島龍一、今村裕、林尚子、馬場秀夫
  • Organizer: 第65回日本消化器外科学会総会
  • Place of Presentation: 下関 下関グランドホテル
  • Year and Date: 2010-07-14
• [Presentation] 食道癌切除症例における在院死亡率の予測 (2010)
  • Author(s): 宮成信友
  • Organizer: 日本外科学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2010-04-08
• [Presentation] Phosphorylated mTOR activation and therapeutic effects of everolimus (RAD001) in esophageal squamous cell carcinoma. (2010)
  • Author(s): Hirashima K, Baba Y, Watanabe M, Sato N, Karashima R, Kurashige J, Imamura Y, Iwatsuki M, Hayashi N,Iyama K, Baba H.
  • Organizer: 7^<th> International symposium on cancer research and therapy (ISCRT)
  • Place of Presentation: 東京 東京会館
• [Presentation] Cerulein induced acute pancreatitis suppress the mTOR activity. (2010)
  • Author(s): Ida S, Ohmuraya M, Hirota M, Nakahara O, Furuhashi S, Abe S, Tanaka H, Horino K, Takamori H, Beppu T, Baba H.
  • Organizer: Joint Meeting of the International Association of Pancreatology and the Japan Pancreas Society 2010.
  • Place of Presentation: 福岡 福岡国際会議場
• [Presentation] Prognostic value of mTOR activation and therapeutic effects of everolimus in esophageal squamous cell carcinoma. (2010)
  • Author(s): Hirashima K, Baba Y, Saito S, Kinoshita K, Satou N, Kurashige J, Karashima R, Imamura Y, Ikeda O, Hayashi N, Watanabe M, Iyama K, Baba H.
  • Organizer: AACR 101^<st> Annual Meeting
  • Place of Presentation: アメリカワシントンWalter E.Washington Convention Center
• [Presentation] 食道扁平上皮癌におけるmTOR発現の意義 (2009)
  • Author(s): 平島浩太郎、渡邊雅之、辛島龍一、佐藤伸隆、日吉幸晴、今村裕、長井洋平、外山栄一郎、林尚子、馬場秀夫
  • Organizer: 第64回日本消化器外科学会総会
  • Place of Presentation: 大阪 リーガロイヤルホテル
  • Year and Date: 2009-07-16
• [Presentation] 当科における食道癌に対するsalvage手術の現状と問題点 (2008)
  • Author(s): 宮成信友
  • Organizer: 第63回日本消化器外科学会総会
  • Place of Presentation: 北海道
  • Year and Date: 2008-07-18
• [Presentation] 食道扁平上皮癌におけるmTOR発現の意義 (2008)
  • Author(s): 平島浩太郎
  • Organizer: 第63回日本消化器外科学会総会
  • Place of Presentation: 北海道
  • Year and Date: 2008-07-17
• [Presentation] E-PASS scoring systemによる高齢者食道癌手術の術後合併症予測 (2008)
  • Author(s): 平島浩太郎
  • Organizer: 第17回日本癌病態治療研究会
  • Place of Presentation: 京都
  • Year and Date: 2008-06-26
• [Presentation] Laminin-332はPI 3K activationを介して食道癌細胞の浸潤能を増加させる (2008)
  • Author(s): 馬場祥史
  • Organizer: 第108回日本外科学会 定期学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2008-05-16
• [Presentation] Laminin-332 promotes the invasion of esophagea1 squamous cell carcinoma via the PI3K activation (2008)
  • Author(s): Baba Y
  • Organizer: AACR Annual Meeting 2008 (第99回米国癌学会議)
  • Place of Presentation: アメリカ(サンディエゴ)
  • Year and Date: 2008-04-14
• [Presentation] Tumor Biology Laminin -332 promotes the invasion of esophageal squamous cell carcinoma via the PI3K activation. (2008)
  • Author(s): Baba Y, Hayashi N, Miyanari N, Iyama K, Baba H.
  • Organizer: AACR Annual Meeting 2008
  • Place of Presentation: アメリカ サンディエゴSandiego Convention Center