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

Laminin-332 的临床意义及其作为治疗靶点的潜力

• 批准号: 20591572
• 负责人: MIYANARI Nobutomo
• 金额: $ 3.08万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591572/
• 关键词: 食道外科学; mTOR; RAD001; ラミミン-332; 食道癌; 消化器癌

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.

层粘连蛋白-332阻断抗体灭活AKT通路可抑制食管癌细胞系的侵袭力。加入纯化的层粘连蛋白-332激活了AKT通路并增加了细胞系的侵袭力。提示Laminin-332可能通过AKT通路参与食管癌的恶性行为。mTOR是AKT通路中的关键分子，并且作为抗癌治疗的潜在靶点越来越重要。因此，我们专注于揭示mTOR抑制剂在食管癌中的临床有用性。p-mTOR过表达与ESCC预后不良独立相关，支持mTOR作为ESCC治疗靶点的潜力。我们目前正在进行进一步的体外和体内研究，以阐明RAD 001（mTOR抑制剂）对ESCC的抗肿瘤作用。

项目成果

Pattern of Lymph Node Involvement in Proximal Gastric Cancer

• DOI: 10.1007/s00268-009-0083-6
• 发表时间: 2009-08-01
• 期刊: WORLD JOURNAL OF SURGERY
• 影响因子: 2.6
• 作者: Ishikawa, Shinji;Shimada, Shinya;Baba, Hideo
• 通讯作者: Baba, Hideo

Phosphorylated mTOR Expression is Associated with Poor Prognosis for Patients with Esophageal Squamous Cell Carcinoma

• DOI: 10.1245/s10434-010-1040-1
• 发表时间: 2010-09-01
• 期刊: ANNALS OF SURGICAL ONCOLOGY
• 影响因子: 3.7
• 作者: Hirashima, Kotaro;Baba, Yoshifumi;Baba, Hideo
• 通讯作者: Baba, Hideo

Clinical significance of Wnt-induced secreted protein-1 (WISP-1/CCN4) in esophageal squamous cell carcinoma.

• 发表时间: 2011-03
• 期刊: Anticancer research
• 影响因子: 2
• 作者: Y. Nagai;Masayuki Watanabe;S. Ishikawa;R. Karashima;J. Kurashige;S. Iwagami;M. Iwatsuki;Y. Baba;Y. Imamura;N. Hayashi;H. Baba

Transcervical superior mediastinal lymph node dissection combined with transhiatal lower esophageal dissection before transthoracic esophagectomy: a safe approach for salvage esophagectomy.

经胸食管切除术前经颈上纵隔淋巴结清扫术联合经裂孔下食管清扫术：挽救性食管切除术的安全方法。

• DOI: 10.1016/j.jamcollsurg.2009.01.018
• 发表时间: 2009
• 期刊: Journal of the American College of Surgeons
• 影响因子: 5.2
• 作者: Masayuki Watanabe;N. Yoshida;R. Karashima;N. Sato;K. Hirashima;Y. Imamura;Y. Hiyoshi;Y. Nagai;S. Iwagami;E. Toyama;N. Hayashi;H. Baba
• 通讯作者: H. Baba

The expression of type IV collagen alpha6 chain is related to the prognosis in patients with esophageal squamous cell carcinoma.

IV型胶原α6链的表达与食管鳞癌患者的预后相关。

• 发表时间: 2008
• 期刊: Annals Surgical Oncology 15
• 作者: Osawa Y;Nagaki M;Ikeda K;Baba Y
• 通讯作者: Baba Y