Analysis of abnormal signaling through KIT and PDGFRA in development of gastrointestinal stromal tumors

胃肠道间质瘤发生过程中 KIT 和 PDGFRA 异常信号传导分析

• 批准号: 17013082
• 负责人: HIROTA Seiichi
• 金额: $ 30.08万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17013082/
• 关键词: GIST; 遺伝子異常; c-kit; PDGFR; 多発性GIST; ノックインマウス; カハールの介在細胞; c-kit遺伝子; 生殖系列; 機能獲得性突然変異; exon 17; 二次耐性; exon17; マスト細胞性腫瘍; 傍細胞膜領域; チロシンキナーゼ領域

We made a model mouse of human family with multiple gastrointestinal stromal tumors and germline exon 17-type c-kit gene mutation. The heterozygous and homozygous model mice had a cecal GIST-like tumor and hyperplasia of interstitial cells of Cajal at stomach and colon. The phenotypes were similar with those observed in previously reported model mice with exon 11 or exon 13 c-kit gene mutation. A molecular targeted drug, imatinib, which inhibits constitutively activated mutant KIT was given to the model mice, and we observed inhibition of both tumor growth and KIT activation. We also examined an effect of another molecular targeted drug, nilotinib, which inhibits constitutively activated mutant KIT on tumor growth and KIT activation, and now the manuscript is in preparation.

我们建立了一个人源性多发性胃肠道间质瘤模型小鼠，该模型小鼠具有c-kit基因外显子17型突变。杂合子和纯合子模型小鼠具有盲肠GIST样肿瘤和胃和结肠的Cajal间质细胞增生。这些表型与先前报道的c-kit基因11号外显子或13号外显子突变模型小鼠的表型相似。一种分子靶向药物，伊马替尼，抑制组成型激活突变KIT给予模型小鼠，我们观察到肿瘤生长和KIT激活的抑制。我们还研究了另一种分子靶向药物尼洛替尼（nilotinib）对肿瘤生长和KIT激活的影响，目前正在准备手稿。

项目成果

A mouse model of human multiple GIST family with KIT-Asp820Tyr mutation generated by knock-in strategy.

通过敲入策略生成具有 KIT-Asp820Tyr 突变的人类多 GIST 家族小鼠模型。

• 发表时间: 2007
• 期刊: J Pathol. 214
• 作者: Takahashi T;Nakajima K;Nishitani A;Souma Y;Hirota S;Sawa Y;Nishida T.;Nakai N
• 通讯作者: Nakai N

Complete response of highly advanced colon cancer with multiple lymph node metastases to irinotecan combined with UFT : report of a case.

伊立替康联合 UFT 治疗伴有多发淋巴结转移的高度晚期结肠癌完全缓解：一例报告。

• 发表时间: 2006
• 期刊: Surg Today 36
• 作者: Takahashi T;Nakajima K;Nishitani A;Souma Y;Hirota S;Sawa Y;Nishida T.;Nakai N;Hasegawa J;Takahashi T;Nakagomi N;Yamamoto S;Fujie Y
• 通讯作者: Fujie Y

Establishment of a lymph node metastasis model from subcutaneous tumors of gastrointestinal stromal tumor model cells

胃肠道间质瘤模型细胞皮下肿瘤淋巴结转移模型的建立

• 发表时间: 2009
• 期刊: Oncol Rep 21
• 作者: S akurama K;Naomoto Y;Ohara T;Watanabe N;Takaoka M;Nagatsuka H;Tomono Y;Tanida T;Noma K;Tanabe S;Fujiwara Y;Motoki T;Shirakawa Y;Yamatsuji T;Hirota S;Taguchi T;Tanaka N
• 通讯作者: Tanaka N

Clinical practice guidelines for gastrointestinal stromal tumor (GIST) in Japan: English version

• DOI: 10.1007/s10147-008-0798-7
• 发表时间: 2008-10-01
• 期刊: INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
• 影响因子: 3.3
• 作者: Nishida, Toshirou;Hirota, Seiichi;Kubota, Tetsuro
• 通讯作者: Kubota, Tetsuro

Efficacy and Safety Profile of Imatinib Mesylate (STI571) in Japanese Patients with Advanced Gastrointestinal Stromal Tumors: a Phase II Study (STI571B1202).

甲磺酸伊马替尼 (STI571) 在日本晚期胃肠道间质瘤患者中的疗效和安全性：一项 II 期研究 (STI571B1202)。

• 发表时间: 2008
• 期刊: Int J Clin Oncol. 13
• 作者: N ishida T;Shirao K;Sawaki A;Koseki M;Okamura T;Ohtsu A;Sugiyama T;Miyakawa K;Hirota S.
• 通讯作者: Hirota S.