Interaction of proinflammatory cytokines and growth factors in gastric carcinogenesis

促炎细胞因子和生长因子在胃癌发生中的相互作用

• 批准号: 14370181
• 负责人: SHINOMURA Yasuhisa
• 金额: $ 8.45万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370181/
• 关键词: gastric cancer; Helicobacter pylori; gastrin; IL-1; HB-EGF; gastritis; CD9; NF-κB; p38-MAPK; メチル化; PKC

We have reported that hypergastrinemia and increased IL-1beta production may contribute to foveolar hyperplasia in Helicobacter pylori-associated enlarged fold gastritis and that gastrin induces heparin binding epidermal growth factor-like growth factor(HB-EGF) and amphiregulin production in the gastric mucosa. The purpose of the present study was to clarify the roles of proinflammatory cytokines and growth factors in gastric carcinogenesis. Gastrin induced IL-8 expression through activation of nuclear factor kappaB in cooperation with IL-1beta. Increased 8-hydroxydeoxyguanosine production and hypermethylation in the region of promoter of tumor suppressor genes were observed in the gastric mucosa of patients with enlarged fold gastritis. HB-EGF expression was associated with CD9 expression in gastric cancer. Anti-CD9 antibody inhibited cell proliferation and induced apoptosis in gastric cancer cells through tyrosine phosphorylation of the p46 Shc isoform. Gastrin and proinflammatory cytokines and growth factors were shown to be involved in gastric carcinogenessis.

我们已经报道，高胃泌素血症和IL-1β产生增加可能导致幽门螺杆菌相关扩大皱襞性胃炎中的小凹增生，并且胃泌素诱导胃粘膜中肝素结合表皮生长因子样生长因子（HB-EGF）和双调蛋白的产生。本研究的目的是阐明促炎细胞因子和生长因子在胃癌发生中的作用。胃泌素通过激活核因子 kappaB 与 IL-1beta 协同诱导 IL-8 表达。在肥厚型胃炎患者的胃粘膜中观察到肿瘤抑制基因启动子区域的 8-羟基脱氧鸟苷产量增加和高甲基化。胃癌中HB-EGF表达与CD9表达相关。抗 CD9 抗体通过 p46 Shc 同种型的酪氨酸磷酸化抑制胃癌细胞的细胞增殖并诱导细胞凋亡。胃泌素、促炎细胞因子和生长因子被证明与胃癌发生有关。

项目成果

Polyclonal nature of diffuse proliferation of interstitial cells of Cajal in patients with familial and multiple gastrointestinal stromal tumors.

家族性和多发性胃肠道间质瘤患者中卡哈尔间质细胞弥漫性增殖的多克隆性质。

• 发表时间: 2002
• 期刊: Gut. 51(6)
• 作者: Chen H;Hirota S;Isozaki K;Sun H;Ohashi A;Kinoshita K;O'Brien P;Kapusta L;Dardick I;Obayashi T;Okazaki T;Shinomura Y;Matsuzawa Y;Kitamura Y
• 通讯作者: Kitamura Y

M.Ogasa, et al.: "Gastrin activates nuclear factor kappaB through a protein kinase C dependent pathway involving NFkappaB inducing kinase, inhibitor kappaB kinase, and tumour necrosis factor receptor associated factor 6 in MKN-28 cells transfected with ga

M.Ogasa 等人：“在转染 ga 的 MKN-28 细胞中，胃泌素通过蛋白激酶 C 依赖性途径激活核因子 kappaB，该途径涉及 NFkappaB 诱导激酶、抑制剂 kappaB 激酶和肿瘤坏死因子受体相关因子 6。

M.Toyota et al.: "Gastrin activates NF-kB through a protein kinase C-dependent pathway involving NF-kB-inducing kinase, IkB kinase and TRF6 in MKN-28 cells transected with gastrin receptor"Gut. (in press). (2003)

M.Toyota 等人：“胃泌素通过蛋白激酶 C 依赖性途径激活 NF-kB，该途径涉及用胃泌素受体横切的 MKN-28 细胞中的 NF-kB 诱导激酶、IkB 激酶和 TRF6”Gut。

Imatinib inhibits various types of activating mutant kit found in gastrointestinal stromal tumors

• DOI: 10.1002/ijc.11025
• 发表时间: 2003-05-20
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Chen, H;Isozaki, K;Hirota, S
• 通讯作者: Hirota, S

K.Kinoshita, et al.: "Absence of c-kit gene mutations in gastrointestinal stromal tumours from neurofibromatosis type 1 patients"J Pathol. 202(1). 80-85 (2004)

K.Kinoshita 等人：“1 型神经纤维瘤病患者的胃肠道间质瘤中不存在 c-kit 基因突变”J Pathol。