Chemoprevention targeting bile acid receptor for esophageal adenocarcinoma

针对食管腺癌胆汁酸受体的化学预防

• 批准号: 17590630
• 负责人: OSAWA Satoshi
• 金额: $ 1.98万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590630/
• 关键词: farnesoid X receptor; guggulsterone; bile acid; Barrett's adenocarcinoma; chemoprevention; farnesoid X受容体; バレット上皮; バレット腺癌

Gastroesophageal reflux of bile acid is associated with the development of Barrett's epithelium and thereafter adenocarcinoma. Although bile acids are reported to activate farnesoid X recepor that is one of the nuclear hormone receptors, it is unknown whether its signaling is involved in the development of Barrett's adenocarcinoma. In this study, we examined the effects of guggulsterone, a farnesoid X receptor antagonist, on the signaling pathway, especially Cdx2 expression in esophageal epithelial cells in vitro. Treatment with DCA and CDCA for 24 h increased the Cdx2 expression in Barrett's adenocarcinoma cells. Guggulsterone decreased not only basal Cdx2 expression but also DCA-or CDCA-induced Cdx2 expression. Bile acid-activating signaling pathways of farnesoid X receptor may be novel drug targets to prevent the development of Barrett's adenocarcinoma.

胃食管胆汁酸反流与巴雷特上皮和腺癌的发展有关。虽然有报道称胆汁酸能激活核激素受体之一的法内甾体X受体，但其信号传导是否参与巴雷特腺癌的发生尚不清楚。在这项研究中，我们在体外研究了guggulsterone（一种法内甾体X受体拮抗剂）对食管上皮细胞信号通路，特别是Cdx2表达的影响。DCA和CDCA作用24h后，Barrett腺癌细胞中Cdx2的表达均增加。Guggulsterone不仅降低Cdx2的基础表达，而且降低dca或cdca诱导的Cdx2的表达。胆汁酸激活法脂类X受体的信号通路可能是预防巴雷特腺癌发展的新的药物靶点。

项目成果

EGF rapidly translocates tight junction proteins from the cytoplasm to the cell-cell contaact via protein kinase C activation in TMK-1 gastric cancer cells

在 TMK-1 胃癌细胞中，EGF 通过蛋白激酶 C 激活，将紧密连接蛋白从细胞质快速易位至细胞间接触

• 发表时间: 2005
• 期刊: Exp. Cell Research 309
• 作者: Osawa S;Kajimura M;Yamamoto S;Ikuma M;Mochizuki C;Iwasaki H;Hishida A;Terakawa S.;Sugimoto M;Furuta T;Yamamoto N;Osawa S;Yamamoto N;Yoshida K
• 通讯作者: Yoshida K

Alteration of intracellular histamine H_2 receptor cycling precedes antagonist-induced up-regulation

细胞内组胺 H_2 受体循环的改变先于拮抗剂诱导的上调

• 发表时间: 2005
• 期刊: Am J Physiol, Gastrointest Liver Physiol 289
• 作者: Osawa S;Kajimura M;Yamamoto S;Ikuma M;Mochizuki C;Iwasaki H;Hishida A;Terakawa S.
• 通讯作者: Terakawa S.

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection.

CYP2C19代谢基因型状态不佳是日本幽门螺杆菌感染患者发生胃癌的危险因素。

• 发表时间: 2005
• 期刊: Aliment Pharmacol Ther. 22
• 作者: Sugimoto M;Sugimura H et al.
• 通讯作者: Sugimura H et al.

Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype status

法莫替丁与兰索拉唑联合给药对与 CYP2C19 基因型状态相关的胃酸分泌的影响

• 发表时间: 2005
• 期刊: Aliment Pharmacol Ther 22
• 作者: Furuta T;Shirai N;Sugimoto M;Nakamura A;Okudaira K;Kajimura M;Hishida A
• 通讯作者: Hishida A

Influences of proinflammatory and anti-inflammatory cytokine polymorphisms on eradication rates of clarithromycin-sensitive strains of Helicobacter pylori by triple therapy

• DOI: 10.1016/j.clpt.2006.03.007
• 发表时间: 2006-07-01
• 期刊: CLINICAL PHARMACOLOGY & THERAPEUTICS
• 影响因子: 6.7
• 作者: Sugimoto, Mitsushige;Furuta, Takahisa;Ishizaki, Takashi
• 通讯作者: Ishizaki, Takashi