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Investigation of the possibility of Trefoil Factor Family as a therapeutics for post-EMR (endoscopic mucosal resection) gastric ulcer

三叶因子家族作为 EMR（内镜粘膜切除术）后胃溃疡治疗药物的可能性的研究

基本信息

批准号：
16390386
负责人：
KANAI Michiyuki
金额：
$ 8.77万
依托单位：
The Tazuke Kofukai
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Intesitnal trefoil factor (ITF) plays an important role in the process of wound healing of gastrointestinal tract. Endoscopic mucosal resection (EMR) is a prevailing procedure for the treatment of early gastric cancers. Following the procedure, patients need limited diet or medication such as anti-acid or muco-protective drugs for the protection of denuded area or facilitating the healing of the artificial ulceration. We have investigated if ITF could be useful as the therapeutics for the artificial ulceration caused by endoscopic mucosal resection (EMR). The effect of ITF was tested in a rat stomach model of EMR. The level of ITF gene expression in rat stomach was almost undetectable. Increased endogenous expression of ITF was observed on 1 day after EMR and maximum level was observed on day 3, which was examined by RT-PCR. Although exogenous ITF sprayed upon ulcer surface stayed only up to postoperative day 1, ITF significantly accelerated the mucosal healing in macroscopically as we … More ll as microscopically. The characteristic appearances of ulcer healing treated by ITF were attenuated the extent or the degree of inflammation, reduced necrosis of epithelial cells adjacent to the ulcer, enhanced re-epithelization of ulcer surface and decreased fibrosis. In aggregate, ITF accelerated the healing of artificial ulceration in a manner similar to natural healing process of gastric ulcer. In the view point of safety of ITF as clinical therapeutics, the stimulatory effect of TFF3 on proliferative response was evaluated in either endogenous TFF3 positive or negative gastric cancer cell lines. ITF did not have any stimulatory effect on all cell lines tested, which suggesting that ITF might be a effective therapeutics for the ulcerations caused by EMR for the management of carcinomas. In summary, our present study demonstrated the clinical importance of restitution, which is an initial phase of epithelial wound healing and promoted by exogenous administration of ITF. ITF might be a new therapeutics against post-EMR gastric ulceration. Less

肠三叶因子（ITF）在胃肠道创伤愈合过程中起重要作用。内镜下黏膜切除术（EMR）是治疗早期胃癌的一种常用方法。手术后，患者需要有限的饮食或药物，如抗酸或粘膜保护药物，以保护裸露区域或促进人工溃疡的愈合。我们已经研究了ITF是否可以作为治疗内镜粘膜切除术（EMR）引起的人工溃疡的有效药物。在EMR的大鼠胃模型中测试ITF的作用。大鼠胃中ITF基因的表达水平几乎检测不到。RT-PCR检测到ITF在EMR后第1天表达增加，第3天达到最高水平。虽然外源性ITF喷洒在溃疡表面仅持续到术后第1天，但ITF在宏观上显著加速了粘膜愈合，因为我们发现， ...更多信息在显微镜下。ITF治疗溃疡愈合的特征表现为减轻炎症的范围或程度，减少溃疡周围上皮细胞的坏死，促进溃疡表面的再上皮化和减少纤维化。总的来说，ITF以类似于胃溃疡自然愈合过程的方式加速人工溃疡的愈合。从ITF作为临床治疗剂的安全性的角度来看，在内源性TFF 3阳性或阴性胃癌细胞系中评价了TFF 3对增殖反应的刺激作用。ITF对所有受试细胞系均无刺激作用，提示ITF可能是一种有效的治疗EMR所致溃疡的药物。总之，我们目前的研究证明了恢复的临床重要性，这是上皮伤口愈合的初始阶段，并通过外源性施用ITF来促进。ITF可能是一种新的治疗EMR后胃溃疡的药物。少

项目成果

期刊论文数量（39）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

SMAD4-deficient intestinal trmors recruit CCR1+ myeloid cells that promote invasion.

SMAD4 缺陷的肠道肿瘤会招募 CCR1 骨髓细胞来促进侵袭。

DOI：
发表时间：
2007
期刊：
Nature Genetics. 39(4)
影响因子：
0
作者：
Kitamura T;Kometani K;Hashida H;Matsunaga A;Miyoshi H;Hosogi H;Aoki M;Oshima M;Hattori M;Takabayashi A;Minato N;Taketo MM.
通讯作者：
Taketo MM.

Overexpression of redox-active protein thioredoxin-1 prevents development of chronic pancreatitis in mice