Project/Area Number |
16390386
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | The Tazuke Kofukai |
Principal Investigator |
KANAI Michiyuki The Tazuke Kofukai, Medical Research Institute 2nd Division, Chief Researcher, 医学研究所第2研究部, 研究主幹 (00322652)
|
Co-Investigator(Kenkyū-buntansha) |
OHASHI Sinya The Tazuke Kofukai, Medical Research Institute 3rd Division, Researcher, 医学研究所第3研究部, 研究員 (20435556)
HASHIDA Hiroki The Tazuke Kofukai, Medical Research Institute 2nd Division, Researcher, 医学研究所第2研究部, 研究員 (70281607)
鷹巣 晃昌 (財)田附興風会, 医学研究所・第1研究部, 研究主幹 (90399345)
木下 浩一 財団法人田附興風会, 医学研究所・第2研究部, 研究員 (60342698)
|
Project Period (FY) |
2004 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
|
Keywords | Epithelial wound healing / promoter of epithelial repair / Trefoil factor family / Intestinal trefoil factor / Endoscopic mucosal resection / artificial gastric ulcer / 消化管の創傷治癒 / 人工潰瘍 |
Research Abstract |
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
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