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Molecular Analysis for the involvment of Helicobacter Pylori in carcinogenis of oral cancer

幽门螺杆菌参与口腔癌致癌的分子分析

基本信息

批准号：
11557159
负责人：
IIZUKA Tadahiko
金额：
$ 2.37万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557159/
关键词：
Helicobacter pylori oral cancer oral lichen planus Pradication Helicobacter pylori oral lichen planus PCR CagA VacA 唾液経口免疫マウス Peyer's Patch

项目摘要

Considering a suspected link between Helicobacter pylori infection and human oral cancer, we had cloned a new H.pylori gene for membrane protein 1 (HP-MP1) at first. Because HP-MP1 induces release of inflammatory cytokines and tumor necrosis factor-alpha acts as both initiator and tumor promoter, we studied the possible involvment of HP-MP1 in carcinogenesis of H.pylori. Two cell lines, BALB/3T3 cells as control and v-Ha-ras-transfected BALB/3T3 cells as putative initiated cells, were each transfected with HP-MP1, urease B genes, or vector alone. All of the Bhas/mpl clones showed strong expression of tumor necrosis factor-alpha gene and produced tumors in 100 % of nude mice. Two Bhas/ure clones showed weak tumorigenicity ; the other Bhas and BALB clones showed none. Results indicate strong carcinogenic activity of HP-MP1 in cooperation with viral Ras protein and weak activity of urease B.Secondly, we often see the changes Oral lichen planus(OLP) for cancer. We found that 50 % of OLP patients infected with H.pylori. So, we analyzed the effect the eradication therapy for H.pylori. 5 OLP patients who had H.pylori infection treated with the eradication therapy. 3 of 5 patients were effective for 3 months, but 2 of 3 patients complaned pain 6 months later. Only one patient was effective for 12months. 2 of 5 patients were not effective at all. Thus, it is considerd that there is ho relationship between H.pylori infection and OLP.

考虑到幽门螺杆菌感染与口腔癌的关系，我们首先克隆了一个新的幽门螺杆菌膜蛋白1（HP-MP 1）基因。由于HP-MP 1诱导炎症细胞因子的释放，而肿瘤坏死因子-α既是启动因子又是肿瘤促进因子，因此我们研究了HP-MP 1在幽门螺杆菌致癌过程中的可能作用。将两种细胞系，即作为对照的BALB/3 T3细胞和作为推定起始细胞的v-Ha-ras转染的BALB/3 T3细胞，各自用HP-MP 1、尿素酶B基因或单独的载体转染。所有的Bhas/mpl克隆均显示出肿瘤坏死因子-α基因的强表达，并且在100%的裸鼠中产生肿瘤。两个Bhas/ure克隆显示出弱致瘤性，其他Bhas和BALB克隆显示无致瘤性。结果表明，HP-MP 1与病毒Ras蛋白协同作用具有较强的致癌活性，而尿素酶B活性较弱。我们发现，50%的OLP患者感染幽门螺杆菌。因此，我们对幽门螺杆菌根除治疗的效果进行了分析。5例接受根除治疗的幽门螺杆菌感染OLP患者。5例患者中3例3个月有效，2例6个月后主诉疼痛。仅1例患者有效12个月。5例患者中有2例完全无效。提示H.pylori感染与口腔扁平苔藓无明显关系。