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Biomolecular investigation on thermotolerance in gastric cancer

胃癌耐热性的生物分子研究

基本信息

批准号：
06671251
负责人：
NIHEI Zenro
金额：
$ 1.09万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

To evaluate the relationship between the prognosis of gastric cancer treated by hyperthermotherapy and the expressions of variant p53 and heat shock protein 72 (hsp72), we investigated the surgical materials immunohistochemically. In the result, however, no positive relationship was identified, so far. In the former report on the experimental study, the level of thymidine phosphorylase (dThdPase) is known to be elevated by hyperthermia treatment in the colonic cancer cell lines. This, together with the facts we had obtained, led to the alternative investigations of thermotolerance and dThdPase. Twenty five frozen specimens of far-advanced or recurrent gastric cancer treated by means of hyperthermia with known prognosis were evaluated in respect of expression of dThdPase immunohistochemically. There were 48% of dThdPase positive cases of which the three year survival rate was 75%, in contrast of cases with dThdPase negative expression being 15%, with significant statistical difference. In addition, using anti-human VIII factor, angiogenesis of the gastric cancer was revealed to have positive relationship with dThdPase, in cases with hyperthermotherapy. In breast cancer without hyperthermia treatment, on the contrary, patients with dThdPase positive expression had better prognosis than those with negative one. One reason of such discrepancy between gastric and breast cancer is thought to be derived from difference of biological behavior of cancer itself and another is due to various kinds of cytokines which may induce the production of dThdPase. Namely, cytokines during the hyperthermia treatment might regulate the dThdPase production. It should be further investigated that thermotolerance would be regulated by dThdPase as well as cytokine network.

为探讨热疗治疗胃癌的预后与p53和热休克蛋白72（hsp 72）表达的关系，我们对热疗治疗胃癌的手术材料进行了组织化学研究。然而，在结果中，到目前为止，没有发现任何积极的关系。在先前的实验研究报告中，已知结肠癌细胞系中的胸苷磷酸化酶（dThdlase）水平通过高温处理而升高。这一点，加上我们所获得的事实，导致了耐热性和dThdfos的替代研究。对25例预后已知的晚期或复发性胃癌经高温治疗的冷冻标本进行了免疫组化dThdPase表达评估。dThdR阳性表达者占48%，其3年生存率为75%，而dThdR阴性表达者仅为15%，差异有统计学意义。此外，使用抗人VIII因子，胃癌的血管生成被揭示在热疗的情况下与dThdR呈正相关。而未经热疗治疗的乳腺癌中，dThdR表达阳性者预后较阴性者好。胃癌与乳腺癌之间差异的一个原因被认为是由于肿瘤本身生物学行为的差异，另一个原因是由于各种细胞因子可能诱导dThdR的产生。也就是说，热疗过程中的细胞因子可能调节dThdR的产生。热耐受性是否受dThdR和细胞因子网络的调节还有待进一步研究。