Biomolecular investigation on thermotolerance in gastric cancer

为探讨高温治疗后胃癌预后与变异体p53和热休克蛋白72 （hsp72）表达的关系，我们对手术材料进行免疫组化研究。然而，到目前为止，结果并没有发现任何积极的关系。在先前的实验研究报告中，已知在结肠癌细胞系中，热疗可以提高胸苷磷酸化酶（dThdPase）的水平。这一点，加上我们已经获得的事实，导致了耐热性和dThdPase的替代研究。采用免疫组织化学方法对25例经热疗治疗且预后已知的远晚期或复发胃癌冷冻标本进行dThdPase的表达评价。dThdPase阳性患者的3年生存率为75%，dThdPase阴性患者的3年生存率为15%，差异有统计学意义。此外，利用抗人VIII因子发现，在高温治疗的情况下，胃癌血管生成与dThdPase呈正相关。而在未经热疗治疗的乳腺癌中，dThdPase阳性表达的患者预后优于阴性表达的患者。胃癌与乳腺癌存在差异的原因，一方面是由于癌症本身的生物学行为不同，另一方面是由于多种细胞因子可诱导dThdPase的产生。即，热疗过程中的细胞因子可能调节dThdPase的产生。耐热性是否受dThdPase和细胞因子网络的调控有待进一步研究。

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.