Feasibility study for an evaluation system of effect and side effect chemotherapy for oral cancer utilizing time PCR

本课题的目的是利用实时荧光定量聚合酶链式反应技术，建立一套较为准确的口腔癌化疗效果和不良反应评价系统。为此，我们试图检测抗癌化疗过程中细针抽吸法获得的口腔鳞癌患者外周血细胞和肿瘤细胞中凋亡相关蛋白的mRNA表达。然而。由于这种检查尚未建立，因此首先对使用或不使用抗癌剂处理的培养细胞进行可行性研究。经妻子顺铂和/或5-FU处理后，部分患者外周血细胞中诱导Fas、Bax、Caspase-2、3、8、9mRNA的表达增加。外周血细胞经顺铂和/或5-FU处理后，部分病例还表现为细胞凋亡抑制蛋白表达增加，包括bcl2、bclX1、c-IAP2、XIAP。提示化疗过程中外周血细胞可能对抗癌药物敏感，可通过检测细胞凋亡相关蛋白的mRNA表达来评价抗癌药物的毒副作用。目前，我们试图在抗癌化疗过程中利用口腔癌患者的外周血细胞进行临床研究。在本研究中，我们将探讨细胞凋亡相关蛋白的mRNA表达水平与临床表现的关系。由于利用外周血细胞可行性研究建立的技术诀窍适用于通过细针抽吸获得的肿瘤细胞的检查，因此本项目提出的评估系统将产生包含抗癌药物效果的有用信息。

The aim of this project is establishment of a mere accurate evaluation system of effect and side effect of chemotherapy for oral cancer utilizing real time PCR. For this purpose, we attempted to examine the mRNA expression of apoptosisrelated proteins in peripheral blood cells and tumor cells of patients with oral squamous cell carcinoma obtained by fine needle aspiration during the course of anticancer chemotherapy. However. Since this kind of examination has not been established so started on a feasibility study using culture cells treated with or without anticancer agents. After the treatment wife cisplatin and/or 5-FU, mRNA expression of apoptosis-mediating proteins inducing Fas,Bax, Caspase-2,3,8,9 in the cultured peripheral blood cells was increased in some cases. On the other hand, in the cultured peripheral blood cells after the treatment with cisplatin and/or 5-FU, some cases also showed increased expression of mRNA of apoptosis-suppressing proteins incliding Bcl-2, Bcl-X_1, c-IAP2, XIAP. These findings suggest that peripheral blood cells may be susceptible to anticancer agents during the course of chemotherapy, and the side effect of the anticancer agents can be evaluated be evaluated by examination of mRNA expression of apoptosis-related proteins. At preaent, we anttempt to start on the clinical study using peripheral blood cells of patients with oral cancer in the course of anticancer chemotherapy. In this study, we will examine the relationship between the expression level of mRNA of apoptosis-related proteins and clinical manifestation of the side effects. Since the know-how that is estabished by feasibility study using peripheral blood cells is applicable to the examination using tumor cells obtained by fine needle aspiration, an evaluation system proposed in this project will yield useful information conceming the effect of anticancer agents.