THYMIDYLATE SYNTHASE EXPRESSION IN COLORECTAL CANCER

本课题主要研究单抗(TS)的应用 106)到人胸苷酸合成酶(TS)用于检测和 专利样品中TS的定量测定。初步调查使用 参加NSABP的直肠癌患者的组织样本 辅助性临床试验表明TS的表达对两者都有预测作用 无病生存和总体生存。有限的数据表明 TS蛋白和基因表达高度相关并可预测 5-氟尿嘧啶联合亚叶酸钙为主的化疗方案疗效观察 转移性结直肠癌。利用免疫学技术，我们的目标是 为东部合作肿瘤学小组(ECOG)的研究小组提供支持 为了明确TS表达水平的临床意义 含氟嘧啶方案的生存和疗效的预测因素 在结直肠癌患者中。这种抗体也提供了 为了量化TS表达的调节对药物的响应 如5-氟尿嘧啶、亚叶酸钙和左旋咪唑。 该建议包含以下两个具体目标：1.确定 胸苷酸合酶的表达作为一种手段的临床意义 预测结直肠癌患者的存活率。我们会 免疫组织化学技术检测胸苷合成酶的表达 用福尔马林固定石蜡包埋的结肠癌组织切片 从ECOG方案EST 2284上输入的患者获得(INT 0035，a 左旋咪唑单药或左旋咪唑联合5-FU AS时相疗效评价 手术辅助治疗切除的结肠癌)和EST 2288(INT 0089，小剂量亚叶酸钙联合5-FU，大剂量的病毒期试验 亚叶酸钙联合5-FU、左旋咪唑联合5-FU或小剂量亚叶酸钙联合5-氟尿嘧啶 结肠癌根治性切除术后FU加左旋咪唑)。2. 确定胸苷合成酶表达与临床的相关性 确定对以氟代嘧啶为基础的方案的反应性的方法。 我们将使用福尔马林切片来评估胸苷合成酶的表达- 获得固定石蜡包埋的结直肠癌组织标本 来自已进入ECOG方案EST 2290(A阶段病)的患者 5-FU与5-FU联合PALA或5-FU联合口服亚叶酸钙或5-FU的疗效比较 亚叶酸钙或5-氟尿嘧啶联合α-干扰素治疗晚期 结直肠癌)。

This project focuses on the application of the monoclonal antibody (TS 106) to human thymidylate synthetase (TS) for the detection and quantitation of TS in patent samples. Preliminary investigations using samples of tissue from patients with rectal cancer enrolled on a NSABP adjuvant clinical trial suggest that TS expression is predictive for both disease-free and overall survival. There are limited data which suggest that TS protein and gene expression are highly correlated and predict for response to 5-FU plus leucovorin based chemotherapy in patients with metastatic colorectal cancer. Using immunological techniques, our aim is to support a study team with the Eastern Cooperative Oncology Group (ECOG) to define the clinical significance of the level of TS expression as a predictor of survival and response to fluoropyrimidine containing regimens in patients with colorectal cancer. This antibody also provides the means for quantitating the regulation of TS expression in response to drugs such as 5-fluorouracil, leucovorin and levamisole. The proposal contains the following two specific aims: 1. Determine the clinical relevance of thymidylate synthase expression as a means for prognosticating survival in patients with colorectal cancer. We will assess thymidylate synthase expression by immunohistochemical technique using sections of formalin-fixed paraffin-embedded colon carcinoma tissue obtained from patients entered on ECOG protocol EST 2284 (INT 0035, a Phase Ill evaluation of levamisole alone or levamisole plus 5-FU as surgical adjuvant treatment for resected colon cancer), and EST 2288 (INT 0089, a Phase Ill trial of low-dose leucovorin plus 5-FU, high-dose leucovorin plus 5-FU, levamisole plus 5-FU or low-dose leucovorin plus 5- FU plus levamisole following curative resection of colon cancer). 2. Determine the clinical relevance of thymidylate synthase expression as a means for determining responsiveness to fluoropyrimidine-based regimens. We will assess thymidylate synthase expression using sections of formalin- fixed paraffin-embedded colorectal carcinoma tissue specimens obtained from patients who have entered ECOG protocol EST 2290 (a Phase Ill evaluation of 5-Fu vs 5-FU plus PALA or 5-FU plus oral leucovorin or 5-FU plus IV leucovorin or 5-FU plus interferon alpha in patients with advanced colorectal cancer).