THYMIDYLATE SYNTHASE EXPRESSION IN COLORECTAL CANCER

本课题主要研究单克隆抗体（TS）在抗肿瘤治疗中的应用 106)人胸苷酸合成酶（TS）用于检测， 专利样品中TS的定量。 初步调查使用 入选NSABP的直肠癌患者的组织样本 辅助临床试验表明，TS表达是预测 无病生存和总生存。 有限的数据表明 TS蛋白和基因表达高度相关， 对5-FU加亚叶酸基础化疗的反应 窝藏egdr突变 利用免疫学技术，我们的目标是 支持东部肿瘤协作组（ECOG）的研究团队 将TS表达水平的临床意义定义为 生存期和对含氟嘧啶方案应答的预测因子 在结直肠癌患者中。 这种抗体还提供了 用于定量TS表达对药物的反应， 如5-氟尿嘧啶、亚叶酸和左旋咪唑。 该提案包含以下两个具体目标：1.确定 胸苷酸合成酶表达的临床意义 结直肠癌患者的生存率。 我们将 免疫组化法检测胸苷酸合成酶表达 使用福尔马林固定石蜡包埋的结肠癌组织切片 从入组ECOG方案EST 2284（INT 0035，a 左旋咪唑单药或左旋咪唑加5-FU作为 切除结肠癌的手术辅助治疗）和EST 2288（INT 0089，一项低剂量甲酰四氢叶酸加5-FU、高剂量 甲酰四氢叶酸加5-FU、左旋咪唑加5-FU或低剂量甲酰四氢叶酸加5-FU 结肠癌根治性切除术后FU加左旋咪唑）。 2. 确定胸苷酸合成酶表达的临床相关性， 用于测定对基于氟嘧啶的方案的响应性的方法。 我们将使用福尔马林切片评估胸苷酸合酶的表达- 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（III期研究）的患者 5-FU与5-FU + PALA或5-FU+口服甲酰四氢叶酸或5-FU的评价 联合静脉注射甲酰四氢叶酸或5-FU联合干扰素α治疗晚期 结肠直肠癌）。

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).