APOPTOSIS AND %S AS PROGNOSTIC FACTORS FOR COLON CANCER

结肠癌的生长是由恶性肿瘤的发生率决定的。 细胞增殖和自然凋亡。 由于分子遗传学 癌细胞的变化这两个过程都可以被破坏， 导致肿瘤生长。 我们假设结肠癌细胞 细胞凋亡是净癌细胞生长的重要决定因素， 细胞凋亡百分比的测量将提供额外的 预后信息的细胞增殖率。 整体 该建议的目标是测量基础凋亡率， 结肠腺癌标本细胞增殖及相关因素的研究 这些测量对预后和分子遗传异常的影响 在相同的肿瘤样本上测定。 石蜡包埋的组织 参与随机、对照NCCTG临床研究的患者 现在有足够的随访数据将这些 结肠癌复发率和生存率。 细胞 增殖和DNA倍性将使用最先进的 流式细胞仪硬件和软件。 细胞凋亡将用 TUNEL技术。 我们建议利用细胞增殖 （S期百分比和G2 M期百分比）和凋亡百分比测量 开发一个公式-结肠癌生长指数（CCGI）- 更好地预测预后。 第二个要检验的假设是， 癌细胞增殖和凋亡的改变是 遗传异常的后果，这些遗传 异常将不同地影响增殖和凋亡。 这项研究为研究细胞增殖提供了独特的机会， 和结肠癌的凋亡率， Steven Thibodeau博士在之前的一项研究中发现了分子异常 （NCCTG 93-46-55）。 通过对临床材料进行这些测定，我们 旨在将这些发现转化为可用于 在临床上制定新的治疗策略， 了解结肠癌的细胞凋亡和细胞增殖。

The growth of a colon cancer is determined by the rates of malignant cell proliferation and natural apoptosis. Because of molecular genetic changes in the cancer cell both of these processes can be disrupted and lead to tumor growth. We hypothesize that the rate of colon cancer cell apoptosis is an important determinant of net cancer cell growth and that a measure of the percent cells in apoptosis will provide additional prognostic information to the cell proliferation rate. The overall goals of this proposal are to measure the rates of basal apoptosis and cell proliferation on specimens of colon adenocarcinomas and relate these measurements to prognosis and the molecular genetic abnormalities determined on the same tumor sample. Paraffin-embedded tissue from patients that participated in randomized, controlled NCCTG clinical trials which now have adequate follow-up data to correlate these measurements to colon cancer recurrence and survival. Cell proliferation and DNA ploidy will be measured using state-of-the-art flow cytometry hardware and software. Apoptosis will be measured with a TUNEL technique. We propose to utilize the cell proliferation (percent S and percent G2M phases) and percent apoptosis measurements to develop a formula - the colon cancer growth index (CCGI) - that better predicts prognosis. The second hypothesis to be tested is that the alterations of cancer cell proliferation and apoptosis are the consequences of genetic abnormalities and that these genetic abnormalities will differentially affect proliferation and apoptosis. This study offers the unique opportunity to study the cell proliferation and apoptosis rates of colon cancers that have already been studied for molecular abnormalities by Dr. Steven Thibodeau in a previous study (NCCTG 93-46-55). By performing these assays on clinical material, we aim to translate these findings into prognostic tools that can be used in the clinic to formulate new treatment strategies based on the knowledge of apoptosis and cell proliferation of colon cancers.