TIMING OF MAMMALIAN CELL CYCLE EVENTS

这个项目的目的是重新评估昼夜节律的证据 人原位癌细胞增殖的细胞动力学变化 使用现代方法，并确定是否增殖 这些肿瘤和非肿瘤细胞的活性响应于 手术或化疗干扰。 早期尝试在人类中进行细胞动力学测量， 受现有方法的限制，除少数例外， 细胞增殖的昼夜节律门控。 肿瘤细胞以及 作为卵巢癌患者的正常组织显示深刻的一天 到夜间细胞百分比的变化， 可能被用于治疗。 将测量肿瘤和非肿瘤二倍体细胞的增殖 在腹部癌病患者中， 手术和化疗前后使用流动 流式细胞术和荧光显微镜测量DNA含量，肿瘤 特异性抗原免疫荧光，窄角度和90度 散射和BUdR免疫荧光。 将计算肿瘤细胞增殖最大值和动力学指数。 与从骨髓和标记中提取的那些相比， 肿瘤细胞从实体瘤释放到腹膜中 将被衡量。

The aim of this project is to reappraise the evidence for circadian cell kinetic changes in proliferation of human cancer cells in situ using modern methods, and to determine whether the proliferative activity of these tumor and nontumor cells changes in response to surgery or is perturbed by chemotherapy. Early attempts to make cell kinetic measurements in humans were limited by available methodology and, with few exceptions, ignored the circadian gating of cell proliferation. Tumor cells as well as normal tissues in patients with ovarian cancer show profound day to night variations in the percentage of cells in a phase that might be exploited for therapeutic benefit. Proliferation of tumor and nontumor diploid cells will be measured in patients with abdominal carcinomatosis prior to and following surgery and prior to and following chemotherapy using flow cytometry and fluorescence microscopy to measure DNA content, tumor specific antigen immunofluorescence, narrow angle and 90 degree scatter and BUdR immunofluorescence. Tumor cell proliferation maxima and kinetic indices will be compared with those taken from the bone marrow and the labeling and release of tumor cells from the solid tumor into the peritoneum will be measured.