MALIGNANT TO BENIGN TUMOR TRANSITION

我们已经建立了三个细胞标记来区分 人非侵袭性良性结肠腺瘤与侵袭性结肠 原代培养中的癌症。与生物相关的肿瘤 直接从切除的肿瘤中检测细胞。癌细胞 是从切除的肿瘤中培养出来的，不含淋巴细胞， 内皮细胞和成纤维细胞，并保持存活和分裂 组织培养2-3周。这种相对的寿命使 癌细胞在组织培养和转移过程中需要调节 通过开发的标记物来衡量更良性的状态。在……里面 最初的实验，分化试剂环六亚甲基 双乙酰胺(HMBA)对三种肿瘤的诱导分化 组织病理学分级为中度分化；HMBA 对一个低分化结肠和两个胶体结肠无效 癌症。 我们建议(1)研究20个原代培养细胞的反应 人结肠癌对HMBA的体外检测；(2) HMBA和TGFbeta对原代培养细胞作用的比较 癌；(3)测定正常组织的终末分化 用转化生长因子β检测结肠上皮细胞的生长 HMBA处理的细胞在体内肾下的潜能 胶囊裸鼠体内试验和体外肿瘤试验 ~3H-TdR连续标记生长分数，(5)至 开始研究纯化HMBA分化分泌的因子(S) HT29细胞。

We have established three cellular markers to distinguish between human noninvasive benign colon adenomas and invasive colon carcinomas in primary culture. The biologically relevant tumor cells are assayed directly from resected tumors. Carcinoma cells are primary cultured from resected tumors free of lymphocytes, endothelial cells, and fibroblasts, and remain viable and dividing in tissue culture for 2-3 weeks. This relative longevity allows the carcinoma cells to be modulated in tissue culture, and transition to a more benign state measured by the markers developed. In initial experiments, the differentiation agent, hexamethylene bisacetamide (HMBA), induced differentiation of three tumors graded as moderately differentiated by histopathology; HMBA was ineffective on one poorly differentiated and two colloid colon carcinomas. We propose (1) to study the response of 20 primary cultured human colon carcinomas to HMBA by our in vitro assays; (2) to compare the effects of HMBA and TGFbeta on primary-cultured carcinomas; (3) to assay for terminal differentiation of normal colonic epithelial cells by TGFbeta; (4) to test the growth potential of the HMBA-treated cells both in vivo in the subrenal capsule assay in nude mice and in vitro by assay of the tumor growth fraction by continuous labeling with 3H-thymidine, (5) to begin studies to purify factor(s) secreted by HMBA-differentiated HT29 cells.