EXPERIMENTAL THERAPY OF COLON CANCER WITH ANTISENSE FUTS

反义 FUTS 治疗结肠癌的实验

• 批准号: 6050932
• 负责人: BRENT W WESTON
• 金额: $ 15万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6050932
• 关键词: RNA splicing; antisense nucleic acid; apoptosis; athymic mouse; cell adhesion; cell proliferation; cis platinum compound; colon neoplasms; combination cancer therapy; genetic transcription; hexosan; hexosyltransferase; metastasis; neoplasm /cancer chemotherapy; nonhuman therapy evaluation; oligonucleotides; selectins; thiophosphate; tissue /cell culture

DESCRIPTION: (adapted from the investigator's abstract): The prognosis of colorectal cancer is adversely affected by liver metastasis, and therapeutic options are limited for advanced disease. Rolling of carcinoma cells along vascular endothelium is mediated through selectin adhesion receptors and their ligands, sialyl Lewis x (sLex) and sialyl Lewis a (sLea). Biosynthesis of these glycans on human colon cancer cells is largely controlled by the alpha(1,3)fucosyltransferases FUT3 and FUT6. Stable transfection of carcinoma cells with antisense FUT3/FUT6 sequences inhibits expression of sLex/sLea, selectin-mediated adhesion, and liver metastasis in nude mice. The proposed experiments extend these results to an in vivo pre-clinical model with FUT antisense oligodeoxynucleotides (AS-ODNs) against highly metastatic HT29-LMM colon carcinoma cells and locally invasive, non-metastatic COLO-205 colon cancer cells. The long-term goals are to extend the use of AS-ODNs to adjunctive treatment of colon carcinoma metastasis and to contribute to the study of glycosyltransferase gene regulation.

描述：（改编自研究者摘要）： 结肠直肠癌受到肝转移的不利影响， 晚期疾病的选择有限。癌细胞沿着滚动 血管内皮是通过选择素粘附受体及其 配体，sialyl刘易斯x（sLex）和sialyl刘易斯a（sLea）。生物合成这些 人结肠癌细胞上的聚糖在很大程度上由 α（1，3）岩藻糖基转移酶FUT 3和FUT 6。癌的稳定转染 具有反义FUT 3/FUT 6序列的细胞抑制sLex/sLea的表达， 选择素介导的粘附和裸鼠肝转移。拟议 实验将这些结果扩展到FUT的体内临床前模型 抗高转移性HT 29-LMM的反义寡核苷酸（AS-ODNs） 结肠癌细胞和局部侵袭性、非转移性科洛-205结肠 癌细胞长期目标是将AS-ODN的使用扩展到 结肠癌转移的持续治疗， 糖基转移酶基因调控研究。