IN VITRO SCREENING OF CHEMOPREVENTIVE AGENTS

化学预防剂的体外筛选

• 批准号: 6325281
• 负责人: Martin Lipkin
• 金额: --
• 依托单位: STRANG CANCER PREVENTION CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-30 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6325281
• 关键词: Li Fraumeni syndrome; biomarker; cancer prevention; carcinogenesis inhibitor; cell cycle; cell line; cell proliferation; cell transformation; chemoprevention; drug screening /evaluation; mammary epithelium; neoplasm /cancer genetics; telomerase; telomere; tissue /cell culture

Bischoff et al (Cancer Res 50:7979, 1990) found that fibroblasts obtained from patients with the Li-Fraumeni syndrome (LFS) containing germline mutations in p53, can develop into immortal cell lines. Subsequently, it was demonstrated by Shay et al (Mol. Cell Biol. 15:425, 1995) that cultured human breast epithelial cells from patients with LFS which are heterozygous for p53, show genomic instability, loss of cell cycle control, and can develop into immortal cell lines. The immortalized human breast epithelial cells exhibit loss of the remaining normal p53 allele, telomerase reactivation, telomere stabilization, and continued cell proliferation. The objective of this contract is to screen selected chemopreventive agents using mechanism-based assays in cultures of LFS breast-derived, "normal" and spontaneously immortalized epithelial cells by analysis of the earliest acquired traits utilizing the following endpoint markers: (1) Spontaneous immortalization (2) Genomic stability (3) Cell cycle and other molecular changes that accompany immortalization (4) Stabilization of telomeric DNA via activation of telomerase or alternative mechanisms. (5) Anchorage independent growth/ability to grow in serum. The key question to determine is if fewer immortalization events occur in the cultures containing the lowest efficacious concentrations of chemopreventive agents that do not cause acute toxicity. The immortalization frequency shall be correlated with a series of other objectively and quantitatively measurable endpoints that can be assessed in the absence or presence of chemopreventive agents. Five agents will be tested.

Bischoff等人（Cancer Res 50:79, 1990）发现成纤维细胞

项目成果

Telomerase and breast cancer.

• DOI: 10.1186/bcr288
• 发表时间: 2001
• 期刊: BREAST CANCER RESEARCH
• 影响因子: 7.4
• 作者: Herbert, BS;Wright, WE;Shay, JW
• 通讯作者: Shay, JW

Spontaneous immortalization of clinically normal colon-derived fibroblasts from a familial adenomatous polyposis patient.

来自家族性腺瘤性息肉病患者的临床正常结肠源性成纤维细胞的自发永生化。

• DOI: 10.1593/neo.4103
• 发表时间: 2004
• 期刊: Neoplasia (New York, N.Y.)
• 作者: Forsyth,NicholasR;Morales,CarmelaP;Damle,Shirish;Boman,Bruce;Wright,WoodringE;Kopelovich,Levy;Shay,JerryW
• 通讯作者: Shay,JerryW