POLYAMINE ANALOGS IN ANTI GENE THERAPY FOR BREAST CANCER

乳腺癌抗基因疗法中的多胺类似物

• 批准号: 6443430
• 负责人: TJ THOMAS
• 金额: $ 1.43万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443430
• 关键词: DNA replication; MCF7 cell; analog; breast neoplasms; cell cycle; cell growth regulation; chemical structure function; cyclins; drug interactions; drug screening /evaluation; enzyme activity; epidermal growth factor; genetic promoter element; growth factor receptors; neoplasm /cancer pharmacology; northern blottings; nucleic acid inhibitor; oligonucleotides; polyamines; protooncogene; triple helix; western blottings

DESCRIPTION (As Adapted From the Investigator's Abstract): The long-term goal for this project is to develop a triplex DNA-based anti-gene strategy for breast cancer treatment. The applicant's studies during the previous funding period have demonstrated a remarkable structural specificity effect of polyamine analogs in stabilizing triplex DNA, and in facilitating the uptake of a triplex forming oligonucleotide (TFO) in breast cancer cells. Their hypothesis is that the selective utilization of polyamine analogs is a viable strategy to increase the stability of triplex DNA, and enhance the therapeutic potential of TFOs. This hypothesis will be tested by: 1) Quantification of the ability of novel polyamine analogs to stabilize triplex DNA at the promoter site sequences of cmyc, her2, and cyclinD1 genes by spectroscopic techniques, fluorescence measurements, and electrophoretic mobility shift assay; 2) elucidation of the role of polyamine -induced TFO condensation in facilitating nuclear uptake of TFOs and determination of TFO accumulation and stability in breast cancer cells; 3) Evaluation of the biologic response of TFOs and polyamine analogs as single agents and in combination on breast cancer cells by Northern and Western blot analysis of target gene expression, and polyamine metabolism pathways; and 4) Elucidation of the mechanism of TFO/polyamine analog action in terms of transcription factors to targeted sites. Results of these studies will help to develop a new therapeutic modality for breast cancer, and advance our knowledge of the mechanism of triplex DNA stabilization in vitro.

描述（根据研究者摘要改编）：长期目标