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BREAST CANCER METABOLISM STUDIES BY P-31 AND C-13 NMR

通过 P-31 和 C-13 NMR 进行乳腺癌代谢研究

基本信息

批准号：
3193749
负责人：
THOMAS VICTOR
金额：
$ 14.18万
依托单位：
EVANSTON HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-04-01 至 1994-03-31
项目状态：
已结题

项目摘要

Breast cancer treatment failure in postmenopausal patients occurs when tumors progress, e.g., express a loss of differentiation, recur after primary therapy, become drug resistant, lose their response to estrogen as a growth factor, or metastasize. These properties emerge as the result of phenotypic diversity or heterogeneity and are expressed metabolically. The purpose of this study is to identify the 31p NMR metabolic changes in breast carcinoma in postmenopausal patients at the time of diagnosis of progression. The NMR data will also be correlated with expression of the neu/HER-2,,l H-ras, c-myc and int-2 oncogenes to determine if these genes play a role in the biochemical expression of a progressive malignant phenotype. These oncogene evaluations constitute a second research project to be conducted by Dr. Douglas E. Merkel. The 31p NMR studies will be performed on cancer tissue explants, perfused tissue extracts and continuous tumor cell lines, in addition to normal breast tissue. 13-C NMR spectroscopy using 13-C-labeled intermediates will provide information about metabolite patterns and flux through glycolysis, gluconeogenesis, and the Krebs cycle in estrogen-dependent tumors. The NMR methodology and the results of this research will potentially add to improved clinical accuracy of prognosis in gauging risks of tumor progression. This work may also lay the foundation for development of better, more specific therapeutic approaches in treatment of breast cancer, based upon the metabolic strategies of the cancer cell.

绝经后患者的乳腺癌治疗失败发生在肿瘤进展，例如，表达分化丧失，复发后主要治疗，成为耐药，失去他们的反应，雌激素，生长因子或转移。这些特性的出现是由于表型多样性或异质性，并在代谢上表达。的本研究的目的是确定31 p NMR代谢的变化，绝经后乳腺癌患者在诊断时，进展 NMR数据也将与表达的蛋白质相关联。 neu/HER-2、lH-ras、c-myc和int-2癌基因，以确定这些基因是否在进行性恶性肿瘤的生化表达中起作用，表型这些致癌基因评估构成了第二个研究项目由道格拉斯E.默克尔。 31 p NMR研究将在灌注的癌组织外植体上进行组织提取物和连续的肿瘤细胞系，除了正常的乳房组织使用13-C标记的中间体的13-C NMR光谱将提供有关代谢物模式和糖酵解通量的信息，雌激素依赖性肿瘤中的三羧酸循环。的NMR 这项研究的方法和结果可能会增加提高了评估肿瘤风险的临床预后准确性进展这项工作也可能为开发更好的，更具体的治疗方法在治疗乳腺癌，基于癌细胞的代谢策略。