CORE MASS SPECTROMETRY RESOURCE FOR CANCER RESEARCH

癌症研究的核心质谱资源

• 批准号: 2907336
• 负责人: RICHARD B VAN BREEMEN
• 金额: $ 23.72万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2907336
• 关键词: DNA damage; adduct; analytical chemistry; biomedical equipment resource; cancer prevention; carcinogenesis; chemoprevention; deoxyadenosines; deoxyguanosine; drug discovery /isolation; electrospray ionization mass spectrometry; liquid chromatography; mass spectrometry; oxidation

The University of Illinois at Chicago has unique facilities and expertise for specialized liquid chromatography-tandem mass spectrometry (LC-MS-MS) measurements in support of cancer research including a unique LC-MS-MS assay for DNA oxidation products as surrogate end-point biomarkers for cancer prevention, and mass spectrometric-based screening of natural product mixtures and metabolite mixtures for the discovery of cancer chemoprevention agents. Existing mass spectrometry instrumentation for this resource includes two LC-MS quadrupole instruments, one magnetic sector mass spectrometer and a new electrospray triple quadrupole mass spectrometer. The instruments are managed by the P.I. who is both a tenured mass spectrometrist in the College of Pharmacy and an NCI-funded cancer researcher. Because no other mass spectrometry laboratory in the Chicago area is directed by a biomedical mass spectrometrist nor a cancer researcher, unique opportunities exist for providing analytical and educational support for cancer research. Developed in the laboratory of the P.I., the LC-MS-MS assay for DNA oxidation products simultaneously measures four oxidized nucleosides including 8-oxo-2'-deoxyguanosine (the only oxidation product measured by the standard HPLC with electrochemical detection method), 8-oxo-2'-deoxyadenosine, thymidine glycol and 5-hydroxymethyl-2'-uridine. Invented in the laboratory of the P.I., pulsed ultrafiltration mass spectrometry facilitates high throughput screening of natural product extracts as a means of drug discovery. Funds are requested to make these resources available to other cancer researchers on campus. In particular, the research of seven NCI-funded investigators is described with reference to how access to this unique mass spectrometry resource will increase their productivity. These research activities encompass both preclinical and clinical studies and include screening of natural products for potential new cancer chemoprevention agents, cancer prevention by selenium, mechanisms of carcinogenesis by estrogens, tamoxifen chemoprevention of breast cancer, and clinical investigations of cancer chemoprevention by the carotenoid lycopene.

芝加哥伊利诺伊大学具有独特的设施和专业知识，可用于支持癌症研究的专业液相色谱串联质谱法（LC-MS-MS）测量，包括用于DNA氧化产物的独特LC-MS-MS分析，作为用于癌症预防，癌症预防和基于质谱的癌症混合物的癌症混合物的替代生物标志物的替代终端生物标记物，并进行了癌症混合物的群体群体，并进行了癌症的群体群体群体化的剂量剂量量身定值。 该资源的现有质谱仪器包括两个LC-MS四极仪器，一个磁性扇形质谱仪和一个新的电喷雾三重四极杆质谱仪。 这些工具由P.I.他既是药学学院的终身质谱师，又是NCI资助的癌症研究员。 由于芝加哥地区没有其他质谱实验室是由生物医学质谱师和癌症研究人员指导的，因此存在为癌症研究提供分析和教育支持的独特机会。 Developed in the laboratory of the P.I., the LC-MS-MS assay for DNA oxidation products simultaneously measures four oxidized nucleosides including 8-oxo-2'-deoxyguanosine (the only oxidation product measured by the standard HPLC with electrochemical detection method), 8-oxo-2'-deoxyadenosine, thymidine glycol and 5-羟甲基-2'-尿苷。 在P.I.实验室发明的脉冲超滤质谱法促进了天然产物提取物的高吞吐量筛选，作为药物发现的手段。 要求资金向校园的其他癌症研究人员提供这些资源。 特别地，描述了七位NCI资助的研究人员的研究，参考了如何获得这种独特的质谱资源将提高其生产率。 这些研究活动涵盖了临床前和临床研究，包括对潜在的新型癌症化学预防剂，硒预防的天然产物，雌激素的癌变机制，雌激素化学预防乳腺癌的化学预防，以及类carotenoid lycopene cance癌进行癌症化学治疗的临床研究。