INDIVIDUAL PREDOCTORAL DENTAL SCIENTIST FELLOWSHIP

个人博士前牙科科学家奖学金

• 批准号: 6516368
• 负责人: YING GU
• 金额: $ 3.04万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6516368
• 关键词: angiogenesis inhibitors; aprotinin; chemoprevention; colon neoplasms; extracellular matrix; metalloendopeptidases; metastasis; neoplasm /cancer pharmacology; protease inhibitor; serine proteinases; tetracyclines; tissue /cell culture; western blottings

The general research goal is to study the therapeutic potential, and mechanisms of action, of tetracyclines(TCs) in protecting extracellular matrix(ECM) and preventing cancer metastasis. My particular interest is in TCs newly discovered ability to suppress the matrix metalloproteinases activity and to prevent angiogenesis. The long-term goal of this research is to demonstrate that TCs, including chemically modified tetracyclines (CMTs) which are devoid antimicrobial properties, can prevent pathologic ECM breakdown. We specifically propose to study the ability of a special formulated non-antimicrobial TC(CMT-3) to inhibit connective tissue breakdown in a tumor cell culture system. A complete interstitial ECM, which is well established in Dr.Simon's lab, will be employed to characterize the tumor cell-mediated ECM degradation. Our preliminary results have demonstrated that tumor proteinases (matrix metalloproteinases and one specific tumor serine proteinase, tumor-associated trypsin) both contributed to the high ECM degradative activities of a human colon carcinoma cell line, COLO 205. We then intend to use COLO 205 as a model system to study the ability and the mechanisms of CMT-3 in protecting ECM from breakdown through its inhibitory effect on tumor enzymes. The ultimate goal is to connect the effect of CMTs on this cancer cell model system to oral cancer and select one or more CMTs for use in preliminary human clinical trial.

总体研究目标是研究四环素（TC）在保护细胞外基质（ECM）和预防癌症转移方面的治疗潜力和作用机制。 我特别感兴趣的是新发现的 TC 抑制基质金属蛋白酶活性和防止血管生成的能力。 这项研究的长期目标是证明 TC，包括缺乏抗菌特性的化学修饰四环素 (CMT)，可以防止病理性 ECM 破坏。 我们特别建议研究特殊配方的非抗菌TC（CMT-3）在肿瘤细胞培养系统中抑制结缔组织分解的能力。 Simon 博士的实验室已建立完整的间质 ECM，将用于表征肿瘤细胞介导的 ECM 降解。 我们的初步结果表明，肿瘤蛋白酶（基质金属蛋白酶和一种特定的肿瘤丝氨酸蛋白酶，肿瘤相关胰蛋白酶）均有助于人结肠癌细胞系 COLO 205 的高 ECM 降解活性。然后我们打算使用 COLO 205 作为一个模型系统，用于研究 CMT-3 通过其对肿瘤酶的抑制作用来保护 ECM 免受破坏的能力和机制。 最终目标是将 CMT 对该癌细胞模型系统的影响与口腔癌联系起来，并选择一种或多种 CMT 用于初步人体临床试验。