Pre Pilot Project

预试点项目

• 批准号: 8546167
• 负责人: Reynold Enriquez
• 金额: $ 1.24万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8546167
• 关键词: 1-Phosphatidylinositol 3-Kinase; Acetates; Animal Model; Animals; Antineoplastic Agents; Apoptosis; Caribbean region; Cells; Chemistry; Clinical; Collaborations; Contracts; Cytoplasm; Data; Development; Doctor of Medicine; Doctor of Philosophy; Drug Kinetics; Drug or chemical Tissue Distribution; Ecosystem; Funding; Goals; Grant; Growth; High Pressure Liquid Chromatography; Human; Human Cell Line; In Vitro; Inhibitory Concentration 50; Injection of therapeutic agent; Intraperitoneal Injections; JUN gene; Knowledge; Label; Lead; Malignant - descriptor; Malignant Glioma; Malignant Neoplasms; Marines; Measures; Medicine; Membrane Potentials; Mitochondria; Mitogen-Activated Protein Kinases; Modeling; Mus; National Cancer Institute; Normal Cell; Organ; Organism; Pathway interactions; Patients; Phase; Phase I Clinical Trials; Piedra; Pilot Projects; Plasma; Play; Porifera; Principal Investigator; Research; Resources; Role; SP600125; Scientist; Sea; Specialist; Structure; Testing; Time; Toxic effect; Toxicology; University of Texas M D Anderson Cancer Center; Xenograft Model; Xenograft procedure; anticancer research; base; cell type; clinical application; cytotoxic; cytotoxicity; in vivo; intraperitoneal; intravenous injection; kinase inhibitor; leukemia; mTOR protein; marine organism; neurosurgery; novel; professor; programs; stress-activated protein kinase 1; subcutaneous; temozolomide; tumor

TITLE: Pilot Project D - Anticancer Effect of Novel Compounds Derived from Gorgonian Octocorals in the Caribbean Sea JO-LEADERS: UPRCCC - Abimael Rodriguez, Ph.D., Professor, Department of Chemistry MDACC - Yasuko Kondo, M.D., Ph.D., Assistant Professor, Neurosurgery- Research ABSTRACT In a pre-pilot study funded by the present U54 grant, we found that eupalmerin acetate (EPA), which was selected from 15 compounds derived from marine organisms in the Caribbean Sea, has significant anticancer effect on human malignant glioma cells both in vitro and in vivo. We have also demonstrated that EPA induces apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase (JNK) pathway. As a successful extension of our pre-pilot project, we have modified the structure of EPA and synthesized 10 additional EPAderived compounds to develop even more potent anticancer agents. We hypothesize that EPA or its derivatives (collectively referred to as EPAs) will show anticancer effect in malignant qlioma and leukemia cells both in vitro and in vivo. Therefore, the objectives of this pilot project are 1) to determine the anticancer efficacy and mechanisms of EPAs in malignant glioma and leukemia cells in vitro, 2) to determine the anticancer effect of the lead compounds in the animal cancer xenograft model, and 3) to examine pharmacokinetics and toxicity of the lead compounds. Relevance of Pilot Project to the Overall Priorities The goal of this proposal is to develop marine compounds isolated from the Caribbean Sea by an established scientist (UPR-Rio Piedras) into novel anticancer agents through collaboration of cancer specialists at MDACC. Our study is tightly associated with the U54 aims as the Co-leaders seek to continue building their existing partnership that started with a pre-pilot (pipeline) project.

标题：试点项目D-从柳珊瑚中提取的新化合物的抗癌作用 加勒比海 工作领导：UPRCCC-Abimael Rodriguez，博士，化学系教授 近藤康子，医学博士，神经外科助理教授- 研究 摘要 在由目前的U54拨款资助的一项前期试验研究中，我们发现醋酸尤帕梅林(EPA)，这是 选自加勒比海海洋生物的15种化合物，具有显著的抗癌作用 在体内外对人脑胶质瘤细胞的影响。我们还证明了环境保护局诱导 恶性胶质瘤细胞通过c-jun NH2末端激酶(JNK)途径的凋亡。作为一个成功的 扩展我们的前期试点项目，我们已经修改了EPA的结构，并合成了另外10个EPA衍生产品 化合物，以开发更有效的抗癌剂。我们假设环保局或其 衍生物(统称为EPA)将在恶性胶质瘤和白血病细胞中显示抗癌作用 在体外和体内都有。因此，这一试点项目的目标是1)确定抗癌效果 以及EPA对恶性胶质瘤和白血病细胞的体外作用机制，2)确定其抗癌作用 动物移植癌模型中的先导化合物，以及3)检测药代动力学和毒性 先导化合物。 试点项目与总体优先事项的相关性 这项提议的目标是开发从加勒比海分离出来的海洋化合物，通过建立一个 科学家(UPR-Rio Piedras)通过与癌症专家的合作研究新型抗癌药物 MDAC.我们的研究与U54目标密切相关，因为联合领导人寻求继续建立他们的 从一个试点(管道)项目开始的现有合作伙伴关系。