Pre Pilot Project

预试点项目

• 批准号: 8382545
• 负责人: Reynold Enriquez
• 金额: $ 63.09万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8382545
• 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：试验项目D -柳珊瑚衍生的新型化合物在癌症中的抗癌作用 加勒比海 工作负责人：UPRCCC - Abimael Rodriguez博士，化学系教授 MDACC - Yasuko Kondo，医学博士，哲学博士、助理教授，神经外科- 研究 摘要 在一项由U 54资助的预试验研究中，我们发现， 从15种来自加勒比海海洋生物的化合物中选出， 对人恶性胶质瘤细胞体内外的作用。我们还证明了EPA诱导 通过c-Jun氨基末端激酶（JNK）途径在恶性胶质瘤细胞中的凋亡。作为一个成功 我们的预试验项目的扩展，我们已经修改了EPA的结构，并合成了10个额外的EPA衍生物 化合物，以开发更有效的抗癌剂。我们假设环保署或其 衍生物（统称EPA）对恶性肿瘤和白血病细胞具有抗癌作用 无论是在体外还是在体内。因此，本试验项目的目标是：1）确定抗癌疗效 体外研究EPA对恶性胶质瘤和白血病细胞的作用机制; 2）确定EPA的抗癌作用 在动物癌症异种移植物模型中的先导化合物，和3）检查药代动力学和毒性 的铅化合物。 试点项目与总体优先事项的相关性 该提案的目标是开发与加勒比海隔离的海洋化合物， 科学家（UPR-Rio Piedras）通过与癌症专家的合作， MDACC。我们的研究与U 54的目标密切相关，因为联合领导人寻求继续建立他们的 现有的伙伴关系始于一个预试点（管道）项目。