DCTD Preclinical In Vivo/In Vitro Assay Development

DCTD 临床前体内/体外检测开发

• 批准号: 8008865
• 负责人: LARRY ARTHUR
• 金额: $ 189.3万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-26 至 2018-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8008865
• 关键词: A549; Agar; Antibodies; Antineoplastic Agents; Biological Assay; Biological Testing; Canis familiaris; Cell Line; Cells; Chemicals; Clinic; Clinical; Clinical Research; Clinical Trials; Collaborations; Cultured Cells; Data; Development; Dichloroacetate; Drug Compounding; Enzyme-Linked Immunosorbent Assay; Enzymes; Fiber; Flow Cytometry; Goals; Harvest; Human; Immunohistochemistry; Implant; In Vitro; Laboratories; Lung Neoplasms; Molecular Target; Mus; Normal tissue morphology; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology and Toxicology; Phase; Probability; Proteomics; Protocols documentation; Publishing; RNA; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Specimen; Surrogate Markers; Techniques; Technology; Therapeutic Agents; Tissues; Topotecan; Transfection; Tumor Cell Line; Tumor Tissue; Tumorigenicity; Validation; Western Blotting; Work; analog; assay development; base; cancer stem cell; cell growth; design; drug development; drug mechanism; glucose metabolism; implantation; improved; in vitro Assay; in vivo; interest; member; neoplastic cell; novel; novel strategies; novel therapeutics; pre-clinical; programs; purine riboside; success; technology validation; tool; tumor; tumor xenograft; working group

Drug Mechanism Group (DMG) - The Drug Mechanism Group (DMG) provides dedicated support to the Biological Testing Branch, DTP, NCI. The DMG is responsible for determining the mechanism of action and identifying potential surrogate markers of drug activity for a select number of compounds slated for preclinical development using microarray- and proteomic-based platforms. Inclusive in the proteomics technology are quantitative, subcellular, chemical, and 2D-PAGE proteomics. Validation technology is extensive and includes diverse technologies such as cell-based assays, enzymatic assays, ELISA, flow cytometry, quantitative RT-PCR, Western blot analysis, immunohistochemistry, and various microbiological based assays such as transient/stable transfection assays. Specialized Assays Laboratory (SAL) - The Specialized Assays Laboratory (SAL) provides dedicated support to the Biological Testing Branch. SAL is responsible for: (1) providing soft agar colony formation assays in support of cancer stem cell identification and characterization studies in collaboration with other groups within DTP and NCI and (2) employing novel approaches to characterizing the in vivo tumorigenicity of cancer stem cells grown in athymic and NOD.SCID mice Stromal Targets Laboratory (STL) - The Stromal Targets Laboratory (STL) provides dedicated support to the Biological Testing Branch (BTB) through its molecular targets program. Staff members are skilled in such varied technology as Western blots, flow cytometry, ELISA and other microtiter plate-based arrays such as Meso Scale Discovery Technology. Through collaboration with the BTB, differences between molecular targets identified in lysates prepared from cells in culture, cells harvested from implanted hollow fibers, tumor tissue, or normal tissue are being studied. The goal of these studies is to design in vivo and in vitro assays that better predict the activity and eventual success of a drug/compound before it goes to the clinic. The STL is involved in the Phase 0 clinical trial effort, providing evidence of the effect of new therapeutic agents on their putative targets.

药物机制组（DMG）-药物机制组（DMG）为NCI DTP生物测试分支提供专门支持。DMG负责使用基于微阵列和蛋白质组学的平台确定作用机制，并为选定数量的临床前开发化合物鉴定药物活性的潜在替代标志物。蛋白质组学技术包括定量、亚细胞、化学和2D-PAGE蛋白质组学。验证技术是广泛的，包括多种技术，如基于细胞的测定、酶测定、ELISA、流式细胞术、定量RT-PCR、Western印迹分析、免疫组织化学和各种基于微生物的测定，如瞬时/稳定转染测定。 专业化验实验室（SAL）-专业化验实验室（SAL）为生物检测分支提供专门支持。SAL负责：（1）提供软琼脂集落形成测定法，以支持与DTP和NCI内的其他小组合作进行的癌症干细胞鉴定和表征研究，以及（2）采用新方法来表征在无胸腺和NOD.SCID小鼠中生长的癌症干细胞的体内致瘤性。 基质靶点实验室（STL）-基质靶点实验室（STL）通过其分子靶点计划为生物检测分支（BTB）提供专门支持。工作人员熟练掌握各种技术，如Western印迹、流式细胞术、ELISA和其他基于微量滴定板的阵列，如Meso Scale Discovery Technology。通过与BTB的合作，正在研究从培养细胞制备的裂解物、从植入的中空纤维、肿瘤组织或正常组织中收获的细胞中鉴定的分子靶点之间的差异。这些研究的目的是设计体内和体外测定，以便在药物/化合物进入临床之前更好地预测其活性和最终成功。STL参与了0期临床试验工作，提供了新治疗药物对其假定靶点的影响的证据。