Core E

临床前测试核心(PTC)将针对新确定的目标验证药物的活性 -发育中的实体瘤细胞系和异种移植瘤细胞。核心的具体目标包括：1) 维持和发展具有代表性的儿科实体瘤细胞系和异种移植瘤细胞系，2)快速 在具有代表性的儿童实体瘤细胞系(Level)中体外筛选潜在的新药物 1)，3)在小鼠MTD进行潜在新制剂的体内测试，以确定那些适合于 高级评估(2级)，以及4)选定药物的体内高级评估(3级)。 1级测试将包括针对一组细胞系的新靶向治疗的体外分析 包括OS、ESFT、RMS、DSRCT和NB。那些在体外表现出细胞毒作用的药物 在人体内或在没有已知MTD的情况下可以达到的浓度 相关化疗药物将进入二级检测。2级测试包括 该化合物的小鼠种属特异性MTD测定及抗肿瘤活性评价 新制剂对荷瘤小鼠MTD的影响。那些显示出有希望的活性的代理 将升级到3级测试。对于非细胞毒性药物，生物终点，如靶向结合或 抑制力，将进行评估。3级试验包括确定以下物质的剂量-反应关系 新化合物的体内药代动力学和潜在相互作用 与合理选择已知化疗药物相结合。包括免疫在内的其他模式 完整或异位/转移性肿瘤将被考虑。临时技术合作中心将促进在具体领域的快速进展 项目通过1)确定那些具有抗儿童肿瘤综合小组活性的药物 体外实验，2)为评价儿童肿瘤异种移植模型中的新药物提供了一种有效的手段 3)为临床研究提供标准化的临床前测试和新药物优先排序系统。

The Preclinical Testing Core (PTC) will validate the activity of agents against newly identified targets in _anels of developmental solid tumor cell lines and xenografts. Specific aims of the core include: 1) maintaining and developing a representative panel of pediatric solid tumor cell lines and xenografts, 2) rapid in vitro screening of potential new agents in a representative panel of pediatric solid tumor cell lines (Level 1), 3) in vivo testing of potential new agents at the murine MTD to identiy those agent appropriate for advanced evaluation (Level 2), and 4) advanced in vivo evaluation of selected agents (Level 3). Level 1 testing will include the in vitro analysis of new targeted therapies against a panel of cell lines including OS, ESFT, RMS, DSRCT and NB. Those agents that demonstrate in vitro cytotoxic effects at concentrations that can be achieved in humans or for agents without a known MTD by comparison with related chemotherapeutic agents will be advanced to Level 2 testing. Level 2 testing includes the determination of the murine species-specific MTD for the compound, and the evaluation of the anti-tumor effect of the new agent at that MTD in tumor-bearing mice. Those agents that demonstrate promising activity will be advanced to Level 3 testing. For non-cytotoxic agents, biologic endpoints, such as target binding or inhibition, will be evaluated. Level 3 testing includes the determination of a dose-response relationship for the new compound, the in vivo pharmacokinetics and the potential interaction of the new compound in combination with rationally chosen known chemotherapeutic agents. Alternative models including immune intact or heterotopic/metastatic tumors will be considered. The PTC will facilitate rapid advances in specific projects by 1) identifying those agents with activity against a comprehensive panel of pediatric tumors in vitro, 2) providing an efficient means of evaluating new agents in xenograft models of pediatric tumors and 3) providing a standardized system of preclinical testing and prioritization of new agents for clinical studies.