Pediatric Preclinical Testing Consortium: Research Programs non-CNS

儿科临床前测试联盟：非中枢神经系统研究项目

• 批准号: 10076139
• 负责人: PETER J HOUGHTON
• 金额: $ 31.52万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10076139
• 关键词: Cells; Childhood; Childhood Solid Neoplasm; Data; Drug Combinations; Ewings sarcoma; Future; In Vitro; Kidney; Kidney Neoplasms; Manuscripts; Modeling; Molecular; New Agents; Pre-Clinical Model; Preclinical Testing; Radiation; Renal carcinoma; Reporting; Research; Rhabdomyosarcoma; Vincristine; Xenograft Model; childhood sarcoma; cohort; exome; exome sequencing; high risk; in vivo; novel; novel drug combination; programs; sarcoma; screening; transcriptome sequencing

The group at GCCRI will continue studies focused on identifying active agents and combinations using xenograft models of pediatric sarcoma and kidney tumors. We will complete ongoing studies, and start new studies as described below. In addition we plan to characterize 18 new sarcoma PDX models (exome seq and RNAseq), and complete characterization of 33 PDX models where we have exome sequence data from the TARGET initiative, but where we lack RNAseq data. This will greatly expand the number of available sarcoma models that can be used in the future PPP being developed by the FNIH. Our aims for the 6 month extension are: Specific Aims Proposed studies during the extension period. 1. Complete studies with Amgen 509 (ES-7, ES-3, EW-5). 2. Complete in vivo studies with ONC201. 3. Undertake screening for PPTC drugs/combinations. 4. Evaluate PLX-038A combined with vincristine in sarcoma and kidney models. 5. Evaluate Talazoparib + Radiation in CHLA258 cell in vitro and in vivo, then expand if justified 6. To characterize 33 models by RNAseq that were omitted from the ALS cohort. 7 To characterize 18 rhabdomyosarcoma and 5 Ewing sarcoma PDX models, not previously characterized. 8. Complete submission of manuscripts reporting PPTC results.

GCCRI的团队将继续专注于识别活性物质和 联合使用儿童肉瘤和肾脏肿瘤的异种移植模型。我们将完成 正在进行的研究，并开始新的研究，如下所述。此外，我们还计划将 18个新的肉瘤PDX模型(Exome seq和RNAseq)，以及33个完整的特征 PDX模型，其中我们有来自目标计划的外显子组序列数据，但我们 缺乏RNAseq数据。这将极大地扩大可用的肉瘤模型的数量 用于FNIH正在开发的未来PPP。我们延长6个月的目标是： 具体目标 在延长期内拟进行的研究。 1.使用Amgen 509(ES-7、ES-3、EW-5)完成研究。 2.利用ONC201完成体内实验。 3.对PPTC药物/组合进行筛查。 4.评价PLX-038A联合长春新碱对肉瘤和肾脏模型的作用。 5.评估他唑帕利布+在体外和体内对CHLA258细胞的辐射，如果合理则扩大 6.用RNAseq对ALS队列中遗漏的33个模型进行特征分析。 7以鉴定18个横纹肌肉瘤和5个尤文肉瘤PDX模型，而不是以前 特色化的。 8.完成PPTC结果报告手稿的提交。