HHSN2612012000201/HHSN26100006 Title: Preclinical In Vitro And In Vivo Screening Assays For Cancer Preventative Reagent Development, Project: Targeting CCK2R for Pancreatic Cancer Prevention

HHSN2612012000201/HHSN26100006 标题：癌症预防试剂开发的临床前体外和体内筛选测定，项目：靶向 CCK2R 预防胰腺癌

• 批准号: 8944735
• 负责人: CHINTHALAPALLY RAO
• 金额: $ 47.46万
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-26 至 2016-08-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8944735
• 关键词: Animal Model; Biological Assay; Biological Markers; Breeding; Clinical Research; Contractor; Contracts; Development; Dose; Gene Expression Profile; In Vitro; Malignant Neoplasms; Malignant neoplasm of pancreas; Maximum Tolerated Dose; Mediating; Messenger RNA; MicroRNAs; Mus; Pathway interactions; Pharmacodynamics; Phase; Positron-Emission Tomography; Pre-Clinical Model; Reagent; Signal Transduction; Toxic effect; Transgenic Mice; Treatment Protocols; cancer chemoprevention; cancer prevention; design; in vivo; mouse model; pancreatic neoplasm; pre-clinical; response; screening; tumor growth

The contract is to evaluate two selective CCR2R antagonists, (YF476 and JNJ-26070109) for pancreatic cancer prevention in preclinical models. Specifically, the Contractor shall establish the optimal dose and maximal tolerated dose (MTD) of these two antagonists in mice and then assess the pancreatic cancer prevention efficacy in p48Cre/+-LSL-KrasG12D/+ transgenic mouse model of pancreatic cancer. In addition, the Contractor shall explore critical biomarkers of pharmacodynamic efficacy, which will be applicable to early-phase clinical studies.

该合同旨在评估两种选择性CCR 2 R拮抗剂（YF 476和JNJ-26070109）在临床前模型中预防胰腺癌的作用。具体而言，承包商应确定这两种拮抗剂在小鼠中的最佳剂量和最大耐受剂量（MTD），然后在p48 Cre/+-LSL-KrasG 12 D/+转基因胰腺癌小鼠模型中评估胰腺癌预防效果。此外，承包商应探索药效学功效的关键生物标志物，这将适用于早期临床研究。