NQO1/SLC711A Assay, Total RNA isolation and running custom TaqMan cards (TLDA) assay on up to 486 PAXgene Blood RNA Samples

NQO1/SLC711A 检测、总 RNA 分离以及对多达 486 个 PAXgene 血液 RNA 样本运行定制 TaqMan 卡 (TLDA) 检测

• 批准号: 10038627
• 负责人: LEONARD FREEDMAND
• 金额: $ 15万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-31 至 2020-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10038627
• 关键词: Acute Myelocytic Leukemia; Adolescent and Young Adult; Adult; Azacitidine; Biological Assay; Biological Markers; Blood; Blood specimen; CDT1 Gene; Carboplatin; Child; Custom; Cytarabine; Dysmyelopoietic Syndromes; Gene Expression; Genes; Immunotherapy; Measures; Multiple Myeloma; NQO1 gene; Non-Small-Cell Lung Carcinoma; Paclitaxel; Patients; Pharmacodynamics; Phase; Proteins; Protocols documentation; RNA; Randomized; Refractory; Relapse; Reverse Transcriptase Polymerase Chain Reaction; Running; Sampling; Ubiquitin Like Proteins; Walkers; Whole Blood; base; feasibility trial; fludarabine; healthy volunteer; phase 2 study; phase II trial; prevent

NCI Protocol(s): 10247 “A randomized phase II trial of pevonedistat with Azacitidine versus Azacitidine in adult relapsed or refractory acute myeloid leukemia”; 10249 “Ixazomib and Pevonedistat in Relapsed/Refractory Multiple Myeloma Patients: A Phase Ib Trial”; 10246 “Pevonedistat and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome”; 10266 “A Phase 2 Study of Pevonedistat in Combination with Carboplatin and Paclitaxel in Advanced NSCLC Previously Treated with Immunotherapy”; ADVL1712 – “A Feasibility Trial of Pevonedistat Given in Combination with Azacitidine, Fludarabine, and Cytarabine, in Children, Adolescents, and Young Adults with Relapsed or Refractory Acute Myeloid Leukemia” NAE activates the ubiquitin-like protein NEDD8 for conjugation to CRLs and, therefore, regulates the proteasomal destruction of CRL substrate proteins. NAE inhibition prevents degradation of CRL substrates (e.g., NRF2, CDT1), leading to their accumulation. To develop a pharmacodynamic assay, Walker et al. (2011) developed a RT-PCR-based assay using blood samples from multiple healthy volunteers that were treated ex vivo with a range of MLN4924 (pevonedistat) concentrations. Eight genes (including the NRF2-regulated genes NQO1 and SLC7A11) displayed a robust induction (>3-fold) in whole blood. This assay is aimed at assessing whether MLN4924 target engagement, as measured by increased NRF2-regulated NQO1 and SLC7A11 gene expression in whole blood by RT-PCR, is a biomarker of MLN4924 activity.

NCI方案(s): 10247“一项随机II期试验，佩维奈远特联合阿扎胞苷与阿扎胞苷治疗成人复发或难治性急性髓性白血病”；10249《伊沙唑米和佩维奈远治疗复发/难治性多发性骨髓瘤：Ib期试验》；[10246]佩伐尼他和贝利诺他治疗复发/难治性急性髓系白血病或骨髓增生异常综合征；10266《佩onedistat联合卡铂和紫杉醇治疗已接受免疫治疗的晚期NSCLC的2期研究》；ADVL1712 -佩维奈远特联合阿扎胞苷、氟达拉滨和阿糖胞苷治疗复发或难治性急性髓性白血病儿童、青少年和年轻人的可行性研究