COG ADVL0416: A PHASE 1 STUDY OF SAHA IN PEDIATRIC PATIENTS WITH RECURRENT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 这是一项辛二酰苯胺异羟肟酸（SAHA）治疗儿童和青少年复发性或难治性实体瘤或白血病的I期研究。SAHA是组蛋白去乙酰化酶（HDAC）的抑制剂，可导致细胞周期转换停滞在G1和G2 M期。已报道其选择性诱导p21 waf/CIP 1细胞周期蛋白依赖性激酶抑制剂的表达，影响细胞周期阻滞1和诱导p53非依赖性凋亡。SAHA的抗肿瘤作用的一个可能的模型是抑制HDAC活性，导致基因转录的激活，这些基因的表达迫使肿瘤分化、凋亡或抑制肿瘤生长。 视黄酸受体在缺乏配体的情况下与HDAC活性募集共调节复合物，这导致基因转录的抑制。 本研究将分三部分进行。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a phase I study of suberoylanilide hydroxamic acid (SAHA) in children and adolescents with recurrent or refractory solid tumors or leukemia. SAHA is an inhibitor of histone deacetylase (HDAC) that causes the arrest of cell cycle transition at G1 and G2M phases. It has been reported to selectively induce expression of p21 waf/CIP1 cyclin-dependent kinase inhibitor, to effect cell cycle arrest1 and to induce p53 independent apoptosis. A possible model for the antitumor action of SAHA is the inhibition of HDAC activity causing the activation of transcription of genes whose expression force tumor differentiation, apoptosis or inhibit tumor growth. Retinoid acid receptors recruit co-regulatory complexes with HDAC activity in the absence of a ligand, which results in repression of gene transcription. This study will be done in 3 parts.