H-26071 ADVL0916 - A PHASE I STUDY OF VORINOSTAT AND BORTEZOMIB IN CHILDREN WITH

H-26071 ADVL0916 - 伏立诺他和硼替佐米治疗儿童的 I 期研究

基本信息

  • 批准号:
    8356745
  • 负责人:
  • 金额:
    $ 1.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-12-01 至 2011-11-30
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Vorinostat (Suberylanilide hydroxamic acid (SAHA), Zolinza¿, IND #71976) is a histone deacetylase inhibitor that inhibits the activity of histone deacetylases (HDACs). HDACs repress gene transcription. In some cancer cells, there is an overexpression of HDACs, or an aberrant recruitment of HDACs to oncogenic transcription factors. Inhibition of HDAC activity results in an open chromatin structure and transcriptional activation. In vitro, vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of vorinostat has not been fully characterized.1 Bortezomib (PS-341, Velcade¿, IND #58443) is a reversible small molecule inhibitor of the 26S proteasome that degrades ubiquitinated proteins. The ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. Bortezomib exerts its antitumor effect through several distinct mechanisms, including inhibition of cell growth and survival pathways, induction of apoptosis, and inhibition of expression of genes that control cellular adhesion, migration, and angiogenesis. The disruption of normal homeostatic mechanisms can lead to cell death.2 The combination of vorinostat and bortezomib has been shown to be synergistic in vitro in a variety of malignancies, including hepatoma,3 multiple myeloma, leukemia, lymphoma and gastrointestinal cancer. These studies showed that there are multiple levels of potential interaction between vorinostat and bortezomib which could explain their observed synergistic activity. These include NF-B inhibition, increased reactive oxygen species production, increased levels of cyclin-dependent kinase inhibitors, increased proteasome inhibition, and increased expression of tumor suppressor genes such as p53, E2F, and Bax. Additionally, vorinostat may disrupt bortezomib-induced aggresome formation resulting in increased cell stress and apoptosis.11 Phase 1 trials in adults of vorinostat in combination of bortezomib demonstrate that this drug combination was generally well-tolerated. This is a phase 1 study of vorinostat administered orally on days 1-5 and 8-12 in combination with bortezomib administered intravenously on days 1, 4, 8, and 11 of a 21 day cycle. It is designed to determine safety of this drug combination in children with refractory or recurrent solid tumors. The correlative studies will assess NF-B inhibition and endoplasmic reticulum stress response in peripheral blood mononuclear cells (PBMC) before and after treatment.
这个子项目是利用这些资源的众多研究子项目之一

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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PATRICK THOMPSON其他文献

PATRICK THOMPSON的其他文献

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{{ truncateString('PATRICK THOMPSON', 18)}}的其他基金

ADVL06B1 A PHARMACOKINETIC-PHARMACODYNAMIC PHARMACOGENETIC STUDY OF ACTINOMYCIN-
ADVL06B1 放线菌素的药代动力学-药效动力学研究
  • 批准号:
    8356706
  • 财政年份:
    2010
  • 资助金额:
    $ 1.42万
  • 项目类别:
CLINICAL TRIAL: ADVL0813 A PHASE I STUDY OF IMC-A12 (ANTI-INSULIN-LIKE GROWTH F
临床试验:ADVL0813 IMC-A12(抗胰岛素样生长 F)的 I 期研究
  • 批准号:
    8356729
  • 财政年份:
    2010
  • 资助金额:
    $ 1.42万
  • 项目类别:
ADVL0911 A PHASE 1 DOSE ESCALATION STUDY OF SENECA
ADVL0911 SENECA 的 1 期剂量递增研究
  • 批准号:
    8356732
  • 财政年份:
    2010
  • 资助金额:
    $ 1.42万
  • 项目类别:
CLINICAL TRIAL: A PHASE 1 STUDY OF TEMSIROLIMUS IN COMBINATION WITH IRINOTECAN
临床试验:替西罗莫司联合伊立替康的 1 期研究
  • 批准号:
    8356756
  • 财政年份:
    2010
  • 资助金额:
    $ 1.42万
  • 项目类别:
CLINICAL TRIAL: A PHASE I STUDY OF VORINOSTAT AND TEMOZOLOMIDE
临床试验:伏立诺他和替莫唑胺的 I 期研究
  • 批准号:
    8356753
  • 财政年份:
    2010
  • 资助金额:
    $ 1.42万
  • 项目类别:
CLINICAL TRIAL: H-25421: ADVL0815: A PHASE I STUDY OF PAZOPANIB AS A SINGLE AGE
临床试验:H-25421:ADVL0815:单龄帕唑帕尼的 I 期研究
  • 批准号:
    8356731
  • 财政年份:
    2010
  • 资助金额:
    $ 1.42万
  • 项目类别:
H-25893 ADVL0912, A PHASE 1/2 STUDY OF PF-02341066, AN ORAL SMALL MOLECULE
H-25893 ADVL0912,口服小分子 PF-02341066 的 1/2 期研究
  • 批准号:
    8356746
  • 财政年份:
    2010
  • 资助金额:
    $ 1.42万
  • 项目类别:
ADVL0919: A PHASE 1 STUDY OF RO4929097, AN ORAL SMALL MOLECULE INHIBITOR OF GAMM
ADVL0919:RO4929097(一种口服 GAMM 小分子抑制剂)的 1 期研究
  • 批准号:
    8356757
  • 财政年份:
    2010
  • 资助金额:
    $ 1.42万
  • 项目类别:
CLINICAL TRIAL: H-23957 ADVL0812 A PHASE I STUDY OF MLN8237, AN ORAL SELECTIVE S
临床试验:H-23957 ADVL0812 MLN8237(一种口服选择性药物)的 I 期研究
  • 批准号:
    8166731
  • 财政年份:
    2009
  • 资助金额:
    $ 1.42万
  • 项目类别:
CLINICAL TRIAL: A PHASE I STUDY OF THE RAF KINASE AND RECEPTOR TYROSINE KINASE I
临床试验:RAF 激酶和受体酪氨酸激酶 I 的 I 期研究
  • 批准号:
    8166686
  • 财政年份:
    2009
  • 资助金额:
    $ 1.42万
  • 项目类别:

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