Modulation of retinoic acid action in renal cancer

视黄酸在肾癌中作用的调节

基本信息

  • 批准号:
    6369218
  • 负责人:
  • 金额:
    $ 35.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-08-03 至 2006-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: (Provided by applicant) Renal cell carcinoma is the most common primary cancer arising from the kidney in adults, and is a frequent cause of cancer morbidity and mortality in the U.S., with over 12,000 deaths per year. Currently, there are no consistently effective chemotherapeutic or biologic treatment modalities for patients with advanced disease. Recent results of clinical trials in patients with advanced renal cancer (RC), and of pre-clinical studies using cell culture and human RC tissue specimens, suggest that natural and synthetic derivatives of vitamin A (retinol), a group of compounds called retinoids, play a role in the therapy of RC. We have preliminary data that intracellular levels of retinoic acid (RA) are significantly diminished in human RC cells and that retinol metabolism is aberrant in RC cells as compared to normal human kidney proximal tubule cells. Furthermore, our data indicate that combining retinoids with agents which augment retinoid actions, such as IFN (IFN) or histone deacetylase (HDAC) inhibitors, significantly increases the anti-tumor effect of RA. In this grant application, we propose to study the effects of modulating retinoid anti-tumor action by combining RA with other therapies. The specific aims are: 1) to perform a series of Phase I-II clinical trials designed to evaluate the safety and efficacy of combining liposomal all trans RA (ATRA) with modulators of RA such as interferon and HDAC inhibitors in patients with metastatic RC; 2) to collect peripheral blood samples and tumor tissues to allow laboratory analysis in order to monitor the presence and magnitude of specific therapies on retinoid metabolites and retinoid related genes; and 3) to analyze modulators of RA such as interferon and HDAC inhibitors at a molecular level in RC cell lines and xenograft models to delineate mechanisms of action, and to use this information to design strategies to test specific drugs in combination with RA in preparation for future clinical trials. These aims will allow us to perform clinical trials and laboratory studies aimed at gaining a better understanding of the involvement of retinoids in the development, progression and therapy of RC. Moreover, the experiments proposed in this application will help to clarify the potential use of retinoids as a therapeutic strategy to treat patients with RC, and may lead to the identification of new therapeutic agents which result in increased retinol actions for the treatment of various stages of renal cancer.
描述:(申请人提供)肾细胞癌是成人肾脏最常见的原发癌症,是引起肾细胞癌的常见原因

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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David M. Nanus其他文献

149: Lentiviral Vector Neutral Endopeptidase Gene Transfer Suppresses Prostate Cancer Tumor Growth
  • DOI:
    10.1016/s0022-5347(18)30414-2
  • 发表时间:
    2007-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Akio Horiguchi;Ruoqian Shen;Rang Zheng;Oscar B. Goodman;Hanjun Guan;Louis B. Hersh;David M. Nanus
  • 通讯作者:
    David M. Nanus
Novel targets in altered tumour metabolism in kidney cancer
肾癌中肿瘤代谢改变的新靶点
  • DOI:
    10.1038/nrurol.2015.168
  • 发表时间:
    2015-07-28
  • 期刊:
  • 影响因子:
    14.600
  • 作者:
    Denise R. Minton;David M. Nanus
  • 通讯作者:
    David M. Nanus
Infrequent <em>ras</em> Oncogene Point Mutations in Renal Cell Carcinoma
  • DOI:
    10.1016/s0022-5347(17)39905-6
  • 发表时间:
    1990-01-01
  • 期刊:
  • 影响因子:
    0.4
  • 作者:
    David M. Nanus;Iris R. Mentle;Robert J. Motzer;Neil H. Bander;Anthony P. Albino
  • 通讯作者:
    Anthony P. Albino
608: Neutral Endopeptidase Targeted to Prostate Cancer Cells Via Fusion with an Anti-Prostate Specific Membrane Antigen Monoclonal Antffiody
  • DOI:
    10.1016/s0022-5347(18)37870-4
  • 发表时间:
    2004-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    David Y.T. Chen;Ruoqian Shen;Daniel Navarro;Neil H. Bander;Michael C. Gong;Michel Sadelain;David M. Nanus
  • 通讯作者:
    David M. Nanus
MP50-19 DOSE-FRACTIONATED ANTI-PSMA RADIOIMMUNOTHERAPY (<sup>177</sup>LU-J591) FOR MCRPC
  • DOI:
    10.1016/j.juro.2016.02.453
  • 发表时间:
    2016-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Jaspreet S. Batra;Beerinder Karir;Kavya Pinto-Chengot;Yuliya S. Jhanwar;Shankar Vallabhajosula;Paul J. Christos;Gillian Hodes;Linda Lam;Ana Molina;Himisha Beltran;Stanley J. Goldsmith;David M. Nanus;Neil H. Bander;Scott T. Tagawa
  • 通讯作者:
    Scott T. Tagawa

David M. Nanus的其他文献

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{{ truncateString('David M. Nanus', 18)}}的其他基金

PHASE II TRIAL OF 177LU-J591 IN METASTATIC, ANDROGEN-INDEPENDENT PROSTATE CANCER
177LU-J591 治疗不依赖雄激素的转移性前列腺癌的 II 期试验
  • 批准号:
    7604180
  • 财政年份:
    2007
  • 资助金额:
    $ 35.17万
  • 项目类别:
PHASE I TRIAL OF ATRA-IV & DEPAKOTE IN PTS W/ADVANCED SOLID TUMOR MALIGNANCIES
ATRA-IV 的 I 期试验
  • 批准号:
    7378405
  • 财政年份:
    2006
  • 资助金额:
    $ 35.17万
  • 项目类别:
PHASE I TRIAL OF ATRA-IV & DEPAKOTE IN PTS W/ADVANCED SOLID TUMOR MALIGNANCIES
ATRA-IV 的 I 期试验
  • 批准号:
    7200405
  • 财政年份:
    2005
  • 资助金额:
    $ 35.17万
  • 项目类别:
Phase I 111-Indium radiolabeled mAb huJ591/ metastatic solid tumors
I 期 111-铟放射性标记单克隆抗体 huJ591/转移性实体瘤
  • 批准号:
    7040610
  • 财政年份:
    2004
  • 资助金额:
    $ 35.17万
  • 项目类别:
Chemoprevention of Prostate Cancer with Finasteride
非那雄胺化学预防前列腺癌
  • 批准号:
    7040595
  • 财政年份:
    2004
  • 资助金额:
    $ 35.17万
  • 项目类别:
Modulation of retinoic acid action in renal cancer
视黄酸在肾癌中作用的调节
  • 批准号:
    6522891
  • 财政年份:
    2001
  • 资助金额:
    $ 35.17万
  • 项目类别:
Modulation of retinoic acid action in renal cancer
视黄酸在肾癌中作用的调节
  • 批准号:
    6642797
  • 财政年份:
    2001
  • 资助金额:
    $ 35.17万
  • 项目类别:
Modulation of retinoic acid action in renal cancer
视黄酸在肾癌中作用的调节
  • 批准号:
    6804992
  • 财政年份:
    2001
  • 资助金额:
    $ 35.17万
  • 项目类别:
Modulation of retinoic acid action in renal cancer
视黄酸在肾癌中作用的调节
  • 批准号:
    6923660
  • 财政年份:
    2001
  • 资助金额:
    $ 35.17万
  • 项目类别:
ANTI TUMOR THERAPIES FOR GENIOTURINARY MALIGNANCIES
泌尿生殖系统恶性肿瘤的抗肿瘤治疗
  • 批准号:
    6377793
  • 财政年份:
    2000
  • 资助金额:
    $ 35.17万
  • 项目类别:

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