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
- 来源:
- 关键词:amidohydrolases clinical trial phase I combination cancer therapy complementary DNA drug screening /evaluation enzyme inhibitors gene induction /repression human subject human therapy evaluation interferon alpha kidney neoplasms laboratory mouse liposomes metastasis neoplasm /cancer chemotherapy neoplasm /cancer genetics neoplasm /cancer immunotherapy neoplasm /cancer nutrition therapy nonhuman therapy evaluation nutrition aspect of cancer nutrition related tag patient oriented research retinoate western blottings
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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