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:6642797
- 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 research clinical trial phase I clinical trial phase II 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:(由申请人提供)肾细胞癌是最常见的 成人肾脏原发性癌症,是导致
癌症发病率和死亡率在美国,每年有超过一万两千人死亡
目前,没有持续有效的化疗或生物制剂,
晚期疾病患者的治疗方式。最近的结果
晚期肾癌(RC)患者的临床试验,
使用细胞培养和人RC组织标本的临床前研究表明,
维生素A(视黄醇)的天然和合成衍生物,
称为类维生素A的化合物在RC的治疗中起作用。我们有
初步数据表明,细胞内维甲酸(RA)水平是
在人RC细胞中显著减少,
与正常人肾近端小管细胞相比,RC细胞中的细胞凋亡异常。
此外,我们的数据表明,将类维生素A与
增强类维生素A作用,如IFN(IFN)或组蛋白脱乙酰酶(HDAC)
抑制剂,显著增加RA的抗肿瘤作用。在这份赠款中,
应用,我们建议研究调节类维生素A抗肿瘤的作用
将RA与其他疗法结合。具体目标是:1)
进行一系列I-II期临床试验,旨在评估
以及脂质体全反式RA(ATRA)与RA调节剂组合的功效
例如干扰素和HDAC抑制剂; 2)
采集外周血样本和肿瘤组织,以便进行实验室分析
为了监测特定治疗的存在和程度,
类维生素A代谢物和类维生素A相关基因;和3)分析调节剂
RA如干扰素和HDAC抑制剂在RC细胞中的分子水平
线和异种移植模型来描绘作用机制,并使用这种
信息设计策略,以测试特定药物与RA的组合
为将来的临床试验做准备。这些目标将使我们能够执行
临床试验和实验室研究旨在更好地了解
类维生素A参与的发展,进展和治疗,
RC.此外,本申请中提出的实验将有助于澄清
类维生素A作为治疗策略的潜在用途,
RC,并可能导致识别新的治疗药物,
在增加视黄醇的作用,用于治疗各种阶段的肾
癌
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:
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:
Modulation of retinoic acid action in renal cancer
视黄酸在肾癌中作用的调节
- 批准号:
6369218 - 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:
6649774 - 财政年份:2000
- 资助金额:
$ 35.17万 - 项目类别:
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