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Grant Details

Grant Number: 7R01CA068565-05 Interpret this number
Primary Investigator: Schwartz, Gary
Organization: Wake Forest University Health Sciences
Project Title: Prostate Cancer & Vitamin D-Receptors, Responses & Race
Fiscal Year: 1998
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Abstract

The Principal lnvestigator and colleagues have pioneered the hypothesis that deficiencies of 1,25-Dihydroxyvitamin D (1,25 D) increase the risk for clinical prostate cancer. This hypothesis led us to investigate the effects of vitamin D on established prostate cancer cell lines. We found that cells from an invasive prostate cancer cell line did not respond to vitamin D despite the presence of vitamin D receptors; whereas, a non- invasive prostate cancer cell line was sensitive to 1 ,25 D. This suggests that a deficient response to 1,25 D may be a characteristic of invasive prostate cancer cells. We will test the hypothesis that invasive prostate cancer cells exhibit diminished biochemical response to vitamin D compared to non-cancer prostate cells. Our Specific Aims are to: 1. ascertain vitamin D receptor levels and vitamin D responsiveness in invasive prostate cancer cells and in non-cancer prostate cells; 2. determine how these receptor levels and responses differ among men from 3 racial/ethnic groups at different risk for prostate cancer. In order to realize these aims we will: 1. Obtain surgical specimens of fresh prostatic tissue from Black, White, and Hispanic prostate cancer patients undergoing radical prostatectomy at the University of Miami/Jackson Memorial Medical Center; 2. Prepare primary cultures of invasive prostate cancer and non-cancer prostate cells from each patient using an in vitro cell invasion assay; 3. Assess vitamin D receptor levels and vitamin D receptor function by reporter gene assay. Our primary goal is to determine whether vitamin D sensitivity differentiates invasive prostate cancer from non-cancerous prostate cells. This research may ultimately permit the identification of those prostate cancers that are likely to be invasive. The identification of invasive prostate cancer is critical in determining which men should receive aggressive treatment for their disease.

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Publications

Vitamin D and the epidemiology of prostate cancer.
Authors: Schwartz G.G. .
Source: Seminars in dialysis, 2005 Jul-Aug; 18(4), p. 276-89.
PMID: 16076349
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The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D.
Authors: Young M.V. , Schwartz G.G. , Wang L. , Jamieson D.P. , Whitlatch L.W. , Flanagan J.N. , Lokeshwar B.L. , Holick M.F. , Chen T.C. .
Source: Carcinogenesis, 2004 Jun; 25(6), p. 967-71.
EPub date: 2004-01-16.
PMID: 14729578
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Evaluation of vitamin D analogs as therapeutic agents for prostate cancer.
Authors: Chen T.C. , Holick M.F. , Lokeshwar B.L. , Burnstein K.L. , Schwartz G.G. .
Source: Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer, 2003; 164, p. 273-88.
PMID: 12899529
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25-Hydroxyvitamin D-1alpha-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer.
Authors: Whitlatch L.W. , Young M.V. , Schwartz G.G. , Flanagan J.N. , Burnstein K.L. , Lokeshwar B.L. , Rich E.S. , Holick M.F. , Chen T.C. .
Source: The Journal of steroid biochemistry and molecular biology, 2002 Jun; 81(2), p. 135-40.
PMID: 12137802
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The G gamma / T-15 transgenic mouse model of androgen-independent prostate cancer: target cells of carcinogenesis and the effect of the vitamin D analogue EB 1089.
Authors: Perez-Stable C.M. , Schwartz G.G. , Farinas A. , Finegold M. , Binderup L. , Howard G.A. , Roos B.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002 Jun; 11(6), p. 555-63.
PMID: 12050097
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The in vitro evaluation of 25-hydroxyvitamin D3 and 19-nor-1alpha,25-dihydroxyvitamin D2 as therapeutic agents for prostate cancer.
Authors: Chen T.C. , Schwartz G.G. , Burnstein K.L. , Lokeshwar B.L. , Holick M.F. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2000 Mar; 6(3), p. 901-8.
PMID: 10741714
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Inhibition of prostate cancer metastasis in vivo: a comparison of 1,23-dihydroxyvitamin D (calcitriol) and EB1089.
Authors: Lokeshwar B.L. , Schwartz G.G. , Selzer M.G. , Burnstein K.L. , Zhuang S.H. , Block N.L. , Binderup L. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 1999 Mar; 8(3), p. 241-8.
PMID: 10090302
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1 alpha,25-Dihydroxyvitamin D (calcitriol) inhibits the invasiveness of human prostate cancer cells.
Authors: Schwartz G.G. , Wang M.H. , Zang M. , Singh R.K. , Siegal G.P. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 1997 Sep; 6(9), p. 727-32.
PMID: 9298581
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