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Prostate cancer chemoprevention with...

The University of Alabama at Birmingham.

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Prostate cancer chemoprevention with genistein and resveratrol in models of spontaneously developing prostate cancer.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Prostate cancer chemoprevention with genistein and resveratrol in models of spontaneously developing prostate cancer./
Author:	Harper, Curt E.
Description:	182 p.
Notes:	Adviser: Coral A. Lamartiniere.
Contained By:	Dissertation Abstracts International69-02B.
Subject:	Health Sciences, Nutrition. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3301375
ISBN:	9780549468417

Prostate cancer chemoprevention with genistein and resveratrol in models of spontaneously developing prostate cancer.
Harper, Curt E.

Prostate cancer chemoprevention with genistein and resveratrol in models of spontaneously developing prostate cancer. - 182 p.

Adviser: Coral A. Lamartiniere.

Thesis (Ph.D.)--The University of Alabama at Birmingham, 2007.

Prostate cancer is the second leading cause of cancer-related death among men in the United States. The goal of this research was to investigate the potential of three nutriceutical polyphenols, genistein, resveratrol, and epigallocatechin-3-gallate (EGCG), to suppress prostate cancer. Cancer chemoprevention and mechanism of action studies were carried out in transgenic models of prostate cancer. In TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, resveratrol suppressed poorly differentiated tumors by 86%, whereas EGCG suppressed precancerous lesions, but failed to prevent late-stage prostate cancer. Agents that were chemopreventive in the TRAMP model were subsequently evaluated alone, and in combination, in the newly developed SV-40 Tag transgenic rat model. Genistein and resveratrol, alone and in combination, suppressed prostate cancer in SV-40 Tag transgenic rats, but not in an additive or synergistic manner when compared to the single agent treatments. Using immunoassay techniques, we demonstrated a reduction in cell proliferation and an induction of apoptosis in polyphenol-treated animals. We also found down-regulation of growth factor signaling and a modulation of sex steroid receptors. Specifically, all polyphenols reduced insulin-like growth factor-1 protein expression and its downstream effector, phospho-extracellular signal regulated kinase in the prostate. Genistein and EGCG down-regulated androgen receptor, whereas genistein decreased epidermal growth factor receptor and resveratrol up-regulated proposed tumor suppressor, estrogen receptor-beta protein expression. We determined genistein and resveratrol concentrations in blood serum via HPLC/MS to be 2160 nM and 212 nM in genistein- and resveratrol-treated rats, respectively. The regulation of biomarkers known to play a role in prostate carcinogenesis, alterations in cell turnover, and high, but biologically achievable concentrations of polyphenols in the blood most likely account for the chemoprevention observed. In summary, genistein and resveratrol are promising weapons in the fight against prostate cancer and the SV-40 Tag transgenic rat model is a useful tool in evaluating the chemopreventive properties of potential agents.

ISBN: 9780549468417Subjects--Topical Terms:

1017801
Health Sciences, Nutrition.

Prostate cancer chemoprevention with genistein and resveratrol in models of spontaneously developing prostate cancer.
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020 $a 9780549468417
035 $a (UMI)AAI3301375
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100 1 $a Harper, Curt E. $3 1021720
245 1 0 $a Prostate cancer chemoprevention with genistein and resveratrol in models of spontaneously developing prostate cancer.
300 $a 182 p.
500 $a Adviser: Coral A. Lamartiniere.
500 $a Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0949.
502 $a Thesis (Ph.D.)--The University of Alabama at Birmingham, 2007.
520 $a Prostate cancer is the second leading cause of cancer-related death among men in the United States. The goal of this research was to investigate the potential of three nutriceutical polyphenols, genistein, resveratrol, and epigallocatechin-3-gallate (EGCG), to suppress prostate cancer. Cancer chemoprevention and mechanism of action studies were carried out in transgenic models of prostate cancer. In TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, resveratrol suppressed poorly differentiated tumors by 86%, whereas EGCG suppressed precancerous lesions, but failed to prevent late-stage prostate cancer. Agents that were chemopreventive in the TRAMP model were subsequently evaluated alone, and in combination, in the newly developed SV-40 Tag transgenic rat model. Genistein and resveratrol, alone and in combination, suppressed prostate cancer in SV-40 Tag transgenic rats, but not in an additive or synergistic manner when compared to the single agent treatments. Using immunoassay techniques, we demonstrated a reduction in cell proliferation and an induction of apoptosis in polyphenol-treated animals. We also found down-regulation of growth factor signaling and a modulation of sex steroid receptors. Specifically, all polyphenols reduced insulin-like growth factor-1 protein expression and its downstream effector, phospho-extracellular signal regulated kinase in the prostate. Genistein and EGCG down-regulated androgen receptor, whereas genistein decreased epidermal growth factor receptor and resveratrol up-regulated proposed tumor suppressor, estrogen receptor-beta protein expression. We determined genistein and resveratrol concentrations in blood serum via HPLC/MS to be 2160 nM and 212 nM in genistein- and resveratrol-treated rats, respectively. The regulation of biomarkers known to play a role in prostate carcinogenesis, alterations in cell turnover, and high, but biologically achievable concentrations of polyphenols in the blood most likely account for the chemoprevention observed. In summary, genistein and resveratrol are promising weapons in the fight against prostate cancer and the SV-40 Tag transgenic rat model is a useful tool in evaluating the chemopreventive properties of potential agents.
590 $a School code: 0005.
650 4 $a Health Sciences, Nutrition. $3 1017801
650 4 $a Health Sciences, Oncology. $3 1018566
650 4 $a Health Sciences, Toxicology. $3 1017752
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710 2 $a The University of Alabama at Birmingham. $3 1019443
773 0 $t Dissertation Abstracts International $g 69-02B.
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790 1 0 $a Lamartiniere, Coral A., $e advisor
791 $a Ph.D.
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856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3301375