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Tea Polyphenols as Prostate Cancer Preventive Agents

By James Francis Thorpe

Abstract

Prostate cancer is an ideal candidate for chemoprevention. Tea drinking is a possible explanation for the rarity of prostate cancer among Chinese men. Tea (Camellia sinensis) contains flavonoid polyphenols called catechins, believed to be responsible for this anti-carcinogenesis. In black tea these catechins are oxidised into theaflavins. Catechins and theaflavins both inhibit human prostate cancer cell proliferation in vitro. Catechins inhibit prostate cancer in the TRAMP mouse animal model of the disease. To determine if tea polyphenols warrant investigation in large trials, evidence is required from animal models and biomarkers of cancer prevention identified in small human studies.\ud In the work presented here, prostate carcinogenesis was inhibited by orally administered tea polyphenols in the TRAMP mouse. Following 26 weeks of polyphenol administration median prostate masses were 0.54g, 0.28g and 1.01g for the theaflavin, catechin and control group respectively. This is the first in vivo evidence of prostate cancer chemoprevention by black tea theaflavins and adds to the previously published evidence for the same effect by green tea catechins. In the catechin group, this chemoprevention was associated with a significant reduction in the concentration of oxidative DNA adduct malondialdehydedeoxyguanosine (M1G) in prostate tissue. M1G, a marker of oxidative DNA damage, was therefore proposed as a putative biomarker of prostate cancer chemoprevention. A human trial was then performed involving 18 men randomised to receive four weeks of catechins, theaflavins or no polyphenol prior to transurethral resection of prostate. A significant reduction in M1G was detected in the DNA from prostate tissue of men who had received catechins.\ud Tea polyphenols and particularly catechins may therefore represent prostate cancer prevention agents suitable for study in a larger human intervention trial however, this finding should be first be tested in further better designed biomarker studies using this result to inform decisions on study population size

Publisher: University of Leicester
Year: 2011
OAI identifier: oai:lra.le.ac.uk:2381/9634

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Citations

  1. [EAU guidelines on prostate cancer]. Actas Urol Esp,
  2. (1994). 5-Alpha-reductase inhibition and prostate cancer prevention.
  3. (2003). 5alpha-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium.
  4. (2002). A case-control study on risk of changing food consumption for colorectal cancer. Cancer Investigations,
  5. (2002). A Nod Scid mouse model to study human prostate cancer. Prostate Cancer Prostatic Dis,
  6. (2000). a Novel Prostate-specific Gene with Homology to a G Protein-coupled Receptor, Is Overexpressed in Prostate Cancer. Cancer Res,
  7. (2003). A Phase II Trial of Green Tea
  8. A pilot study of use of the cyclooxygenase-2 inhibitor celecoxib in recurrent prostate cancer after definitive radiation therapy or radical prostatectomy.
  9. (2002). A population-based study of daily nonsteroidal antiinflammatory drug use and prostate cancer. Mayo Clin Proc,
  10. (2001). A Probasin-Large T Antigen Transgenic Mouse Line Develops Prostate Adenocarcinoma and Neuroendocrine Carcinoma with Metastatic Potential. Cancer Res,
  11. (2003). A prospective study of intake of fish and marine fatty acids and prostate cancer. Cancer Epidemiol Biomarkers Prev,
  12. (2002). A Prospective Study of Tomato Products, Lycopene, and Prostate Cancer Risk.
  13. (2002). A Randomized Trial Comparing Radical Prostatectomy with Watchful Waiting
  14. (2006). A review of the effects and mechanisms of polyphenolics in cancer. Crit Rev Food Sci Nutr,
  15. (1983). A severe combined immunodeficiency mutation in the mouse. Nature,
  16. (2004). A statistical framework for the design of microarray experiments and effective detection of differential gene expression. Bioinformatics,
  17. (2001). Age-related Radical-induced DNA Damage Is Linked to Prostate Cancer. Cancer Res,
  18. (1999). Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner.
  19. (1998). Alcohol and other beverage use and prostate cancer risk among Canadian men.
  20. (2006). Amygdalin Induces Apoptosis through Regulation of Bax and
  21. (2003). An overview of the kallikrein gene families in humans and other species: emerging candidate tumour markers. Clin Biochem,
  22. (2001). Analysis of theaflavins in biological fluids using liquid chromatography-electrospray mass spectrometry.
  23. (2008). Androgen manipulation alters oxidative DNA adduct levels in androgen-sensitive prostate cancer cells grown in vitro and in vivo. Cancer Letters,
  24. (1994). Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res,
  25. (1999). Angiogenesis inhibited by drinking tea. Nature,
  26. (2003). Antioxidant Effects of Tea: Evidence from Human Clinical Trials.
  27. (1994). Antioxidative and antimutagenic effects of theaflavins from black tea. Mutation Research Letters,
  28. (1996). Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death.
  29. (2008). Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies? Arch Biochem Biophys,
  30. (1995). Assessment of cell proliferation in pathology--what next? Histopathology,
  31. (2000). Association Between Alpha-Tocopherol, GammaTocopherol, Selenium, and Subsequent Prostate Cancer.
  32. (1987). Autochthonous prostate adenocarcinomas in Lobund-Wistar rats: a model system. Prostate,
  33. (2000). Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death Differ,
  34. (2005). Bioavailability and antioxidant effect of epigallocatechin gallate administered in purified form versus as green tea extract in healthy individuals.
  35. (1986). Black Tea Consumption and Cancer Risk: A Prospective Study.
  36. (1999). Black tea increases the resistance of human plasma to lipid peroxidation in vitro, but not ex vivo. Free Radical Biology and Medicine,
  37. (2002). Black tea polyphenols inhibit IGF-I-induced signaling through Akt in normal prostate epithelial cells and Du145 prostate carcinoma cells. Carcinogenesis,
  38. (1998). Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer Epidemiol Biomarkers Prev,
  39. (2007). Breast cancer prevention by green tea catechins and black tea theaflavins in the C3(1) SV40 T,t antigen transgenic mouse model is accompanied by increased apoptosis and a decrease in oxidative DNA adducts. J Agric Food Chem,
  40. (1997). Cancer Incidence on Five Continents VII.
  41. Cancer Prevention by Tea Polyphenols Is Linked to Their Direct Inhibition of Antiapoptotic Bcl-2-Family Proteins. Cancer Research,
  42. (2002). Cancer Survival Among US Whites and Minorities: A SEER (Surveillance, Epidemiology,
  43. (1997). Cancer-Preventive Effects of Drinking Green Tea among a Japanese Population,. Preventive Medicine,
  44. (1997). Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med,
  45. Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors.
  46. (1997). Caspases: the executioners of apoptosis. Biochem J,
  47. (2005). Challenges in Prostate Cancer Research: Animal Models for Nutritional Studies of Chemoprevention and Disease
  48. (2009). Characterization of preclinical models of prostate cancer using PET-based molecular imaging.
  49. (2006). Chemoprevention of Human Prostate Cancer by Oral Administration of Green Tea Catechins in Volunteers with High-Grade Prostate Intraepithelial Neoplasia: A Preliminary Report from a One-Year Proof-of-Principle Study. Cancer Res,
  50. (2004). Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial.
  51. (1999). Chemopreventive Effects of Tea Extracts and Various Components on Human Pancreatic and Prostate Tumor Cells In Vitro. Nutrition and Cancer,
  52. Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis.
  53. Clinical Results of Long-Term Follow-Up of a Large, Active Surveillance Cohort With Localized Prostate Cancer
  54. (2006). Commentary: carcinogenesis as Darwinian evolution? Do the math!
  55. Daily aspirin use and prostate cancer risk in a large, multiracial cohort in the US. Cancer Causes Control,
  56. Determination of catechins and catechin gallates in tissues by liquid chromatography with coulometric array detection and selective solid phase extraction.
  57. (1998). Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay. Carcinogenesis,
  58. (1993). Development and testing of the AIN-93 purified diets for rodents: results on growth, kidney calcification and bone mineralization in rats and
  59. (1997). Development of monoclonal antibodies to the malondialdehyde-deoxyguanosine adduct, pyrimidopurinone. Chem Res Toxicol,
  60. (2002). Dietary catechins and cancer incidence among postmenopausal women: the Iowa Women's Health Study (United States). Cancer Causes Control,
  61. Dietary Fat and Prostate Cancer.
  62. (2010). Dietary zinc and prostate cancer in the TRAMP mouse model.
  63. (2000). Differential Effects of Theaflavin Monogallates on Cell Growth, Apoptosis, and Cox-2 Gene Expression in Cancerous versus Normal Cells. Cancer Res,
  64. (2007). Direct inhibition of insulin-like growth factor-I receptor kinase activity by (-)-epigallocatechin-3-gallate regulates cell transformation. Cancer Epidemiol Biomarkers Prev,
  65. (2007). Does PSA play a role as a promoting agent during the initiation and/or progression of prostate cancer? The Prostate,
  66. (2000). Effect of black and green tea polyphenols on c-jun phosphorylation and H2O2 production in transformed and non-transformed human bronchial cell lines: possible mechanisms of cell growth inhibition and apoptosis induction. Carcinogenesis,
  67. (2003). Effect of Increased Tea Consumption on Oxidative DNA Damage among Smokers:
  68. (2005). Effect of pooling samples on the efficiency of comparative studies using microarrays. Bioinformatics,
  69. Effective suppression of dihydrotestosterone (DHT) by GI198745, a novel, dual 5 alpha reductase inhibitor.
  70. (2005). Effects of Dosing Condition on the Oral Bioavailability of Green Tea Catechins after Single-Dose Administration of Polyphenon E in Healthy Individuals. Clinical Cancer Research,
  71. (2002). Efficacy and safety of a dual inhibitor of 5-alphareductase types
  72. (2001). EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells.
  73. (2004). Enhanced redundancy in Akt and mitogenactivated protein kinase-induced survival of malignant versus normal prostate epithelial cells. Cancer Res,
  74. (2000). Environmental and Heritable Factors in the Causation of Cancer -- Analyses of Cohorts of Twins from Sweden,
  75. (1985). Epidemiological study of prostatic cancer by matched-pair analysis. Prostate,
  76. (1999). Epidermal growth factor (EGF) receptor blockade inhibits the action of EGF, insulin-like growth factor I, and a protein kinase A activator on the mitogen-activated protein kinase pathway in prostate cancer cell lines. Cancer Res,
  77. (2008). Epigallocatechin-3-gallate (EGCG) inhibits PC-3 prostate cancer cell proliferation via MEK-independent ERK1/2 activation. Chemico-Biological Interactions,
  78. (2003). Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells.
  79. (2004). ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions.
  80. (1974). Errors in DNA Replication as a Basis of Malignant Changes. Cancer Res,
  81. (1986). Establishment and characterization of seven dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostatic cancers. The Prostate,
  82. (2008). Evaluation of toxicity of green tea catechins with 90-day dietary administration to F344 rats. Food and Chemical Toxicology,
  83. Evidence That Insulin-Like Growth Factor I and Growth Hormone Are Required for Prostate Gland Development.
  84. (1991). Experimental oncogene induced prostate cancer. Cancer Surv,
  85. Fatty fish consumption and risk of prostate cancer.
  86. (2001). Fatty fish consumption and risk of prostate cancer. The Lancet,
  87. (2001). Gene expression and amplification in breast carcinoma cells with intrinsic and acquired doxorubicin resistance. Oncogene,
  88. (1994). Generation of mutagens during arachidonic acid metabolism. Cancer Metastasis Rev,
  89. (2004). Genistein alters growth factor signaling in transgenic prostate model (TRAMP). Mol Cell Endocrinol,
  90. (2009). Genistein and resveratrol, alone and in combination, suppress prostate cancer in SV-40 tag rats. Prostate,
  91. (1999). Genistein Inhibits NF-kB Activation in Prostate Cancer Cells. Nutrition and Cancer,
  92. Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation.
  93. (2001). Green tea catechins and vitamin E inhibit angiogenesis of human microvascular endothelial cells through suppression of IL-8 production. Nutr Cancer,
  94. Green Tea Catechins Inhibit Vascular Endothelial Growth Factor Receptor Phosphorylation. Cancer Res,
  95. (2007). Green tea catechins suppress the DNA synthesis marker MCM7 in the TRAMP model of prostate cancer. Mol Oncol,
  96. (1997). Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells.
  97. (2005). Green tea constituent epigallocatechin-3-gallate selectively inhibits COX-2 without affecting COX-1 expression in human prostate carcinoma cells.
  98. (2004). Green tea consumption and subsequent risk of gastric cancer by subsite: the JPHC Study. Cancer Causes Control,
  99. (1997). Green tea consumption and the risk of pancreatic and colorectal cancers.
  100. (1998). Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Letters,
  101. (2003). Green tea polyphenol targets the mitochondria in tumor cells inducing caspase 3-dependent apoptosis. Anticancer Res,
  102. Green tea polyphenols for prostate cancer chemoprevention: a translational perspective.
  103. (2000). Growth Inhibition, Cell-Cycle Dysregulation, and Induction of Apoptosis by Green Tea Constituent (-)-Epigallocatechin-3-gallate in Androgen-Sensitive and Androgen-Insensitive Human Prostate Carcinoma Cells. Toxicology and Applied Pharmacology,
  104. (2009). Hepatotoxicity from green tea: a review of the literature and two unpublished cases.
  105. (1985). Hereditary cancer, oncogenes, and antioncogenes. Cancer Res,
  106. (1993). Hereditary Prostate Cancer: Epidemiologic and Clinical Features.
  107. (1996). Heteronuclear ribonucleoproteins C1 and C2, components of the spliceosome, are specific targets of interleukin 1betaconverting enzyme-like proteases in apoptosis.
  108. (2003). High-dose weekly oral calcitriol in patients with a rising PSA after prostatectomy or radiation for prostate carcinoma. Cancer,
  109. (2000). Hippuric acid as a major excretion product associated with black tea consumption. Xenobiotica,
  110. Hospital Department of Clinical Chemistry for analysis of PSA, Sodium, Potassium, Urea, Creatinine, Alkaline phosphatase, Alanine transaminase, Bilirubin and Albumin.
  111. (1980). Human prostatic adenocarcinoma: some characteristics of a serially transplantable line
  112. I agree to donate the tissue samples as detailed below and allow their use in medical Patient name, address,
  113. I confirm that I have read and understand the information sheet dated ....................... version ............ for the above study and have had the opportunity to ask questions.
  114. I understand that I may withdraw my consent to my tissue being used at any time without justifying my decision and without affecting my normal care and medical management.
  115. I understand that my participation is voluntary and that I am free to withdraw at any time, without giving any reason, without my medical care or legal rights being affected.
  116. (2000). I.J.T.a.Z.M.J., Prostate cancer, in Clinical Oncology 2nd edn,
  117. (1992). Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
  118. (2002). Immunohistochemical Demonstration of Phospho-Akt in High Gleason Grade Prostate Cancer. Clin Cancer Res,
  119. (1999). Implications of the mechanisms of action of tea polyphenols as antioxidants in vitro for chemoprevention in humans.
  120. (2005). In vivo models of prostate cancer metastasis to
  121. (1998). Indirect mutagenesis by oxidative DNA damage: Formation of the pyrimidopurinone adduct of deoxyguanosine by base propenal. PNAS,
  122. (2001). Induction of apoptosis by green tea catechins in human prostate cancer DU145 cells. Life Sciences,
  123. (1998). Induction of apoptosis in prostate cancer cell lines by the green tea component, (-)-epigallocatechin3-gallate. Cancer Letters,
  124. (2005). Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations.
  125. Inhibition of CWR22Rnu1 tumor growth and PSA secretion in athymic nude mice by green and black teas. Carcinogenesis,
  126. (1999). Inhibition of cyclin-dependent kinases 2 and 4 activities as well as induction of Cdk inhibitors p21 and p27 during growth arrest of human breast carcinoma cells by (-)-epigallocatechin-3-gallate. J Cell Biochem,
  127. Inhibition of growth and induction of apoptosis
  128. (1997). Inhibition of peroxynitrite-mediated tyrosine nitration by catechin polyphenols.
  129. (2001). Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. PNAS,
  130. (1997). Inhibitory effect of black tea on the growth of established skin tumors in mice: effects on tumor size, apoptosis, mitosis and bromodeoxyuridine incorporation into DNA. Carcinogenesis,
  131. (1999). Inhibitory effect of tea flavonoids on the ability of cells to oxidize low density lipoprotein. Biochemical Pharmacology,
  132. (1998). Insulin receptor substrate 2 and Shc play different roles in insulin-like growth factor I signaling.
  133. (1997). Insulin-like Growth Factor (IGF)-binding
  134. (1998). Insulin-like growth factor 1 and prostate cancer risk: a population- based, case-control study.
  135. (2001). Insulin-like growth factor and prostate cancer. Urology,
  136. (1991). Insulin-like growth factors (IGFs), IGF receptors, and IGFbinding proteins in primary cultures of prostate epithelial cells.
  137. (2000). Inverse association of prostate cancer and non-steroidal anti-inflammatory drugs (NSAIDs): results of a case-control study. Oncol Rep,
  138. (1990). Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res,
  139. (1978). Isolation of a human prostate carcinoma cell line (DU 145). Int
  140. Laparoscopic standard pelvic node dissection for carcinoma of the prostate: is it accurate?
  141. (1996). Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues. Cancer Epidemiol Biomarkers Prev,
  142. (1983). LNCaP model of human prostatic carcinoma. Cancer Res,
  143. (2001). Lobe-specific increases in malondialdehyde DNA adduct formation in the livers of mice following infection with Helicobacter hepaticus. Carcinogenesis,
  144. (2001). Low levels of prostate-specific antigen predict long-term risk of prostate cancer: results from the altimore ongitudinal tudy of ging. Urology,
  145. (1999). Lower Prostate Cancer Risk in Men with Elevated Plasma Lycopene Levels: Results of a Prospective Analysis. Cancer Res,
  146. (2007). Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: diagnostic and cost-effectiveness and comparison with current detection strategies. J Clin Oncol,
  147. (2003). Malondialdehyde, a Product of Lipid Peroxidation, Is Mutagenic in Human Cells.
  148. (1996). Metastatic prostate cancer in a transgenic mouse. Cancer Res,
  149. (2003). Meydani,, Green tea catechins inhibit VEGFinduced angiogenesis vitro</I> through suppression of VE-cadherin phosphorylation and inactivation of Akt molecule.
  150. (1998). Model systems of prostate cancer: uses and limitations. Cancer Metastasis Rev,
  151. (2004). Modulation of phosphatidylinositol-3-kinase/protein kinase B- and mitogen-activated protein kinase-pathways by tea polyphenols in human prostate cancer cells.
  152. (2003). Molecular pathway for (-)-epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells.
  153. (2002). Mouse models of prostate carcinogenesis. Trends Genet,
  154. (1992). MR imaging in adenocarcinoma of the prostate: interobserver variation and efficacy for determining stage C disease.
  155. (1995). Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.
  156. (2003). Multiple mutations and cancer.
  157. (1999). Multiple Signaling Pathways of the Insulin-Like Growth Factor 1 Receptor in Protection from Apoptosis.
  158. (1997). Mutagenicity in Escherichia coli of the major DNA adduct derived from the endogenous mutagen malondialdehyde. PNAS,
  159. (2003). Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell,
  160. (1988). Normal histology of the prostate.
  161. (2005). Novel insights into the implication of the IGF-1 network in prostate cancer. Trends in Molecular Medicine,
  162. Oligonol, an oligomerized lychee fruit-derived polyphenol, activates the Ras/Raf-1/MEK1/2 cascade independent of the IL6 signaling pathway in rat primary adipocytes.
  163. (2004). Oral Consumption of Green Tea Polyphenols Inhibits Insulin-Like Growth Factor-I-Induced Signaling in an Autochthonous Mouse Model of Prostate Cancer. Cancer Res,
  164. Oral treatment of the TRAMP mice with doxazosin suppresses prostate tumor growth and metastasis.
  165. (2000). Overall survival after prostate-specific-antigendetected recurrence following conformal radiation therapy. International journal of radiation oncology, biology, physics,
  166. (2006). p53 and its downstream proteins as molecular targets of cancer. Molecular Carcinogenesis,
  167. (2003). Pharmacokinetics and Safety of Green Tea Polyphenols after Multiple-Dose Administration of Epigallocatechin Gallate and Polyphenon E in Healthy Individuals. Clin Cancer Res,
  168. (2001). Phase I Pharmacokinetic Study of Tea Polyphenols following Single-dose Administration of Epigallocatechin Gallate and Polyphenon E. Cancer Epidemiology Biomarkers and Prevention,
  169. (2001). Phosphorylation of Mitogen-activated Protein Kinase is Inhibited by Calcitonin
  170. (1998). Plasma Insulin-Like Growth Factor-I and Prostate Cancer Risk: A Prospective Study. Science,
  171. (1995). Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch Biochem Biophys,
  172. (1995). Polyphenolic Flavanols as Scavengers of Aqueous Phase Radicals and as Chain-Breaking Antioxidants. Archives of Biochemistry and Biophysics,
  173. Possible Controversy over Dietary Polyphenols:  Benefits vs Risks. Chemical Research
  174. (1996). Prediction of male cancer mortality by plasma levels of interacting vitamins: 17-year follow-up of the prospective Basel study.
  175. (2003). Prevention of Prostate Cancer with Finasteride: US/European Perspective. European Urology,
  176. (1999). Prooxidant activity of flavonoids: copper-dependent strand breaks and the formation of 8-hydroxy-2'-deoxyguanosine in DNA. Mol Genet Metab,
  177. (2004). Prostate Cancer Chemoprevention Agent Development: The National Cancer Institute, Division of Cancer Prevention Portfolio.
  178. (1999). Prostate Cancer Chemoprevention by Green Tea:
  179. (2003). Prostate cancer epidemiology. The Lancet,
  180. Prostate Cancer in a Transgenic Mouse.
  181. (2001). Prostate cancer pathology, screening, and epidemiology. Rev Urol,
  182. (1999). Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case-control study.
  183. (2000). Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control,
  184. (2003). Prostate cancer.
  185. (2004). Prostate carcinoma and green tea: PSA-triggered basement membrane degradation and MMP-2 activation are inhibited by (-)epigallocatechin-3-gallate.
  186. (1992). Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma.
  187. (2004). Prostate-specific antigen: A review of the validation of the most commonly used cancer biomarker. Cancer,
  188. (2000). Prostatic neoplasia in transgenic mice with prostatedirected overexpression of the c-myc oncoprotein. Prostate,
  189. Protective Effect of Green Tea Against Prostate Cancer: A Case-Control Study in Southeast China.
  190. (1999). Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis. Jama,
  191. (2005). Radical prostatectomy for clinically advanced (cT3) prostate cancer since the advent of prostate-specific antigen testing: 15-year outcome. BJU Int,
  192. (1993). Re-evaluation of the need for pelvic lymphadenectomy in low grade prostate cancer.
  193. (1986). Reaction of malonaldehyde with nucleic acid. III. Studies of the fluorescent substances released by enzymatic digestion of nucleic acids modified with malonaldehyde. Chem Pharm Bull (Tokyo),
  194. (1986). Reaction of malondialdehyde with guanine nucleosides: formation of adducts containing oxadiazabicyclononene residues in the base-pairing region.
  195. (2008). Repletion of antioxidant status by EGCG and retardation of oxidative damage induced macromolecular anomalies in aged rats. Exp Gerontol,
  196. (1994). Results of conservative management of clinically localized prostate cancer.
  197. (2004). Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. The Lancet,
  198. (2004). Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem,
  199. (2003). Role of p53 and NF-kappa B in epigallocatechin-3-gallateinduced apoptosis of LNCaP cells. Oncogene,
  200. (2003). Role of secondary hormonal therapy in the management of recurrent prostate cancer. Urology,
  201. (2007). Roles of G-protein-coupled receptor signaling in cancer biology and gene transcription. Current Opinion in Genetics & Development,
  202. (2001). Safety and efficacy of exisulind for treatment of recurrent prostate cancer after radical prostatectomy.
  203. (2001). SELECT: the next prostate cancer prevention trial. Selenum and Vitamin E Cancer Prevention Trial.
  204. (2004). Selenium and Vitamin E Cancer Prevention Trial. Ann NY Acad Sci,
  205. (2002). Selenium and vitamin E supplements for prostate cancer: evidence or embellishment? Urology,
  206. (2003). Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial.
  207. (1993). Smoking, alcohol, coffee, tea, caffeine, and theobromine: risk of prostate cancer in Utah (United States). Cancer Causes Control,
  208. (2003). Soy isoflavones in the treatment of prostate cancer. Nutr Cancer,
  209. (1996). Specific cleavage of the retinoblastoma protein by an ICE-like protease in apoptosis. Embo J,
  210. (1993). Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Research,
  211. (2007). Spectrum of activity and mechanism of action of VEGF/PDGF inhibitors. Cancer Control,
  212. (1998). Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer.
  213. (1999). Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev,
  214. Supplementation of Jurkat T Cells with Green Tea Extract Decreases Oxidative Damage Due to Iron Treatment.
  215. (2004). Suppression of Prostate Carcinogenesis by Dietary Supplementation of Celecoxib in Transgenic Adenocarcinoma of the Mouse Prostate Model. Cancer Res,
  216. (1988). SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell,
  217. (2002). Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma. Cancer,
  218. (1979). T antigen is bound to a host protein in SV40-transformed cells. Nature,
  219. (2000). Tea and other beverage consumption and prostate cancer risk: a Canadian retrospective cohort study.
  220. (2003). Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit Rev Food Sci Nutr,
  221. (1992). Tea consumption and cancer risk. Nutrition and Cancer,
  222. (2008). Tea Consumption and Prostate Cancer Risk in Japanese Men: A Prospective Study.
  223. (2000). Tea Intake and Squamous Cell Carcinoma of the Skin: Influence of Type of Tea Beverages. Cancer Epidemiol Biomarkers Prev,
  224. (2006). Tea Polyphenols and Theaflavins Are Present
  225. (2009). Tea Polyphenols Decrease Serum Levels of ProstateSpecific Antigen, Hepatocyte Growth Factor, and Vascular Endothelial Growth Factor
  226. (2000). Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells. Oncogene,
  227. (2004). Tea variety and brewing techniques influence flavonoid content of black tea.
  228. (2001). Testosterone and prostate specific antigen stimulate generation of reactive oxygen species in prostate cancer cells 10.1093/carcin/22.11.1775 Carcinogenesis
  229. (1996). The antioxidant properties of theaflavins and their gallate esters -- radical scavengers or metal chelators? FEBS Letters,
  230. (1998). The association between baseline vitamin E, selenium, and prostate cancer in the alpha-tocopherol, beta-carotene cancer prevention study. Cancer Epidemiol Biomarkers Prev,
  231. (2006). The case for early chemotherapy for the treatment of metastatic disease.
  232. (1997). The chemistry of tea flavonoids.
  233. (1976). The clonal evolution of tumor cell populations. Science,
  234. (2005). The finasteride prostate cancer prevention trial (PCPT) - What have we learned?
  235. (2000). The hallmarks of cancer. Cell,
  236. (2006). The increased rate of prostate specific antigen testing has not affected prostate cancer presentation in an inner city population in the UK.
  237. (2003). The Influence of Finasteride on the Development of Prostate Cancer.
  238. (1999). The insulin-like growth factor axis and prostate cancer: lessons from the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Cancer Res,
  239. (2000). The mediating role of caspase-3 protease in the intracellular mechanism of genistein-induced apoptosis in human prostatic carcinoma cell lines, DU145 and LNCaP. Biol Cell,
  240. The pathogenesis of deferred cancer; a study of the after-effects of methylcholanthrene upon rabbit skin.
  241. (1959). The Principles of Humane Experimental Technique.
  242. (1994). The rat probasin gene promoter directs hormonally and developmentally regulated expression of a heterologous gene specifically to the prostate in transgenic mice. Mol Endocrinol,
  243. (1993). The reaction of no with superoxide. Free Radic Res Commun,
  244. (2004). The specific role of isoflavones in reducing prostate cancer risk. Prostate,
  245. The Veterans Administration Cooperative Urologic Research Group: histologic grading and clinical staging of prostatic carcinoma.,
  246. (2004). Theaflavin-3,3'-digallate and penta-Ogalloyl-{beta}-D-glucose inhibit rat liver microsomal 5{alpha}-reductase activity and the expression of androgen receptor in LNCaP prostate cancer cells. Carcinogenesis,
  247. (2007). Theaflavins induced apoptosis of LNCaP cells is mediated through induction of p53, down-regulation of NF-kappa B and mitogenactivated protein kinases pathways. Life Sciences,
  248. (2003). Toenail Selenium Levels and the Subsequent Risk of Prostate Cancer: A Prospective Cohort Study. Cancer Epidemiol Biomarkers Prev,
  249. (1988). Toxicology and Carcinogenesis Studies of Malondialdehyde Sodium Salt (3-hydroxy-2-propenal, sodium salt)
  250. (1998). Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol).
  251. (2005). Treatment options for prostate cancer: evaluating the evidence. Am Fam Physician,
  252. (2000). Trends in prostate cancer incidence, mortality and survival in England and Wales 1971-1998. BJU Int,
  253. (1997). Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR. J Pharmacol Exp Ther,
  254. (2000). Use of nude mouse xenograft models in prostate cancer research. Prostate,
  255. (1997). Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in situ and in vitro expression of VEGF by human prostate cancer cells. J Urol,
  256. (2001). Vascular endothelial growth factor induction of the angiogenic phenotype requires Ras activation.
  257. (2005). WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res,
  258. (1997). Why Drinking Green Tea Could Prevent Prostate Cancer. Nature,
  259. (1988). Zonal distribution of prostatic adenocarcinoma. Correlation with histologic pattern and direction of spread.

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