Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data from a population-based study of newly diagnosed cases of prostate cancer (n = 362) and age-matched controls (n = 685) conducted in Utah (United States) between 1983 and 1986 were used to determine if cigarette smoking, alcohol, coffee, tea, caffeine, and theobromine were associated with prostate cancer risk. These factors were examined since their use differs in the Utah population, which is comprised predominantly of members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormon), from most other populations. Pack-years of cigarettes smoked, alcohol intake, and consumption of alcohol, coffee, tea, and caffeine were not associated with prostate cancer risk. Compared with men with very low levels of theobromine intake, older men consuming 11 to 20 and over 20 mg of theobromine per day were at increased risk of prostate cancer (odds ratio [OR] for all tumors = 2.06, 95 percent confidence interval [CI] = 1.33-3.20, and OR = 1.47, CI = 0.99-2.19, respectively; OR for aggressive tumors = 1.90, CI = 0.90-3.97, and OR = 1.74, CI = 0.91-3.32, respectively). We present biological mechanisms for a possible association between prostate cancer and theobromine. This finding needs further exploration in studies with a wider range of theobromine exposures and more men with aggressive tumors.
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PMID:Smoking, alcohol, coffee, tea, caffeine, and theobromine: risk of prostate cancer in Utah (United States). 828 Aug 34

Common urologic complaints in the midlife man include bladder outlet obstruction, bladder hyperactivity, and large urinary output. Obstruction can result from benign prostate hypertrophy or some other problem distal to the bladder neck, such as urethral stricture. Hyperactivity can be induced by stress and caffeine or can suggest neurologic disease or bladder neoplasia. Large urinary output suggests excessive fluid intake, diabetes insipidus or mellitus, or mobilization of fluid from the use of diuretics or reclining at night. Sexual dysfunction may be caused by stress, but it is more often linked to peripheral vascular disease. Screening for prostate cancer is controversial; the benefit of PSA testing is most clear in patients at elevated risk (eg, due to race or family history).
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PMID:Urologic 'nuisances': how to work up and relieve men's symptoms. 905 86

The caffeine test measures the activity of cytochrome p450 (CYP1A2) which is a major enzyme involved in the activation of flutamide. The usefulness of this test in predicting flutamide-induced hepatic injury in patients with prostate cancer was examined. The subjects were: (1). five patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l or higher following the start of flutamide (moderately injured group); (2). four patients whose AST and ALT levels were higher than normal but less than 100 IU/l (mildly injured group); and (3). two patients whose hepatic function remained normal (normal group). The subjects were each given canned coffee to drink. Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U) levels were measured 4-5 h later. The metabolite ratio, (17U+17X)/137X, was calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for the moderately injured group (3.98+/-1.56) and the mildly injured group (5.55+/-1.42) were lower than that for the normal group (9.56). The results suggest that a decrease in CYP1A2 activity is involved in the onset of flutamide-induced hepatic injury, and that the caffeine test seems to provide a useful means of its prediction.
Prostate Cancer Prostatic Dis 2002
PMID:Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer. 1249 2

Research on cancer chemoprevention is an important approach for decreasing both the incidence and number of deaths from cancer. The use of tamoxifen to prevent breast cancer, finasteride to prevent prostate cancer, and aspirin to prevent colon cancer are recent examples of cancer chemoprevention. This article describes research from my laboratory and related research from other laboratories on the effects of enzyme induction on chemical carcinogenesis as an approach to cancer chemoprevention, as well as studies on the inhibitory effects of curcumin, caffeine, (-)-epigallocatechin gallate (EGCG), and tea in animal models of carcinogenesis. The later substances appear to work, at least in part, by enhancing apoptosis in DNA-damaged cells or in tumors. The results of our studies and those of others provide a rationale for clinical trials on the potential chemopreventive effects of curcumin, caffeine, EGCG, and tea on the formation of cancer of the skin, mouth, esophagus, stomach, and colon in people with precancerous lesions and a high risk of developing these cancers. It was pointed out that several compounds that are effective cancer chemopreventive agents in one experimental setting can enhance carcinogenesis in another experimental setting. These results suggest that it may be necessary to tailor the cancer chemopreventive regimen to individual subjects with known carcinogen exposures or to high cancer risk individuals with mechanistically understood pathways of carcinogenesis so that chemopreventive agents with known mechanisms of action can be better customized to the individual and selected on a more rational basis.
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PMID:Enzyme induction and dietary chemicals as approaches to cancer chemoprevention: the Seventh DeWitt S. Goodman Lecture. 1461 89

To determine if bone mineral density (BMD) substantially influences health-related behaviors in men at risk for osteoporosis, we surveyed 102 men who were participating in a study of prostate cancer and bone loss. Subjects included 68 men with prostate cancer, 44 of whom were hypogonadal on androgen deprivation therapy, and 34 healthy age-matched controls without prostate cancer. At least 6 mo after an initial evaluation, assessment of BMD, and osteoporosis information session, men were administered a questionnaire regarding their healthrelated behaviors. We found that men with osteopenia were 4 times as likely (13%) and men with osteoporosis were more than 10 times as likely (41%) to start taking bisphosphonates compared to men with a normal bone mass (3%, p < 0.0001). Men with low bone mass were more likely to begin taking calcium (p < 0.05) and vitamin D supplements (p < 0.05). Hypogonadal men were 10 times as likely to begin using bisphosphonates (34%) compared to the control group (3%, p < 0.0001) and twice as likely to begin using calcium supplements (57% vs 24%, p < 0.05). Caffeine consumption, alcohol consumption, dietary calcium intake, exercise, and smoking habits were not different in men with osteoporosis or those who were hypogonadal compared to controls. We conclude that men with low bone mass and hypogonadism were more likely to start using bisphosphonates, calcium supplements, and vitamin D supplements after having a bone density test. However, they were not more likely to make significant health-related lifestyle changes after obtaining the results of their bone mass.
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PMID:Does bone mineral density and knowledge influence health-related behaviors of elderly men at risk for osteoporosis? 1471 44

Bone mass is a major determinant of fracture, but there have been few comprehensive studies of the correlates of bone mineral density (BMD) in older men. The objective of the current cross-sectional analysis was to determine the factors associated with BMD of the lumbar spine and proximal femur in a large population-based sample of older men enrolled in The Osteoporotic Fractures in Men Study, "Mr.OS." We enrolled 5,995 men 65 years of age or older, 89% Caucasian, in Mr.OS at six US clinical centers. Demographic, medical and family history and lifestyle information was obtained by interview and physical function and anthropometric data by examination. Spine and hip BMD was measured using dual-energy X-ray absorptimetry. The multivariable linear regression models predicted 19 and 10% of the overall variance in BMD of the femoral neck and spine, respectively. African-American men had 6 to 11% higher BMD than Caucasian men independent of multiple factors. Hip BMD declined with advancing age, while spine BMD increased. Body weight (per 10 kg) and self report of diabetes were each associated with 2 to 4% higher BMD, while history of a non-trauma fracture and current use of selective serotonin reuptake inhibitors, but not other antidepressants, were associated with at least 4% lower BMD. Both maternal and paternal histories of fracture were associated with 1.4-1.7% lower BMD. Osteoarthritis, physical activity, grip strength, alcohol intake, and dietary calcium were positively related to BMD, while a history of chronic lung disease, prostate cancer, and kidney stones was associated with lower BMD. Smoking, caffeine intake, and thiazide diuretics were not related to BMD in older men. A number of lifestyle and behavioral characteristics and medical conditions were associated with BMD in older men. Identification of these correlates could improve methods to identify men at risk for fracture and improve our understanding of fracture etiology.
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PMID:Factors associated with the lumbar spine and proximal femur bone mineral density in older men. 1588 16

Green tea catechins (GTCs) proved to be effective in inhibiting cancer growth in several experimental models. Recent studies showed that 30% of men with high-grade prostate intraepithelial neoplasia (HG-PIN) would develop prostate cancer (CaP) within 1 year after repeated biopsy. This prompted us to do a proof-of-principle clinical trial to assess the safety and efficacy of GTCs for the chemoprevention of CaP in HG-PIN volunteers. The purity and content of GTCs preparations were assessed by high-performance liquid chromatography [(-)-epigallocathechin, 5.5%; (-)-epicatechin, 12.24%; (-)-epigallocatechin-3-gallate, 51.88%; (-)-epicatechin-3-gallate, 6.12%; total GTCs, 75.7%; caffeine, <1%]. Sixty volunteers with HG-PIN, who were made aware of the study details, agreed to sign an informed consent form and were enrolled in this double-blind, placebo-controlled study. Daily treatment consisted of three GTCs capsules, 200 mg each (total 600 mg/d). After 1 year, only one tumor was diagnosed among the 30 GTCs-treated men (incidence, approximately 3%), whereas nine cancers were found among the 30 placebo-treated men (incidence, 30%). Total prostate-specific antigen did not change significantly between the two arms, but GTCs-treated men showed values constantly lower with respect to placebo-treated ones. International Prostate Symptom Score and quality of life scores of GTCs-treated men with coexistent benign prostate hyperplasia improved, reaching statistical significance in the case of International Prostate Symptom Scores. No significant side effects or adverse effects were documented. To our knowledge, this is the first study showing that GTCs are safe and very effective for treating premalignant lesions before CaP develops. As a secondary observation, administration of GTCs also reduced lower urinary tract symptoms, suggesting that these compounds might also be of help for treating the symptoms of benign prostate hyperplasia.
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PMID: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. 1642 63

We have previously posited that the global sympathetic bias that emerges with aging may constitute the common etiologic thread that links a myriad of ailments associated with aging. Recent data suggests that benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) may also be caused by sympathetic bias as an independent etiology from androgen dysfunction. The association of BPH with heart disease, independent of other variables, supports the view that both entities represent downstream manifestations of global sympathetic bias. The risk for development of BPH increases with caffeine intake and decreases with alcohol consumption, factors which wield opposing effects on autonomic balance. Heavy smoking, which induces chronic sympathetic bias, also increases the risk of BPH, a link also previously attributed to hormonal alterations. Sympathetic dysfunction appears to have a mitogenic effect on the prostate. The high prevalence of prostate cancer, a condition detected in the autopsy of many elderly men, may arise from this activity combined with a Th2 shift induced by sympathetic bias, leading to decreased cancer surveillance by the immune system. Exercise may improve BPH by restoring autonomic balance and normalizing the sympathovagal ratio. The benefits of alpha-adrenergic blockers on BPH, generally felt to achieve symptomatic relief afforded by bladder wall and sphincter remodeling, may independently exert a direct effect on prostate growth and enlargement. Sympathetic bias may play a role in adaptive enlargement of other organs such as the salivary glands, heart, liver, spleen, and skeletal muscles in response to stress. We envision novel pharmacologic and device-based neuromodulation therapies for BPH and related urologic dysfunctions based on these principles.
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PMID:Opening the floodgates: benign prostatic hyperplasia may represent another disease in the compendium of ailments caused by the global sympathetic bias that emerges with aging. 1642 46

Green and black tea have shown promise in the chemoprevention of prostate cancer. The objective of this study was to determine the bioavailability and bioactivity of tea polyphenols (PP) and theaflavins in human serum and human and mouse tissues. A decaffeinated black tea diet was administered to C57BL/6 mice. PPs and theaflavins were found in the small and large intestine, liver, and prostate in conjugated and free forms. The relative prostate bioavailability of theaflavin was 70% higher than that of epigallocatechin gallate (EGCG). In the second mouse study, a green tea (GT) diet was administered followed by the control diet for 1-5 d. Epicatechin (EC), EGCG, and epicatechin gallate (ECG) concentrations in prostate tissue were significantly decreased after 1 d of consuming the control diet. Epigallocatechin gallate (EGC), however, did not decrease significantly. For the human study, 20 men scheduled for surgical prostatectomy were randomly assigned to consume 1.42 L daily of GT, BT, or a caffeine-matched soda control (SC) for 5 d before radical prostatectomy. Tea PPs were greater in prostate samples from men consuming BT and GT than in men consuming SC (P = 0.0025). Although tea PP were not detectable in serum, ex vivo LNCaP prostate cancer cell proliferation was less when cells were grown in media containing patient serum collected after BT (P < 0.001) and GT (P = 0.025) consumption relative to baseline serum This is the first human study to show that tea polyphenols and theaflavins are bioavailable in the prostate where they may be active in the prevention of prostate cancer.
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PMID:Tea polyphenols and theaflavins are present in prostate tissue of humans and mice after green and black tea consumption. 1677 46

We recently reported that gallic acid is a major active agent responsible for grape seed extract activity in DU145 human prostate carcinoma cells. The present study was conducted to examine its efficacy and associated mechanism. Gallic acid treatment of DU145 cells resulted in a strong cell growth inhibition, cell cycle arrest, and apoptotic death in a dose- and time-dependent manner, together with a decrease in cyclin-dependent kinases and cyclins but strong induction in Cip1/p21. Additional mechanistic studies showed that gallic acid induces an early Tyr(15) phosphorylation of cell division cycle 2 (cdc2). Further upstream, gallic acid also induced phosphorylation of both cdc25A and cdc25C via ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (Chk2) activation as a DNA damage response evidenced by increased phospho-histone 2AX (H2A.X) that is phosphorylated by ATM in response to DNA damage. Time kinetics of ATM phosphorylation, together with those of H2A.X and Chk2, was in accordance with an inactivating phosphorylation of cdc25A and cdc25C phosphatases and cdc2 kinase, suggesting that gallic acid increases cdc25A/C-cdc2 phosphorylation and thereby inactivation via ATM-Chk2 pathway following DNA damage that induces cell cycle arrest. Caffeine, an ATM/ataxia telangiectasia-rad3-related inhibitor, reversed gallic acid-caused ATM and H2A.X phosphorylation and cell cycle arrest, supporting the role of ATM pathway in gallic acid-induced cell cycle arrest. Additionally, gallic acid caused caspase-9, caspase-3, and poly(ADP)ribose polymerase cleavage, but pan-caspase inhibitor did not reverse apoptosis, suggesting an additional caspase-independent apoptotic mechanism. Together, this is the first report identifying gallic acid efficacy and associated mechanisms in an advanced and androgen-independent human prostate carcinoma DU145 cells, suggesting future in vivo efficacy studies with this agent in preclinical prostate cancer models.
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PMID:Gallic acid causes inactivating phosphorylation of cdc25A/cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells. 1717 33


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