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)

The effects of androgen deprivation therapy (ADT) include not only suppression of tumor growth, but also adverse effects on various bodily functions. The aim of this study was to determine the metabolic effects of ADT in patients with nonmetastatic prostate cancer. Forty-nine men with prostate cancer were treated with ADT before beginning radical therapy for 6 months. Body weight, peripheral red blood cell counts, hemoglobin, hematocrit, fasting blood sugar, serum total cholesterol, blood urea nitrogen, uric acid, compensated calcium, inorganic phosphorus, bone-specific alkaline phosphatase, urinary deoxypyridinoline, and radial bone density determined using dual energy x-ray absorptiometry were examined before and 6 months after ADT treatment. Body weight (P = 0.037) and the levels of fasting blood sugar (P = 0.014), serum total cholesterol (P = 0.017), blood urea nitrogen (P = 0.030), compensated calcium (P < 0.001), inorganic phosphorus (P < 0.001), bone-specific alkaline phosphatase (P < 0.001), and compensated urinary deoxypyridinoline (P < 0.001) increased significantly. Peripheral red blood cell counts (P < 0.001), hemoglobin level (P < 0.001), hematocrit (P < 0.001), uric acid (P < 0.001), and radial bone density (P = 0.023) decreased significantly. These effects of ADT on various bodily functions warrant systematic study in clinical trials. We should be aware of the far-reaching consequences of ADT and incorporate strategies for preventing and managing adverse effects into routine practice.
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PMID:The influence of androgen deprivation therapy on metabolism in patients with prostate cancer. 1556 7

Here we demonstrate 2 patients who showed marked hyperglycemia after androgen-deprivation therapy for prostate cancer and the efficacy of the thiazolidinedione pioglitazone on their glycemic control. Case 1 was a 61-year-old man diagnosed with prostate cancer who had type 2 diabetes mellitus for 7 years. His glycemic control had been good for the previous 5 years because of diet therapy and acarbose administration. He was given the gonadotropin-releasing hormone agonist leuprolide acetate and the androgen receptor antagonist flutamide for the treatment of prostate cancer. After the second injection of leuprolide acetate, fasting glucose and hemoglobin A1c (HbA1c) levels were found to be markedly elevated (22.8 mmol/L and 10.5%, respectively). Case 2 was an 81-year-old man whose fasting glucose and HbA1c had been normal 10 months ago. He was injected with leuprolide acetate for the treatment of prostate cancer. Six months after starting the leuprolide treatment, the patient complained of thirst and weight loss and was diagnosed with diabetes mellitus with a fasting glucose of 19.4 mmol/L and HbA1c of 9.9%. The correct homeostasis model assessment evaluation indexes for pancreatic beta-cell function (HOMA-%beta )A and for insulin sensitivity (HOMA-%S) were reduced in these 2 patients compared with control men. Their serum testosterone and 17beta -estradiol concentrations were depressed. After improvement of hyperglycemia by insulin treatment, their glycemic control remained good after treatment with pioglitazone without use of insulin. The values of HOMA-%beta and HOMA-%S increased to control ranges. Insulin resistance after the androgen-deprivation therapy might lead to marked hyperglycemia in these patients.
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PMID:Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and usefulness of pioglitazone for its treatment. 1556 80

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0-141.0) U/l at baseline, 19.1 (3.0-486.0) U/l after 3 months, 20.8 (3.0-702.0) U/l after 6 months and 39.4 (3.0-414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.
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PMID:Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease. 1578 43

The detection of prostate-specific antigen (PSA) mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in the bloodstream of prostate cancer patients has been hypothesized as a prognostic marker, however little data are available concerning the association between this molecular marker and other laboratory values of potential importance. In this study, in patients with hormone-refractory prostate cancer (HRPC), relationships were determined between PSA RT-PCR positivity, survival, and various relevant markers including serum PSA, LDH, albumin, alkaline phosphatase and hemoglobin. A total of 19/30 HRPC patients were positive for PSA by RT-PCR. Positivity was significantly linked to serum PSA (P=0.004) and serum alkaline phosphatase (P=0.026) but not to the other laboratory variables. Median survival time for RT-PCR-positive patients was 9 months, compared to 19 months for RT-PCR-negative patients (P=0.035). Median survival time for patients with a hemoglobin>or=11 g/dL was 12 months, compared to 9 months for patients with <11 g/dL (P=0.005). Dichotomized (>or=or<median) serum PSA, LDH, alkaline phosphatase, and albumin were not significantly associated with survival in univariate analyses. In multivariate analysis, only dichotomized hemoglobin (<11 g/dL vs. >or=11 g/dL) remained statistically significant (P=0.019), indicating that RT-PCR had no independent association with survival after controlling for hemoglobin status in this study.
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PMID:Relationships between reverse transcriptase-polymerase chain reaction for prostate specific antigen, survival, and various prognostic laboratory factors in patients with hormone refractory prostate cancer. 1590 15

In the present study we aimed to demonstrate the efficacy of short-term pretreatment with finasteride in patients undergoing transurethral resection of the prostate (TUR-P). For this purpose 40 patients with BPH, who were candidates for TUR-P, were randomized into two groups. The first group (n=20) received 5 mg finasteride/day for 4 weeks prior to surgery and the second group (n=20) remained as the control. Patients who underwent prior prostate or urethral surgery and had a diagnosis of prostate cancer or chronic renal failure, patients who received finasteride, aspirin, coumadin or similar anticoagulant drugs prior to surgery and patients who had capsule perforations or open sinuses during the surgery were excluded from the study. All patients had a normal digital rectal examination and PSA values less than 4 ng/ml. As we look at the results there was no statistically significant difference between the finasteride group and control group regarding age, IPSS, PSA, prostate volumes, preoperative serum hemoglobin, hematocrit values and mean operating times and used irrigating fluids. The total amount of bleeding and bleeding per gram resected tissue were significantly lower in the finasteride group regardless of prostate volume. Furthermore the decrease in the hemoglobin and hematocrit values was higher in the control group. As a conclusion four weeks of finasteride pretreatment provided a significant decrease in peroperative bleeding regardless of prostate volume without any major side effects.
Prostate Cancer Prostatic Dis 2005
PMID:Effect of short-term finasteride therapy on peroperative bleeding in patients who were candidates for transurethral resection of the prostate (TUR-P): a randomized controlled study. 1599 18

Catalase is an endogenous antioxidant enzyme that neutralizes hydrogen peroxide and is induced by oxidative challenge. A -262C --> T polymorphism in the promoter region of the gene (CAT) is associated with risk of several conditions related to oxidative stress. We sought to determine the functional effects of the CAT polymorphism on enzyme activity in erythrocytes and the potential modifying effects of demographic and lifestyle factors on genotype/phenotype relationships, using specimens and data from controls from breast and prostate cancer studies in Arkansas (n = 420). There was a dose-response reduction in catalase activity by genotype, with geometric means of 115.4 units/mg hemoglobin for those with CC genotypes, 82.1 units/mg for those with CT genotypes, and 73.5 units/mg for those with TT genotypes. Associations were only observed among Caucasians (P < 0.0001), with no effects among African Americans (P = 0.91), and were stronger among women than men, although numbers in stratified analyses were small. Differences in catalase activity by genotype were most pronounced among those in the highest tertiles of consumption of fruits and vegetables (-35%, P = 0.003), with weaker relationships among those who were lower consumers (-21.8%, P = 0.16). Among those with CC genotypes, there was no change in activity by consumption, but there were notable decreases in activity by tertiles of consumption for those with at least one T allele. These data indicate that the CAT -262C --> T polymorphism predicts a portion of catalase phenotype, which may be limited to Caucasians. Associations between genotype and phenotype were modified by dietary factors, illustrating the biochemical complexity of studies of genetic polymorphisms and disease risk.
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PMID:Associations between catalase phenotype and genotype: modification by epidemiologic factors. 1677 84

The development of photodynamic therapy into a modality for treatment of prostate cancer calls for reliable optical dosimetry. We employ, for the first time, interstitial time-resolved spectroscopy to determine in vivo optical properties of human prostate tissue. Nine patients are included in the study, and measurements are conducted prior to primary brachytherapy treatment of prostate cancer. Intrasubject variability is examined by measuring across three tissue volumes within each prostate. The time-resolved instrumentation proves its usefulness by producing good signal levels in all measurements. We are able to present consistent values on reduced scattering coefficients (mu(s)'), absorption coefficients (mu(a)), and effective attenuation (mu(eff)) at the wavelengths 660, 786, and 916 nm. At 660 nm, mu(s)' is found to be 9+/-2 cm(-1), and mu(a) is 0.5+/-0.1 cm(-1). Derived values of mu(eff) are in the range of 3 to 4 cm(-1) at 660 nm, a result in good agreement with previously published steady state data. Total hemoglobin concentration (THC) and oxygen saturation are spectroscopically determined using derived absorption coefficients. Derived THC values are fairly variable (215+/-65 microM), while derived values of oxygen saturation are gathered around 75% (76+/-4%). Intrasubject variations in derived parameters correlate (qualitatively) with the heterogeneity exhibited in acquired ultrasound images.
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PMID:In vivo optical characterization of human prostate tissue using near-infrared time-resolved spectroscopy. 1734 97

We have previously shown that the anticancer agent doxorubicin undergoes oxidation and inactivation when exposed to myeloperoxidase-containing human leukemia HL-60 cells, or to isolated myeloperoxidase, in the presence of hydrogen peroxide and nitrite. In the current study we report that commercial fetal bovine serum (FBS) alone oxidizes doxorubicin in the presence of hydrogen peroxide and that nitrite accelerates this oxidation. The efficacy of inactivation was dependent on the concentration of serum present; no reaction was observed when hydrogen peroxide or serum was omitted. Peroxidase activity assays, based on oxidation of 3,3',5,5'-tetramethylbenzidine, confirmed the presence of a peroxidase in the sera from several suppliers. The peroxidative activity was contained in the >10000 MW fraction. We also found that hemoglobin, a heme protein likely to be present in commercial FBS, is capable of oxidizing doxorubicin in the presence of hydrogen peroxide and that nitrite further stimulates the reaction. In contrast to intact doxorubicin, the serum + hydrogen peroxide + nitrite treated drug appeared to be nontoxic for PC3 human prostate cancer cells. Together, this study shows that (pseudo)peroxidases present in sera catalyze oxidation of doxorubicin by hydrogen peroxide and that this diminishes the tumoricidal activity of the anthracycline, at least in in vitro settings. Finally, this study also points out that addition of H2O2 to media containing FBS will stimulate peroxidase-type of reactions, which may affect cytotoxic properties of studied compounds.
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PMID:Inactivation of anthracyclines by serum heme proteins. 1749 96

We show that vasoactive intestinal peptide (VIP) exerts trophic and proangiogenic activities in experimental prostate cancer in vivo. Nude mice were subcutaneously injected with Matrigel impregnated with LNCaP prostate cancer cells. Cell treatment with 100 nM VIP for 1h before xenograft resulted in increased tumor growth after 8 and, more remarkably, 15 days of injection. The same occurred with the mRNA expression of the main angiogenic factor, vascular endothelial growth factor (VEGF), as shown by real-time RT-PCR quantification. The proangiogenic activity of VIP was further established by showing increases of hemoglobin levels, Masson trichromic staining, and immunohistochemical CD34 staining in tumors excised 15 days after subcutaneous injection of VIP-treated cells as compared to control conditions. All these parameters indicate that VIP increases vessel formation. This xenograft model is a useful tool to study in vivo the effects of VIP-related peptides in tumor growth and development of blood supply as well as their therapeutical potential in prostate cancer.
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PMID:Vasoactive intestinal peptide enhances growth and angiogenesis of human experimental prostate cancer in a xenograft model. 1754 69

We analyzed clinical data to identify prognostic indicators in prostate cancer patients with bone metastasis. The subjects were 60 patients with bone metastasis out of 165 patients diagnosed with prostate cancer at our clinic over 6 years from January 1998 to December 2003. The age at the initial diagnosis was 61 to 91 (mean: 73.7 +/- 7.5) years old. The following items were considered to be possible prognostic indicators: T (type) classification, N (node) classification, Gleason score, prostate specific antigen (PSA) value before therapy, disease grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), serum calcium (Ca), hemoglobin (Hgb), and platelet count (Plt). The 5-year overall survival rate was 45.7% in the 60 patients. Univariate analysis showed statistically significant differences in N (1), Gleason score 7 + 8/Gleason score 9 + 10, and LDH level (p = 0.0053, 0.0261, and 0.0049, respectively). Multivariate Cox proportional hazard analysis of these three items showed a statistically significant difference in LDH level and Gleason score 9 +/- 10 (p = 0.0167 and 0.0371). LDH was suggested to be an excellent prognostic indicator, because of its objectivity and convenience of measurement, in prostate cancer patients with bone metastasis.
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PMID:Lactate dehydrogenase is a prognostic indicator for prostate cancer patients with bone metastasis. 1756 11


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