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 majority of men with prostate cancer are aged > or =65 years. Men, as they age, are more likely to suffer from impaired physical function. The standard treatment for recurrent prostate cancer is androgen-deprivation therapy (ADT). Well-established toxicities from ADT include lean weight loss or sarcopenia, muscle weakness, fatigue, and reduced activity levels. Frailty is a term from geriatrics that describes older individuals with limited physiologic reserve who are at significant risk for adverse outcomes, including falls, disability, hospitalization, and death. An increasingly accepted definition of frailty is a syndrome in which > or =3 of the following are present: unintentional (lean) weight loss > or =10 pounds in the past year, weakness (measured by grip strength), slow walking speed, self-reported exhaustion, and low physical activity. This clinical syndrome overlaps closely with the known toxicities of ADT. In addition, alterations in the inflammatory system, neuroendocrine system, and energy production are associated with this syndrome, as evidenced by biomarkers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. For this article, the authors reviewed the evidence for the effect of ADT on each of the 5 frailty components plus the identified biomarkers, and the evidence indicates that ADT may accelerate the development of frailty in vulnerable older men with prostate cancer. Given the association of frailty with important clinical outcomes such as hospitalization and death, this potential consequence of ADT should be considered carefully when initiating therapy in older patients with recurrent prostate cancer.
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PMID:Does androgen-deprivation therapy accelerate the development of frailty in older men with prostate cancer?: a conceptual review. 1796 Jun 9

This study examined 328 CFS sera in a study with 17 CCFP, 8 Gulf War Veterans (GWV), 24 Prostate Cancer (PC), and 52 normal sera in the modified Membrane Immunobead Assay (MIA) procedure for CTX. Three hundred and twenty-eight CFS patients' sera were examined by the modified MIA with purified MAb-CTX and 91.2% gave a titre > or =1:40. 76% of the 17 CCFP sera samples and 100% of the 8 GWV sera samples also had a titre > or =1:40. 92.3% of 52 normal sera showed titres of 1:20 or less, while 4 gave titres of > or =1:40. In addition, 41 sera were examined for Anti-Cardiolipin (aCL) by a commercial ELISA procedure with 87.8% demonstrating IgM, IgM+IgA, or IgM+IgG aCL antibodies. These results showed mostly the IgM aCL antibody alone in the sera samples. In addition, 41 serum samples were examined for aCL, with 37 showing positive for aCL, representing 90.2% positive for the three disease categories examined: CFS, CCFP and GWV. Examination for antiMitochondrial-M2 autoantibody (aM-M2) in 28 patients (CFS (18), CCFP (5), and GWV (5)) was negative for aM-M2. Inhibition analysis with antigens, CTX, CFS "Acute Phase Lipids", commercial Cardiolipin (CL) and 1,2-Dipalmitoyl-sn-Glycero-3-[Phospho-L-Serine] (PS) and antibodies, MAb-CTX and aCL from patients' serum show that the phospholipids in CL and CTX are antigenically indistinguishable with antibodies MAb-CTX and CFS-aCL. Preliminary chemical analyses have shown the lipids to be phospholipids associated with CL of the mitochondria. We designate this "Acute Phase Lipid" comparable to "Acute Phase Proteins" (C-reactive protein (CRP) and Serum Amyloid A (SAA)) in inflammatory conditions.
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PMID:Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins. 1834 9

The cardio protective effect of estrogen in women has come under scrutiny as recent evidence from long-term trials has demonstrated negative findings. In contrast, the effect of endogenous sex hormones, specifically estrogen, on cardiovascular disease, inflammation and clotting parameters in men has not been well-studied. Men receiving androgen deprivation therapy for prostate cancer provide a unique model to study the effect of estrogen alone on inflammation and clotting factors. In a short-term randomized controlled trial of 17-beta estradiol (E(2)) versus placebo, we measured sex hormones, markers of inflammation including homocysteine (HC), C-reactive protein (CRP), interleukin-6 (IL-6) and coagulation factors including fibrinogen, plasminogen activator-inhibitor-1 (PAI-1) and anti-thrombin-III (AT-III) in 27 older men without bone metastases receiving androgen deprivation therapy or neoadjuvant treatment for prostate cancer. After 9 weeks of E(2) treatment, there was no difference in inflammation or clotting parameters between groups, but after 9 weeks of treatment AT-III increased in the E(2) treated group and decreased in the placebo group. CRP, homocysteine and IL-6 did not show any significant differences. We also evaluated the above parameters in 12 men 3 weeks after acute steroid withdrawal with androgen deprivation therapy and found no significant changes. We found an increase in AT-III in men receiving E(2) which may be related to gonadal steroid withdrawal, but no significant differences in other inflammatory or clotting factor parameters. While the current report is very preliminary in a small group of subjects, further studies are needed to determine the long-term effects of E(2) in this population of hypogonadal men.
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PMID:The effect of short-term estradiol therapy on clotting and inflammatory markers in older men receiving hormonal suppression therapy for prostate cancer. 1857 58

Chronic inflammation is a risk factor for many diseases of aging. Endogenous oxidants are thought to mediate the effects of inflammation and gamma-Tocopherol (gamma-Toc) may mitigate damage from nitrogen-based oxidants; however, no physiological requirement for gamma-Toc has been established. Regulation of tocopherols and their functional significance are poorly defined, thereby limiting their application in prevention. Using stored plasma samples from 657 male control subjects in a previous study of prostate cancer, we have analyzed associations of the tocopherols, inflammation markers, and 25-hydroxy (OH) vitamin D. Plasma alpha-Toc and gamma-Toc were inversely correlated, whereas delta-Toc and alpha-Toc levels were positively correlated, suggesting a unique regulatory mechanism. gamma-Toc levels were positively and alpha-Toc negatively associated with plasma C-reactive protein (CRP) and urinary isoprostane F(2t), which are markers of inflammation and oxidation. Ethnic variability in tocopherols was observed; however, this may be explained by differences in plasma 25-OH vitamin D, as gamma-Toc levels varied inversely and alpha-Toc positively with 25-OH vitamin D. In these data, all-cause mortality appeared to be positively associated with CRP and inversely with 25-OH vitamin D. We hypothesize that plasma levels of tocopherols may serve as markers of systemic inflammation, complicating epidemiologic assessment of their role in cancer etiology.
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PMID:Elevated plasma gamma-tocopherol and decreased alpha-tocopherol in men are associated with inflammatory markers and decreased plasma 25-OH vitamin D. 1900 77

Interleukin-6 (IL-6) and C-reactive protein (CRP) are elevated in prostate cancer patients, but the role of prediagnostic levels of these inflammatory mediators on prostate cancer outcomes is unclear. We undertook a large, prospective case-control study to evaluate the relation between prediagnostic levels of IL-6 and CRP and prostate cancer incidence and mortality. We also investigated the role of the IL-6 (-174 G/C) polymorphism in relation to circulating levels of IL-6 and CRP, as well as cancer risk and mortality. We used unconditional logistic regression that adjusted for matching factors to analyze prostate cancer risk. For analyses of prostate cancer mortality, we conducted survival analyses in cases. Because of the strong link between inflammatory markers and body mass index (BMI), we assessed interactions between BMI and plasma levels on prostate cancer outcomes. Neither IL-6 nor CRP plasma levels varied significantly by IL-6 genotype. Genotype was not associated with prostate cancer risk or survival. Though neither IL-6 nor CRP was associated with prostate cancer incidence overall, we observed a statistically significant interaction between IL-6 and BMI on prostate cancer incidence (p(interaction) < 0.01). Increasing IL-6 levels were positively associated with risk in healthy weight men, but inversely associated with risk in overweight men. Further, prediagnostic IL-6 was associated with time to prostate cancer progression/death among healthy weight prostate cancer cases (p(trend) = 0.02). Adjusted hazard ratios were 1.73 (95% CI: 0.86, 3.51) comparing the highest to lowest IL-6 level. Our study suggests that IL-6 may potentially be involved in the development or progression of prostate cancer.
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PMID:Circulating prediagnostic interleukin-6 and C-reactive protein and prostate cancer incidence and mortality. 1918 3

Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (-174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95% CI = 1.03-2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation.
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PMID:C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older. 1926 50

Serum prostate-specific antigen complexed to alpha2-macroglobulin is occult and is not detected by conventional immunoassays. Conditions affecting alpha2-macroglobulin levels may alter the specificity of prostate-specific antigen free/total ratio in predicting prostate cancer. A group of patients (n=24) undergoing surgical stress due to a coronary artery bypass grafting was followed pre- and postoperatively up to 6 days. Total and free prostate-specific antigen, alpha2-macroglobulin, and C-reactive protein were measured by electrochemiluminescence, immunonephelometry, and immunoturbidimetry, respectively. Total prostate-specific antigen and C-reactive protein increased significantly postsurgery and remained elevated. Free/total ratio correlated negatively with C-reactive protein only (p = 0.000) using xtgee panel data analysis, after correction for plasma volume changes using albumin. Increased C-reactive protein may reflect falsely decreased free/total ratio. Therefore, prostate-specific antigen free/total ratio would be more reliable if interpreted in combination with information about CRP. However, it is recommended to defer the measurement of free/total ratio if CRP is highly elevated.
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PMID:Variations in prostate-specific antigen free/total ratio in acute stress. 1937 35

Growing evidence points to a role for inflammation in prostate carcinogenesis. The significance of C-reactive protein (CRP), an inflammatory and innate immunity molecule, has not been evaluated thoroughly in prostate cancer (PC). In this study of 739 Finnish patients with PC and 760 healthy men, we evaluated the associations of CRP genotypes and haplotypes with total PC risk and PC progression, using prostate-specific antigen (PSA) as a marker of metastatic disease. Although the haplotype frequencies were similar in patients and controls, an association between haplotype ACCCA and patients' PSA levels was found. The carriers more often had a high PSA than non-carriers (P=0.0002) and the SNP rs2794521 A-allele and rs1800947 C-allele carriers had a higher PSA than non-carriers (P=0.009 and P=0.0004, respectively). A trend for a younger age at diagnosis was found among the carriers of ACCCA (P=0.07) and the rs1800947 C-allele (P=0.06), as well as a trend for the latter to have more likely metastases (P=0.06), but not after Bonferroni correction (alpha=0.00208). This is the first study to suggest association between PSA and CRP variants in PC and, therefore, further studies are warranted. CRP alleles previously found to protect against increased CRP levels are now suggested to be associated with metastatic PC, indicated by elevated PSA.
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PMID:C-reactive protein haplotype is associated with high PSA as a marker of metastatic prostate cancer but not with overall cancer risk. 1943 91

Subjects diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN) at biopsy are at increased risk for developing prostate cancer (CaP). A prospective clinical trial was done to determine the safety and tolerability of a novel herbal amalgam, Zyflamend (New Chapter, Inc., Brattleboro, VT), with various dietary supplements in subjects with HGPIN. Men ages 40 to 75 years with HGPIN were eligible. Subjects were evaluated for 18 months. Every 3 months, standard blood chemistries and prostate-specific antigen (PSA) were monitored. Rebiopsy was done every 6 months. Tissue was evaluated for HGPIN or CaP and stained for cyclooxygenase-2, nuclear factor kappaB (NF-kappaB), interleukin-6, and thromboxane. Twenty-three subjects were evaluable. The median age was 64.1 years (range 46-75 years), and the mean (+/- SD) PSA level was 6.13 +/- 3.56 ng/mL. Side effects, when present, were mild and gastrointestinal in nature. There were no reported serious adverse events or toxicities. No significant changes in blood chemistries, testosterone, or cardiac function were noted. Forty-eight percent of subjects demonstrated a 25 to 50% decrease in PSA after 18 months. Of subjects who had the 18-month biopsy, 60% (9 of 15) had benign tissue, 26.7% (4 of 15) had HGPIN in one core, and 13.3% (2 of 15) had CaP at 18 months. A reduction in serum C-reactive protein was observed (95% confidence interval [CI] 0.7-1.7, p = .045). Immunoreactive staining demonstrated a reduction in NF-kappaB in the 18-month samples (95% CI 0.8-3.0, p = .017). Zyflamend alone and in combination with various dietary supplements is associated with minimal toxicity and no serious adverse events when administered orally for 18 months. Further studies are warranted to evaluate these agents in patients who are at risk for CaP.
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PMID:Zyflamend in men with high-grade prostatic intraepithelial neoplasia: results of a phase I clinical trial. 1947 38

The authors conducted a nested case-control study of serum inflammatory markers and risk of symptomatic benign prostatic hyperplasia (BPH), using data from the placebo arm of the Prostate Cancer Prevention Trial (1993-2003). Incident BPH (n = 676) was defined as treatment, report of 2 International Prostate Symptom Score (IPSS) values >14, or 2 increases of > or = 5 from baseline values with at least one value > or = 12. Controls (n = 683) were men who reported no BPH treatment or IPSS values >7 over the 7-year trial. Baseline serum was analyzed for C-reactive protein, tumor necrosis factor alpha (monomer), soluble tumor necrosis factor receptors I and II (sTNF-RI and sTNF-RII), interleukin 6, and interferon gamma. Controlled for age and race, a high C-reactive protein concentration was associated with increased BPH risk (for quartile 4 vs. quartile 1, odds ratio (OR) = 1.40, 95% confidence interval (CI): 1.04, 1.88); this was attenuated after control for body mass index (OR = 1.30, 95% CI: 0.95, 1.75). Low sTNF-RII and high interleukin 6 concentrations were associated with increased BPH risk (for quartile 4 vs. quartile 1, sTNF-RII: OR = 0.61, 95% CI: 0.46, 0.82; interleukin 6: OR = 1.79, 95% CI: 1.32, 2.42); these associations were only in men aged <65 years. Results suggest that systemic inflammation or lower levels of soluble receptors that bind inflammatory cytokines increase BPH risk.
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PMID:Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. 2014 96


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