Lipoproteins, sex hormones and inflammatory markers in association with prostate cancer.
ABSTRACT To evaluate lipoprotein profile and sex hormones in patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their possible associations with some inflammatory markers linked to PCa.
A total of 150 men (50-65 years), matched by age and body mass index (BMI), included in this study and divided into three groups according to total prostate specific antigen (PSA), digital rectal examination and prostate biopsy: 50 PCa, 50 BPH and 50 controls. Total cholesterol (Chol), HDL-chol, LDL-chol, triglycerides (TG), total testosterone (T), free T (FT), bioavailable T (BioT), estradiol and SHBG were measured. The free androgen index (FAI) and TG/HDL-chol were calculated. In 25 PCa and 25 controls, C-reactive protein (hs-CRP), adiponectin and insulin were determined.
Patients with PCa showed higher TG/HDL-chol and diminished HDL-chol than Controls and BPH. PSA correlated inversely with HDL-chol and directly with TG/HDL-chol. FAI, FT, BioT and estradiol levels were higher, and SHBG and adiponectin were lower in PCa than in Controls. No differences were found in androgens between BPH and PCa.
Our most novel findings are that the patients with PCa presented lower total Chol and HDL-chol and higher TG/HDL-chol than BPH and Controls. Patients with PCa showed higher androgens and lower adiponectin than Controls.
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ABSTRACT: Adiponectin is an adipokine that can suppress the proliferation of various human carcinoma cells. Although its anti-tumor activities have been suggested by many clinical investigations and animal studies, the underlying mechanisms are not fully characterized. In MMTV-polyomavirus middle T antigen (MMTV-PyVT) transgenic mice models, reduced- or complete loss-of-adiponectin expression promotes mammary tumor development. The present study demonstrated that while tumor development in control MMTV-PyVT mice is associated with a progressively decreased circulating cholesterol concentration, adiponectin deficient MMTV-PyVT mice showed significantly elevated total- and low density lipoprotein (LDL)-cholesterol levels. Cholesterol contents in tumors derived from adiponectin deficient mice were dramatically augmented. High fat high cholesterol diet further accelerated the tumor development in adiponectin deficient PyVT mice. The protein levels of LDL receptor (LDLR) were found to be upregulated in adiponectin-deficient tumor cells. In human breast carcinoma cells, treatment with LDL-cholesterol or overexpressing LDLR elevates nuclear beta-catenin activity and facilitates tumor cell proliferation. On the other hand, adiponectin decreased LDLR protein expression in breast cancer cells and inhibited LDL-cholesterol-induced tumor cell proliferation. Both in vivo and in vitro evidence demonstrated a stimulatory effect of adiponectin on autophagy process, which mediated the down-regulation of LDLR. Adiponectin-induced reduction of LDLR was blocked by treatment with a specific inhibitor of autophagy, 3-methyladenine. In conclusion, the study demonstrates that adiponectin elicits tumor suppressive effects by modulating cholesterol homeostasis and LDLR expression in breast cancer cells, which is at least in part attributed to its role in promoting autophagic flux.Oncotarget 10/2013; · 6.64 Impact Factor
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ABSTRACT: Prostate cancer is a common disease in modern, developed societies and has a high incidence and mortality. High-density lipoprotein cholesterol (HDL-C) has recently received much attention as a possible risk marker of prostate cancer development and prognosis. In the present article, we summarized findings from epidemiologic studies of the association between HDL-C and prostate cancer. Low HDL-C level was found to be a risk and prognostic factor of prostate cancer in several epidemiologic studies, although the overall linkage between HDL and prostate cancer has not been definitively established. The mechanisms for this association remain uncertain; however, limited data from experimental studies imply a possible role of HDL in the pathophysiology of prostate cancer. More epidemiologic research, in combination with experimental studies, is needed in this field.Journal of Epidemiology 08/2013; · 2.11 Impact Factor
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ABSTRACT: Abstract Objective. Recent studies show an inverse relationship between testosterone levels and prostate cancer (PCa). The usefulness of hormonal patterns in PCa diagnosis is controversial. This study aimed to determine the relationship between hormonal patterns and PCa, and to find a cut-off point of hormone levels to assess PCa risk. Material and methods. A prospective analysis was undertaken of 279 patients referred for first or second prostate biopsy in the Hospital Clínic Barcelona from November 2006 to May 2009. The indication for prostate biopsy was suspicion of PCa based on the results of digital rectal examination (DRE) and/or elevation of serum prostate-specific antigen (PSA). Screening was carried out with a 5+5-core transrectal ultrasound-guided prostate biopsy. Age, prostate volume, DRE (normal or abnormal), biopsy findings (normal or report of PCa), PSA, free-to-total PSA, PSA density, testosterone and sex hormone-binding globulin (SHBG) were also prospectively recorded. Free and bioavailable testosterone were calculated using Vermeulen's formula. Results. In the multivariate analysis, abnormal DRE [odds ratio (OR = 5.46, p < 0.001], SHBG levels ≥ 66.25 nmol/l [OR = 3.27; 95% confidence interval (CI) 1.52 to 7.04, p < 0.002] and bioavailable testosterone levels ≤ 104 ng/dl (OR = 4.92, 95% CI 1.78 to 13.59, p = 0.002) were related to the diagnosis of prostate adenocarcinoma. Age, free testosterone, PSA, testosterone, PSA/testosterone, PSA/free testosterone and PSA/bioavailable testosterone were not related to PCa diagnosis. Conclusions. Low bioavailable testosterone levels and high SHBG levels were related to a 4.9- and 3.2-fold risk of detection of PCa on prostate biopsy owing to PSA elevation or abnormal DRE. This fact may be useful in the clinical scenario in counselling patients at risk for PCa.Scandinavian Journal of Urology and Nephrology 11/2012; · 1.01 Impact Factor