Lowered Serum Testosterone Concentration Is Associated With Enhanced Inflammation and Worsened Lipid Profile in Men.

The negative relationship between testosterone and inflammatory cytokines has been reported for decades, although the exact mechanisms of their interactions are still not clear. At the same time, little is known about the relation between androgens and acute phase proteins. Therefore, in this investigation, we aimed to study the relationship between androgen status and inflammatory acute phase reactants in a group of men using multi-linear regression analysis. Venous blood samples were taken from 149 men ranging in age from 18 to 77 years. Gonadal androgens [testosterone (T) and free testosterone (fT)], acute phase reactants [C-reactive protein (CRP), ferritin (FER), alpha-1-acid glycoprotein (AAG), and interleukin-6 (IL-6)], cortisol (C), and lipid profile concentrations were determined. It was demonstrated that the markers of T and fT were negatively correlated with all acute phase proteins (CRP, FER, and AAG; p < 0.02) and the blood lipid profile [total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG); p < 0.03]. Multivariate analysis showed that T, fT, and the fT/C ratio were inversely correlated with the CRP, AAG, and FER concentrations independently of age and blood lipids. When adjustment for BMI was made, T, fT, and the fT/C ratio were negatively correlated with the AAG concentrations only. In addition, it was demonstrated that gonadal androgens were positively correlated with physical activity level (p < 0.01). We have concluded that a lowered serum T concentration may promote inflammatory processes independently of adipose tissue and age through a reduced inhibition of inflammatory cytokine synthesis, which leads to enhanced acute phase protein production. Therefore, a low serum T concentration appears to be an independent risk factor in the development of atherosclerosis and cardiovascular diseases. Moreover, the positive correlation between testosterone and physical activity level suggests that exercise training attenuates the age-related decrease in gonadal androgens and, in this way, may reduce the enhancement of systemic low-grade inflammation in aging men.

Human Epididymis Protein 4 (HE4) in Patients with Small-Cell Lung Cancer.

BACKGROUND: The aim of the present study was to compare the diagnostic utility of HE4 with NSE, ProGRP, CYFRA 21-1, CEA, and CA 125 and evaluate their prognostic value in patients with small-cell lung cancer (SCLC). METHODS: HE4, ProGRP, NSE, CYFRA 21-1, CEA, and CA 125 assays were performed in 63 patients with smallcell lung cancer (limited disease (LD) - 41, extensive disease (ED) - 22) and in 66 individuals of the reference group. RESULTS: Area under the ROC curves for HE4, ProGRP, NSE, CA 125, CYFRA 21-1, and CEA were 0.884, 0.923, 0.826, 0.796, 0.739, and 0.704, respectively. The tumor marker serum concentrations were associated with tumor stage (HE4, ProGRP, NSE, CYFRA 21-1, CEA), and disease progression occurred within one year (HE4, ProGRP, NSE, CYFRA 21-1). The tumor advancement, performance status, gender and tumor markers, except CEA and CA 125, were significantly associated with survival. Independent, unfavourable prognostic factors included extensive disease (HR 4.14, p < 0.0001) and NSE concentration above 35 g/l (HR 2.62, p = 0.0009). CONCLUSIONS: Diagnostic utility of HE4 was similar to that of NSE and ProGRP. Complementary to NSE, determination of HE4 seems to be helpful in evaluation of SCLC patients' prognosis.

ProGRP and NSE in therapy monitoring in patients with small cell lung cancer.

The usefulness of serum pro-gastrin-releasing peptide (ProGRP) as a tumor marker in patients with small cell lung cancer has recently drawn the attention of many research centers. The aim of the study was the evaluation of ProGRP, neuron-specific enolase (NSE), soluble fragment of cytokeratin 19 (CYFRA 21-1) and lactate dehydrogenase (LDH) levels at the time of diagnosis and during chemo- and radiotherapy of small cell lung cancer patients with limited disease (SCLC-LD). The studies were performed on a group of 64 patients with SCLC-LD who had received no prior therapy. All the patients were given the same treatment regimen. ProGRP, NSE, CYFRA 21-1 and LDH were measured before each course of chemotherapy and then at 3 and 6 months after the end of treatment. Prior to therapy, elevated levels of ProGRP, NSE, CYFRA 21-1 and LDH were found in 79.7%, 57.8%, 23.4%, and 12.5% of the patients respectively. Before the second chemotherapy course, all the tumor marker levels except LDH decreased significantly in comparison with the pretreatment concentrations. However, only ProGRP levels showed a progressive drop during consecutive courses of therapy, while NSE and CYFRA 21-1 fluctuated within reference ranges. When the study group was divided with respect to the effect of treatment evaluated six months from its termination, significant differences in ProGRP levels were found between both subgroups throughout all therapy and follow-up, except for the fifth course of chemotherapy. Differences in NSE levels were only significant for the first two courses and follow-up. Univariate analysis showed significant relationships between disease-free survival and the initial levels of NSE and CYFRA 21-1 as well as between overall survival and prophylactic cranial irradiation (PCI) and the initial ProGRP, NSE and CYFRA 21-1 levels. Changes of ProGRP level seem to be more precise than NSE as a tool for monitoring therapy in SCLC patients with limited disease, but for prediction of relapse, in addition to NSE determinations of ProGRP seem to be optimal.