Vitamin D receptor gene polymorphisms and prostate cancer.

Prostate cancer (PC) is the most common cancer among men worldwide and its pathogenesis is complex. The development of PC depends on family and environmental factors. Vitamin D can be associated with both of these factors. Its reduced serum concentration has been reported in a number of tumors. However, in the case of PC, the study results are conflicting. Polymorphism of VDR gene may also be involved in the development of this cancer. The aim of the study was to compare the frequency of selected polymorphisms in patients with PC and in men without this disease. Seventy-two Caucasian males aged 35-75 years with histologically proven PC (T1/T2) were enrolled in the study group. Seventy-two random age-matched Caucasian out-patient subjects formed the control group. VDR (FokI, BsmI and TaqI) gene polymorphism (rs2228570, rs1544410, rs731236) was determined by TaqMan® SNP Genotyping. The Hardy-Weinberg Equilibrium (HWE) - p> 0.05 was in all studied polymorphisms. Deviations from the HWE were not found. There were no differences between the study group and the control group. No difference was found when the groups were compared in terms of age or the Gleason score.

Effect of trimetazidine on serum interleukin-6 and C-reactive protein concentrations in patients with stable coronary artery disease.

Trimetazidine is widely used in the treatment of stable coronary artery disease (CAD) and its cytoprotective effect has been confirmed in animal studies and in many clinical trials. Given the inflammatory milieu of CAD and trimetazidine effect on the inflow of neutrophilis to the ischemic area, it is interesting to consider whether trimetazidine actions could be also explained through the inhibition of inflammatory mediators, including cytokines. The aim of this study was to (i) examine the influence of treadmill exercise test (TET) on serum C-reactive protein (CRP) and interleukin-6 (IL-6), and (ii) the influence of three-month trimetazidine therapy on serum CRP and IL-6 concentrations. One hundred and fifty-six patients with stable CAD were included. TET was performed (according to the standard Bruce protocol) twice for all subjects – at baseline and after the three-month trimetazidine treatment. Serum IL-6 and CRP concentrations were determined prior to and after performing each TET. Exercise led to the increase of CRP (2.35 vs 2.81 mg/L, p < 0.05) and IL-6 concentrations (1.64 vs 1.92 pg/ml, p=0.0318) in patients without trimetazidine. Three-month treatment resulted in the increase in the TET duration (378.0s vs 410.9s, p < 0.05) and decrease in serum CRP concentration, both before (2.35 vs 1.51 mg/L, p < 0.05) and after TET (2.81 vs 1.69 mg/L, p < 0.05). There was no significant increase of CRP after the second TET (1.51 vs 1.69 mg/l, p=NS). Three-month trimetazidine treatment increased IL-6 concentrations (1.64 vs 2.23 pg/mL, p < 0.05). TET was not associated with further changes in IL-6 concentrations (2.23 vs 2.18 pg/mL, p=NS). Serum IL-6 and CRP concentrations increase during exercise in patients without trimetazidine. Three-month trimetazidine prolonged the duration of TET. Moreover, it resulted in the reduction of CRP concentration The increase of IL-6 concentration after three-month trimetazidine treatment and the lack of changes of its concentration after TET is associated with yet another mechanism of trimetazidine.

Serum concentration of insulin-like growth factor-I, but not tumor necrosis factor-alpha, measured twelve months after stenting of the infarct-related artery, is associated with in-stent restenosis.

Percutaneous coronary intervention (PCI) has revolutionized the management of and outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The role of insulin-like growth factor-I (IGF-I) and tumor necrosis factor-alpha (TNF-alpha) in restenosis has been intensively studied. We aimed to investigate the power of serum IGF-I and TNF-alpha concentrations to predict restenosis in patients who had previously undergone PCI for STEMI. Thirty-seven patients were enrolled in the study. Twelve months prior to the study they underwent successful PCI with stent placement for STEMI. The patients were divided into two groups: group 1 - patients with in-stent restenosis in the infarct-related artery (N=9); group 2 - patients without in-stent restenosis in the infarct-related artery (N=28). Baseline profile was similar in both groups. The mean diameter and length of placed stents were similar in both groups. Smaller minimal lumen diameter (MLD) and greater lumen loss (LL) were observed in group 1. Median IGF-I concentrations were substantially higher in patients with ISR compared to those without ISR (170 ng/mL vs 115 ng/mL, p=0.004). Strikingly, median TNF-alpha levels were lower in group 1 (2.4 pg/mL vs 4.1 pg/mL, p=0.05). Correlation analysis showed that serum IGF-I levels were significantly associated with diameter stenosis (R=0.29 p=0.05), LL (R=0.37 p=0.02), MLD (R= -0.38 p=0.03), and stent length (R=0.30 p=0.05). The cut-off value to predict restenosis for IGF-I was less than 158 ng/mL (sensitivity 55 percent, specificity 93 percent, positive predictive value 71 percent, negative predictive value 87 percent). IGF-I detected twelve months after stent placement during the acute phase of AMI may be a late determinant of restenosis. High concentrations of IGF-I could play a permissive role in the progression of NIH and subsequently restenosis. It seems that as far as TNF-alpha is concerned, diagnostic value remains inconclusive.

Simvastatin decreases concentration of interleukin-2 in hypercholesterolemic patients after treatment for 12 weeks.

UNLABELLED: Statins, HMG-CoA reductase inhibitors are drugs with a potent lipid-lowering effect. They are also able to inhibit proliferation of smooth muscle cells, T-lymphocytes, to restore endothelial activity and to inhibit inflammatory responses. These effects have been called the pleiotropic effect of statins. Statins have demonstrated contrast to the inflammatory activity of macrophages. The aim of the study was to assess the influence of simvastatin on serum levels of proinflammatory cytokines such as IL-2 and TNFalpha in hypercholesterolemic patients. METHODS: In 58 non-smoking men with total cholesterol (TC) >7.8 mmol/L, LDL-cholesterol>5.5 mmol/L and fasting triglycerides<4.6 mmol/L serum IL-2 and TNFalpha were determined at the beginning of the study, after 3 months diet and after 3 months of simvastatin therapy (20 mg/day). The control group was composed of 10 healthy volunteers with correct lipid values: TC<5.2 mmol/L, LDL-cholesterol <2.3 mmol/L, HDL-cholesterol >1.5 mmol/L and triglycerides<2.3 mmol/L. RESULTS: There were significant reductions in IL-2 concentration after 3 months diet (p=0.0059) and significant (p=0.0003) decrease of IL-2 after 3 months of simvastatin therapy. Meanwhile we observed a significant decrease of TNFalpha concentration after 3 months diet (p=0.0001) and no significant decrease after 3 months of simvastatin therapy.

[Evaluation of quality of life in patients with advanced colorectal cancer treated with topotecan]. / Ocena jakosci zycia chorych z zaawansowanym rakiem jelita grubego leczonych topotekanem.

UNLABELLED: During last years a few new directions appeared in therapy of advanced colorectal cancer. Topotecan, a camptothecin analog, seems to be one of the promising novel drug in these cases. Its unique mechanism of action is connected with inhibition of the nuclear enzyme topoizomerase I. Assessing therapeutic effects of new cytotoxic drugs we should consider their impact on survival time and quality of life as well. The aim of our study was the attempt to assess the quality of life of patients with advanced colorectal cancer (IV stage in TNM scale), treated by topotecan. Clinical trial was performed in the group of 10 patients. Topotecan was administered intravenously at 1.5 mg/m2/day for 5 days and repeated every 21 days. Quality of life assessment was performed at special time points using Rotterdam Symptom Checklist. We observed improvement in quality of life in six out ten patients having advanced colorectal cancer. Two patients did not show any change in quality of life and two patients with progression of disease demonstrated lower quality of life during topotecan treatment. CONCLUSION: Topotecan has a positive influence on quality of life of patients with advanced colorectal cancer. Further study are needed to confirm this observation.

Decrease of erythropoietin level by human recombinant tumour necrosis factor alpha (hrec TNFalpha) in patients with advanced cancer.

UNLABELLED: Anaemia is a frequent complication of chronic inflammation, infectious diseases and cancer. Inappropriate erythropoietin production is regarded as one of the main causative factors responsible for the occurrence of anaemia. The pathogenesis of TNFalpha induced-anaemia has not been fully clarified yet and its influence on hematopoiesis has been suggested. We performed a clinical study to access the influence of hrec TNFalpha administration on plasma EPO concentration and the degree of anaemia in patients with advanced solid tumours for whom no other kind of therapy but palliative treatment was available. All these patients exposed mild anaemia (HT 36.1 +/- 1.0%). Plasma EPO was estimated at 8 a.m. before and after 5 days of TNFalpha therapy with a dose of 75 pg/day iv (cycle I). Two weeks later plasma EPO was estimated again before and after 5 days of TNFalpha administration of a double dose (150 microg/day) (cycle II). The control group comprised 8 non-cancer patients (5M/3F, age 48.5 +/- 6yr) with the same degree of anaemia (HT 36 +/- 1.1%) due to haemorrhage. In the control group the plasma EPO level was significantly higher (54.2 +/- 8 mU/ml) than in cancer patients before cycle I (17.1 +/- 2.5 mU/ml) and II (14.6 +/- 3.8 mU/ml) respectively.TNF administration was followed by a significant decline of plasma EPO both after the first (17.1 +/- 2.5 vs 9.0 +/- 1.5 mU/ml) and second cycle (14.6 +/- 3.8 vs 8.4 +/- 2.0 mU/ml) of TNF treatment. CONCLUSIONS: Patients with solid cancer and mild anaemia are characterised by inappropriate low plasma EPO concentration. Therapy with TNFalpha exerts a suppressive effect on EPO secretion in these patients.