Expression of ADAM28 and IGFBP-3 genes in patients with colorectal cancer - a preliminary report.

Adamalisynes (ADAMs) play an important role in inter-membrane interactions, cell adhesion and fusion processes and protein shedding from the cell surface. Many reports indicate that members of the ADAMs family are overexpressed in human cancer. The aim of the present study was to evaluate ADAM28 and Insulin Like Growth Factor Binding Protein-3 (IGFBP-3)) gene expression in colorectal carcinoma tissues with regard to the overweight or obese status of the patients using an oligonucleotide microarray technique. Fresh tissue specimens were obtained from colorectal cancer patients during surgical treatment. Eighteen specimens from tumour and 18 normal tissue specimens from colorectal cancer patients at clinical stages III and IV were analysed. The examined patients were divided into two groups; those with BMI greater than or equal to 25 and those with normal BMI. The control group consisted of 18 specimens of non-neoplastic colon tissues, which were divided between overweight/obese and normal body weight patients. The gene transcriptional activity from the specimens was analysed using an oligonucleotide microarray technique. Microarrays and rinsing and marking solutions were prepared according to the procedure in the Gene Expression Analysis Technical Manual. The following conclusions were made: i) change of ADAM28 and IGFBP-3 genes expression are present in the normal tissue in overweight/obese patients with colorectal cancer only; ii) the observed molecular variability of ADAM28 and IGFBP-3 expression may be an initial process of cancer proliferation; iii) the histopathologically normal surgical margin in this group of patients was not equal to the molecular margin.

The role of interleukin-6 and transforming growth factor-beta1 in predicting restenosis within stented infarct-related artery.

Despite high efficacy of percutaneous coronary intervention (PCI), in-stent restenosis proves to be a significant problem of therapy. Restenosis concerns around 30 percent of patients. Studies have suggested that restenosis is initiated by cells which participate in intense inflammatory reaction caused by stent implantation. Atherosclerotic plaque rupture during stent implantation and PCI-associated injury of the vessel wall lead to hemorrhage and release of various cytokines. They are probably responsible for quick recurrence of vascular lumen stenosis (restenosis). Interleukin-6 (IL-6) is known as a main pro-inflammatory cytokine, whereas Transformig Growth Factor-beta1 (TGF-beta1) has anti-inflammatory properties. The study population comprised 36 patients with myocardial infarction treated with PCI with stent implantation. They underwent control coronary angiography after 12 months. At this time plasma concentration of IL-6 and TGF-beta was measured in peripheral blood. Serum IL-6 concentration in the analyzed population correlates with lumen loss (p<0.01) and the severity of stenosis (p<0.001). No such correlation was found between serum TGF-beta1 concentration and lumen loss (p=NS) or the severity of stenosis (p=NS). The IL-6 plasma concentration may be a marker of in-stent restenosis in patients after PTCA, while the concentration of TGF-beta1 is not associated with the occurrence of restenosis at one year of follow-up.

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.

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.