Helicobacter pylori VacA toxin up-regulates vascular endothelial growth factor expression in MKN 28 gastric cells through an epidermal growth factor receptor-, cyclooxygenase-2-dependent mechanism.

PURPOSE: Helicobacter pylori causes gastric damage and is involved in gastric carcinogenesis. Vascular endothelial growth factor (VEGF) plays a major role in gastric mucosa repair and is overexpressed in gastric cancer. We investigated: (a) whether H. pylori, and in particular H. pylori VacA toxin, affected VEGF expression in gastric epithelial cells in culture; and (b) the signal transduction pathway involved in any effect exerted by H. pylori. EXPERIMENTAL DESIGN: MKN-28 cells were incubated with uninoculated BCF (control) or with BCF obtained from VacA-producing wild-type H. pylori 60190 strain or from its isogenic mutant 60190:v1, specifically lacking vacA gene in the presence or absence of ZD 1839, a selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, PD098059, a selective inhibitor of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase, the kinase responsible for ERK phosphorylation, or SC-236, a selective inhibitor of cyclooxygenase (COX)-2 for 24-48 h. RESULTS: (a) Toxigenic H. pylori up-regulated VEGF mRNA and protein expression and caused a 2.5-fold increase in VEGF release compared with control, whereas nontoxigenic H. pylori did not; (b) H. pylori VacA toxin-induced up-regulation of VEGF was counteracted by selective inhibition of EGFR tyrosine kinase; (c) toxigenic H. pylori activated the ERK/MAP kinase cascade, and inhibition of MAP kinase activation counteracted H. pylori-induced VEGF up-regulation; (d) toxigenic H. pylori up-regulated COX-2 expression, and this effect was counteracted by blockade of EGFR tyrosine kinase; and (e) COX-2 selective inhibition counteracted H. pylori-induced up-regulation of VEGF. CONCLUSION: (a) H. pylori up-regulates VEGF expression in gastric epithelial cells; and (b) this effect is specifically related to VacA toxin and seems to depend on the activation of an EGFR-, MAP kinase-, and COX-2-mediated pathway.     

The effects of somatostatin in the polycystic ovary syndrome.

Eighteen obese women (body mass index 30 +/- 6.1 kg/m2) with hyperinsulinaemia and with the polycystic ovary syndrome took octreotide at the dose of 100 mug s.c. The effect of the drug was assessed on plasma levels of gonadotropins luteinising hormone (LH), follicle stimulating hormone (FSH), of insulin, insulin-like growth factor-1 (IGF-1), androstenedione, testosterone, dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG) and insulin-like growth factor-binding protein-3 (IGFBP-3). Octreotide significantly reduced LH (31.8%), insulin (52%), IGF-1 (14%), androstenedione (22.6%) and testosterone (20%) and increased IGFBP-3 (25%).     

Acute effects of air pollution in Rome

Two time-series studies, aimed at evaluating the acute health effect of air pollution among Rome inhabitants, were carried out. In the first study the correlation between daily mortality (1992 to 1995) and daily concentrations of five air pollutants (particles, SO2, NO2, CO, O3) was analyzed. In the second study the association between daily levels of the same pollutants and hospital admissions for respiratory and cardiovascular disease (1995-97) was evaluated. Poisson regression models were used to estimate the association between pollutant levels and health effect variables; the models included smooth functions of day of study, mean temperature, mean humidity and indicator variables for day of the week and holidays. Daily total mortality was associated with particle average concentration on that day and with NO2 levels of one or two days before. Hospital admissions for cardiovascular disease were positively correlated to particles, SO2, NO2, e CO. Hospital admissions for respiratory disease were associated with NO2 and CO levels of the same day and of two days before among children (0-14 years) and among adults (15-64 years). Increments of ozone were associated with increments of total respiratory and of acute respiratory diseases in children (0-14 years).     

IGF-I, IGFBP-3 and breast cancer in young women: a pooled re-analysis of three prospective studies.

Prospective cohort studies on breast cancer risk among premenopausal women and insulin-like growth factor I (IGF-I) concentrations have so far included only few cases, and have shown inconsistent relative risk estimates. We pooled 220 cases of breast cancer diagnosed before age 50, and 434 control subjects, from three prospective studies in New York (USA), Ume? (Northern Sweden) and Milan (Italy), and we measured IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) with common enzyme-linked immunosorbent assays. Overall, IGF-I and IGFBP-3 measurements obtained by the common method showed a positive but not significant relationship with breast cancer risk (odds ratios (ORs) 0.90 [95% confidence intervals (95% CI) 0.50-1.62], 1.63 [0.89-2.97], 1.46 [0.78-2.73] and 1.41 [0.75-2.63] for quintiles of IGF-I, and ORs 0.98 [0.54-1.75], 1.06 [0.59-1.91], 1.04 [0.58-1.87] and 1.77 [0.97-3.24] for quintiles of IGFBP-3). Our results give only moderate support for an association of blood IGF-I with breast cancer risk in young women.