Bisphenol A induce ovarian cancer cell migration via the MAPK and PI3K/Akt signalling pathways

Bisphenol A (BPA), is present in a multitude of products, including food and water containers, food can linings, dentistry sealants, and thermal paper. BPA can induce the growth of human ovarian cancer cell lines. Reduction of adhesion and the initiation of metastasis are important events in cancer progression; therefore, this study investigated the effects of BPA (0.1–100 nM) on the migration of OVCAR-3 ovarian cancer cells and the expression levels of metalloproteinases (MMPs) and cadherins. The oestrogenic compound 17β-estradiol (40 nM) was used as a positive control for estrogenic properties of bisphenol A. BPA stimulated cell migration, and the effect of BPA was similar to that of 17β-estradiol. BPA-induced cell migration was accompanied by up-regulation of the migration-related factors MMP-2, MMP-9 and N-cadherin, but E-cadherin expression and activity was unaffected. The stimulatory effects of BPA on cell migration were abolished by pre-treatment of the cells with inhibitors of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase pathways (PI3K). In conclusion, the results presented here show that BPA induces OVCAR-3 cells migration by activating MAPK and PI3K/Akt signalling pathways.     

Evidence of an increased nitric oxide production in primary biliary cirrhosis

OBJECTIVE: Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation. METHODS: Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis. RESULTS: Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55+/-1.75 arbitrary units vs 1.95+/-0.57 and 0.84+/-0.34, p = 0.0004 and p < 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7+/-192.0 microg/L vs 51.1+/-34.3 and 38.0+/-11.5, p < 0.0001 and p < 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls. CONCLUSIONS: Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide.     

Nosocomial infections in critically ill infectious disease patients: Results of a 7-year focal surveillance

Summary An incidence study on nosocomial infections in critically ill infectious disease patients was carried out in the intensive care unit (ICU) of a university hospital for infectious diseases over a 7-year period (1 January 1990 to 31 December 1996). A total 660 patients who stayed in the ICU for over 48 h were prospectively observed. The patients were divided into two groups: one with central nervous system infections (442 patients) and the other with other severe infections (218 patients). The risk of nosocomial sepsis and pneumonia was significantly higher in patients suffering from severe central nervous system infections. The incidence of sepsis was 24.2% vs 11.4% (relative risk 1.95; 95% confidence interval 1.32–2.89); the incidence of pneumonia was 30.5% vs 14.7% (relative risk 2.09; 95% confidence interval 1.47–2.96). The incidence of urinary tract infection was 14.3% vs 13.3% (relative risk 1.07; 95% confidence interval 0.71–1.61). Density rates of nosocomial septic episodes were 21.1±37.1 vs 11.7±32.4 episodes/100 central venous-line days (P<0.006). Nosocomial pneumonia occurred only in mechanically ventilated patients (36.9±61.2 vs 28.5±65.8 episodes per 1000 ventilatory days, P=0.012). Nosocomial urinary tract infection occurred only in patients with urinary catheters (11.6±60.7 episodes/1000 urinary catheter days vs 18.7±90.1, P=0.886). Multivariate regression analysis identified age, diagnosis of CNS infection, duration of urinary tract catheterization, the use of central venous lines and mechanical ventilation as independent risk factors of nosocomial sepsis. Duration of mechanical ventilation, use of steroids and diagnosis of CNS infection were independent risk factors of nosocomial pneumonia. A subanalysis identified tetanus patients to be at particular risk of nosocomial infections.     

The in vitro treatment with vitamin D3 is ineffective on the expression of PKC isoenzymes,but decreases further the impaired production of IL-2 in the T lymphocytes of SLE patients

The objective of the study was to investigate the possibility whether the in vitro treatment with vitamin D₃ can restore the impaired expression of protein kinase C (PKC) isoenzymes and IL-2 production in the lymphocytes of patients with systemic lupus erythematosus (SLE). Purified T lymphocytes from 14 patients with SLE and 13 healthy controls were cultured for 48 h in the presence and absence of 1 and 100 nM doses of vitamin D₃. The expressions of various PKC isoenzymes were tested by Western blot analysis, and the amounts of various cytokines were detected by ELISA in the culture supernatants. Neither the low (1 nM) nor the high (100 nM) doses of vitamin D₃ (1α,-25-dihydroxyvitamin) applied in vitro for 48 h were able to restore the decreased expression of PKC isoenzymes in the T cells of SLE patients. However, 100 nM of vitamin D₃ significantly increased the release of IL-10, but suppressed the production of IL-2, IL-6, interferon γ and TNF α in the culture supernatants of both groups. As the low production of IL-2 is one of the main pathologic features of SLE, we recommend to avoid the use of high doses of vitamin D₃ for treatment of lupus patients with vitamin D₃ deficiency.     

Elderly deaths in Ankara,Turkey

According to World Health Organization, the life expectancy at birth is increasing. An increase in life expectancy might result in increased morbidity and mortality in elderly. The increase in the elderly population also leads to an increase in medico-legal problems, as well. Autopsy is of high importance for determination of cause of death in clinical and forensic cases. The purpose of this study was to find out general characteristics elderly deaths by examining forensic autopsy records.     

EGFR Mutation Testing Practice in Advanced Non-Small Cell Lung Cancer

Purpose

Testing tumor samples for the presence of a mutation in the epithelial growth factor receptor (EGFR) gene is recommended for advanced non-squamous non-small cell lung cancer (NSCLC) patients. We aimed to collect data about common practice among Medical Oncologists treating lung cancer patients, regarding EGFR mutation testing in advanced NSCLC patients.

Methods

An internet-based survey was conducted among members of the Israeli Society for Clinical Oncology and Radiotherapy involved in the treatment of lung cancer patients.

Results

24 Oncologists participated in the survey. The participants encompass the Oncologists treating most of the lung cancer patients in Israel. 79 % of them use EGFR testing routinely for all advanced NSCLC patients. Opinions were split regarding the preferable biopsy site for EGFR testing material. 60 % of participants recommend waiting for EGFR test results prior to initiation of first-line therapy.

Conclusions

EGFR testing is requested in Israel routinely by most treating Oncologists for all advanced NSCLC patients, regardless of histology. In most cases, systemic treatment is deferred until the results of this test are received.