Ovarian cancer (OC) is the fifth cancer death cause in women worldwide. The malignant nature of this disease stems from its unique dissemination pattern. Epithelial-to-mesenchymal transition (EMT) has been reported in OC and downregulation of Epithelial cadherin (E-cadherin) is a hallmark of this process. However, findings on the relationship between E-cadherin levels and OC progression, dissemination and aggressiveness are controversial. In this study, the evaluation of E-cadherin expression in an OC tissue microarray revealed its prognostic value to discriminate between advanced- and early-stage tumors, as well as serous tumors from other histologies. Moreover, E-cadherin, Neural cadherin (N-cadherin), cytokeratins and vimentin expression was assessed in TOV-112, SKOV-3, OAW-42 and OV-90 OC cell lines grown in monolayers and under anchorage-independent conditions to mimic ovarian tumor cell dissemination, and results were associated with cell aggressiveness. According to these EMT-related markers, cell lines were classified as mesenchymal (M; TOV-112), intermediate mesenchymal (IM; SKOV-3), intermediate epithelial (IE; OAW-42) and epithelial (E; OV-90). M- and IM-cells depicted the highest migration capacity when grown in monolayers, and aggregates derived from M- and IM-cell lines showed lower cell death, higher adhesion to extracellular matrices and higher invasion capacity than E- and IE-aggregates. The analysis of E-cadherin, N-cadherin, cytokeratin 19 and vimentin mRNA levels in 20 advanced-stage high-grade serous human OC ascites showed an IM phenotype in all cases, characterized by higher proportions of N- to E-cadherin and vimentin to cytokeratin 19. In particular, higher E-cadherin mRNA levels were associated with cancer antigen 125 levels more than 500 U/mL and platinum-free intervals less than 6 months. Altogether, E-cadherin expression levels were found relevant for the assessment of OC progression and aggressiveness.
Asthma is a common chronic disorder which may be increasing in prevalence. However, little is known of its distribution and determinants. The European Community Respiratory Health Survey (ECRHS) is a multicentre survey of the prevalence, determinants and management of asthma. This paper presents a descriptive account of the variation in self-reported attacks of asthma and asthma symptoms across Europe, and in part fulfils the first aim of the study. A screening questionnaire, including seven questions relating to the 12 month prevalence of symptoms of asthma, was distributed to representative samples of 20-44 year old men and women in 48 centers, predominantly in Western Europe. The median response rate to the questionnaire was 75% but, after removing from the denominator those who were the wrong age, were known to have moved out of the area, or had died, it was 78% (range 54-100). The prevalence of all symptoms varied widely. Although these were generally lower in northern, central and southern Europe and higher in the British Isles, New Zealand, Australia and the United States, there were wide variations even within some countries. Centres with a high prevalence of self-reported attacks of asthma also reported high prevalences of nasal allergies and of waking at night with breathlessness. The use of asthma medication was more common where wheeze and asthma attacks were more frequent. In most centres in The Netherlands, Sweden, New Zealand and the United Kingdom over 80% of those with a diagnosis of asthma were currently using asthma medication. In Italy, France and Spain the rate was generally less than 70%. These data are the best evidence to date that geographical differences in asthma prevalence exist, are substantial and are not an artefact of the use of noncomparable methods.
This report is based on a Hygienist Panel Meeting held at St Anne's Manor, Wokingham on 24–25 June 2009. The panel agreed that greater use should be made of antiseptics to reduce reliance on antibiotics with their associated risk of antibiotic resistance. When choosing an antiseptic for clinical use, the Biocompatibility Index, which considers both the microbiocidal activity and any cytotoxic effects of an antiseptic agent, was considered to be a useful tool. The need for longer and more proactive post-discharge surveillance of surgical patients was also agreed to be a priority, especially given the current growth of day-case surgery. The introduction of surgical safety checklists, such as the World Health Organization's Safe Surgery Saves Lives initiative, is a useful contribution to improving safety and prevention of SSIs and should be used universally. Considering sutures as ‘implants’, with a hard or non-shedding surface to which micro-organisms can form biofilm and cause surgical site infections, was felt to be a useful concept.
Washed human platelets bound radioiodinated low density lipoprotein ( 125 I-LDL) to a class of saturable binding sites; they numbered 1,348±126 per platelet, and the dissociation constant (K D ) was 50.7±9 nM. I25I-LDL binding to platelets was reversible, and apparent equilibrium was attained within 25 minutes at 22°C and was characterized by forward and reverse rate constants of 1.47xlO4 Xsec"'xM" 1 and 8xlO~4xsec~' xM" 1 , respectively. Such binding was largely unaltered by temperature, divalent ions, and chelating agents. In addition, neither did receptor regulation (up or down) occur when platelets were loaded with cholesterol, nor did prostaglandin E, (PGE,) increase the binding of 12S I-LDL to platelets. On the other hand, the specificity of LDL binding was not typical of the LDL receptor of nucleated cells. Lipoproteins competed for the occupancy of LDL binding sites in platelets with the following order of potency: very low density >> intermediate density > high density subfraction 2. High density lipoprotein subfraction 3, heparin, and PGE, had no effect on this binding.
Ovarian cancer is the most lethal gynecological malignancy due to the silent nature on its early onset and the rapid acquisition of drug resistance. Histologically heterogeneous, it includes several subtypes with different mutational landscapes, hampering the development of effective targeted therapies. Non-coding RNAs are emerging as potential new therapeutic targets in cancer. To search for a microRNA signature related to ovarian carcinomas and study its potential as effective targeted therapy, we examined the expression of 768 miRNA in a large collection of tumor samples and found miR-654-5p to be infraexpressed in ovarian serous carcinomas, the most common and aggressive type. Restoration of miR-654-5p levels reduced tumor cell viability in vitro and in vivo and impaired sphere formation capacity and viability of ovarian cancer patient-derived ascitic cells ex vivo. CDCP1 and PLAGL2 oncogenes were found to be the most relevant direct miR-654-5p targets and both genes convey in a molecular signature associated with key cancer pathways relevant to ovarian tumorigenesis, such as MYC, WNT and AKT pathways. Together, we unveiled the tumor suppressor function of miR-654-5p, suggesting that its restoration or co-targeting of CDCP1 and PLAGL2 may be an effective therapeutic approach for ovarian cancer.
Objectives: To compare two job exposure matrices (JEMs) for the evaluation of asthma risks related to specific occupational exposures in a communitybased study. Methods: A questionnaire on self-reported asthma, respiratory symptoms and current occupation was sent to the participants of the European Community Respiratory Health Survey in five areas in Spain. Both an asthma-specific JEM, including expert judgment steps and a general JEM, were applied to occupational codes. Risks of current asthma symptoms and wheeze in the last year associated with the obtained exposure estimates were evaluated. Correlations between specific exposures were investigated using explanatory factor analysis. Results: Occupational exposures to the highmolecular-weight (MW) agents flour dust, enzymes, mites and animal-derived proteins as obtained by the asthma-specific JEM were positively associated with asthma outcomes. The effect of additional expert judgment steps was limited. High exposures to biological dust assessed by the general JEM without expert judgment was also associated with asthma. Many of the exposed individuals worked in environments with multiple exposures. Conclusions: Asthma risks associated with occupational exposures to specific high-MW agents could be identified from a population-based study using an asthma-specific JEM. Application of JEMs can be a useful tool to estimate asthma risks attributable to specific occupational exposures in the general population. However, these specific exposure risks should be interpreted in connection with the whole of concomitant exposures constituting the work environment.
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