Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure. Part 1: Oral route

Synthetic amorphous silica (SAS) in its nanosized form is now used in food applications although the potential risks for human health have not been evaluated. In this study, genotoxicity and oxidative DNA damage of two pyrogenic (NM‐202 and 203) and two precipitated (NM‐200 and ‐201) nanosized SAS were investigated in vivo in rats following oral exposure. Male Sprague Dawley rats were exposed to 5, 10, or 20 mg/kg b.w./day for three days by gavage. DNA strand breaks and oxidative DNA damage were investigated in seven tissues (blood, bone marrow from femur, liver, spleen, kidney, duodenum, and colon) with the alkaline and the (Fpg)‐modified comet assays, respectively. Concomitantly, chromosomal damage was investigated in bone marrow and in colon with the micronucleus assay. Additionally, malondialdehyde (MDA), a lipid peroxidation marker, was measured in plasma. When required, a histopathological examination was also conducted. The results showed neither obvious DNA strand breaks nor oxidative damage with the comet assay, irrespective of the dose and the organ investigated. Similarly, no increases in chromosome damage in bone marrow or lipid peroxidation in plasma were detected. However, although the response was not dose‐dependent, a weak increase in the percentage of micronucleated cells was observed in the colon of rats treated with the two pyrogenic SAS at the lowest dose (5 mg/kg b.w./day). Additional data are required to confirm this result, considering in particular, the role of agglomeration/aggregation of SAS NMs in their uptake by intestinal cells. Environ. Mol. Mutagen. 56:218–227, 2015. © 2014 Wiley Periodicals, Inc.     

Water, trachoma and conjunctivitis.

The incidence of eye infections in a community is generally accepted as an indicator of the adequacy of water supply for their needs. However, discrepancies in the published results from various studies seem to challenge this view. We have reanalysed the published data on trachoma in relation to the most relevant indicators of water accessibility, using prevalence ratios as the single parameter for risk assessment. A definite trend emerges from this review: the incidence of infectious conjunctivitis is not sensitive to differences in water accessibility; on the other hand, a reduction in the risk of trachoma is consistently associated with better access to water. This conclusion may support the efforts of WHO and other multilateral and bilateral agencies to sustain the commitment towards the water supply sector beyond the International Drinking Water Supply and Sanitation Decade.     

Dorsal intramedullary spinal epidermoid cysts: Report of two cases and review of literature

Intramedullary epidermoid cysts of the spinal cord are rare tumors, especially those not associated with spinal dysraphism. About 50 cases have been reported in the literature. Of these, only seven cases have had magnetic resonance imaging (MRI) studies. We report two cases of spinal intramedullary epidermoid cysts with MR imaging. Both were not associated with spina bifida. In one patient, the tumor was located at D4 vertebral level; while in the other, within the conus medullaris. The clinical features, MRI characteristics and surgical treatment of intramedullary epidermoid cyst are presented with relevant review of the literature.     

Bariatric surgery and the gut-brain communication—The state of the art three years later

ObjectiveThis review analyzes the literature concerning gut peptides and bariatric surgery, from 2005 to July 2009. In particular, we are interested in whether, and how, gastrointestinal peptide alterations following surgery interfere with appetite/satiety, and what role they might play in the resolution of comorbidities.Research methods and procedurePubMed/MEDLINE and ISI Web of Knowledge were used to search for human studies concerning gut peptides profiles after any bariatric operation technique.ResultsMost of the studies reviewed had longitudinal design, short follow-up, and low statistical power. The diversity of study results may be partially explained by methodological aspects. Glucagon-like peptide-1, gastric inhibitory peptide, and peptide YY alterations may contribute to the excellent results in glycemic control of diabetics. Results do vary depending on bariatric operation technique; this is particularly evident in the case of ghrelin, which has been much studied in recent years. Ghrelin suppression has been linked to increased satiety, alterations in energy homeostasis, and better glucose metabolism.ConclusionsThere is a lack of long-term data on gastrointestinal hormone profiles after bariatric surgery and the studies have many methodological pitfalls. We still need prospective, long-term, good methodological studies in this area.     

Non-cultured cell transplantation in an ovine model of non-ischemic heart failure.

OBJECTIVE: Cell therapy may be a promising alternative or adjunct to current treatment modalities for ischemic heart failure. But little is known on the impact of myogenic cell transplantation in large animal models of non-ischemic cardiomyopathy. The aim of the present study was to explore whether an ovine model of toxin-induced heart disease could benefit from non-cultured skeletal muscle cell transplantation. METHODS: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic detection of myocardial dysfunction. Sheep were then randomly assigned to either non-cultured cell transplantation (n=8) or placebo injection (n=5). For the cell therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each animal approximately 3h before grafting. After thoracotomy, 20 epicardial injections were carried out. The animals were assessed one last time before sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red fluorescence) and characterized with immunohistochemistry with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. RESULTS: Two months after intramyocardial grafting, tissue Doppler imaging and conventional echocardiographic assessment of the groups showed a marked improvement in the non-cultured cell therapy group. Ejection fraction (EF) (p<0.05) as well as systolic endocardial velocities (p<0.01) improved versus the placebo group. CmDiI and skeletal myosin heavy chain expression was detected in all animals at 2 months after implantation confirming engraftment of skeletal muscle cells. CONCLUSIONS: In conclusion, our data indicate that non-cultured muscle cell transplantation is feasible and may translate into a functional benefit in an ovine model of dilated heart failure.