Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

Ramucirumab in metastatic colorectal cancer: evidence to date and place in therapy.

Abstract: Colorectal cancer is the third most frequent cancer worldwide Overall survival rates have improved greatly over the last few years due, at least in part, to the addition of targeted therapies to standard of care chemotherapy Angiogenesis plays an important role in colorectal cancer, and therapies directed against the vascular endothelial growth factor (VEGF) axis have contributed significantly to improving the outcome of patients with metastatic colorectal cancer Over the past few years, several new targeted antiangiogenic agents have been approved for this patient population, confirming the value of inhibiting tumour angiogenesis The most recent among them is ramucirumab, a fully humanized monoclonal antibody that targets the extracellular domain of VEGF receptor 2 It has proven valuable in multiple tumour types including colorectal cancer Several phase I and II clinical trials showed a favourable toxicity profile and promising clinical antitumour efficacy in colorectal cancer patients In the phase III RAISE clinical trial, the addition of ramucirumab to FOLFIRI-based chemotherapy resulted in an improvement of overall survival in patients with metastatic colorectal cancer who had been previously treated with bevacizumab, oxaliplatin and a fluoropyrimidine On the basis of these results, ramucirumab was approved by the US Food and Drug Administration for this setting We present an overview of the key preclinical and clinical studies in the development of ramucirumab in the context of metastatic colorectal cancer

E-cadherin: A determinant molecule associated with ovarian cancer progression, dissemination and aggressiveness

Abstract: 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

Drug therapy for preventing post-dural puncture headache

Abstract: Background Post-dural (post-lumbar or post-spinal) puncture headache (PDPH) is one of the most common complications of diagnostic, therapeutic or inadvertent lumbar punctures. Many drug options have been used to prevent headache in clinical practice and have also been tested in some clinical studies, but there are still some uncertainties about their clinical effectiveness. Objectives To assess the effectiveness and safety of drugs for preventing PDPH in adults and children. Search methods The search strategy included the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 5), MEDLINE (from 1950 to May 2012), EMBASE (from 1980 to May 2012) and CINAHL (from 1982 to June 2012). There was no language restriction. Selection criteria We considered randomised controlled trials (RCTs) that assessed the effectiveness of any drug used for preventing PDPH. Data collection and analysis Review authors independently selected studies, assessed risks of bias and extracted data. We estimated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous outcomes. We calculated a 95% confidence interval (CI) for each RR and MD. We did not undertake meta-analysis because participants' characteristics or assessed doses of drugs were too different in the included studies. We performed an intention-to-treat (ITT) analysis. Main results We included 10 RCTs (1611 participants) in this review with a majority of women (72%), mostly parturients (women in labour) (913), after a lumbar puncture for regional anaesthesia. Drugs assessed were epidural and spinal morphine, spinal fentanyl, oral caffeine, rectal indomethacin, intravenous cosyntropin, intravenous aminophylline and intravenous dexamethasone. All the included RCTs reported data on the primary outcome, i.e. the number of participants affected by PDPH of any severity after a lumbar puncture. Epidural morphine and intravenous cosyntropin reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to placebo. Also, intravenous aminophylline reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention, while intravenous dexamethasone increased it. Spinal morphine increased the number of participants affected by pruritus when compared to placebo, and epidural morphine increased the number of participants affected by nausea and vomiting when compared to placebo. Oral caffeine increased the number of participants affected by insomnia when compared to placebo. The remainder of the interventions analysed did not show any relevant effect for any of the outcomes. None of the included RCTs reported the number of days that patients stayed in hospital. Authors' conclusions Morphine and cosyntropin have shown effectiveness for reducing the number of participants affected by PDPH of any severity after a lumbar puncture, when compared to placebo, especially in patients with high risk of PDPH, such as obstetric patients who have had an inadvertent dural puncture. Aminophylline also reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention in patients undergoing elective caesarean section. Dexamethasone increased the risk of PDPH, after spinal anaesthesia for caesarean section, when compared to placebo. Morphine also increased the number of participants affected by adverse events (pruritus and nausea and vomiting) There is a lack of conclusive evidence for the other drugs assessed (fentanyl, caffeine, indomethacin and dexamethasone). These conclusions should be interpreted with caution, owing to the lack of information, to allow correct appraisal of risk of bias and the small sample sizes of studies.

Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal models of neuroinflammation.

Abstract: In recent years it has become increasingly clear that the metallothionein (MT) family of proteins is important in neurobiology. MT-I and MT-II are normally dramatically up-regulated by neuroinflammation. Results for MT-III are less clear. MTs could also be relevant in human neuropathology. In Alzheimer disease (AD), a major neurodegenerative disease, clear signs of inflammation and oxidative stress were detected associated with amyloid plaques. Furthermore, the number of cells expressing apoptotic markers was also significantly increased in these plaques. As expected, MT-I and MT-II immunostaining was dramatically increased in cells surrounding the plaques, consistent with astrocytosis and microgliosis, as well as the increased oxidative stress elicited by the amyloid deposits. MT-III, in contrast, remained essentially unaltered, which agrees with some but not all studies, of AD. In situ hybridization results in a transgenic mouse model of AD amyloid deposits, the Tg2576 mouse, which expresses human Abeta precursor protein harboring the Swedish K670N/M671L mutations, are in accordance with results in human brains. Overall, these and other studies strongly suggest specific roles for MT-I, MT-II, and MT-III in brain physiology.