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.

ADAM17 (TACE) regulates TGFβ signaling through the cleavage of vasorin.

Abstract: The activity of a variety of extracellular signaling factors is tightly regulated by proteins containing A Disintegrin And a Metalloprotease domain (ADAM) metalloproteases through limited proteolysis. Thus, the identification of ADAM substrates may unveil novel components and mechanisms of cell signaling pathways. We report the identification of the transmembrane protein vasorin (VASN), a transforming growth factor-β (TGFβ) trap, as a substrate of ADAM17. The metalloprotease efficiently generates a soluble fragment encompassing the extracellular domain of VASN. Despite the importance of TGFβ in normal development and tumor progression, the regulation of VASN is completely unknown. Here, we show that only the soluble form of VASN inhibits TGFβ and that the secretion of VASN is tightly controlled by ADAM17. Hence, inhibition of ADAM17 leads to the upregulation of TGFβ signaling. Adding a new level of complexity to the function of ADAM17, we finally show that, through the cleavage of VASN, the metalloprotease controls TGFβ-mediated epithelial-to-mesenchymal transition.

Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial.

Abstract: Summary Background Tumour Treating Fields (TTFields) are a regional, antimitotic treatment for solid tumours, which is based on the delivery of low-intensity alternating electric fields. The aim of the STELLAR study was to test the activity of TTFields delivered to the thorax in combination with systemic chemotherapy for the front-line treatment of patients with unresectable malignant pleural mesothelioma. Methods STELLAR was a prospective, single-arm, phase 2 trial done at 12 European academic and non-academic sites (five in Italy, three in Poland, one in France, one in Belgium, one in Spain, and one in the Netherlands) for treatment-naive patients with histologically confirmed unresectable malignant pleural mesothelioma. Patients were aged at least 18 years, had an Eastern Cooperative Oncology Group performance status of 0–1, and at least one measurable or evaluable lesion according to modified Response Evaluation Criteria in Solid Tumors for mesothelioma. Patients received continuous TTFields at a frequency of 150 kHz to the thorax and concomitant chemotherapy with intravenous pemetrexed (500 mg/m2 on day 1) plus intravenous platinum (either cisplatin 75 mg/m2 on day 1 or carboplatin area under the curve 5 on day 1) every 21 days for up to six cycles. Patients not progressing after completion of chemotherapy received TTFields as maintenance treatment until progression, patient or physician decision, or unacceptable toxic effects. The primary endpoint of the trial was overall survival. Survival analyses were done in the intention-to-treat population, and safety analyses were done in all patients who received at least 1 day of TTFields treatment. This trial is registered with ClinicalTrials.gov , NCT02397928 . Findings Between Feb 9, 2015 and March 21, 2017, 80 patients were enrolled in the study. Median follow-up was 12·5 months (IQR 7·4–16·6). Median overall survival was 18·2 months (95% CI 12·1–25·8). The most common grade 3 or worse adverse events were anaemia (nine [11%] patients), neutropenia (seven [9%]), and thrombocytopenia (four [5%]). Skin reaction was the only adverse event associated with TTFields and was reported as grade 1–2 in 53 (66%) patients, and as grade 3 in four (5%) patients. No treatment-related deaths were observed. Interpretation The trial showed encouraging overall survival results, with no increase in systemic toxicity. TTFields (150 kHz) delivered to the thorax concomitant with pemetrexed and platinum was an active and safe combination for front-line treatment of unresectable malignant pleural mesothelioma. Further investigation in a randomised trial is warranted. Funding Novocure.

Shared heritability and functional enrichment across six solid cancers

Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

Statistical reviewers improve reporting in biomedical articles: a randomized trial.

Abstract: Background Although peer review is widely considered to be the most credible way of selecting manuscripts and improving the quality of accepted papers in scientific journals, there is little evidence to support its use. Our aim was to estimate the effects on manuscript quality of either adding a statistical peer reviewer or suggesting the use of checklists such as CONSORT or STARD to clinical reviewers or both. Methodology and Principal Findings Interventions were defined as 1) the addition of a statistical reviewer to the clinical peer review process, and 2) suggesting reporting guidelines to reviewers; with “no statistical expert” and “no checklist” as controls. The two interventions were crossed in a 2×2 balanced factorial design including original research articles consecutively selected, between May 2004 and March 2005, by the Medicina Clinica (Barc) editorial committee. We randomized manuscripts to minimize differences in terms of baseline quality and type of study (intervention, longitudinal, cross-sectional, others). Sample-size calculations indicated that 100 papers provide an 80% power to test a 55% standardized difference. We specified the main outcome as the increment in quality of papers as measured on the Goodman Scale. Two blinded evaluators rated the quality of manuscripts at initial submission and final post peer review version. Of the 327 manuscripts submitted to the journal, 131 were accepted for further review, and 129 were randomized. Of those, 14 that were lost to follow-up showed no differences in initial quality to the followed-up papers. Hence, 115 were included in the main analysis, with 16 rejected for publication after peer review. 21 (18.3%) of the 115 included papers were interventions, 46 (40.0%) were longitudinal designs, 28 (24.3%) cross-sectional and 20 (17.4%) others. The 16 (13.9%) rejected papers had a significantly lower initial score on the overall Goodman scale than accepted papers (difference 15.0, 95% CI: 4.6–24.4). The effect of suggesting a guideline to the reviewers had no effect on change in overall quality as measured by the Goodman scale (0.9, 95% CI: −0.3–+2.1). The estimated effect of adding a statistical reviewer was 5.5 (95% CI: 4.3–6.7), showing a significant improvement in quality. Conclusions and Significance This prospective randomized study shows the positive effect of adding a statistical reviewer to the field-expert peers in improving manuscript quality. We did not find a statistically significant positive effect by suggesting reviewers use reporting guidelines.