Institution
Rappaport Faculty of Medicine
About: Rappaport Faculty of Medicine is a based out in . It is known for research contribution in the topics: Population & Heparanase. The organization has 3205 authors who have published 3915 publications receiving 114533 citations.
Topics: Population, Heparanase, Medicine, Cancer, Pregnancy
Papers published on a yearly basis
Papers
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TL;DR: Nuclear localization of heparanase suggests that the enzyme may fulfill nontraditional functions (ie, regulation of gene expression and signal transduction) apart of its well-documented involvement in cancer metastasis, angiogenesis and inflammation.
101 citations
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TL;DR: This review summarizes the main findings in oxidative stress/inflammation in the context of OSA and its consequences to possible cardiovascular outcomes through the development of endothelial dysfunction and early clinical signs of atherosclerosis.
Abstract: Obstructive sleep apnea syndrome (OSA) is a breathing disorder in sleep. In recent years, this entity has emerged as a major public health problem due to its high prevalence and the profound impact on patients' health and quality of life. A large body of evidence identified OSA as an independent risk factor for cardiovascular morbidity and mortality. Also an association was demonstrated with additional cardiovascular risk factors. This has led to intensive research on the mechanisms involved. The main characteristics of OSA are the recurrent pauses in respiration which result in intermittent hypoxia (IH) and hypercapnia, accompanied by decreased blood oxygen saturation and arousals during sleep. The associations of OSA with cardiovascular morbidities rely on the cyclic nature of the IH, and implicate the apnea related multiple cycles of hypoxia/reoxygenation with increased production of reactive oxygen species (ROS), thereby initiating inflammation. This review summarizes the main findings in oxidative stress/inflammation in the context of OSA and its consequences to possible cardiovascular outcomes through the development of endothelial dysfunction and early clinical signs of atherosclerosis.
100 citations
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TL;DR: A large-scale analysis of the dynamics of this evolutionary process within tumors, with a focus on breast cancer, reveals the uniqueness of the cancer evolutionary process and the particular importance of globally expressed genes in driving cancer initiation and progression.
Abstract: Cancer is an evolutionary process in which cells acquire new transformative, proliferative and metastatic capabilities. A full understanding of cancer requires learning the dynamics of the cancer evolutionary process. We present here a large-scale analysis of the dynamics of this evolutionary process within tumors, with a focus on breast cancer. We show that the cancer evolutionary process differs greatly from organismal (germline) evolution. Organismal evolution is dominated by purifying selection (that removes mutations that are harmful to fitness). In contrast, in the cancer evolutionary process the dominance of purifying selection is much reduced, allowing for a much easier detection of the signals of positive selection (adaptation). We further show that, as a group, genes that are globally expressed across human tissues show a very strong signal of positive selection within tumors. Indeed, known cancer genes are enriched for global expression patterns. Yet, positive selection is prevalent even on globally expressed genes that have not yet been associated with cancer, suggesting that globally expressed genes are enriched for yet undiscovered cancer related functions. We find that the increased positive selection on globally expressed genes within tumors is not due to their expression in the tissue relevant to the cancer. Rather, such increased adaptation is likely due to globally expressed genes being enriched in important housekeeping and essential functions. Thus, our results suggest that tumor adaptation is most often mediated through somatic changes to those genes that are important for the most basic cellular functions. Together, our analysis reveals the uniqueness of the cancer evolutionary process and the particular importance of globally expressed genes in driving cancer initiation and progression.
100 citations
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TL;DR: The observations described in this article point to the existence of increased oxidative stress and systemic inflammation in sleep apnea and have paved the way for establishingSleep apnea as an independent risk factor for cardio- and cerebrovascular morbidities.
100 citations
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Manchester Academic Health Science Centre1, Lund University2, Paris Descartes University3, University of Oxford4, University of Manchester5, University of Pécs6, University of Erlangen-Nuremberg7, University of Zurich8, Royal Free London NHS Foundation Trust9, Salford Royal NHS Foundation Trust10, Radboud University Nijmegen Medical Centre11, Grigore T. Popa University of Medicine and Pharmacy12, French Institute of Health and Medical Research13, McGill University14, University of Florence15, Rappaport Faculty of Medicine16, Oslo University Hospital17, Queen Elizabeth Hospital Birmingham18, St. Vincent's Health System19, University of Cologne20, University of Cambridge21, University of Nantes22, University of Liverpool23, Glasgow Royal Infirmary24, Leeds Teaching Hospitals NHS Trust25, Stanford University26, University of Belgrade27, North Bristol NHS Trust28, Nottingham University Hospitals NHS Trust29, The Queen's Medical Center30, University of Copenhagen31, University of East Anglia32, Royal National Hospital for Rheumatic Diseases33, University of Giessen34, University of Lübeck35, Charité36, Royal Perth Hospital37, University of Limoges38, Lille University of Science and Technology39, Istanbul University40, James Cook University Hospital41, Royal Adelaide Hospital42, University of Gothenburg43, Monash University, Clayton campus44, University of Lyon45
TL;DR: Findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
Abstract: OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. TRIAL REGISTRATION NUMBER: NCT02339441.
100 citations
Authors
Showing all 3205 results
Name | H-index | Papers | Citations |
---|---|---|---|
Barry M. Brenner | 121 | 540 | 65006 |
Robert R. Edelman | 119 | 605 | 49475 |
David M. Goldenberg | 108 | 1238 | 48224 |
Moussa B.H. Youdim | 107 | 574 | 42538 |
Aaron Ciechanover | 105 | 315 | 58698 |
Israel Vlodavsky | 98 | 494 | 34150 |
Basil S. Lewis | 96 | 651 | 60124 |
Michael Aviram | 94 | 479 | 31141 |
Abraham Weizman | 81 | 1011 | 31083 |
Thomas N. Robinson | 81 | 309 | 26121 |
Peretz Lavie | 81 | 320 | 21532 |
Jacob M. Rowe | 75 | 328 | 20043 |
Hossam Haick | 72 | 279 | 15646 |
Walid Saliba | 70 | 359 | 19254 |
Gad Rennert | 67 | 350 | 17349 |