University of Crete

About: University of Crete is a education organization based out in Rethymno, Greece. It is known for research contribution in the topics: Population & Galaxy. The organization has 8681 authors who have published 21684 publications receiving 709078 citations. The organization is also known as: Panepistimio Kritis.

The Akt pathway in oncology therapy and beyond (Review)

Abstract: Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and division, apoptosis suppression and angiogenesis. Akt protein kinase displays important metabolic effects, among which are glucose uptake in muscle and fat cells or the suppression of neuronal cell death. Disruptions in the Akt-regulated pathways are associated with cancer, diabetes, cardiovascular and neurological diseases. The regulation of the Akt signaling pathway renders Akt a valuable therapeutic target. The discovery process of Akt inhibitors using various strategies has led to the identification of inhibitors with great selectivity, low side-effects and toxicity. The usefulness of Akt emerges beyond cancer therapy and extends to other major diseases, such as diabetes, heart diseases, or neurodegeneration. This review presents key features of Akt structure and functions, and presents the progress of Akt inhibitors in regards to drug development, and their preclinical and clinical activity in regards to therapeutic efficacy and safety for patients.

Sat0173 a systematic literature review informing the 2019 update of the joint european league against rheumatism and european renal association–european dialysis and transplant association (eular/era-edta) recommendations for the management of lupus nephritis

Abstract: Background: Systemic Lupus Erythematosus (SLE) is clinically and immunologically heterogeneous with a variable response to treatment. MASTERPLANS is an MRC-funded consortium that seeks to identify immunophenotypic subgroups of patients that predict response to therapy. Autoantibody profiles can differentiate subgroups of patients and have potential to predict response to treatment. Objectives: To determine whether known and novel autoantibodies are associated with response to rituximab (RTX), and analyse the association between these antibodies and disease involvement in various organ systems. Methods: Serum was obtained from 224 SLE patients in the BILAG Biologics Registry who received rituximab according to NHS England criteria (2). Patients were recruited if they were starting a first cycle of rituximab for active SLE (BILAG A or 2xBILAG B) despite previous cyclophosphamide or mycophenolate mofetil. Evidence of any single organ system involvement previous or current was taken as having a BILAG score of A-D but not E. Disease activity was measured using BILAG-2004. Clinical response was defined as improvement by >=1 grade in active BILAG-2004 systems with no worsening in other systems. Autoantibodies were measured by immunoprecipitation of proteins by sera from 35S-labelled K562 cell lines, followed by SDS-PAGE separation and autoradiography. Autoantibodies not able to be detected by this technique (anti-Ro52, anti-dsDNA and aCL) were measured by ELISA. Autoantibody data was analysed in IBM SPSS and GraphPad Prism v8.2. Association between autoantibodies and RTX response was analysed using binary logistic interaction terms and Pearson’s Chi-Square test. Results: Of the 224 patients (201 female, 23 male, median age 40 years) the most common system involvement from the 9 BILAG domains was musculoskeletal (164 patients) and the least ophthalmic (11 patients). Patients with anti-Ro52 and anti-U1RNP/Sm had more frequent involvement of mucocutaneous (p There were 136 patients with sufficient data to define as either responders (n=67) or non-responders (n=69) to RTX at 6 months. RTX responders had a higher frequency of anti-U1RNP/Sm compared to non-responders (Figure 1). Further Pearson’s Chi-Square analysis showed a significant association between presence of anti-U1RNP/Sm and better response to RTX (p Conclusion: Our findings suggest that the presence of U1RNP/Sm autoantibodies in a cohort of patients who have received treatment with RTX is associated with more frequent musculoskeletal and mucocutaneous involvement and predicts a more favourable response to treatment. Acknowledgments : Funded by a grant from the Medical Research Council, grant number MR/M01665X/1. BILAG BR has been funded by unrestricted educational donations from Roche, GSK and LUPUS UK. Part-funded by a grant from LUPUS UK. Disclosure of Interests: : Danyang Li: None declared, Hui Lu: None declared, Juliet Dunphy: None declared, Theresa Smith: None declared, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GSK, and UCB, Consultant of: Eli Lilly, AstraZeneca, UCB, Iltoo, and Merck Serono, Speakers bureau: UCB, Neil McHugh: None declared

No clear submillimeter signature of suppressed star formation among x-ray luminous active galactic nuclei

Abstract: Many theoretical models require powerful active galactic nuclei (AGNs) to suppress star formation in distant galaxies and reproduce the observed properties of today's massive galaxies. A recent study based on Herschel-SPIRE submillimeter observations claimed to provide direct support for this picture, reporting a significant decrease in the mean star formation rates (SFRs) of the most luminous AGNs (L{sub X} >10{sup 44} erg s{sup -1}) at z Almost-Equal-To 1-3 in the Chandra Deep Field-North (CDF-N). In this Letter, we extend these results using Herschel-SPIRE 250 {mu}m data in the COSMOS and Chandra Deep Field-South fields to achieve an order-of-magnitude improvement in the number of sources at L{sub X} >10{sup 44} erg s{sup -1}. On the basis of our analysis, we find no strong evidence for suppressed star formation in L{sub X} >10{sup 44} erg s{sup -1} AGNs at z Almost-Equal-To 1-3. The mean SFRs of the AGNs are constant over the broad X-ray luminosity range of L{sub X} Almost-Equal-To 10{sup 43}-10{sup 45} erg s{sup -1} (with mean SFRs consistent with typical star-forming galaxies at z Almost-Equal-To 2; (SFRs) Almost-Equal-To 100-200 M{sub Sun} yr{sup -1}). We suggest that the previous CDF-N results were likely due to low number statistics. We discuss ourmore » results in the context of current theoretical models.« less

Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFNET-EHRA consensus conference 'research perspectives in AF'.

Abstract: Atrial fibrillation (AF) causes important mortality and morbidity on a population-level. So far, we do not have the means to prevent AF or AF-related complications adequately. Therefore, over 70 experts on atrial fibrillation convened for the 2nd AFNET/EHRA consensus conference to suggest directions for research to improve management of AF patients (Appendix 1). The group defined three main areas in need for research in AF: 1. better understanding of the mechanisms of AF; 2. Improving rhythm control monitoring and management; and 3. comprehensive cardiovascular risk management in AF patients. The group put forward the hypothesis that successful therapy of AF and its associated complications will require comprehensive therapy. This applies e.g. to the "old" debate of "rate versus rhythm control", since rhythm control is generally added to underlying (continued) rate control therapy, but also to the emerging debate of "antiarrhythmic drugs versus catheter ablation", of which both may be needed in most patients to maintain sinus rhythm, but also to therapy of conditions that predispose to AF and contribute to cardiovascular complications such as stroke, cognitive decline, heart failure, and acute coronary syndromes. We call for research initiatives aiming at a better understanding of the different causes of AF and its complications, and at development and validation of mechanism-based therapies. The future of AF therapy may require a combination of management of underlying and concomitant conditions, early and comprehensive rhythm control therapy, adequate control of ventricular rate and cardiac function, and continuous therapy to prevent AF-associated complications (e.g. antithrombotic therapy). The reasons for these suggestions are detailed in this paper.