The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis

Malignant astrocytomas are highly aggressive brain tumours with poor prognosis. While a number of structural genomic changes and dysregulation of signalling pathways in gliomas have been described, the identification of biomarkers and druggable targets remains an important task for novel diagnostic and therapeutic approaches. Here, we show that the Wnt-specific secretory protein Evi (also known as GPR177/Wntless/Sprinter) is overexpressed in astrocytic gliomas. Evi/Wls is a core Wnt signalling component and a specific regulator of pan-Wnt protein secretion, affecting both canonical and non-canonical signalling. We demonstrate that its depletion in glioma and glioma-derived stem-like cells led to decreased cell proliferation and apoptosis. Furthermore, Evi/Wls silencing in glioma cells reduced cell migration and the capacity to form tumours in vivo. We further show that Evi/Wls overexpression is sufficient to promote downstream Wnt signalling. Taken together, our study identifies Evi/Wls as an essential regulator of glioma tumourigenesis, identifying a pathway-specific protein trafficking factor as an oncogene and offering novel therapeutic options to interfere with the aberrant regulation of growth factors at the site of production

The accessory papillary muscle with inferior J-waves - peculiarity or hidden danger?

Originally described in 1953, today the so-called J-wave is the source of much controversy. As a marker of so-called "early repolarization", this variant has been regarded as a totally benign variant since the 1960's. However, since then a wealth of data have indicated that the J-wave may be a marker of a highly arrhythmogenic substrate with a resultant high risk of sudden cardiac death

Overexpression of Prothymosin Alpha Predicts Poor Disease Outcome in Head and Neck Cancer

In our recent study, tissue proteomic analysis of oral pre-malignant lesions (OPLs) and normal oral mucosa led to the identification of a panel of biomarkers, including prothymosin alpha (PTMA), to distinguish OPLs from histologically normal oral tissues. This study aimed to determine the clinical significance of PTMA overexpression in oral squamous cell hyperplasia, dysplasia and head and neck squamous cell carcinoma (HNSCC).Immunohistochemistry of PTMA protein was performed in HNSCCs (n = 100), squamous cell hyperplasia (n = 116), dysplasia (n = 50) and histologically normal oral tissues (n = 100). Statistical analysis was carried out to determine the association of PTMA overexpression with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients.<0.001). Chi-square analysis showed significant association of nuclear PTMA with advanced tumor stages (III+IV). Kaplan Meier survival analysis indicated reduced disease free survival (DFS) in HNSCC patients (p<0.001; median survival 11 months). Notably, Cox-multivariate analysis revealed nuclear PTMA as an independent predictor of poor prognosis of HNSCC patients (p<0.001, Hazard's ratio, HR = 5.2, 95% CI = 2.3–11.8) in comparison with the histological grade, T-stage, nodal status and tumor stage.Nuclear PTMA may serve as prognostic marker in HNSCC to determine the subset of patients that are likely to show recurrence of the disease

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Managing atrial fibrillation in the very elderly patient: challenges and solutions

Nikolaos Karamichalakis, Konstantinos P Letsas, Konstantinos Vlachos, Stamatis Georgopoulos, Athanasios Bakalakos, Michael Efremidis, Antonios Sideris Laboratory of Cardiac Electrophysiology, &quot;Evangelismos&quot; General Hospital of Athens, Athens, Greece Abstract: Atrial fibrillation (AF) is the most common arrhythmia affecting elderly patients. Management and treatment of AF in this rapidly growing population of older patients involve a comprehensive assessment that includes comorbidities, functional, and social status. The cornerstone in therapy of AF is thromboembolic protection. Anticoagulation therapy has evolved, using conventional or newer medications. Percutaneous left atrial appendage closure is a new invasive procedure evolving as an alternative to systematic anticoagulation therapy. Rate or rhythm control leads to relief in symptoms, fewer hospitalizations, and an improvement in quality of life. Invasive methods, such as catheter ablation, are the new frontier of treatment in maintaining an even sinus rhythm in this particular population. Keywords: elderly, atrial fibrillation, anticoagulation, drugs, catheter ablatio