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Prospective study of merkel cell polyomavirus and risk of merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare type of skin cancer that has a characteristically increased incidence among immunosuppressed subjects. The DNA of Merkel cell polyomavirus (MCV) is regularly found in most MCC tumors. We investigated whether Merkel cell polyomavirus (MCV) infection increases the risk for future Merkel cell carcinoma (MCC). Two large biobank cohorts (Southern Sweden Microbiolog

Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency.

Ebf1 is a transcription factor with documented dose dependent functions in normal and malignant B-lymphocyte development. To understand more about the roles of Ebf1 in malignant transformation, we investigated the impact of reduced functional Ebf1 dosage on mouse B-cell progenitors. Gene expression analysis suggested that Ebf1 was involved in the regulation of genes important for DNA repair as wel

Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development.

Hypoxia, or low oxygen tension, is a major regulator of tumor development and aggressiveness. However, how cancer cells adapt to hypoxia and communicate with their surrounding microenvironment during tumor development remain important questions. Here, we show that secreted vesicles with exosome characteristics mediate hypoxia-dependent intercellular signaling of the highly malignant brain tumor gl

Prediction of Significant Prostate Cancer Diagnosed 20 to 30 Years Later With a Single Measure of Prostate-Specific Antigen at or Before Age 50

BACKGROUND: We previously reported that a single prostate-specific antigen (PSA) measured at ages 44-50 was highly predictive of subsequent prostate cancer diagnosis in an unscreened population. Here we report an additional 7 years of follow-up. This provides replication using an independent data set and allows estimates of the association between early PSA and subsequent advanced cancer (clinical

Upregulation of miR-96 Enhances Cellular Proliferation of Prostate Cancer Cells through FOXO1.

Aberrant expression of miR-96 in prostate cancer has previously been reported. However, the role and mechanism of action of miR-96 in prostate cancer has not been determined. In this study, the diagnostic and prognostic properties of miR-96 expression levels were investigated by qRT-PCR in two well documented prostate cancer cohorts. The miR-96 expression was found to be significantly higher in pr

TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells.

TRIM28 is a corepressor that mediates transcriptional silencing by establishing local heterochromatin. Here, we show that deletion of TRIM28 in neural progenitor cells (NPCs) results in high-level expression of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. We find that NPCs use TRIM28-mediated histone modifications to dynamically regulate transcription and silencing of ERVs, wh

Low production of reactive oxygen species in granulocytes is associated with organ damage in systemic lupus erythematosus

Introduction: Polymorphonuclear leukocytes (PMN) are main effector cells in the acute immune response. While the specific role of PMN in systemic lupus erythematosus (SLE) and autoimmunity is still unclear, their importance in chronic inflammation is gaining more attention. Here we investigate aspects of function, bone marrow release and activation of PMN in patients with SLE. Methods: The followi

Increase in percent free prostate-specific antigen in men with chronic kidney disease.

BACKGROUND: Prostate-specific antigen (PSA) occurs in different molecular forms in serum: free PSA (fPSA) and complexed PSA (cPSA), the sum of which corresponds to total PSA (tPSA). In addition to tPSA, percent fPSA is widely used in the detection of prostate cancer. Free PSA, approximately 28 kDa, is eliminated by glomerular filtration. Previous data showed that men with end-stage renal dysfuncti

Exploring the multifaceted nature of the common lymphoid progenitor compartment.

While the common lymphoid progenitor compartment was originally thought to be a rather homogenous cell population, it has become increasingly clear that this compartment is highly heterogeneous both with regard to phenotypic and functional features. The exploration of this cellular complexity has generated novel molecular insights into regulatory events in lymphoid lineage restriction and provided

Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all

Metastasis stimulation by hypoxia and acidosis-induced extracellular lipid uptake is mediated by proteoglycan-dependent endocytosis

Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in

Impaired phagocytosis and reactive oxygen species production in phagocytes is associated with systemic vasculitis

BACKGROUND: Anti-neutrophil cytoplasmic antibodies associated vasculitides (AAV) is a group of autoimmune diseases, characterized by small vessel inflammation. Phagocytes such as neutrophils and monocytes are the main effector cells found around the inflamed vessel wall. Therefore, we wanted to investigate aspects of function and activation of these cells in patients with AAV.METHODS: Flow cytomet

Fast-track access to urologic care for patients with macroscopic haematuria is efficient and cost-effective : results from a prospective intervention study

Background:The delay between onset of macroscopic haematuria and diagnosis of bladder cancer is often long.Methods:We evaluated timely diagnosis and health-care costs for patients with macroscopic haematuria given fast-track access to diagnostics. During a 15-month period, a telephone hotline for fast-track diagnostics was provided in nine Swedish municipalities for patients aged ⩾50 years with ma

Germline CDKN2A Mutation Status and Survival in Familial Melanoma Cases

BACKGROUND: Germline mutations in CDKN2A have been associated with increased risk of melanoma and tobacco-related cancers in respiratory and upper digestive tissues. In CDKN2A wild-type (wt) melanoma families, other known high-risk, melanoma-predisposing mutations are rare, and no increased risk has been observed for nonskin cancers in this group. This study is the first to compare survival in ger

prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk.

Thyroid hormones influence both normal breast cell differentiation and breast cancer cell proliferation and stimulate the angiogenesis of certain cancer forms. Several cross-sectional studies have measured thyroid hormones / auto antibodies in breast cancer ceases vs. controls, but it is difficult to determine the cause-effect direction in these studies. Only three prospective studies have reporte

Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score.

Aims: The aim of this study was to evaluate the prevalence of triple antithrombotic therapy (TT) (warfarin, aspirin and clopidogrel) in patients following an acute coronary syndrome (ACS), the bleeding risk compared to double antiplatelet therapy (DAPT) (aspirin and clopidogrel) and evaluate the accuracy of the HAS-BLED risk score in predicting serious bleeding events in TT patients. Methods and r

Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells.

Highly malignant tumors, such as glioblastomas, are characterized by hypoxia, endothelial cell (EC) hyperplasia, and hypercoagulation. However, how these phenomena of the tumor microenvironment may be linked at the molecular level during tumor development remains ill-defined. Here, we provide evidence that hypoxia up-regulates protease-activated receptor 2 (PAR-2), i.e., a G-protein-coupled recept

Cyclosporine, tacrolimus and sirolimus retain their distinct toxicity profiles despite low doses in the Symphony study.

BACKGROUND: Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and