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Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.

Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melan

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

Radioimmunotherapy for Prostate Cancer-Current Status and Future Possibilities.

Prostate cancer (PCa) is one of the most common cancers in men and is the second leading cause of cancer-related deaths in the USA. In the United States, it is the second most frequently diagnosed cancer after skin cancer, and in Europe it is number one. According to the American Cancer Society, approximately 221,000 men in the United States would be diagnosed with PCa during 2015, and approximate

Intratumorally implanted mesenchymal stromal cells potentiate peripheral immunotherapy against malignant rat gliomas.

Bone marrow-derived mesenchymal stromal cells (MSCs) target glioma extensions and micro-satellites efficiently when implanted intratumorally. Here, we report that intratumoral implantation of MSCs and peripheral immunotherapy with interferon-gamma (IFNγ) producing tumor cells improve the survival of glioma-bearing rats (54% cure rate) compared to MSC alone (0% cure rate) or immunotherapy alone (21

Fibroblasts Cultured on Nanowires Exhibit Low Motility, Impaired Cell Division, and DNA Damage.

Nanowires are commonly used as tools for interfacing living cells, acting as biomolecule-delivery vectors or electrodes. It is generally assumed that the small size of the nanowires ensures a minimal cellular perturbation, yet the effects of nanowires on cell migration and proliferation remain largely unknown. Fibroblast behaviour on vertical nanowire arrays is investigated, and it is shown that c

Inherited variation in the PARP1 gene and survival from melanoma

We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting f

RBM3-Regulated Genes Promote DNA Integrity and Affect Clinical Outcome in Epithelial Ovarian Cancer.

The RNA-binding motif protein 3 (RBM3) was initially discovered as a putative cancer biomarker based on its differential expression in various cancer forms in the Human Protein Atlas (HPA). We previously reported an association between high expression of RBM3 and prolonged survival in breast and epithelial ovarian cancer (EOC). Because the function of RBM3 has not been fully elucidated, the aim of

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

Low expression of CysLT(1)R and high expression of CysLT(2)R mediate good prognosis in colorectal cancer

Colorectal cancer is the third most common cancer type in the western world. in search of new treatment possibilities, the inflammation mediators, know as cysteinyl leukotrienes (CysLTs), have been shown to regulate intestinal epithelial cell survival and proliferation via the CysLT(1)R, and cell differentiation via the CysLT(2)R. These results prompted us to investigate the significance of CysLT(

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

Stem cell-based therapy for malignant glioma.

Stem cells have been extensively investigated as tumour-tropic vectors for gene delivery to solid tumours. In this review, we discuss the potential for using stem cells as cellular vector systems in gene therapy for malignant gliomas, with a focus on neural stem cells, and multipotent mesenchymal stromal cells. Tumour cell-derived substances and factors associated with tumour-induced inflammation

Inhibition of Microglial Activation Protects Hippocampal Neurogenesis and Improves Cognitive Deficits in a Transgenic Mouse Model for Alzheimer's Disease

Background: Activated microglia with macrophage-like functions invade and surround beta-amyloid (A beta) plaques in Alzheimer's disease (AD), possibly contributing to the turnover of A beta, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis. Objectives/Methods: To determine the role of mi

Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3.

We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on beta-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSM

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