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Probing the Virtual Proteome to Identify Novel Disease Biomarkers

BACKGROUND: Proteomic approaches allow measurement of thousands of proteins in a single specimen, which can accelerate biomarker discovery. However, applying these technologies to massive biobanks is not currently feasible because of the practical barriers and costs of implementing such assays at scale. To overcome these challenges, we used a "virtual proteomic" approach, linking genetically predi

Prostate cancer risk-associated single-nucleotide polymorphism affects prostate-specific antigen glycosylation and its function

BACKGROUND: Genetic association studies have reported single-nucleotide polymorphisms (SNPs) at chromosome 19q13.3 to be associated with prostate cancer (PCa) risk. Recently, the rs61752561 SNP (Asp84Asn substitution) in exon 3 of the kallikrein-related peptidase 3 (KLK3) gene encoding prostate-specific antigen (PSA) was reported to be strongly associated with PCa risk (P 2.3 108). However, the bi

Uptake of nanowires by human lung adenocarcinoma cells

Semiconductor nanowires are increasingly used in optoelectronic devices. However, their effects on human health have not been assessed fully. Here, we investigate the effects of gallium phosphide nanowires on human lung adenocarcinoma cells. Four different geometries of nanowires were suspended in the cell culture for 48 hours. We show that cells internalize the nanowires and that the nanowires ha

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302) : final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study

BACKGROUND: Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall s

Enzalutamide in metastatic prostate cancer before chemotherapy

BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy.METHODS: In

Cell-type-specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes

Most expression quantitative trait locus (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type-specific regulatory landscape of human melanocytes, which give rise to melanoma but account for <5% of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We i

Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy

Background: Enhancer of zeste 2 (EZH2) promotes prostate cancer progression. We hypothesized that increased EZH2 expression is associated with postradiotherapy metastatic disease recurrence, and may promote radioresistance. Methods: EZH2 expression was investigated using immunohistochemistry in diagnostic prostate biopsies of 113 prostate cancer patients treated with radiotherapy with curative int

Physical inactivity increases the risk of endometrial cancer and premenopausal breast cancer

Background. Epidemiological studies indicate that physical activity reduces the risk of cancer. Physical inactivity or sedentary behavior, has recently been suggested as a risk factor independent of physical activity level. Breast and endometrial cancer incidence have both been associated with physical activity, and endometrial cancer incidence with physical inactivity/sedentary behavior. The purp

Tamoxifen treated patients have a better survival than patients treated with aromatase inhibitors - A population based registry study in Sweden

Background. Randomised trials suggest that therapy with aromatase inhibitors improves survival in breast cancer compared with tamoxifen therapy in postmenopausal cases with hormone receptor positive breast cancer. Whether these results from randomized studies transform into the general population is unknown. We have therefore compared survival for all breast cancer cases in Sweden diagnosed 2000-2

Functional and Oncologic Outcomes Between Open and Robotic Radical Prostatectomy at 24-month Follow-up in the Swedish LAPPRO Trial

BACKGROUND: The adoption of robot-assisted laparoscopic radical prostatectomy (RALP) has increased rapidly, despite lack of conclusive evidence of its superiority regarding long-term outcomes over open retropubic RP (RRP). In 2015, we reported on 12-mo follow-up from the LAPPRO trial showing a moderate advantage of RALP regarding erectile dysfunction. No significant differences were seen for urina

Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer

BACKGROUND: Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined.METHODS: In this double-blind,

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer

BACKGROUND: Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.METHODS: In this double-blind, placebo-contro

Expert consensus document : Semantics in active surveillance for men with localized prostate cancer - results of a modified Delphi consensus procedure

Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of t

Kallikrein markers performance in pretreatment blood to predict early prostate cancer recurrence and metastasis after radical prostatectomy among very high-risk men

Background: To assess whether a prespecified statistical model based on the four kallikrein markers measured in blood—total, free, and intact prostate-specific antigen (PSA), together with human kallikrein-related peptidase 2 (hK2)—or any individual marker measured in pretreatment serum were associated with biochemical recurrence-free (BCR) or metastasis-free survival after radical prostatectomy (

The β2-Adrenergic Receptor Is a Molecular Switch for Neuroendocrine Transdifferentiation of Prostate Cancer Cells

The incidence of treatment-related neuroendocrine prostate cancer (t-NEPC) is rising as more potent drugs targeting the androgen signaling axis are clinically implemented. Neuroendocrine transdifferentiation (NEtD), an putative initial step in t-NEPC development, is induced by androgen-deprivation therapy (ADT) or anti-androgens, and by activation of the β2-adrenergic receptor (ADRB2) in prostate

With increasing age at tumor diagnosis in familial cancer: Cancer is limited to fewer organs

Hereditary cancer that has monogenic inheritance affects every tenth patient, on average, who is diagnosed with cancer, and it has been suggested, based on twin studies, that approximately 30% of all cancer patients have a genetic predisposition to developing cancer. In this article, the author posited that familial syndromes become more organ specific with increasing age at tumor presentation to

Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation

Background: In atopic asthma, chronic Th2-biased inflammation is associated with an increased risk of pneumococcal infection. The anionic phosphoglycoprotein osteopontin (OPN) is highly expressed in asthma and has been ascribed several roles during inflammation. This study aimed to investigate whether OPN affects inflammation and vulnerability to pneumococcal infection in atopic asthma. Methods: H

New Hope in Prostate Cancer Precision Medicine? miRNA Replacement and Epigenetics

SPINK1+/ETS- prostate cancer is an aggressive disease with poor clinical outcome. New data suggest a novel treatment by upregulating the expression of miR-338-5p/-421 through epigenetic modulation or by miRNA replacement. This is a new and interesting concept that warrants further exploration in clinical trials.See related article by Bhatia et al., p. 2755.

Lung cancer in young women in southern Sweden : A descriptive study

Introduction: Lung cancer, a common malignancy and cause of cancer-related deaths, is strongly linked to several environmental exposures, and thus primarily affects the elderly. Formerly a man's disease, its incidence is rising among women, and lung cancer is now more common in women than men in Sweden. Women are particularly over-represented among young patients. While overall cancer mortality in