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Genetic Associations with Valvular Calcification and Aortic Stenosis

Background Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease. Methods We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the stu

A prospective, population-based study of 40000 women regarding host factors, UV exposure and sunbed use in relation to risk and anatomic site of cutaneous melanoma.

Prospective cohort studies about cutaneous melanoma (CM) risk are still few. Host factor- and UVR exposure data were collected prospectively by questionnaire in this population-based cohort study including 40000 Swedish born women, aged 25-64 years at enrolment (1990). Risk for CM (Cox regression and Stepwise Cox regression [SCR], hazard ratios [HRs] with 95 % Confidence Intervals [CI]) in relatio

Increased incidence of childhood, prostate and breast cancers in relatives of childhood cancer patients.

Whether cancer predisposing familial factors are associated with childhood tumors is unclear. The purpose was to study the incidence of childhood and adult tumors in extended families of children with cancer. Family history of cancer was obtained through questionnaires, and the Swedish Population-, and Cancer Registries for 194 childhood cancer patients aged ≤18 years, diagnosed 1972-2009. Standar

Low expression of SHP-2 is associated with less favorable prostate cancer outcomes.

ABSTACT: Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is an important regulator of cell signaling because of its ability to dephosphorylate receptors of growth factors as well as the cytokines and tyrosine-phosphorylated proteins associated with these receptors. In the current study, we used four different prostate cancer cell lines: PC3, DU145, LNCaP and LNCaP-IL6+. Tumor speci

Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations.

Cholecystokinin (CCK-) positive basket cells form a distinct class of inhibitory GABAergic interneurons, proposed to act as fine-tuning devices of hippocampal gamma-frequency (30-90 Hz) oscillations, which can convert into higher frequency seizure activity. Therefore, CCK-basket cells may play an important role in regulation of hyper-excitability and seizures in the hippocampus. In normal conditio

Feasibility Study on Measuring Selected Proteins in Malignant Melanoma Tissue by SRM Quantification.

Currently there are no clinically recognized molecular biomarkers for malignant melanoma (MM) for either diagnosing disease stage or measuring response to therapy. The aim of this feasibility study was to develop targeted selected reaction monitoring (SRM) assays for identifying candidate protein biomarkers in metastatic melanoma tissue lysate. In a pilot study applying the SRM assay, the tissue e

Molecular and genetic diversity in the metastatic process of melanoma.

Diversity between metastatic melanoma tumours in individual patients is known; however, the molecular and genetic differences remain unclear. To examine the molecular and genetic differences between metastatic tumours, we performed gene-expression profiling of 63 melanoma tumours obtained from 28 patients (two or three tumours/patient), followed by analysis of their mutational landscape, using tar

Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival.

Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival in epithelial ovarian cancer.

Pioneering, chromatin remodeling, and epigenetic constraint in early T-cell gene regulation by SPI1 (PU.1)

SPI1 (also known as PU.1) is a dominant but transient regulator in early T-cell precursors and a potent transcriptional controller of developmentally important pro-T-cell genes. Before T-lineage commitment, open chromatin is frequently occupied by PU.1, and many PU.1 sites lose accessibility when PU.1 is later down-regulated. Pioneering activity of PU.1 was tested in this developmentally dynamic c

Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids with Aortic Stenosis

Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets. Objective: To identify novel genetic loci and pathways associated with AS. Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44703 participants (3469 cases of AS) of self-reported European ance

Prospective isolation of radiation induced erythroid stress progenitors reveals unique transcriptomic and epigenetic signatures enabling increased erythroid output

Massive expansion of erythroid progenitor cells is essential for surviving anemic stress. Research towards understanding this critical process, referred to as stress-erythropoiesis, has been hampered due to the lack of specific marker-combinations enabling analysis of the distinct stress-progenitor cells capable of providing radioprotection and enhanced red blood cell production. Here we present a

Deep proteomic analysis on biobanked paraffine-archived melanoma with prognostic/predictive biomarker read-out

The discovery of novel protein biomarkers in melanoma is crucial. Our introduction of formalin-fixed paraffin-embedded (FFPE) tumor protocol provides new opportunities to understand the progression of melanoma and open the possibility to screen thousands of FFPE samples deposited in tumor biobanks and available at hospital pathology departments. In our retrospective biobank pilot study, 90 FFPE sa

Proteomic analysis enables distinction of early- versus advanced-stage lung adenocarcinomas

BACKGROUND: A gel-free proteomic approach was utilized to perform in-depth tissue protein profiling of lung adenocarcinoma (ADC) and normal lung tissues from early and advanced stages of the disease. The long-term goal of this study is to generate a large-scale, label-free proteomics dataset from histologically well-classified lung ADC that can be used to increase further our understanding of dise

No particle mass enhancement from induced atmospheric ageing at a rural site in northern Europe

A large portion of atmospheric aerosol particles consists of secondary material produced by oxidation reactions. The relative importance of secondary organic aerosol (SOA) can increase with improved emission regulations. A relatively simple way to study potential particle formation in the atmosphere is by using oxidation flow reactors (OFRs) which simulate atmospheric ageing. Here we report on the

Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The hum

Physical Activity and Health Related Quality of Life in Relation to Allergic Disease among Adolescents: : Results from a Crosssectional Study

Aim: The overall aim of was to investigate the impact of self-reportedallergic disease on physical activity (PA) and health-related quality oflife (HRQoL) among adolescents.Methods: A cross-sectional analysis of 1 181 adolescents aged 13-14years (251 with current allergic disease), participating in the baselineinvestigation of the Southern Sweden allergy cohort, including a surveywith questions on

Harnessing androgen receptor pathway activation for targeted alpha particle radioimmunotherapy of breast cancer

Purpose: The impact of androgen receptor (AR) activity Results: D-Norgestrel and DHT activated the AR pathway, in breast cancer biology is unclear. We characterized and while 17b-Estradiol did not. Competitive binding for AR tested a novel therapy to an AR-governed target in breast protein showed similar affinity between DHT and D-Norges-cancer. trel, indicating direct AR–ligand interaction. In vi

Association Between Lead Time and Prostate Cancer Grade : Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening

Background: Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening. Objective: To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is s

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men

Background: Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. Objective: To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Design, setting, participants: Study base