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Azithromycin augments rhinovirus-induced IFNβ via cytosolic MDA5 in experimental models of asthma exacerbation

Deficient production of anti-viral interferons (IFNs) may be involved in causing viral-induced asthma exacerbations. Hence, drugs inducing lung IFN production would be warranted. Azithromycin may reduce asthma exacerbations but its modus operandi is unknown. Here, we investigated if azithromycin induces IFNβ expression in vitro in rhinovirus-infected bronchial epithelial cells from asthmatic donor

Vitamin D receptor expression in invasive breast tumors and breast cancer survival

Background: Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highest levels respectively, as compared to the intermediate group. Vitamin D exerts

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

Diagnostic pathway efficacy for urinary tract cancer : population-based outcome of standardized evaluation for macroscopic haematuria

Objective: This study assessed a national healthcare intervention launched in Sweden in 2015 to reduce the time between macroscopic haematuria, diagnosis and treatment of urinary tract cancer. Methods: The outcome of the first 11 months was evaluated in 1697 individuals referred to a standardized care pathway for urinary tract cancer compared with 174 patients with conventionally diagnosed urothel

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

Occupational sedentariness and breast cancer risk

Background: Epidemiological studies have indicated that physical activity reduces the risk of developing breast cancer. More recently, sedentary behavior has been suggested as a risk factor independent of physical activity level. The purpose of the present study was to investigate occupational sedentariness and breast cancer risk in pre- and postmenopausal women. Materials and methods: In a popula

Preclinical Characterization of 3β-(N-Acetyl l -cysteine methyl ester)-2aβ,3-dihydrogaliellalactone (GPA512), a Prodrug of a Direct STAT3 Inhibitor for the Treatment of Prostate Cancer

The transcription factor STAT3 is a potential target for the treatment of castration-resistant prostate cancer. Galiellalactone (1), a direct inhibitor of STAT3, prevents the transcription of STAT3 regulated genes. In this study we characterized 6 (GPA512, Johansson, M.; Sterner, O. Patent WO 2015/132396 A1, 2015), a prodrug of 1. In vitro studies showed that 6 is rapidly converted to 1 in plasma

The absence of aldehyde dehydrogenase 1 A1-positive cells in benign mammary stroma is associated with risk factors for breast cancer

In this study, aldehyde dehydrogenase 1 (ALDH1)-expressing cells in stroma of histologically normal breast tissue from premenopausal women were investigated in situ regarding cellular morphology, cell distribution, and relation to the additional stem cell markers, CD44 (+) and CD24 (-). These results were correlated with hormonal and genetic risk factors for breast cancer. Triple immunofluorescenc

Validation of novel biomarkers for prostate cancer progression by the combination of bioinformatics, clinical and functional studies

The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clin

An integrated acousto- and dielectrophoresis device for tumor cell separation, concentration, and single-cell trapping

Many microfluidic devices have been developed to separate rare cells, e.g. circulating tumor cells. The collection and analysis of the separated rare cells pose a challenge as it may lead to loss of target cells since extremely small number of cells are usually suspended in a large volume after separation. Here, we present an integrated device that allows acoustophoretic target cell separation and

Treatment with the WNT5A-mimicking peptide Foxy-5 effectively reduces the metastatic spread of WNT5A-low prostate cancer cells in an orthotopic mouse model

Prostate cancer patients with high WNT5A expression in their tumors have been shown to have more favorable prognosis than those with low WNT5A expression. This suggests that reconstitution of Wnt5a in low WNT5A-expressing tumors might be an attractive therapeutic approach. To explore this idea, we have in the present study used Foxy-5, a WNT5A mimicking peptide, to investigate its impact on primar

Low physical activity is related to clustering of risk factors for fracture—a 2-year prospective study in children

Summary: The study investigates the effect of physical activity (PA) on a composite score for fracture risk in pre-pubertal children. Low PA in children is related to the composite score for fracture risk and the pre-pubertal years seem to be a period when PA positively affects the score. Introduction: This study evaluates if PA in children is related to clustering of risk factors for fracture. Re

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

Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes

BackgroundWhile genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS).ResultsGWAS data on 7319 MM cases and 234,3

Determinants for non-sentinel node metastases in primary invasive breast cancer : A population-based cohort study of 602 consecutive patients with sentinel node metastases

Background: Sentinel node biopsy (SNB) is the standard procedure for axillary staging in patients with clinically lymph node negative invasive breast cancer. Completion axillary lymph node dissection (c-ALND) may not be necessary for all patients as a significant number of patients have no further metastases in non-sentinel nodes (non-SN) and c-ALND may not improve survival. The first aim of our s

An inflamed subtype of difficult-to-treat depression

BACKGROUND: Chronic low-grade inflammation may play a role in the pathophysiology of depression, at least in a subset of patients. High-sensitivity C-reactive protein (hs-CRP) has been used to define an inflamed subgroup of depression with specific clinical characteristics and symptoms. In this study we investigated biochemical and clinical characteristics in patients with difficult-to-treat depre

Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing

Hematopoiesis is regulated by the bone marrow (BM) stroma. However, cellular identities and functions of the different BM stromal elements in humans remain poorly defined. Based on single-cell RNA sequencing (scRNAseq), we systematically characterized the human non-hematopoietic BM stromal compartment and we investigated stromal cell regulation principles based on the RNA velocity analysis using s

Using Cluster Theory to Calculate the Experimental Structure Factors of Antibody Solutions

Monoclonal antibody solutions are set to become a major therapeutic tool in the years to come, capable of targeting various diseases by clever design of their antigen binding site. However, the formulation of stable solutions suitable for patient self-administration typically presents challenges, as a result of the increase in viscosity that often occurs at high concentrations. Here, we establish