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Dynamical modelling of haematopoiesis: an integrated view over the system in homeostasis and under perturbation.

A very high number of different types of blood cells must be generated daily through a process called haematopoiesis in order to meet the physiological requirements of the organism. All blood cells originate from a population of relatively few haematopoietic stem cells residing in the bone marrow, which give rise to specific progenitors through different lineages. Steady-state dynamics are governe

Canonical BMP signaling is dispensable for hematopoietic stem cell function in both adult and fetal liver hematopoiesis, but essential to preserve colon architecture.

Numerous publications have described the importance of Bone Morphogenetic Protein (BMP) signaling in the specification of hematopoietic tissue in developing embryos. Here we investigate the full role of canonical BMP signaling in both adult and fetal liver hematopoiesis using conditional knockout strategies, since conventional disruption of components of the BMP signaling pathway result in early d

Ezrin expression predicts local recurrence and development of metastases in soft tissue sarcomas.

Background Ezrin is a cytoskeletal protein involved in tumour growth and invasion. Ezrin expression has been suggested to play a role in metastasis in paediatricosteosarcoma and rhabdomyosarcoma. Aim To evaluate the prognostic role of ezrin in a large series of soft tissue sarcoma of the extremities and trunk wall. Methods Ezrin expression was evaluated by immunohistochemistry on tissue microarray

Prediction of outcome after diagnosis of metachronous contralateral breast cancer.

BACKGROUND: Although 2-20% of breast cancer patients develop a contralateral breast cancer (CBC), prognosis after CBC is still debated. Using a unique patient cohort, we have investigated whether time interval to second breast cancer (BC2) and mode of detection are associated to prognosis. METHODS: Information on patient-, tumour-, treatment-characteristics, and outcome was abstracted from patien

Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers.

Background Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the sing

SATB2 in Combination With Cytokeratin 20 Identifies Over 95% of all Colorectal Carcinomas.

The special AT-rich sequence-binding protein 2 (SATB2), a nuclear matrix-associated transcription factor and epigenetic regulator, was identified as a tissue type-specific protein when screening protein expression patterns in human normal and cancer tissues using an antibody-based proteomics approach. In this respect, the SATB2 protein shows a selective pattern of expression and, within cells of e

Blood Biomarker Levels to Aid Discovery of Cancer-Related Single-Nucleotide Polymorphisms: Kallikreins and Prostate Cancer.

Polymorphisms associated with prostate cancer include those in three genes encoding major secretory products of the prostate: KLK2 (encoding kallikrein-related peptidase 2; hK2), KLK3 (encoding prostate-specific antigen; PSA), and MSMB (encoding beta-microseminoprotein). PSA and hK2, members of the kallikrein family, are elevated in sera of men with prostate cancer. In a comprehensive analysis tha

A prognostic model for soft tissue sarcoma of the extremities and trunk wall based on size, vascular invasion, necrosis, and growth pattern.

BACKGROUND:: In soft tissue sarcoma, better distinction of high-risk and low-risk patients is needed to individualize treatment and improve survival. Prognostic systems used in clinical practice identify high-risk patients based on various factors, including age, tumor size and depth, histological type, necrosis, and grade. METHODS:: Whole-tumor sections from 239 soft tissue sarcomas of the extrem

Lipoprotein-associated phospholipase A2 activity, genetics and calcific aortic valve stenosis in humans

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been shown to predict calcific aortic valve stenosis (CAVS) outcomes. Our objective was to test the association between plasma Lp-PLA2 activity and genetically elevated Lp-PLA2 mass/activity with CAVS in humans. Methods and results: Lp-PLA2 activity was measured in 890 patients undergoing cardiac surgery, including 476 pati

Incisional negative pressure wound therapy in the prevention of surgical site infection after vascular surgery with inguinal incisions: rational and design of a randomized controlled trial (INVIPS-Trial).

Background/Aims: Inguinal incisions are a common route of access in vascular surgery. Due to anatomical challenges and a diverse bacterial flora in this area, surgical site infections (SSI) represent a common, debilitating and sometimes life-threatening complication. The INVIPS-Trial evaluates the role of Negative Pressure Wound Therapy (NPWT) on closed inguinal incisions in elective vascular surg

The STAT3 inhibitor galiellalactone inhibits the generation of MDSC-like monocytes by prostate cancer cells and decreases immunosuppressive and tumorigenic factors

Background: The transcription factor signal transducer and activator of transcription 3 (STAT3) is implicated in cancer drug resistance, metastasis, and immunosuppression and has been identified as a promising therapeutic target for new anticancer drugs. Myeloid-derived suppressor cells (MDSCs) play a major role in the suppression of antitumor immunity and STAT3 is involved in the accumulation, ge

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8

Female white-collar workers remain at higher risk of breast cancer after adjustments for individual risk factors related to reproduction and lifestyle

Objectives The aim was to investigate the variation in risk of breast cancer between occupational groups with a focus on white-collar and blue-collar workers and to investigate to what extent the differences were explained by risk factors related to reproduction and lifestyle. Methods Between 1991 and 1996, 14 119 women born between 1923 and 1950 and residents of Malmö, Sweden, were included in th

Habits and self-assessed quality of life, negative intrusive thoughts and depressed mood in patients with prostate cancer : a longitudinal study

Objective: The aim of this study was to evaluate the association of self-assessed preoperative physical activity, alcohol consumption and smoking with self-assessed quality of life, negative intrusive thoughts and depressed mood after radical prostatectomy. Materials and methods: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, controlled, non-randomized longitudinal tri

Circulating Tumor Cells as a Marker for Progression-free Survival in Metastatic Castration-naïve Prostate Cancer

BACKGROUND: Analysis of circulating tumor cells (CTC) is a promising prognostic marker in castration-resistant prostate cancer (CRPC). The aim of this study was to investigate CTC detection and phenotyping as prognostic biomarkers for response to primary androgen deprivation therapy (ADT) of metastatic prostate cancer (PC). METHODS: PC patients presenting with a prostate specific antigen (PSA) >80

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

Risk of bacteremia in patients presenting with shaking chills and vomiting - A prospective cohort study

Chills and vomiting have traditionally been associated with severe bacterial infections and bacteremia. However, few modern studies have in a prospective way evaluated the association of these signs with bacteremia, which is the aim of this prospective, multicenter study. Patients presenting to the emergency department with at least one affected vital sign (increased respiratory rate, increased he

Screening for Prostate Cancer Starting at Age 50-54 Years. A Population-based Cohort Study

Background: Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening. Objective: To evaluate the effect of prostate-specific antigen (PSA) screening versus zero screening, starting at age 50-54 yr, on prostate cancer mortality. Design, setting, and participants: This is a population-based cohort study comparing 3479 men aged 50 yr through 54 yr r

A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovar