Institutt for medisinsk biologi: Nye registreringer
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High number of kinome-mutations in non-small cell lung cancers associated with reduced immune response and poor relapse-free survival
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-04-07)Lung cancer is the leading cause of cancer related death, and the past years’ improved insight into underlying molecular events has significantly improved outcome for specific subsets of patients. In particular, several new therapies that target protein kinases have been implemented, and many more are becoming available. We have investigated lung cancer specimens for somatic mutations in a targeted ... -
Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-10-29)Modified vaccinia virus Ankara (MVA) is the vector of choice for human and veterinary applications due to its strong safety profile and immunogenicity in vivo. The use of MVA and MVA-vectored vaccines against human and animal diseases must comply with regulatory requirements as they pertain to environmental risk assessment, particularly the characterization of potential adverse effects to humans, ... -
Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-06-12)Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, ... -
Oncolytic peptide LTX-315 induces an immune-mediated abscopal effect in a rat sarcoma model
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-08-17)LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration ... -
Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-02)Selective autophagy is a catabolic process with which cellular material is specifically targeted for degradation by lysosomes. The function of selective autophagic degradation of self-components in the regulation of innate immunity is still unclear. Here we show that Drosophila Kenny, the homolog of mammalian IKKγ, is a selective autophagy receptor that mediates the degradation of the IκB kinase ... -
B Cell Tolerance to Deiminated Histones in BALB/c, C57BL/6, and Autoimmune-Prone Mouse Strains
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-30)Deimination, a posttranslational modification of arginine to citrulline carried out by peptidylarginine deiminases, may compromise tolerance of self-antigens. Patients with connective tissue autoimmunity, particularly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or Felty’s syndrome, present with autoantibodies to deiminated histones (dH), which thus form a category of antibodies ... -
Ligand-guided homology modelling of the GABAb2 subunit of the GABAb receptor
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-21)γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, and disturbances in the GABAergic system have been implicated in numerous neurological and neuropsychiatric diseases. The GABA<sub>B</sub> receptor is a heterodimeric class C G protein-coupled receptor (GPCR) consisting of GABA<sub>B1a/b</sub> and GABA<sub>B2</sub> subunits. Two GABA<sub>B</sub> receptor ... -
High miR-205 expression in normal epithelium is associated with biochemical failure - An argument for epithelial crosstalk in prostate cancer?
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-24)Due to insufficient prognostic tools, failure to predict aggressive prostate cancer (PC) has left patient selection for radical treatment an unsolved challenge. This has resulted in overtreatment with radical therapy. Better prognostic tools are urgently warranted. MicroRNAs (miRs) have emerged as important regulators of cellular pathways, resulting in altered gene expressions. miR-205 has previously ... -
Regulation of atypical MAP kinases ERK3 and ERK4 by the phosphatase DUSP2
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-02)The atypical MAP kinases ERK3 and ERK4 are activated by phosphorylation of a serine residue lying within the activation loop signature sequence S-E-G. However, the regulation of ERK3 and ERK4 phosphorylation and activity is poorly understood. Here we report that the inducible nuclear dual-specificity MAP kinase phosphatase (MKP) DUSP2, a known regulator of the ERK and p38 MAPKs, is unique amongst ... -
Ionizing radiation abrogates the pro-tumorigenic capacity of cancer-associated fibroblasts co-implanted in xenografts
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-04-25)Cancer-associated fibroblasts (CAFs) are abundantly present in solid tumors and affect tumorigenesis and therapeutic responses. In the context of clinical radiotherapy, the impact of irradiated CAFs to treatment outcomes is largely unexplored. Aiming at improving radiotherapy efficacy, we have here explored the effect of radiation on the inherent pro-tumorigenic capacity of CAFs in animals. Ionizing ... -
Expression and function of the miR-143/145 cluster in vitro and in vivo in human breast cancer
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-10-26)MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators of gene expression and are dysregulated in cancer. Studies of miRNAs to explore their potential as diagnostic and prognostic markers are of great scientific interest. Here, we investigate the functional properties and expression of the miR-143/145 cluster in breast cancer (BC) in vitro and in vivo. The ER ... -
Lupus nephritis progression in FcγRIIB-/-yaa mice is associated with early development of glomerular electron dense deposits and loss of renal DNase I in severe disease.
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-30)FcγRIIB<sup>-/-</sup>yaa mice develop severe lupus glomerulonephritis due to lack of an inhibitory immune cell receptor combined with a Y-chromosome linked autoimmune accelerator mutation. In the present study, we have investigated nephritis development and progression in FcγRIIB<sup>-/-</sup>yaa mice to find shared features with NZB/NZW F1 lupus prone mice and human disease. We sacrificed 25 male ... -
Fecal carriage of extended spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae after urinary tract infection - A three year prospective cohort study
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-07)We have performed a prospective cohort study to investigate the duration of and risk factors for prolonged fecal carriage of ESBL-producing Escherichia coli or Klebsiella pneumoniae in patients with community acquired urinary tract infection caused by these bacteria. From 2009 to 2011, 101 Norwegian patients were recruited. Stool swabs and questionnaires were collected every three months for one ... -
Molecular and epidemiological characterization of carbapenemase-producing Enterobacteriaceae in Norway, 2007 to 2014
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-15)The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) is increasing worldwide. Here we present associated patient data and molecular, epidemiological and phenotypic characteristics of all CPE isolates in Norway from 2007 to 2014 confirmed at the Norwegian National Advisory Unit on Detection of Antimicrobial Resistance. All confirmed CPE isolates were characterized pheno- and genotypically, ... -
Fetal exposure to maternal human platelet antigen-1a does not induce tolerance. An analytical observational study
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-08-24)Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that may cause severe bleeding complications with risk of perinatal death or lifelong disability. The main cause of FNAIT is maternal antibodies against human platelet antigen (HPA)-1a. Both fetomaternal bleeding and transplacental trafficking of fetal cells during pregnancy could be the cause of alloimmunization. Persistence of ... -
Delivery is key: lessons learnt from developing splice-switching antisense therapies
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-13)The use of splice-switching antisense therapy is highly promising, with a wealth of pre-clinical data and numerous clinical trials ongoing. Nevertheless, its potential to treat a variety of disorders has yet to be realized. The main obstacle impeding the clinical translation of this approach is the relatively poor delivery of anti- sense oligonucleotides to target tissues ... -
Evaluation of the proliferation marker Ki-67 in a large prostatectomy cohort
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-15)The tumor proliferation index marker Ki-67 is strongly associated with tumor cell proliferation, growth and progression, and is widely used in routine clinicopathological investigation. Prostate cancer is a complex multifaceted and biologically heterogeneous disease, and overtreatment of localized, low volume indolent tumors, is evident. Here, we aimed to assess Ki-67 expression and related ... -
Low adiponectin is associated with diastolic dysfunction in women: A cross-sectional study from the Tromsø Study
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-14)Background: Heart failure with preserved ejection fraction is closely associated with diastolic dysfunction and related to obesity and female sex. We investigated whether adiponectin, an adipocyte-secreted protein hormone with cardioprotective effects, was associated with indices of diastolic dysfunction, and whether the association was sex dependent. <br>Methods: We conducted a cross-sectional ... -
A comparison of extended spectrum β-lactamase producing Escherichia coli from clinical, recreational water and wastewater samples associated in time and location
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-10-17)Extended spectrum β-lactamase producing Escherichia coli (ESBL-EC) are excreted via effluents and sewage into the environment where they can re-contaminate humans and animals. The aim of this observational study was to detect and quantify ESBL-EC in recreational water and wastewater, and perform a genetic and phenotypic comparative analysis of the environmental strains with geographically associated ... -
Cleavage of the urokinase receptor (uPAR) on oral cancer cells: Regulation by transforming growth factor - beta1 (TGF-beta1) and potential effects on migration and invasion
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-05-19)Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment ...