Institutt for medisinsk biologi: Recent submissions
Now showing items 381-400 of 1154
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Intestinal fungi are causally implicated in microbiome assembly and immune development in mice
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-05-22)The gut microbiome consists of a multi-kingdom microbial community. Whilst the role of bacteria as causal contributors governing host physiological development is well established, the role of fungi remains to be determined. Here, we use germ-free mice colonized with defined species of bacteria, fungi, or both to differentiate the causal role of fungi on microbiome assembly, immune development, ... -
Stroma-induced phenotypic plasticity offers phenotype-specific targeting to improve melanoma treatment
(Journal article; Tidsskriftartikkel; Peer reviewed, 2018-09-18)Cancer cells' phenotypic plasticity, promoted by stromal cells, contributes to intra-tumoral heterogeneity and affects response to therapy. We have disclosed an association between fibroblast-stimulated phenotype switching and resistance to the clinically used BRAF inhibitor (BRAFi) vemurafenib in malignant melanoma, revealing a challenge in targeting the fibroblast-induced phenotype. Here we compared ... -
Molecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer - the MetAction study
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-25)<i>Background</i>: In precision cancer medicine, the challenge is to prioritize DNA driver events, account for resistance markers, and procure sufficient information for treatment that maintains patient safety. The MetAction project, exploring how tumor molecular vulnerabilities predict therapy response, first established the required workflow for DNA sequencing and data interpretation (2014–2015). ... -
Epidemiological and molecular characterization of Streptococcus pneumoniae carriage strains in pre-school children in Arkhangelsk, northern European Russia, prior to the introduction of conjugate pneumococcal vaccines
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-04-15)<p><i>Background - </i>The 13-valent Pneumococcal Conjugate Vaccine (PCV-13) was introduced in the National Immunization Programme (NIP) schedule in Russia in March 2014. Previously, the 7-valent Pneumococcal Conjugate Vaccine (PCV-7) was marketed in Russia in 2009 but has never been offered for mass vaccination. A carriage study was performed among children in Arkhangelsk in 2006. The objective was ... -
Targeting mitochondrial oxidative stress with MitoQ reduces NET formation and kidney disease in lupus-prone MRL-lpr mice
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-04-16)<i>Objectives</i> - Recent investigations in humans and mouse models with lupus have revealed evidence of mitochondrial dysfunction and production of mitochondrial reactive oxygen species (mROS) in T cells and neutrophils. This can provoke numerous cellular changes including oxidation of nucleic acids, proteins, lipids and even induction of cell death. We have previously observed that in T cells ... -
Promoter activity of Merkel cell Polyomavirus variants in human dermal fibroblasts and a Merkel cell carcinoma cell line.
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-04-19)<p><i>Background - </i>Merkel cell polyomavirus (MCPyV) is a human polyomavirus that establishes a life-long harmless infection in most individuals, with dermal fibroblasts believed to be the natural host cell. However, this virus is the major cause of Merkel cell carcinoma (MCC), an aggressive skin cancer. Several MCPyV variants with polymorphism in their promoter region have been isolated, but it ... -
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-09)Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death ... -
The expression of the long NEAT1_2 isoform is associated with human epidermal growth factor receptor 2-positive breast cancers
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-28)The long non-coding RNA <i>NEAT1</i> locus is transcribed into two overlapping isoforms, <i>NEAT1_1</i> and <i>NEAT1_2</i>, of which the latter is essential for the assembly of nuclear paraspeckles. <i>NEAT1</i> is abnormally expressed in a wide variety of human cancers. Emerging evidence suggests that the two isoforms have distinct functions in gene expression regulation, and recently it was shown ... -
Molecular interaction studies of initial electrostatic attraction between trypsin and the human PAR-2 receptor
(Master thesis; Mastergradsoppgave, 2020-01-16)Workers in livestock and fish cultivation are at increased risk of occupational airway damage caused by proteases. Proteases, such as trypsin, activate PAR-2 which in turn triggers an inflammatory response, potentially causing airway damage over time. There has been some speculation that PAR-2 receptors easier attract trypsin form species where this enzyme has a more negative electrostatic charge. ... -
Structural basis of p62/SQSTM1 helical filaments and their role in cellular cargo uptake
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-23)p62/SQSTM1 is an autophagy receptor and signaling adaptor with an N-terminal PB1 domain that forms the scaffold of phase-separated p62 bodies in the cell. The molecular determinants that govern PB1 domain filament formation in vitro remain to be determined and the role of p62 filaments inside the cell is currently unclear. We here determine four high-resolution cryo-EM structures of different human ... -
Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in Haemophilus influenzae
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-29)<i>Haemophilus influenzae</i> colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. Resistance to extended-spectrum cephalosporins in <i>H. influenzae</i> is rare in Europe. In this study, we defined acquired resistance gene loci and <i>ftsI</i> mutations in multidrug-resistant (MDR) and/or PBP3-mediated beta-lactam-resistant (rPBP3) <i>H. influenzae</i> ... -
Loss of S100A14 expression at the tumor-invading front correlates with poor differentiation and worse prognosis in oral squamous cell carcinoma
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-23)<i>Background</i> - We previously showed a tumor‐suppressive function of S100A14 in oral squamous cell carcinoma (OSCC). This study aimed to examine the prognostic significance and differentiation‐related function of S100A14 in OSCC.<p><p> <i>Methods</i> - S100A14 expression was examined in 170 OSCCs from Norwegian and Nepalese populations using immunohistochemistry. Pro‐differentiation function ... -
Serum levels of inflammation-related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-24)Angiogenesis is necessary for tumor growth and has been targeted in breast cancer; however, it is unclear which patients will respond and benefit from antiangiogenic therapy. We report noninvasive monitoring of patient response to neoadjuvant chemotherapy given alone or in combination with anti‐vascular endothelial growth factor (bevacizumab) in a randomized clinical trial. At four time points during ... -
Regulation of urokinase receptor (uPAR) cleavage by cancer associated fibroblasts (CAFs) in oral cancer
(Master thesis; Mastergradsoppgave, 2019-05-15)Oral squamous cell carcinoma (OSCC) is one of the frequently diagnosed type of oral cancers and is a leading cause of cancer associated mortality and morbidity worldwide. Cancer associated fibroblasts (CAFs) are activated fibroblasts that are found in association with cancer cells. CAFs are the most abundant stromal cells in the tumor microenvironment (TME). In the TME, cell interactions mediated ... -
Identifying Staphylococcus haemolyticus surface proteins. Development of a novel method for detection of bacterial surface proteins expressed during colonisation of human keratinocytes
(Master thesis; Mastergradsoppgave, 2018-05-15)The aim was to develop a method for identification of expressed surface proteins of Staphylococcus haemolyticus when colonising human keratinocytes. S. haemolyticus and HaCaT cells were grown together and separated with FACS prior to surface protein shaving using the LPI™FlowCell technology (Nanoxis Consulting AB). TMT-tags were used to investigate up- and downregulation of proteins comparing S. ... -
Immune-modulating properties of carcinoma-associated fibroblasts and their changes during radiotherapy. In vitro study of primary non-small cell lung carcinoma-associated fibroblasts
(Master thesis; Mastergradsoppgave, 2015-05-15)Background/aim of the study: Carcinoma-associated Fibroblasts (CAFs) comprise a heterogeneous population of cells and often represent the major cellular component of solid malignancies playing critical roles in tumor progression and metastasis. The purpose of this study was to gain more knowledge on the immunosuppressive traits of CAFs isolated from non-small cell lung carcinomas (NSCLC), and to ... -
Moderate but not severe hypothermia causes pro-arrhythmic changes in cardiac electrophysiology
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-02-07)<i>Aims</i> - Treatment of arrhythmias evoked by hypothermia/rewarming remains challenging, and the underlying mechanisms are unclear. This <i>in vitro</i> experimental study assessed cardiac electrophysiology in isolated rabbit hearts at temperatures occurring in therapeutic and accidental hypothermia.<p><p> <i>Methods and results</i> - Detailed ECG, surface electrogram, and panoramic optical ... -
Study of human PRKAR1A and its role in autophagy
(Master thesis; Mastergradsoppgave, 2018-05-11)The human PRKAR1A gene is a 381- amino acid protein encoding the regulatory subunit (RIα) of the cAMP dependent Protein Kinase A (PKA). The main function of PRKAR1A is to regulate the catalytic activity of PKA. PRKAR1A is shown to regulate autophagy via association with mTOR kinase and colocalization with the autophagy marker proteins LC3B, Rab7 and Rab9. Contradictory findings regarding the ... -
Dietary calanus oil recovers metabolic flexibility and rescues postischemic cardiac function in obese female mice
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-16)The aim of this study was to find out whether dietary supplementation with Calanus oil (a novel marine oil) or infusion of exenatide (an incretin mimetic) could counteract obesity-induced alterations in myocardial metabolism and improve postischemic recovery of left ventricular (LV) function. Female C57bl/6J mice received high-fat diet (HFD, 45% energy from fat) for 12 wk followed by 8-wk feeding ... -
Drug-Loaded Photosensitizer-Chitosan Nanoparticles for Combinatorial Chemo- and Photodynamic-Therapy of Cancer
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-02-24)In this study we have developed biodegradable polymeric nanoparticles (NPs) containing the cytostatic drugs mertansine (MRT) or cabazitaxel (CBZ). The NPs are based on chitosan (CS) conjugate polymers synthesized with different amounts of the photosensitizer tetraphenylchlorin (TPC). These TPC–CS NPs have high loading capacity and strong drug retention due to π–π stacking interactions between the ...