A5083092486- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Cervical Cancer and HPV Research
- RNA modifications and cancer
- Colorectal Cancer Treatments and Studies
- Inflammatory Biomarkers in Disease Prognosis
- Genetic factors in colorectal cancer
- ATP Synthase and ATPases Research
- Vitamin D Research Studies
- Galectins and Cancer Biology
- Extracellular vesicles in disease
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Mitochondrial Function and Pathology
- Cancer, Lipids, and Metabolism
- Muscle Physiology and Disorders
- Tissue Engineering and Regenerative Medicine
- Cardiovascular Effects of Exercise
- Ferroptosis and cancer prognosis
- Advanced Proteomics Techniques and Applications
- Cancer Research and Treatments
- Connective tissue disorders research
Akershus University Hospital
2017-2024
University of Oslo
2014-2022
University of Cincinnati
1986
We report that bepridil, a Ca++ channel blocker and calmodulin antagonist, which has been shown to enter myocytes, stimulates the mechanical biochemical activity of cardiac myofilaments. Bepridil increased significantly level Ca++-dependent actomyosin Mg++-ATPase myofibrils submaximal force developed by chemically skinned trabeculae pig heart. In range concentrations (10-100 microM) in bepridil showed this stimulatory activity, diltiazem verapamil were without effect. The effect on...
Hypoxia is an important and common characteristic of many human tumors. It a challenge clinically due to the correlation with poor prognosis resistance radiation chemotherapy. Understanding biochemical response hypoxia would facilitate development novel therapeutics for cancer treatment. Here, we investigate alterations in gene expression by quantitative proteome analysis using stable isotope labeling amino acids cell culture (SILAC) conjunction LCMS/MS. Human HeLa cells were kept either...
Tumor hypoxia contributes to therapy resistance and metastatic progression of locally advanced rectal cancer (LARC). We postulated that the tumor mitochondrial metabolism, manifested by reactive oxygen species (ROS) DNA (mtDNA) damage, reflects how hypoxic conditions connect cancer-induced systemic inflammation poor outcome. Levels ROS mtDNA damage were analyzed in three colorectal (CRC) cell lines cultured for 24 hours under normoxia (21% O2) or (0.2% serum sampled at time diagnosis from 35...
Abstract Background In colorectal cancer, the inflamed tumour microenvironment with its angiogenic activities is immune- tolerant and incites progression to liver metastasis. We hypothesised that inflammatory factors in serum samples from patients non-metastatic rectal cancer could inform on metastasis risk. Methods measured 84 markers sampled at time of diagnosis within population-based cohort 122 stage I–III patients. a stepwise manner, statistically strongest proteins associated...
Recent reports have demonstrated that the entire mitochondrial genome can be secreted in extracellular vesicles (EVs), but biological attributes of this cell-free DNA (mtDNA) remain insufficiently understood. We used next-generation sequencing to compare plasma EV-derived mtDNA whole blood (WB), peripheral mononuclear cells (PBMCs), and formalin-fixed paraffin-embedded (FFPE) tumor tissue from eight rectal cancer patients WB fresh-frozen (FF) colon patients.Total was isolated before enriched...
Abstract Targeted cancer immunotherapy offers increased efficacy concomitantly with reduced side effects. One antibody promising clinical potential is 14F7, which specifically recognises the NeuGc GM3 ganglioside. This antigen found in plasma membrane of a range tumours, but essentially absent from healthy human cells. 14F7 can discriminate very similar NeuAc GM3, common component cell membranes. The molecular basis for this unique specificity poorly understood. Here we designed and...
Abstract Purpose: Most CRC patients harbor primarily non-immunogenic MSS tumor. The randomized METIMMOX trial (NCT03388190) examined if with previously untreated, unresectable abdominal metastases from MSS-CRC may achieve therapeutic efficacy short-course oxaliplatin-based chemotherapy (FLOX) and sequential ICB (nivolumab) repeatedly. Half of study assigned to this experimental treatment had significantly extended progression-free survival (PFS) while the other half shortened PFS, compared...
Abstract Background: Hypoxia is an important feature of the tumor microenvironment and correlates with radiotherapy resistance metastatic progression. Additionally, as malignant phenotype promotes aerobic glycolysis contributes to microenvironmental acidification, underlying mechanism in radiation metastasis likely linked metabolic changes caused by mitochondrial reprogramming. We hypothesized that ROS mtDNA damage might be indicators poor therapy response dissemination rectal cancer....
<h3>Background</h3> Use of circulating tumor DNA (ctDNA) has potential value as a minimally invasive approach for the diagnosis, monitoring, and management cancer patients. Here, we investigated using HPV16 ctDNA levels predictive biomarker clinical response to therapeutic HPV16-specific vaccine VB10.16, designed unique modular technology based on linking antigens CCL3L1 targeting module developed treat HPV16-associated premalignant malignant lesions, in combination with atezolizumab...
We reported previously that rectal cancer patients given curative-intent chemotherapy, radiation, and surgery for non-metastatic disease had enhanced risk of metastatic progression death if circulating levels 25-hydroxyvitamin D [25(OH) D] were low. Here we investigated whether the association between vitamin status prognosis pertains to general, unselected population patients.Serum 25(OH) at time diagnosis was assessed in 129 patients, enrolled 2013-2017 representing entire range stages,...
Abstract Purpose A significant percentage of colorectal cancer patients proceeds to metastatic disease. We hypothesised that mitochondrial DNA (mtDNA) polymorphisms, generated by the high mtDNA mutation rate energy-demanding clonal immune cell expansions and assessable in peripheral blood, reflect how efficiently systemic immunity impedes metastasis. Patients methods studied 44 rectal from a population-based prospective biomarker study, given curative-intent neoadjuvant radiation radical...
Cancer immunotherapy represents a promising approach to specifically target and treat cancer. The most common mechanisms by which monoclonal antibodies kill cells include antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity apoptosis, but also other have been described. 14F7 is an antibody raised against the tumor-associated antigen NeuGc GM3, was previously reported cancer without inducing apoptotic pathways. induce giant membrane lesions in tumor cells, with...
Abstract Immunotherapy is a growing field in cancer research. A privileged tumor-associated antigen that has received much attention N -glycolyl (NeuGc) GM3. This ganglioside present several types of cancer, but almost undetectable human healthy tissues. However, its non-hydroxylated variant, NeuAc GM3, abundant all mammals. Due to deletion the gene encoding key enzyme for synthesis NeuGc, humans, contrast other mammals, cannot synthesize NeuGc Therefore presence this cells represents an...
e15641 Background: Tumor-promoting inflammation is an established hallmark of cancer. C-reactive protein (CRP) one the most studied negative prognostic markers systemic inflammatory response (SIR) and known to be implicated in detrimental immune responses. Circulating CRP, as measured routine practice, a pentameric structure (pCRP). However, when pCRP binds activated membranes, dissociates into subunits termed monomeric CRP (mCRP). Pro-inflammatory characteristics mCRP have been reported...
Abstract Background: Assessment of vaccine-induced T cell responses is a primary pharmacodynamic readout in cancer vaccine clinical trials. High-throughput sequencing receptors (TCRs) emerging as rapid and scalable method, suitable for late-stage trials, offers sensitive accurate quantification the full repertoire. Here we performed ELISpot TCR on serial peripheral blood mononuclear (PBMC) samples from phase 2 trial investigating therapeutic HPV16 VB10.16 combination with atezolizumab...
e16132 Background: High rates of systemic failure after curative-intent therapy in locally advanced rectal cancer (LARC) call for new diagnostic tools to improve risk-based treatment stratification. We hypothesized that blood mtDNA polymorphisms, generated by the high mutation rate when mitochondrial biogenesis is mobilized during clonal immune cell activation, correlate with control LARC dissemination and thus can be used as marker. Methods: 41 patients given neoadjuvant (chemo)radiotherapy...
Abstract Introduction: EVs released from cells are nanosized vesicles (containing proteins and nucleic acids) that serve as a communication system with other or expel cellular waste. Variations in the mtDNA sequence can act functional adaptors allowing tumor immune to adjust metabolic needs imposed by various tissue environments during cancer progression. Recent reports have demonstrated entire mitochondrial genome be encapsulated secreted EVs. However, biological attributes of cell-free...
<h3>Background</h3> Circulating tumor DNA (ctDNA) can potentially provide a valuable tumor-specific and non-invasive biomarker for longitudinal monitoring of patient's response to therapy. We aimed quantify HPV16 ctDNA in patients with advanced cervical cancer explore the potential use predict on treatment clinical responses VB10.16 combination atezolizumab. <h3>Methods</h3> This open-label, single-arm, Phase 2a trial was conducted HPV16-positive recurrent or metastatic cancer. Patients...
A significant percentage of colorectal cancer patients proceeds to metastatic disease. We hypothesised that mitochondrial DNA (mtDNA) polymorphisms, generated by the high mtDNA mutation rate energy-demanding clonal immune cell expansions and assessable in peripheral blood, reflect how efficiently systemic immunity impedes metastasis. studied 44 rectal from a population-based prospective biomarker study, given curative-intent neoadjuvant radiation radical surgery for high-risk tumour stage...
Abstract Background: We reported previously that rectal cancer patients given curative-intent chemotherapy, radiation, and surgery for non-metastatic disease had enhanced risk of metastatic progression death if circulating levels 25-hydroxyvitamin D [25(OH)D] were low. Here we investigated whether the association between vitamin status prognosis pertains to general, unselected population patients. Methods: Serum 25(OH)D at time diagnosis was assessed in 129 patients, enrolled 2013-2017...