A5049850477- Multiple Myeloma Research and Treatments
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Drug Transport and Resistance Mechanisms
- interferon and immune responses
- PI3K/AKT/mTOR signaling in cancer
- Immunotherapy and Immune Responses
- Cutaneous Melanoma Detection and Management
- DNA Repair Mechanisms
- RNA modifications and cancer
- Sarcoma Diagnosis and Treatment
- Neuroendocrine Tumor Research Advances
- Cell Adhesion Molecules Research
- Cancer Mechanisms and Therapy
- Cancer therapeutics and mechanisms
- Microtubule and mitosis dynamics
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Epigenetics and DNA Methylation
- Telomeres, Telomerase, and Senescence
- Growth Hormone and Insulin-like Growth Factors
- Cytokine Signaling Pathways and Interactions
- Mechanisms of cancer metastasis
Science for Life Laboratory
2024
Karolinska Institutet
2023-2024
Oncopeptides (Sweden)
2019-2023
Svenska Örtmedicinska Institute
2023
Oslo University Hospital
2009-2021
Medivir (Sweden)
2019
Norwegian Cancer Society
2005-2015
The Wistar Institute
2012-2015
Royal University Hospital
2006
University of Oslo
2005
Notoriously resistant malignant melanoma is one of the most increasing forms cancer worldwide; there thus a precarious need for new treatment options. The Wee1 kinase major regulator G2/M checkpoint, and halts cell cycle by adding negative phosphorylation on CDK1 (Tyr15). Additionally, has function in safeguarding genome integrity during DNA synthesis. To assess role development progression we examined its expression panel paraffin-embedded patient derived tissue benign nevi primary-...
Abstract Cancer cells fuel their increased need for nucleotide supply by upregulating one-carbon (1C) metabolism, including the enzymes methylenetetrahydrofolate dehydrogenase–cyclohydrolase 1 and 2 (MTHFD1 MTHFD2). TH9619 is a potent inhibitor of dehydrogenase cyclohydrolase activities in both MTHFD1 MTHFD2, selectively kills cancer cells. Here, we reveal that, cells, targets nuclear MTHFD2 but does not inhibit mitochondrial MTHFD2. Hence, overflow formate from mitochondria continues...
We have previously shown that Wnt5A drives invasion in melanoma. also promotes resistance to therapy designed target the BRAF(V600E) mutation Here, we show melanomas characterized by high levels of respond therapeutic stress increasing p21 and expressing classical markers senescence, including positivity for senescence-associated β-galactosidase (SA-β-gal), heterochromatic foci (SAHF), H3K9Me chromatin marks, PML bodies. find despite this, these cells retain their ability migrate invade....
Multiple myeloma (MM) is characterized by extensive immunoglobulin production leading to an excessive load on protein homeostasis in tumor cells. Aminopeptidases contribute proteolysis catalyzing the hydrolysis of amino acids from proteins or peptides and function downstream ubiquitin–proteasome pathway. Notably, aminopeptidases can be utilized delivery antibody peptide-conjugated drugs, such as melflufen, currently clinical trials. We analyzed expression 39 aminopeptidase genes MM samples...
Our purpose was to analyze, by immunohisto-chemistry, the expression of activated serine-threonine protein kinase B (p-Akt) and phosphatase tensin homologue deleted on chromosome 10 (PTEN) in benign nevi primary metastatic melanomas correlate level with clinical variables. We observed cytoplasmic and/or nuclear p-Akt 22 (54%) 41 nevi, 112 (71.3%) 157 tumors, 50 (71%) 70 metastases. Cytoplasmic PTEN staining 0 (0%), 152 (87.7%), 64 (90%) 162 71 metastases, respectively. A significant positive...
Abstract Background The molecular mechanisms underlying melanoma tumor development and progression are still not completely understood. One of the new candidates that emerged from a recent gene expression profiling study is fatty acid-binding protein 7 ( FABP7) , involved in lipid metabolism, regulation, cell growth differentiation. Methods We studied functional role FABP7 human lines using immunohistochemistry analyzed its pattern clinical 11 nevi, 149 primary melanomas 68 metastases....
Malignant melanoma has an increasing incidence rate and the metastatic disease is notoriously resistant to standard chemotherapy. Loss of cell cycle checkpoints frequently found in many cancer types makes cells reliant on compensatory mechanisms control progression. This feature may be exploited therapy, kinases involved checkpoint regulation, such as Wee1 Chk1/2, have thus become attractive therapeutic targets. In present study we combined a inhibitor (MK1775) with Chk1/2 (AZD7762)...
We evaluated 123 formalin-fixed, paraffin-embedded samples, including neuroendocrine tumors, adult brain, mesonephric tissues, and from various other sites. A pre-B lymphoma cell line, Daudi, a small carcinoma NCL-H128, were by Western blot. All tissues immunostained mouse monoclonal anti-Pax-5 antibody using standard, synthetic polymer-based detection methods. Our study describes for the first time distribution of Pax-5 in brain tissue, periaqueductal gray matter midbrain, area postrema...
Friend leukemia integration site 1 (Fli-1) has been reported as the first nuclear marker of endothelial differentiation; it is expressed in leukocytes and recently demonstrated melanomas. Formalin-fixed, paraffin-embedded tissue sections from 97 melanomas including 69 cases primary 28 metastatic were evaluated by immunohistochemistry. Five melanoma cell lines Western blot immunocytochemistry. Fli-1 expression was observed all lines. higher than tumors (r=0.208, p=0.041, Spearman...
Abstract Background/aims Breast cancer metastasis suppressor 1 (BRMS1) blocks in melanoma xenografts; however, its usefulness as a biomarker human melanomas has not been widely studied. The goal was to measure BRMS1 expression benign nevi, primary and metastatic evaluate impact on disease progression prognosis. Methods Paraffin-embedded tissue from 155 melanomas, 69 metastases 15 nevi examined for using immunohistochemistry. siRNA mediated down-regulation used study invasion migration cell...
Abstract Flavopiridol (FP) is a pan-cyclin dependent kinase inhibitor, which shows strong efficacy in inducing cancer cell apoptosis. Although FP potent against most cells vitro , unfortunately it proved less efficacious clinical trials various aggressive cancers. To date, the molecular mechanisms of resistance are mostly unknown. Here, we report that small fraction human prostate DU145 can survive long-term treatment and emerge as FP-resistant (DU145 ). These show accumulated mitochondrial...
Abstract The insulin like growth factor (IGF) signaling pathway has been shown to contribute melanoma progression, but little is known about the role of IGF binding protein 3 (IGFBP‐3) in biology. aim present study was characterize expression, function and regulation IGFBP‐3 malignant melanomas its potential as a biomarker. expression varied between different human cell lines reintroduction non‐expressing cells led induction apoptosis. Interestingly, expressing endogenous IGFBP‐3, siRNA...
Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in malignant cells while leaving normal unharmed, making it a desirable anticancer target. In the present study, metastatic melanoma cell lines were treated with lexatumumab (Human Genome Sciences, Inc.) high-affinity monoclonal antibody agonistic TRAIL receptor 2 (DR5). Binding of led activation extrinsic pathway approximately 20% cells. However, by combining subtoxic concentrations protein...
Cyclin B1-CDK1 complex plays an important role in the regulation of cell cycle. Activation B1 and CDK1 formation G2/M are under multiple regulations involving many regulators such as isoforms 14-3-3 CDC25 Wee1. Abnormal expression has been detected various tumors. However, to our knowledge no previous study investigated vulvar cancer. Therefore, we evaluated statuses CDK1Tyr15, pCDK1Thr161, (total) pCyclin B1Ser126 297 cases squamous carcinomas by immunohistochemistry. Statistical analyses...
Our purpose was to analyze, by immunohisto-chemistry, the expression of activated serine-threonine protein kinase B (p-Akt) and phosphatase tensin homologue deleted on chromosome 10 (PTEN) in benign nevi primary metastatic melanomas correlate level with clinical variables. We observed cytoplasmic and/or nuclear p-Akt 22 (54%) 41 nevi, 112 (71.3%) 157 tumors, 50 (71%) 70 metastases. Cytoplasmic PTEN staining 0 (0%), 152 (87.7%), 64 (90%) 162 71 metastases, respectively. A significant positive...
MX2 protein is a dynamin-like GTPase2 that has recently been identified as an interferon-induced restriction factor of HIV-1 and other primate lentiviruses. A single nucleotide polymorphism (SNP), rs45430, in intron the gene, was previously reported novel melanoma susceptibility locus genome-wide association studies. Functionally, however, it still unclear whether how contributes to tumorigenesis. Here, we show differentially expressed tumors cell lines, with most metastatic lines showing...
Abstract Melphalan flufenamide (hereinafter referred to as “melflufen”) is a peptide‐conjugated drug currently in phase 3 trials for the treatment of relapsed or refractory multiple myeloma. Due its lipophilic nature, it readily enters cells, where converted known alkylator melphalan leading enrichment hydrophilic payloads. Here, we have analysed vitro and vivo efficacy melflufen on normal cancerous breast epithelial lines. D492 normal‐derived nontumorigenic progenitor cell line whereas...