• Novel human melanoma brain metastasis models in athymic nude fox1nu mice: Site-specific metastasis patterns reflecting their clinical origin 

      Svendsen, Henrik Aasrum; Meling, Torstein Ragnar; Nygaard, Vigdis; Waagene, Stein; Russnes, Hege Elisabeth Giercksky; Juell, Siri; Rogne, Siril Gudmundson; Pahnke, Jens; Helseth, Eirik; Fodstad, Øystein; Mælandsmo, Gunhild Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-06)
      Background: Malignant melanomas frequently metastasize to the brain, but metastases in the cerebellum are underrepresented compared with metastases in the cerebrum.<p> <p>Methods: We established animal models by injecting intracardially in athymic nude fox1<sup>nu</sup> mice two human melanoma cell lines, originating from a cerebral metastasis (HM19) and a cerebellar metastasis (HM86).<p> <p>Results: ...
    • O-GlcNAc Transferase Inhibition Differentially Affects Breast Cancer Subtypes 

      Barkovskaya, Anna; Seip, Kotryna; Hilmarsdòttir, Bylgja; Mælandsmo, Gunhild Mari; Moestue, Siver Andreas; Itkonen, Harri (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-04-05)
      Post-translational modifcation of intracellular proteins with a single N-acetylglucosamine sugar (O-GlcNAcylation) regulates signaling, proliferation, metabolism and protein stability. In breast cancer, expression of the enzyme that catalyzes O-GlcNAcylation – O-GlcNAc-transferase (OGT), and the extent of protein O-GlcNAcylation, are upregulated in tumor tissue, and correlate with cancer progression. ...
    • Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer 

      Fleten, Karianne Giller; Eksteen, Johannes J.; Mauseth, Brynjar; Camilio, Ketil André; Vasskog, Terje; Sveinbjørnsson, Baldur; Rekdal, Øystein; Mælandsmo, Gunhild Mari; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-03-24)
      Oncolytic peptides represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities, including colorectal cancer (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, a feature of particular interest in non-immunogenic CRC. Oncolytic peptides DTT-205 and DTT-304 were administered by intratumoral injection ...
    • p38 MAPK activation through B7-H3-mediated DUSP10 repression promotes chemoresistance 

      Flem-Karlsen, Karine; Tekle, Christina; Øyjord, Tove Ragnhild; Flørenes, Vivi Ann; Mælandsmo, Gunhild Mari; Fodstad, Øystein; Nunes-Xavier, Caroline Elisabeth (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-04-09)
      Immunoregulatory protein B7-H3 is involved in the oncogenic and metastatic potential of cancer cells, as well as in drug resistance. Resistance to conventional chemotherapy is an important aspect of melanoma treatment, and a better understanding of how B7-H3 enhances drug resistance may lead to the development of more effective therapies. We investigated the <i>in vitro</i> and <i>in vivo</i> ...
    • Prognostic biomarkers for immunotherapy with ipilimumab in metastatic melanoma 

      Nyakas, Marta Sølvi; Aamdal, Elin; Jacobsen, Kari Dolven; Guren, Tormod Kyrre; Aamdal, Steinar; Hagene, Kirsten Thorin; Brunsvig, Paal Fr.; Yndestad, Arne; Halvorsen, Bente; Tasken, Kristin Austlid; Aukrust, Pål; Mælandsmo, Gunhild Mari; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-03-01)
      New therapies, including the anti‐cytotoxic T lymphocyte antigen (CTLA)‐4 antibody, ipilimumab, is approved for metastatic melanoma. Prognostic biomarkers need to be identified, because the treatment has serious side effects. Serum samples were obtained before and during treatment from 56 patients with metastatic or unresectable malignant melanoma, receiving treatment with ipilimumab in a national ...
    • Protein kinase C isozymes associated with relapse free survival in non-small cell lung cancer patients 

      Halvorsen, Ann Rita; Haugen, Mads Haugland; Øjlert, Åsa Kristina; Lund-Iversen, Marius; Jørgensen, Lars Hilmar; Solberg, Steinar; Mælandsmo, Gunhild Mari; Brustugun, Odd Terje; Helland, Åslaug (Journal article; Tidsskriftartikkel, 2020-11-25)
      <i>Introduction</i>: Protein expression is deregulated in cancer, and the proteomic changes observed in lung cancer may be a consequence of mutations in essential genes. The purpose of this study was to identify protein expression associated with prognosis in lung cancers stratified by smoking status, molecular subtypes, and EGFR-, TP53-, and KRAS-mutations.<p> <p><i>Methods</i>: We performed ...
    • Protein signature predicts response to neoadjuvant treatment with chemotherapy and bevacizumab in HER2-negative breast cancers 

      Haugen, Mads Haugland; Lingjærde, Ole Christian; Hedenfalk, Ingrid; Garred, Øystein; Borgen, Elin; Loman, Niklas; Hatschek, Thomas; Børresen-Dale, Anne-Lise; Naume, Bjørn; Mills, Gordon B.; Mælandsmo, Gunhild Mari; Engebråten, Olav (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-01-28)
      <p>PURPOSE: Antiangiogenic therapy using bevacizumab has proven effective for a number of cancers; however, in breast cancer (BC), there is an unmet need to identify patients who benefit from such treatment. <p>PATIENTS AND METHODS: In the NeoAva phase II clinical trial, patients (N = 132) with large (≥ 25 mm) human epidermal growth factor receptor 2 (HER2)-negative primary tumors were randomly ...
    • Responsiveness to PD-1 Blockade in End-Stage Colon Cancer with Gene Locus 9p24.1 Copy-Number Gain 

      Ree, Anne Hansen; Nygaard, Vigdis; Russnes, Hege Elisabeth Giercksky; Heinrich, Daniel; Nygaard, Vegard; Johansen, Christin; Bergheim, Inger Riise; Hovig, Eivind; Beiske, Klaus; Negård, Anne; Børresen-Dale, Anne-Lise; Flatmark, Kjersti; Mælandsmo, Gunhild Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-02-25)
      Most patients whose large bowel cancer has spread to other organs do not respond to immune therapy. We detected a rare gene mutation, termed 9p24.1 copy-number gain (CNG), in an otherwise incurable colorectal cancer that provoked an immune therapy response. We identified this gene mutation by gene-panel sequencing of DNA from a liver metastasis biopsy from a patient who had disease refractory to ...
    • Serglycin is Involved in TGF-β induced epithelial-mesenchymal transition and is highly expressed by immune cells in breast cancer tissue 

      Tellez Gabriel, Marta; Tekpli, Xavier; Reine, Trine M.; Hegge, Beate; Nielsen, Stephanie Rose; Chen, Meng; Moi, Line; Normann, Lisa Svartdal; Rasmussen Busund, Lill-Tove; Calin, George A.; Mælandsmo, Gunhild Mari; Perander, Maria; Theocharis, Achilleas D.; Kolset, Svein Olav; Knutsen, Erik (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-14)
      Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of ...
    • Serum levels of inflammation-related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers 

      Nome, Marianne Eikhom; Euceda, Leslie R.; Jabeen, Shakila; Debik, Julia; Bathen, Tone Frost; Giskeødegård, Guro F.; Tasken, Kristin Austlid; Mælandsmo, Gunhild Mari; Halvorsen, Bente; Yndestad, Arne; Borgen, Elin; Garred, Øystein; Aukrust, Pål; Ueland, Thor; Engebraaten, Olav; Kristensen, Vessela N.; Tekpli, Xavier (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 ...
    • Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma 

      Fiorito, Elisa; Szybowska, Patrycja Maria; Haugsten, Ellen Margrethe; Kostas, Michal Janusz; Øy, Geir Frode; Wiedlocha, Antoni; Singh, Sachin Kumar; Nakken, Sigve; Mælandsmo, Gunhild Mari; Fletcher, Jonathan A.; Meza, Leonardo Zepeda; Wesche, Jørgen (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-09-12)
      Background: Rhabdomyosarcoma (RMS) is a paediatric cancer driven either by fusion proteins (e.g., PAX3-FOXO1) or by mutations in key signalling molecules (e.g., RAS or FGFR4). Despite the latter providing opportunities for precision medicine approaches in RMS, there are currently no such treatments implemented in the clinic.<p> <p>Methods: We evaluated biologic properties and targeting strategies ...
    • Stroma-induced phenotypic plasticity offers phenotype-specific targeting to improve melanoma treatment 

      Seip, Kotryna; Jørgensen, Kjetil Nordbø; Haselager, Marco Vincent; Albrecht, Marco; Haugen, Mads Haugland; Egeland, Eivind Valen; Lucarelli, Philippe; Engebråten, Olav; Sauter, Thomas; Mælandsmo, Gunhild Mari; Prasmickaite, Lina (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 ...
    • A Three-dimensional Ex Vivo Viability Assay Reveals a Strong Correlation Between Response to Targeted Inhibitors and Mutation Status in Melanoma Lymph Node Metastases 

      Flørenes, Vivi Ann; Flem-Karlsen, Karine; McFadden, Erin; Bergheim, Inger Riise; Nygaard, Vigdis; Nygård, Vegard Mokleiv; Farstad, Inger Nina; Øy, Geir Frode; Emilsen, Elisabeth; Fleten, Karianne Giller; Ree, Anne Hansen; Flatmark, Kjersti; Gullestad, Hans Petter; Hermann, Robert; Ryder, Truls; Wernhoff, Patrik; Mælandsmo, Gunhild Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-05-13)
      Although clinical management of melanoma has changed considerably in recent years, intrinsic treatment resistance remains a severe problem and strategies to design personal treatment regimens are highly warranted. We have applied a three-dimensional (3D) <i>ex vivo</i> drug efficacy assay, exposing disaggregated cells from 38 freshly harvested melanoma lymph node metastases and 21 patient derived ...