• Cabazitaxel-loaded Poly(2-ethylbutyl cyanoacrylate) nanoparticles improve treatment efficacy in a patient derived breast cancer xenograft 

      Fusser, Markus; Øverbye, Anders; Pandya, Abhilash D.; Mørch, Ýrr Asbjørg; Borgos, Sven Even F.; Kildal, Wanja; Snipstad, Sofie; Sulheim, Einar; Fleten, Karianne Giller; Askautrud, Hanne Arenberg; Engebraaten, Olav; Flatmark, Kjersti; Iversen, Tore Geir; Sandvig, Kirsten; Skotland, Tore; Mælandsmo, Gunhild Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-12-04)
      The effect of poly(2-ethyl-butyl cyanoacrylate) nanoparticles containing the cytotoxic drug cabazitaxel was studied in three breast cancer cell lines and one basal-like patient-derived xenograft model grown in the mammary fat pad of immunodeficient mice. Nanoparticle-encapsulated cabazitaxel had a much better efficacy than similar concentrations of free drug in the basal-like patient-derived xenograft ...
    • Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide 

      Øverbye, Anders; Holsæter, Ann Mari; Fusser, Markus; Skalko-Basnet, Natasa; Iversen, Tore Geir; Torgersen, Maria Lyngaas; Sønstevold, Tonje; Engebråten, Olav; Flatmark, Kjersti; Mælandsmo, Gunhild; Skotland, Tore; Sandvig, Kirsten (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-08-12)
      Doxorubicin, a widely used chemotherapeutic drug, has several potential high- risk side effects including cardiomyopathy. Furthermore, cellular resistance to this drug develops with time. By using liposomes as carrier vesicles both the side effects and drug resistance might be avoided. In this study we have investigated the cytotoxic effect of doxorubicin encapsulated in liposomes with and ...
    • Clinical significance of disseminated tumour cells in non-small cell lung cancer 

      Rud, Ane Kristine Kongsgaard; Borgen, Elin; Mælandsmo, Gunhild; Flatmark, Kjersti; Le, Hang Ngoc Thi; Josefsen, Dag; Solvoll, Ingjerd; Schirmer, Cecilie; Helland, Åslaug; Jørgensen, Lars Hilmar; Brustugun, Odd Terje; Fodstad, Øystein; Boye, Kjetil (Journal article; Tidsskriftartikkel; Peer reviewed, 2013-08-13)
      Background: Early-stage non-small cell lung cancer (NSCLC) patients have a high risk of disease relapse despite curatively intended surgical resection, and the detection of tumour cells in the bone marrow could be one method of determining the presence of the disseminated disease in its early stages.<p> <p>Methods: Bone marrow aspirates were collected from 296 patients at the time of surgery, and ...
    • A comprehensive framework for analysis of microRNA sequencing data in metastatic colorectal cancer 

      Høye, Eirik; Fromm, Bastian; Böttger, Paul H.M.; Domanska, Diana; Kristensen, Annette Torgunrud; Lund-Andersen, Christin; Abrahamsen, Torveig Weum; Fretland, Åsmund Avdem; Dagenborg, Vegar Johansen; Lorenz, Susanne; Edwin, Bjørn von Gohren; Hovig, Eivind; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-01-14)
      Although microRNAs (miRNAs) contribute to all hallmarks of cancer, miRNA dysregulation in metastasis remains poorly understood. The aim of this work was to reliably identify miRNAs associated with metastatic progression of colorectal cancer (CRC) using novel and previously published nextgeneration sequencing (NGS) datasets generated from 268 samples of primary (pCRC) and metastatic CRC (mCRC; ...
    • Cost-effectiveness of molecularly matched off-label therapies for end-stage cancer–the MetAction precision medicine study 

      Ree, Anne Hansen; Mælandsmo, Gunhild Mari; Flatmark, Kjersti; Russnes, Hege Elisabeth Giercksky; Casteneda, Monica Gomez; Aas, Eline (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-08-09)
      Background: Precision cancer medicine (PCM), frequently used for the expensive and often modestly efficacious off-label treatment with medications matched to the tumour genome of end-stage cancer, challenges healthcare resources. We compared the health effects, costs and cost-effectiveness of our MetAction PCM study with corresponding data from comparator populations given best supportive care ...
    • EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer 

      Boye, Kjetil; Nesland, Jahn M; Sandstad, Berit; Haugen, Mads Haugland; Mælandsmo, Gunhild; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2012-07-10)
      BACKGROUND: Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. METHODS: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively ...
    • Impact of KRAS, BRAF and microsatellite instability status after cytoreductive surgery and HIPEC in a national cohort of colorectal peritoneal metastasis patients 

      Larsen, Stein; Goscinski, Mariusz Adam; Dueland, Svein; Steigen, Sonja Eriksson; Hofsli, Eva; Kristensen, Annette Torgunrud; Lund-Iversen, Marius; Dagenborg, Vegar Johansen; Flatmark, Kjersti; Sørbye, Halvdan (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-09)
      Background - Patients with metastatic colorectal cancer (mCRC) carrying BRAF (mutBRAF) or KRAS mutation (mutKRAS) have an inferior prognosis after liver or lung surgery, whereas the prognostic role in the context of peritoneal metastasis (PM) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been less investigated.<p> <p>Methods - In total, 257 patients ...
    • Increased Local Inflammatory Response to MOC31PE Immunotoxin After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy 

      Thorgersen, Ebbe Billmann; Asvall, Jørund; Frøysnes, Ida Storhaug; Schjalm, Camilla; Larsen, Stein Gunnar; Dueland, Svein; Andersson, Yvonne; Fodstad, Øystein; Mollnes, Tom Eirik; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-05-21)
      Background - Despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), most patients with resectable peritoneal metastases from colorectal cancer experience disease relapse. MOC31PE immunotoxin is being explored as a novel treatment option for these patients. MOC31PE targets the cancer-associated epithelial cell adhesion molecule, and kills cancer cells by ...
    • Low Concordance Between T-Cell Densities in Matched Primary Tumors and Liver Metastases in Microsatellite Stable Colorectal Cancer 

      Johansen Dagenborg, Vegard; Marshall, Serena Elizabeth; Grzyb, Krzyzstof; Fretland, Åsmund Avdem; Lund-Iversen, Marius; Mælandsmo, Gunhild Mari; Hansen Ree, Anne; Edwin, Bjørn; Yaqub, Sheraz; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-06-09)
      Background: The subtype, density and location of tumor infiltrating T-cells are being explored as prognostic and predictive biomarkers in primary colorectal cancer (pCRC) and colorectal liver metastases (CLM). Very limited data exist comparing findings in pCRC and matched CLM.<p> <p>Patients and methods: Fifty-eight patients with available pCRC and matched CLM (57/58 microsatellite stable) were ...
    • Molecular signatures reflecting microenvironmental metabolism and chemotherapy-induced immunogenic cell death in colorectal liver metastases 

      Østrup, Olga; Dagenborg, Vegar Johansen; Rødland, Einar Andreas; Skarpeteig, Veronica; Silwal-Pandit, Laxmi; Grzyb, Krzysztof; Berstad, Audun Elnæs; Fretland, Åsmund Avdem; Mælandsmo, Gunhild; Børresen-Dale, Anne-Lise; Ree, Anne Hansen; Edwin, Bjørn; Nygaard, Vigdis; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-07-18)
      Background: Metastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to ...
    • Molecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer - the MetAction study 

      Ree, Anne Hansen; Nygaard, Vigdis; Pedersen, Kjetil Boye; Heinrich, Daniel; Dueland, Svein; Bergheim, Inger Riise; Johansen, Christin; Beiske, Klaus; Negård, Anne; Lund-Iversen, Marius; Nygaard, Vegard; Hovig, Eivind; Nakken, Sigve; Nasser, Salah; Julsrud, Lars; Reisse, Claudius; Ruud, Espen Asak; Kristensen, Vessela N.; Flørenes, Vivi Ann; Geitvik, Gry; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise; Russnes, Hege Elisabeth Giercksky; Mælandsmo, Gunhild Mari; Flatmark, Kjersti (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). ...
    • Nuclear Legumain Activity in Colorectal Cancer 

      Haugen, Mads Haugland; Johansen, Harald Thidemann; Pettersen, Solveig; Solberg, Rigmor; Brix, Klaudia; Flatmark, Kjersti; Mælandsmo, Gunhild (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)
      The cysteine protease legumain is involved in several biological and pathological processes, and the protease has been found over-expressed and associated with an invasive and metastatic phenotype in a number of solid tumors. Consequently, legumain has been proposed as a prognostic marker for certain cancers, and a potential therapeutic target. Nevertheless, details on how legumain advances ...
    • 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 ...
    • Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy 

      Pedersen, Kjetil Boye; Jacob, Havjin; Frikstad, Kari-Anne; Nesland, Jahn M; Mælandsmo, Gunhild; Dahl, Olav; Nesbakken, Arild; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-06-08)
      Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis-promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 exp ...
    • 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 ...
    • T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases 

      Høye, Eirik; Dagenborg, Vegar Johansen; Kristensen, Annette Torgunrud; Lund-Andersen, Christin; Fretland, Åsmund Avdem; Lorenz, Susanne; Edwin, Bjørn von Gohren; Hovig, Eivind; Fromm, Bastian; Inderberg, Else Marit; Greiff, Victor; Ree, Anne Hansen; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-05-10)
      Background - Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite-stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumor-infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and ...
    • 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 ...