• Cancer associated fibroblasts in stage I-IIIA NSCLC: Prognostic impact and their correlations with tumor molecular markers 

      Kilvær, Thomas Karsten; Rakaeekhanehkenari, Mehrdad; Hellevik, Turid; Al-Saad, Samer; Paulsen, Erna-Elise; Busund, Lill-Tove; Dønnem, Tom; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-08-07)
      Background Cancer Associated Fibroblasts (CAFs) are thought to regulate tumor growth and metastasis. Fibroblast Activating Protein 1 (FAP-1) is a marker for fibroblast activation and by many recognized as the main marker of CAFs. Alpha Smooth Muscle Actin (α-SMA) is a general myofibroblast marker, and can be used to identify CAFs. This study investigates the prognostic impact of FAP-1 and α-SMA ...
    • Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced 

      Hellevik, Turid; Pettersen, ingvild; Berg, Vivian; Winberg, Jan-Olof; Moe, Bjørn Torvald Greve; Bartnes, Kristian; Paulssen, Ruth H; Busund, Lill-Tove; Bremnes, Roy M.; Chalmers, Antony; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)
      BACKGROUND: Cancer-Associated Fibroblasts (CAFs) are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR), equivalent to single fractions delivered by stereotactic ...
    • Cancer-associated fibroblasts from lung tumors maintain their immunosuppressive abilities after high-dose irradiation 

      Gorchs, Laia; Hellevik, Turid; Bruun, Jack-Ansgar; Camilio, Ketil Andre; Al-Saad, Samer; Stuge, Tor Brynjar; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-05-12)
      Accumulating evidence supports the notion that high-dose (>5 Gy) radiotherapy (RT) regimens are triggering stronger pro-immunogenic effects than standard low-dose (2 Gy) regimens. However, the effects of RT on certain immunoregulatory elements in tumors remain unexplored. In this study, we have investigated the effects of high-dose radiotherapy (HD-RT) on the immunomodulating functions of cancer-associated ...
    • Cancer-associated fibroblasts in radiotherapy: Bystanders or protagonists? 

      Martinez, Inigo Zubiavrre; Hellevik, Turid (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-05-11)
      Background - The primary goal of radiotherapy (RT) is to induce cellular damage on malignant cells; however, it is becoming increasingly recognized the important role played by the tumor microenvironment (TME) in therapy outcomes. Therapeutic irradiation of tumor lesions provokes profound cellular and biological reconfigurations within the TME that ultimately may influence the fate of the ...
    • Changes in the secretory profile of NSCLC-associated fibroblasts after ablative radiotherapy: Potential impact on angiogenesis and tumor growth 

      Hellevik, Turid; Pettersen, Ingvild; Berg, Vivian; Bruun, Jack-Ansgar; Bartnes, Kristian; Busund, Lill-Tove; Chalmers, Anthony; Bremnes, Roy M.; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2014-03-05)
      In the context of radiotherapy, collateral effects of ablative ionizing radiation (AIR) on stromal components of tumors remains understudied. In this work, cancer-associated fibroblasts (CAFs) isolated from freshly resected human lung tumors were exposed to AIR (1x18Gy) and analyzed for their release of paracrine factors. Inflammatory mediators and regulators of angiogenesis and tumor growth were ...
    • Cleavage of the urokinase receptor (uPAR) on oral cancer cells: Regulation by transforming growth factor - beta1 (TGF-beta1) and potential effects on migration and invasion 

      Magnussen, Synnøve; Hadler-Olsen, Elin Synnøve; Costea, Daniela Elena; Berg, Eli; Cavalcanti Jacobsen, Cristiane de Albuquerque; Mortensen, Bente; Salo, Tuula; Martinez, Inigo Zubiavrre; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjørg (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-05-19)
      Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment ...
    • Co-expression of 1α-hydroxylase and vitamin D receptor in human articular chondrocytes 

      Hansen, Ann Kristin; Figenschau, Yngve Anton; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-06)
      Background: <br> The aim was to investigate whether resident chondrocytes in human articular cartilage and in subculture express vitamin D receptor (VDR) and the enzyme that hydroxylates the prohormone 25(OH)D3 to the active hormone 1α,25(OH)2D3, namely 1α-hydroxylase (CYP27B1). Any putative effects of vitamin D on chondrocytes were also explored. <br> Methods: <br> Cartilage from human osteoarthritic ...
    • Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs 

      Ben-Batalla, Isabel; Cubas-Cordova, Miguel; Udonta, Florian; Wroblewski, Mark; Waizenegger, Jonas S.; Janning, Melanie; Sawall, Stefanie; Gensch, Victoria; Zhao, Lin; Martinez, Inigo Zubiavrre; Riecken, Kristoffer; Fehse, Boris; Pantel, Klaus; Bokemeyer, Carsten; Loges, Sonja (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-01-31)
      Anti-angiogenic therapies were approved for different cancers. However, significant primary and secondary resistance hampers efficacy in several tumor types including breast cancer. Thus, we need to develop clinically applicable strategies to enhance efficacy of anti-angiogenic drugs. We report that anti-angiogenic therapies can induce upregulation of cyclooxygenase-2 (Cox-2) and of its product ...
    • Differential prognostic impact of platelet-derived growth factor receptor Expression in NSCLC 

      Kilvær, Thomas Karsten; Rakaee, Mehrdad; Hellevik, Turid; Vik, Jørg; de Petris, Luigi; Dønnem, Tom; Strell, Carina; Østman, Arne; Busund, Lill-Tove; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-15)
      Preclinical evidence suggests that stromal expression of platelet-derived growth factor receptors (PDGFRs) stimulates tumor development and diminishes intratumoral drug uptake. In non-small cell lung cancer (NSCLC), the clinical relevance of stromal PDGFR expression remains uncertain. Tumor specimens from 553 patients with primary operable stage I-IIIB NSCLC was obtained and tissue micro-arrays (TMA) ...
    • Dynamic expression of VDR and 1-­alpha-­hydroxylase in differentiated and re-­differentiated human articular chondrocytes 

      Hansen, Ann Kristin; Figenschau, Yngve Anton; Martinez, Inigo Zubiavrre (Conference object; Konferansebidrag, 2016-09)
      <p><i>Purpose:</i> The goal was to investigate potential roles played by vitamin D in the regulation of joint cartilage biology. We studied the expression of two central elements of vitamin D metabolism, namely the vitamin D receptor and its converting enzyme 1­α­hydroxylase in human knee cartilage and chondrocytes. <p><i>Methods and Materials:</i> Expression of receptor and enzyme was determined ...
    • Expression and function of Leukotriene B4 receptors in human articular chondrocytes 

      Hansen, Ann Kristin; Indrevik, Jill-Tove; Figenschau, Yngve Anton; Martinez, Inigo Zubiavrre; Sveinbjørnsson, Baldur (Conference object; Konferansebidrag, 2013)
      Leukotriene B4 (LTB4) is linked to osteoarthritis (OA) development however the expression of LTB4 receptors in cartilage cells and the physiological effects of LTB4 on cartilage tissue remain unknown. In this study we find that human articular chondrocytes express LTB4 receptors and that these receptors are functional, however, LTB4 does not seem to affect importantly some primary chondrocyte functions.
    • Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation 

      Berzaghi, Rodrigo; Akhtar, Muhammad Asad; Islam, Md Ashraful; Pedersen, Brede Dille; Hellevik, Turid; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-05-17)
      The abilities of cancer-associated fibroblasts (CAFs) to regulate immune responses in the context of radiotherapy remain largely unknown. This study was undertaken to determine whether ionizing radiation alters the CAF-mediated immunoregulatory effects on macrophages. CAFs were isolated from freshly-resected non-small cell lung cancer tumors, while monocyte-derived macrophages were prepared from ...
    • Human articular chondrocytes express functional Leukotriene B4 receptors 

      Hansen, Ann Kristin; Indrevik, Jill-Tove; Figenschau, Yngve Anton; Martinez, Inigo Zubiavrre; Sveinbjørnsson, Baldur (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-02-09)
      Leukotriene B<sub>4</sub> (LTB<sub>4</sub>) is a potent chemoattractant associated with the development of osteoarthritis (OA), while its receptors BLT1 and BLT2 have been found in synovium and subchondral bone. In this study, we have investigated whether these receptors are also expressed by human cartilage cells and their potential effects on cartilage cells. The expression of LTB<sub>4</sub> ...
    • Human endogenous retrovirus W Activity in cartilage of osteoarthritis patients 

      Bendiksen, Signy; Martinez, Inigo Zubiavrre; Tümmler, Conny; Knutsen, Gunnar; Elvenes, Jan; Olsen, Elisabeth; Olsen, Randi; Moens, Ugo (Journal article; Tidsskriftartikkel; Peer reviewed, 2014)
    • Immunobiology of cancer-associated fibroblasts in the context of radiotherapy 

      Hellevik, Turid; Berzaghi, Rodrigo; Lode, Kristin; Islam, Md Ashraful; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-18)
      Radiotherapy (RT) still represents a mainstay of treatment in clinical oncology. Traditionally, the effectiveness of radiotherapy has been attributed to the killing potential of ionizing radiation (IR) over malignant cells, however, it has become clear that therapeutic efficacy of RT also involves activation of innate and adaptive anti-tumor immune responses. Therapeutic irradiation of the tumor ...
    • In vitro chondrogenic potency of surplus chondrocytes from autologous transplantation procedures does not predict short-term clinical outcomes 

      Islam, Md Ashraful; Fossum, Vegard; Hansen, Ann Kristin; Urbarova, Ilona; Knutsen, Gunnar; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-01-10)
      <p><i>Background</i>: Autologous chondrocyte implantation (ACI) has been used over the last two decades to treat focal cartilage lesions aiming to delay or prevent the onset of osteoarthritis; however, some patients do not respond adequately to the procedure. A number of biomarkers that can forecast the clinical potency of the cells have been proposed, but evidence for the relationship between in ...
    • The influence of oxygen tension on the structure and function of isolated liver sinusoidal endothelial cells 

      Martinez, Inigo Zubiavrre; Warren, A; Le Couteur, D.G.; Nedredal, Geir Ivar; Øie, Cristina Ionica; Johansen, oddmund; Smedsrød, Bård (Journal article; Tidsskriftartikkel; Peer reviewed, 2008)
    • Ionizing radiation curtails immunosuppressive effects from cancer-associated fibroblasts on dendritic cells 

      Berzaghi, Rodrigo; Tornaas, Stian; Lode, Kristin; Hellevik, Turid; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-06-09)
      Cancer-associated fibroblasts (CAFs) participate actively in tumor development and affect treatment responses, by among other mechanisms, promoting an immunosuppressive tumor microenvironment. In contrast to normal fibroblasts, reactive CAFs secrete a myriad of immunomodulatory soluble factors at high levels, i.e. growth factors, cytokines, and chemokines, which directly influence tumor immunity and ...
    • Irradiated tumor fibroblasts avoid immune recognition and retain immunosuppressive functions over natural killer cells 

      Yang, Nannan; Lode, Kristin; Berzaghi, Rodrigo; Islam, Md Ashraful; Martinez, Inigo Zubiavrre; Hellevik, Turid (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-01-22)
      Recent studies have demonstrated that radiotherapy is able to induce anti-tumor immune responses in addition to mediating direct cytotoxic effects. Cancer-associated fibroblasts (CAFs) are central constituents of the tumor stroma and participate actively in tumor immunoregulation. However, the capacity of CAFs to influence immune responses in the context of radiotherapy is still poorly understood. ...
    • Irradiated tumor fibroblasts avoid immune recognition and retain immunosuppressive functions over NK cells 

      Yang, Nannan; Lode, Kristin; Berzaghi, Rodrigo; Islam, Md Ashraful; Martinez, Inigo Zubiavrre; Hellevik, Turid (Journal article; Tidsskriftartikkel, 2021-01-22)
      Recent studies have demonstrated that radiotherapy is able to induce anti-tumor immune responses in addition to mediating direct cytotoxic effects. Cancer-associated fibroblasts (CAFs) are central constituents of the tumor stroma and participate actively in tumor immunoregulation. However, the capacity of CAFs to influence immune responses in the context of radiotherapy is still poorly understood. ...