• Assessing PDL-1 and PD-1 in NoneSmall Cell Lung Cancer: A Novel Immunoscore Approach 

      Paulsen, Erna-Elise; Kilvær, Thomas Karsten; Rakaee, Mehrdad; Al-Saad, Samer; Hald, Sigurd; Andersen, Sigve; Richardsen, Elin; Ness, Nora; Busund, Lill-Tove; Bremnes, Roy M.; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-10-05)
      Novel immune biomarkers could complement the TNM classification for nonesmall cell cancer (NSCLC), improving the prognostic accuracy. The present study evaluated the prognostic significance of the immune checkpoint molecules programmed cell death protein 1 (PD-1) and PD-1 ligand (PD-L1) in 536 patients with stage I to IIIA NSCLC using an Immunoscore approach. Independently, and in combination, ...
    • 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 ...
    • CD4/CD8 co-expression shows independent prognostic impact in resected non-small cell lung cancer patients treated with adjuvant radiotherapy 

      Hald, Sigurd; Bremnes, Roy M.; Al-Shibli, Khalid; Al-Saad, Samer; Andersen, Sigve; Stenvold, Helge; Busund, Lill-Tove; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)
    • CD45RO+ Memory T Lymphocytes – a Candidate Marker for TNM-Immunoscore in Squamous Non-Small Cell Lung Cancer 

      Paulsen, Erna-Elise; Kilvær, Thomas Karsten; Rakaeekhanehkenari, Mehrdad; Johansen Maurseth, Ramona; Al-Saad, Samer; Hald, Sigurd; Al-Shibli, Khalid; Andersen, Sigve; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M.; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11)
      Tumor-infiltrating lymphocytes (TILs) are vital in limiting cancer progression and may supplement the TNM classification. CD45RO+ memory TILs show major prognostic impact in various malignancies but have not been extensively explored in non–small cell lung cancer (NSCLC). In this study, we aimed to evaluate their potential in a NSCLC TNM-Immunoscore. Tissue microarrays were constructed from tumor ...
    • 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 ...
    • CTLA-4 expression in the non-small cell lung cancer patient tumor microenvironment: diverging prognostic impact in primary tumors and lymph node metastases 

      Paulsen, Erna-Elise; Kilvær, Thomas Karsten; Rakaee, Mehrdad; Richardsen, Elin; Hald, Sigurd; Andersen, Sigve; Busund, Lill-Tove; Bremnes, Roy M.; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-07-13)
      The immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 ...
    • Detection of MicroRNAs in Archival Cytology Urine Smears 

      Simonato, Francesca; Ventura, Laura; Sartori, Nicola; Cappellesso, Rocco; Fassan, Matteo; Busund, Lill-Tove; Fassina, Ambrogio (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)
      MicroRNAs’ dysregulation and profiling have been demonstrated to be clinically relevant in urothelial carcinoma (UC). Urine cytology is commonly used as the mainstay non-invasive test for secondary prevention and follow-up of UC patients. Ancillary tools are needed to support cytopathologists in the diagnosis of low-grade UC. The feasibility and reliability of microRNAs profiling by qRT-PCR ...
    • 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) ...
    • Disease-specific outcomes of Radical Prostatectomies in Northern Norway; A case for the impact of perineural infiltration and postoperative PSA-doubling time 

      Andersen, Sigve; Richardsen, Elin; Nordby, Yngve; Ness, Nora; Størkersen, Øystein; Al-Shibli, Khalid; Dønnem, Tom; Bertilsson, Helena; Busund, Lill-Tove; Angelsen, Anders; Bremnes, Roy M. (Tidsskriftartikkel; Journal article; Peer reviewed, 2014)
      Background Prostate cancer is the most common male malignancy and a mayor cause of mortality in the western world. The impact of clinicopathological variables on disease related outcomes have mainly been reported from a few large US series, most of them not reporting on perineural infiltration. We therefore wanted to investigate relevant cancer outcomes in patients undergoing radical prostatectomy ...
    • Estrogen receptors α and β and aromatase as independent predictors for prostate cancer outcome 

      Grindstad, Thea; Skjefstad, Kaja; Andersen, Sigve; Ness, Nora; Nordby, Yngve; Al-Saad, Samer; Fismen, Silje; Dønnem, Tom; Rakaee, Mehrdad; Busund, Lill-Tove; Bremnes, Roy M.; Richardsen, Elin (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-09-09)
      Androgens are considered important in normal prostate physiology and prostate cancer (PCa) pathogenesis. However, androgen-targeted treatment preventing PCa recurrence is still lacking. This indicates additional mediators contributing to cancer development. We sought to determine the prognostic significance of estrogen receptors, ERα and -β, and the aromatase enzyme in PCa. Tissue microarrays ...
    • Evaluation of the proliferation marker Ki-67 in a large prostatectomy cohort 

      Richardsen, Elin; Andersen, Sigve; Al-Saad, Samer; Rakaee, Mehrdad; Nordby, Yngve; Pedersen, Mona Irene; Ness, Nora; Grindstad, Thea K.W.; Movik, Ingeborg; Dønnem, Tom; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-15)
      The tumor proliferation index marker Ki-67 is strongly associated with tumor cell proliferation, growth and progression, and is widely used in routine clinicopathological investigation. Prostate cancer is a complex multifaceted and biologically heterogeneous disease, and overtreatment of localized, low volume indolent tumors, is evident. Here, we aimed to assess Ki-67 expression and related ...
    • Evaluation of the proliferation marker Ki-67 in a large prostatectomy cohort. 

      Richardsen, Elin; Andersen, Sigve; Al-Saad, Samer; Rakaee, Mehrdad; Nordby, Yngve; Pedersen, Mona Irene; Ness, Nora; Grindstad, Thea K.W.; Movik, Ingeborg; Dønnem, Tom; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-15)
      The tumor proliferation index marker Ki-67 is strongly associated with tumor cell proliferation, growth and progression, and is widely used in routine clinicopathological investigation. Prostate cancer is a complex multifaceted and biologically heterogeneous disease, and overtreatment of localized, low volume indolent tumors, is evident. Here, we aimed to assess Ki-67 expression and related ...
    • Expression and function of the miR-143/145 cluster in vitro and in vivo in human breast cancer 

      Johannessen, Charles; Moi, Line; Kiselev, Yury; Pedersen, Mona Irene; Dalen, Stig Manfred; Braaten, Tonje; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-10-26)
      MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators of gene expression and are dysregulated in cancer. Studies of miRNAs to explore their potential as diagnostic and prognostic markers are of great scientific interest. Here, we investigate the functional properties and expression of the miR-143/145 cluster in breast cancer (BC) in vitro and in vivo. The ER ...
    • Expression of phosphatase of regenerating liver (PRL)-3, is independently associated with biochemical failure, clinical failure and death in prostate cancer 

      Andersen, Sigve; Richardsen, Elin; Rakaee, Mehrdad; Bertilsson, Helena; Bremnes, Roy; Børset, Magne; Busund, Lill-Tove; Slørdahl, Tobias (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-30)
      Background: Prostate cancer (PC) stratification needs new prognostic tools to reduce overtreatment. Phosphatase of regenerating liver (PRL-3) is a phosphatase found at high levels in several cancer types, where its expression is associated with survival. A recent PC cell line study has shown it to be involved in PC growth and migration. <br>Methods: We used a monoclonal antibody to evaluate ...
    • Fibroblast growth factor 2 orchestrates angiogenic networking in non-GIST STS patients 

      Kilvær, Thomas Karsten; Valkov, Andrey Yurjevich; Sørbye, Sveinung Wergeland; Smeland, Eivind; Bremnes, Roy M.; Busund, Lill-Tove; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)
      Non-gastrointestinal stromal tumor soft-tissue sarcomas (non-GIST STSs) constitute a heterogeneous group of tumors with poor prognosis. Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor-1 (FGFR-1), in close interplay with platelet-derived growth factor-B (PDGF-B) and vascular endothelial growth factor receptor-3 (VEGFR-3), are strongly involved in angiogenesis. This study ...
    • Fibroblast miR-210 overexpression is independently associated with clinical failure in Prostate Cancer – a multicenter (in situ hybridization) study 

      Andersen, Sigve; Richardsen, Elin; Moi, Line; Dønnem, Tom; Nordby, Yngve; Ness, Nora; Eilertsen Holman, Marte; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-11-08)
      There is a need for better prognostication in prostate cancer (PC). “The micromanager of hypoxia”, microRNA-210 (miR-210) is directly linked to hypoxia, is overexpressed in PC and has been implied in tumor cell-fibroblast crosstalk. We investigated the prognostic impact of miR-210 in tumor cells and fibroblasts in PC. Tumor and stromal samples from a multicenter PC cohort of 535 prostatectomy patients ...
    • A gender specific improved survival related to stromal miR-143 and miR-145 expression in non-small cell lung cancer 

      Skjefstad, Kaja Konstanse; Johannessen, Charles; Grindstad, Thea K.W.; Kilvær, Thomas Karsten; Paulsen, Erna Elise; Pedersen, Mona Irene; Dønnem, Tom; Andersen, Sigve; Bremnes, Roy M.; Richardsen, Elin; Al-Saad, Samer; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-06-04)
      Micro RNAs (miRNA) are small non-coding RNAs that post-transcriptionally regulate gene expression. Dysregulation of miRNA cluster 143/145 has been reported in several malignancies, but their role in non-small cell lung cancer (NSCLC) remains elusive. This study investigates the prognostic impact of miR-143 and miR-145 in primary tumors and metastatic lymph nodes in NSCLC tissue. Tissue from 553 ...
    • High expression of CD20+ lymphocytes in soft tissue sarcomas is a positive prognostic indicator 

      Sørbye, Sveinung Wergeland; Kilvær, Thomas Karsten; Valkov, Andrey Yurjevich; Dønnem, Tom; Smeland, Eivind; Al-Shibli, Khalid Ibrahim; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel, 2012)
      The immune status is important in cancer patients. Tissue microarrays from 249 patients with soft tissue sarcomas were constructed. Immunohistochemistry was used to evaluate the CD3+, CD4+, CD8+, CD20+ and CD45+ lymphocytes in tumors. High density of CD20+ lymphocytes is an independent positive prognostic indicator for these patients.
    • High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence 

      Nordby, Yngve; Richardsen, Elin; Rakaee, Mehrdad; Ness, Nora; Dønnem, Tom; Patel, Hitendra R.H.; Busund, Lill-Tove; Bremnes, Roy M.; Andersen, Sigve (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-02-24)
      Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the ...