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Sune Munthe, Stine Asferg Petterson, Rikke Hedegaard Dahlrot, Frantz Rom Poulsen, Steinbjørn Hansen, Bjarne Winther Kristensen
Gliomas are highly infiltrative tumors incurable with surgery. Although surgery removes the bulk tumor, tumor cells in the periphery are left behind resulting in tumor relapses. The aim of the present study was to characterize the phenotype of tumor cells in the periphery focusing on tumor stemness, proliferation and chemo-resistance. This was investigated in situ in patient glioma tissue as well as in orthotopic glioblastoma xenografts. We identified 26 gliomas having the R132 mutation in Isocitrate DeHydrogenase 1 (mIDH1)...
2016: PloS One
Thomas Urup, Rikke Hedegaard Dahlrot, Kirsten Grunnet, Ib Jarle Christensen, Signe Regner Michaelsen, Anders Toft, Vibeke Andrée Larsen, Helle Broholm, Michael Kosteljanetz, Steinbjørn Hansen, Hans Skovgaard Poulsen, Ulrik Lassen
BACKGROUND: Predictive markers and prognostic models are required in order to individualize treatment of recurrent glioblastoma (GBM) patients. Here, we sought to identify clinical factors able to predict response and survival in recurrent GBM patients treated with bevacizumab (BEV) and irinotecan. MATERIAL AND METHODS: A total of 219 recurrent GBM patients treated with BEV plus irinotecan according to a previously published treatment protocol were included in the initial population...
2016: Acta Oncologica
Rikke H Dahlrot, Frantz R Poulsen, Nina N T T Nguyen, Bjarne W Kristensen, Steinbjørn Hansen, Niels V Holm
BACKGROUND: Tumors in the central nervous system (CNS) comprise a heterogeneous group of tumors with different treatment strategies and prognoses. Current treatment regimens are based on studies on patients mainly younger than 70 years. The aim of the present study was to analyze and describe trends in incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on patients older than 70 years. MATERIAL AND METHODS: Tumors in the CNS were defined as ICD-10 codes C70-72, D32-33 and D42-43...
2016: Acta Oncologica
Stine Asferg Petterson, Rikke Hedegaard Dahlrot, Simon Kjær Hermansen, Sune K A Munthe, Michael Tveden Gundesen, Helle Wohlleben, Tine Rasmussen, Christoph Patrick Beier, Steinbjørn Hansen, Bjarne Winther Kristensen
The tyrosine kinase receptor c-Met has been suggested to be involved in crucial parts of glioma biology like tumor stemness, growth and invasion. The aim of this study was to investigate the prognostic value of c-Met in a population-based glioma patient cohort. Tissue samples from 238 patients with WHO grade I, II, III and IV tumors were analyzed using immunohistochemical staining and advanced image analysis. Strong c-Met expression was found in tumor cells, blood vessels, and peri-necrotic areas. At the subcellular level, c-Met was identified in the cytoplasm and in the cell membrane...
May 2015: Journal of Neuro-oncology
Rikke H Dahlrot, Mia D Sørensen, Ann Mari Rosager, Sofie Hellwege, Julie A Bangsø, Tine Rosenberg, Stine A Petterson, Jacob Klitkou, Sigurd Fosmark, Steinbjørn Hansen, Bjarne W Kristensen
The therapeutic paradigm of gliomas is changing from a general approach towards an individualized and targeted approach. Accordingly, the search for prognostic and predictive biomarkers, as well as the demand for quantitative, feasible and robust methods for biomarker analysis increases. We find that software classifiers can identify and quantify the expression of a given biomarker within different subcellular compartments and that such classifiers can exclude frequently occurring nontumor cells, thereby avoiding potential bias...
July 2014: CNS Oncology
Rikke Hedegaard Dahlrot
UNLABELLED: Gliomas are the most frequent brain tumours among adults, and it is estimated that gliomas constitute half of the about 1500 new brain tumours diagnosed in Denmark every year. Existing treatment strategies include neurosurgery, radiation, and chemotherapy. Therapy selection is based on experiences from clinical trials, with the risk that the results obtained are restricted to highly selected patients only. Moreover, these studies provided only little knowledge of the clinical behaviour of the tumours...
October 2014: Danish Medical Journal
Rikke H Dahlrot, Steinbjørn Hansen, Stine S Jensen, Henrik D Schrøder, Jacob Hjelmborg, Bjarne W Kristensen
Cancer stem cell-related (CSC) markers have been suggested to have promising potentials as novel types of prognostic and predictive markers in gliomas. However no single CSC-related marker is currently used in clinical decisions. The aim of this study was to investigate the prognostic value of CD133 and nestin separately and in combination using a novel quantitative approach in a well-characterized population-based cohort of glioma patients. The expression of CD133 and nestin was measured by systematic random sampling in stained paraffin sections from 239 glioma patients diagnosed between 2005 and 2009...
2014: International Journal of Clinical and Experimental Pathology
Justin D Lathia, Meizhang Li, Maksim Sinyuk, Alvaro G Alvarado, William A Flavahan, Kevin Stoltz, Ann Mari Rosager, James Hale, Masahiro Hitomi, Joseph Gallagher, Qiulian Wu, Jody Martin, Jason G Vidal, Ichiro Nakano, Rikke H Dahlrot, Steinbjørn Hansen, Roger E McLendon, Andrew E Sloan, Shideng Bao, Anita B Hjelmeland, Christian T Carson, Ulhas P Naik, Bjarne Kristensen, Jeremy N Rich
Stem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell (CSC) adhesion, we performed a flow cytometry screen on patient-derived glioblastoma (GBM) cells and identified junctional adhesion molecule A (JAM-A) as a CSC adhesion mechanism essential for self-renewal and tumor growth. JAM-A was dispensable for normal neural stem/progenitor cell (NPC) function, and JAM-A expression was reduced in normal brain versus GBM...
January 16, 2014: Cell Reports
Rikke H Dahlrot, Steinbjørn Hansen, Jørn Herrstedt, Henrik D Schrøder, Jacob Hjelmborg, Bjarne W Kristensen
The aim of this study was to investigate the prognostic value of the RNA-binding protein Musashi-1 in adult patients with primary gliomas. Musashi-1 has been suggested to be a cancer stem cell-related marker in gliomas, and high levels of Musashi-1 have been associated with high tumor grades and hence poor prognosis. Samples of 241 gliomas diagnosed between 2005 and 2009 were stained with an anti-Musashi-1 antibody using a fluorescent staining protocol followed by automated image acquisition and processing...
December 2013: Journal of Neuro-oncology
Rikke H Dahlrot, Bjarne W Kristensen, Jacob Hjelmborg, Jørn Herrstedt, Steinbjørn Hansen
Low-grade gliomas (LGG) have a slow growth rate, but transformations into malignant gliomas with a rapid deterioration occur in many patients. The aim of this study was to evaluate clinical prognostic factors in a population-based cohort of patients with LGG. In addition we investigated the expression and prognostic value of the isocitrate dehydrogenase 1 (IDH1) R132H mutation. Seventy-four patients diagnosed between 2005 and 2009 in the Region of Southern Denmark were identified using the Danish Cancer Register and The Danish Pathology Databank...
September 2013: Journal of Neuro-oncology
Christine Hilbrandt, Sathya Sathyadas, Rikke H Dahlrot, Bjarne W Kristensen
It is often easy to distinguish between primary brain tumors and metastases based on morphology alone. However, in some cases immunohistochemistry (IHC) is necessary to obtain a diagnosis, but, as the present case report illustrates, this is not always straightforward. A 75-year old man was admitted to the hospital with left-sided loss of motor function. A MRI revealed a 6 cm tumor in the right temporoparietal area. The histology was consistent with both glioblastoma multiforme (GBM) and small cell lung carcinoma (SCLC) but IHC was suggestive of a SCLC metastasis...
July 2013: Clinical Neuropathology
Rikke Hedegaard Dahlrot, Simon Kjær Hermansen, Steinbjørn Hansen, Bjarne Winther Kristensen
Recent data indicate that cancer stem cells (CSCs) are responsible for resistance of glioblastomas to radiotherapy and chemotherapy, thereby contributing to the poor survival of these patients. In order to identify novel prognostic markers in gliomas, several CSC markers have been investigated. This review summarizes current reports on putative glioma CSC markers and reviews the prognostic value of the individual immunohistochemical markers reported in the literature. Using the Pubmed database, twenty-seven CSC studies looking at membrane markers (CD133, podoplanin, CD15, and A2B5), filament markers (nestin), RNA-binding proteins (Musashi-1) and transcription factors (BMI1, SOX2, Id1 and Oct-4) qualified for this review...
2013: International Journal of Clinical and Experimental Pathology
Rikke H Dahlrot, Bjarne W Kristensen, Jacob Hjelmborg, Jørn Herrstedt, Steinbjørn Hansen
UNLABELLED: High-grade gliomas have a dismal prognosis, and prognostic factors are needed to optimize treatment algorithms. In this study we identified clinical prognostic factors as well as the prognostic value of isocitrate dehydrogenase 1 (IDH1) status in a population-based group of patients with high-grade gliomas. Using the Danish Cancer Registry and the Danish Pathology Databank we identified 359 patients: 234 had WHO grade IV gliomas, 58 had WHO grade III gliomas, and 67 were diagnosed clinically...
2013: International Journal of Clinical and Experimental Pathology
Simon Kjær Hermansen, Rikke Hedegaard Dahlrot, Boye Schnack Nielsen, Steinbjørn Hansen, Bjarne Winther Kristensen
High-grade gliomas are some of the most lethal forms of human cancer, and new clinical biomarkers and therapeutic targets are highly needed. MicroRNAs (miRNAs), a group of short noncoding RNAs, hold great potential as new biomarkers and targets as they are commonly deregulated in a variety of diseases including gliomas. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in several cancers including gliomas and is therefore very promising as a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in gliomas, paraffin-embedded glioma tissue samples from 193 patients with grade I, II, III, and IV tumors were analyzed by in situ hybridization (ISH) using LNA-DNA chimeric probes...
January 2013: Journal of Neuro-oncology
L W Vestermark, E Holtved, R Dahlrot, M K Brimnes, I M Svane, L Bastholt
BACKGROUND: Central nervous system (CNS) metastases develop in nearly half of patients with advanced melanoma and in 15-20% CNS is the first site of relapse. Median overall survival is short, ranging from two to four months, and one-year survival rate is only 10-15%. THA has been shown to have both anti-angiogenetic and immuno-modulating effects. TMZ is an oral alkylating agent with an excellent oral bioavailability and it is highly lipophillic with an ability to penetrate the blood-brain barrier...
2008: Ecancermedicalscience
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