A5064110734- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Brain Metastases and Treatment
- Plant Molecular Biology Research
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Radiomics and Machine Learning in Medical Imaging
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Autophagy in Disease and Therapy
- MicroRNA in disease regulation
- Cancer-related gene regulation
- Neuroblastoma Research and Treatments
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Cytomegalovirus and herpesvirus research
- Cancer-related molecular mechanisms research
- Medical Imaging Techniques and Applications
- Immunotherapy and Immune Responses
- Nanoplatforms for cancer theranostics
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
University of Bergen
2015-2024
Haukeland University Hospital
2021-2024
University of Oslo
2009-2014
University of Development Alternative
2010
École Polytechnique Fédérale de Lausanne
2009
Laboratoire de Cristallographie et Sciences des Matériaux
2009
University of Zagreb
2009
MRC Laboratory of Molecular Biology
2009
Therapy of recurrent glioblastoma (GBM) is challenging due to lack standard treatment. We investigated physicians’ treatment choice at recurrence and prognostic predictive factors for survival in GBM patients from Norway’s two largest regional hospitals. Clinicopathological data n = 467 treated Haukeland Oslo university hospitals January 2015 December 2017 was collected. Data included tumour location, promoter methylation O 6 methylguanine-DNA methyltransferase ( MGMT ) mutation isocitrate...
Glioblastoma (GBM) is the most aggressive brain malignancy in adults, where survival approximately 14.6 months. Novel therapies are urgently needed and immunotherapy has hailed a new dawn for treatment of solid tumors. Natural killer (NK) cells may be amenable therapeutic effectors against heterogeneous GBM, since they also do not require co-stimulation antigen specificity. However, it unclear how culture media routinely used pre-clinical studies affect GBM cell responses to NK mediated...
Glioblastoma cells assemble to a syncytial communicating network based on tumor microtubes (TMs) as ultra-long membrane protrusions. The relationship between architecture and transcriptional profile remains poorly investigated. Drugs that interfere with this connectivity such meclofenamate (MFA) may be highly attractive for glioblastoma therapy.
Chromatin structure and gene expression are regulated by posttranslational modifications (PTMs) on the N-terminal tails of histones. Mono-, di-, or trimethylation lysine residues histone methyltransferases (HKMTases) can have activating repressive functions depending position context modified lysine. In Arabidopsis, 9 H3 (H3K9me3) is mainly associated with euchromatin transcribed genes, although low levels this mark also detected at transposons repeat sequences. Besides evolutionarily...
Abstract The stem cell niche of the Arabidopsis (Arabidopsis thaliana) primary root apical meristem is composed quiescent (or organizing) center surrounded by (initial) cells for different tissues. Initial generate a population transit-amplifying that undergo limited number divisions before elongating and differentiating. It unclear whether these occur stochastically or in an orderly manner. Using thymidine analog 5-ethynyl-2′-deoxyuridine to monitor DNA replication meristems, we identified...
Resistance to temozolomide (TMZ) is due in part enhanced DNA repair mediated by high expression of O6-methyl guanine methyltransferase (MGMT) that often characterised unmethylated promoter. Here, we investigated pre-treatment glioblastoma (GBM) cells with the 26S-proteasome inhibitor bortezomib (BTZ) as a strategy interfere MGMT and thus sensitise them TMZ.Cell lines patient GBM-derived were examined vitro, latter also implanted orthotopically into NOD-SCID C.B.-Igh-1b/lcrTac-Prkdc mice...
Background: Natural killer (NK) cells are potential effectors in anti-cancer immunotherapy; however only a subset potently kills cancer cells. Here, we examined whether pretreatment of glioblastoma (GBM) with the proteasome inhibitor, bortezomib (BTZ), might sensitize tumour to NK cell lysis by inducing stress antigens recognized NK-activating receptors. Methods: Combination immunotherapy BTZ was studied vitro against GBM and GBM-bearing mouse model. Tumour were derived from primary GBMs...
By affecting immunological presentation, the presence of cytomegalovirus in some glioblastomas may impact progression. In this study, we examined a hypothesized role for natural killer (NK) cells impacting disease progression setting. We characterized 108 glioblastoma patients and 454 healthy controls HLA-A,-B,-C, NK-cell KIR receptors, CMV-specific antibodies correlated these metrics with clinical parameters. Exome sequences from large validation set control individuals were silico...
Glioblastomas (GBMs) are aggressive brain tumours with a dismal prognosis, despite combined surgery, radio- and chemotherapy. Close to 90 % of all GBMs harbour deregulated PI3K pathway, which is essential in regulating central cellular functions such as proliferation, cell growth, motility survival. Thus, represents potential target for molecular therapy GBM. We investigated the anti-tumour efficacy inhibitor buparlisib (NVP-BKM120) GBM lines vitro vivo, when treatment was initiated after...
Glioblastomas (GBMs) are highly malignant brain tumours with a poor prognosis, and current cytotoxic regimens provide only limited survival benefit. The PI3K/Akt/mTOR pathway has been an attractive target for therapy due to its high activation in GBMs as well other cancers. dual pan-PI3K/mTOR kinase inhibitor dactolisib (NVP-BEZ235) is anti-neoplastic compound currently under investigation. However, little known about efficacy human GBMs. We aimed at evaluating the of glioblastoma cells,...
Abstract Background Glioblastoma (GBM) is an aggressive malignant brain tumor where median survival approximately 15 months after best available multimodal treatment. Recurrence inevitable, largely due to O 6 methylguanine DNA methyltransferase ( MGMT ) that renders the tumors resistant temozolomide (TMZ). We hypothesized pretreatment with bortezomib (BTZ) 48 hours prior TMZ deplete levels would be safe and tolerated by patients recurrent GBM harboring unmethylated promoter. The secondary...
Introduction: Glioblastoma (GBM) is invariably resistant to temozolomide (TMZ) chemotherapy. Inhibiting the proteasomal pathway an emerging strategy accumulate damaged proteins and inhibit their lysosomal degradation. We hypothesized that pre-treatment of glioblastoma with bortezomib (BTZ) might sensitize by abolishing autophagy survival signals augment DNA damage apoptosis. Methods: P3 patient-derived cells, as well tumour cell lines U87, HF66, A172, T98G were investigated for clonogenic...
Human cytomegalovirus (HCMV) antigens in glioblastoma (GBM) present opportunities for personalised immunotherapy. However, their presence GBM tissue is still under debate, and evidence of impact on functional immune responses prognosis sparse. Here, we investigated the pp65 (UL83) immediate early 1 (IE-1) HCMV a cohort Norwegian patients (n = 177), using qPCR, immunohistochemistry, serology. status was then used to investigate whether viral influenced cell phenotype, infiltration, activation...
Little is known about the role of glial host cells in brain tumours. However, supporting stromal have been shown to foster tumour growth other cancers. We isolated from patient-derived glioblastoma (GBM) xenografts established GFP-NOD/scid mice. With simultaneous removal CD11b+ immune and CD31+ endothelial by fluorescence activated cell sorting (FACS), we obtained a population tumour-associated cells, TAGs, expressing markers terminally differentiaed types or progenitors. This was...
In eukaryotes, different chromatin states facilitate or repress gene expression and restrict the activity of transposable elements. Post-translational modifications (PTMs) amino acid residues on N-terminal tails histones are suggested to define such states. The histone lysine methyltransferase (HKMTase) SU(VAR)3-9 RELATED4 (SUVR4) Arabidopsis thaliana functions as a repressor transposon activity. Binding ubiquitin by WIYLD domain facilitates addition two methyl groups monomethylated 9 H3. By...
Abstract The microenvironment and architecture of peritumoral tissue have been suggested to affect permissiveness for infiltration malignant cells. Astrocytes constitute a heterogeneous population cells linked proliferation, migration, drug sensitivity glioblastoma (GBM) Through double‐immunohistochemical staining platelet‐derived growth factor receptor α (PDGFRα) glial fibrillary acidic protein (GFAP), this study explored the intercase variability among 45 human GBM samples regarding...
Tumor burden assessment is essential for radiation therapy (RT), treatment response evaluation, and clinical decision-making. However, manual tumor delineation remains laborious challenging due to radiological complexity. The objective of this study was investigate the feasibility HD-GLIO tool, an ensemble pre-trained deep learning models based on nnUNet-algorithm, segmentation, prediction, its potential deployment.We analyzed predicted contrast-enhanced (CE) non-enhancing (NE) output in 49...
Abstract Background: Glioblastoma (GBM) is the most malignant primary brain tumor with a median survival of 15 months despite aggressive multimodal treatment. There an urgent need for novel drug discovery GBM. CSPG4/NG2 transmembrane proteoglycan validated target, upregulated in 50% GBM patient tumours, drives progression and independently prognostic poor survival. We have recently identified cancer specific 13 bp frameshift deletion gene (CSPG4/NG2del13), which leads to reduced protein...
Abstract Background: Glioblastoma (GBM) has dismal prognosis, where median survival is approximately 12 months for patients harboring unmethylated O6−methylguanine DNA methyltransferase (MGMT) promoter (uMGMT) due to temozolomide (TMZ) chemotherapy resistance. In preclinical studies, we showed that sequential administration of bortezomib (BTZ) prior TMZ depleted MGMT protein, abrogated autophagic flux and sensitized uMGMT GBM cells TMZ. Thus, a phase I/II was launched investigate clinical...
Abstract BACKGROUND Glioblastoma (GBM) is amongst the deadliest malignancies in adults, but especially for patients with unmethylated MGMT promoter (uMGMT) who gain limited benefit from standard treatment. We previously demonstrated that proteosome inhibitor bortezomib (BTZ), inhibited NFkB activation,depleted protein and sensitized uMGMT GBM cells to Temozolomide (TMZ). Thus, a phase I/II trial testing sequential combination BTZ+TMZ was launched investigate safety clinical benefit. METHODS...
Abstract Background: Glioblastoma with unmethylated O6-methyl guanine DNA methyltransferase (MGMT) promoter is highly resistant to temozolomide (TMZ) chemotherapy. Strategies that ameliorate drug resistance are sorely needed. Recent trials of the proteasome inhibitor bortezomib (BTZ) (Velcade) in combination various drugs failed due inappropriate schedule timing and dosing. We hypothesized pretreatment BTZ prior TMZ administration may sensitize glioblastoma cell Methods: investigated...
Abstract The neurodevelopmental transcription factor POU3F2 (also called OCT7 / BRN2) is expressed during neurogenesis. Moreover, expression has been reported as a promoter of proliferation and invasion in malignant melanoma the skin. Since both melanomas CNS-malignancies arise organs neuro-ectodermal origin, we investigated whether human gliomas role glioma tumorigenesis. We performed immunohistochemistry 149 grade II-IV from our tumor bank, subsequently western blots qPCR 12 samples each...