A5089337607- PI3K/AKT/mTOR signaling in cancer
- BRCA gene mutations in cancer
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Angiogenesis and VEGF in Cancer
- TGF-β signaling in diseases
- Cancer, Hypoxia, and Metabolism
- Breast Cancer Treatment Studies
- Cancer Cells and Metastasis
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- Nanoplatforms for cancer theranostics
- Kruppel-like factors research
- Cancer Treatment and Pharmacology
- Synthesis and biological activity
- HER2/EGFR in Cancer Research
- Cellular Mechanics and Interactions
- Cancer Genomics and Diagnostics
- Nanoparticle-Based Drug Delivery
- CRISPR and Genetic Engineering
- Fibroblast Growth Factor Research
- Lymphatic System and Diseases
- Cell Adhesion Molecules Research
- Cancer, Lipids, and Metabolism
University of Bergen
2013-2024
Haukeland University Hospital
2012-2024
Harvard University
2009-2018
Beth Israel Deaconess Medical Center
2008-2018
The University of Texas MD Anderson Cancer Center
2018
Weatherford College
2012-2014
Lymphatic remodeling in tumor microenvironments correlates with progression and metastasis, local lymphatic vessels play complex poorly understood roles immunity. Tumor lymphangiogenesis is associated increased immune suppression, yet are required for fluid drainage cell trafficking to lymph nodes, where adaptive responses mounted. Here, we examined the contribution of inflammation immunity using a mouse model that lacks dermal (K14-VEGFR3-Ig mice). Melanomas implanted these mice grew...
•We observed an objective response to olaparib in 18 out of 32 (56%) unselected, primary triple negative breast cancers.•Homologous recombination deficiency (HRD) was determined by targeted DNA sequencing and BRCA1 methylation.•HRD predictive present 16 responders.•HRD also beyond germline BRCA1/2 gPALB2 mutations; 12 14 responders.•Olaparib associated with minor side-effects did not influence subsequent tolerance chemotherapy. BackgroundThe antitumor efficacy PARP inhibitors (PARPi) for...
Germline BRCA1/2 testing of breast and ovarian cancer patients is growing rapidly as the result affects both treatment prevention in relatives. Through DNA-BONus study we offered familial risk assessment to all new with (N=893) or (N=122) diagnosed between September 2012 April 2015, irrespective family history age, without prior face-to-face genetic counselling. was accepted by 405 (45.4%) 83 (68.0%) cancer, respectively. A pathogenic variant found 7 (1.7%) 19 (22.3%) patients. In...
Importance About 25% of all triple-negative breast cancers (TNBCs) and 10% to 20% high-grade serous ovarian (HGSOCs) harbor BRCA1 promoter methylation. While constitutional methylation has been observed in normal tissues some individuals, the potential role tissue as a risk factor for incident TNBC or HGSOC is unknown. Objective To assess association between white blood cell subsequent HGSOC. Design, Setting, Participants This case-control study included women who were participating Women’s...
Poly(ADP)ribosylation inhibitors (PARPis) are toxic to cancer cells with homologous recombination (HR) deficiency but not HR-proficient in the tumor microenvironment (TME), including tumor-associated macrophages (TAMs). As TAMs can promote or inhibit growth, we set out examine effects of PARP inhibition on BRCA1-related breast (BC). The PARPi olaparib causes reprogramming toward higher cytotoxicity and phagocytosis. A PARPi-related surge NAD+ increases glycolysis, blunts oxidative...
Abstract Purpose: The identification of patients with homologous recombination deficiency (HRD) beyond BRCA1/2 mutations is an urgent task, as they may benefit from PARP inhibitors. We have previously developed a method to detect mutational signature 3 (Sig3), termed SigMA, associated HRD clinical panel sequencing data, that able reliably the limited data derived gene-focused sequencing. Experimental Design: apply this two independent datasets: (i) high-grade serous ovarian cancer and...
Abstract Background Normal cell BRCA1 epimutations have been associated with increased risk of triple-negative breast cancer (TNBC). However, the fraction TNBCs that may as their underlying cause is unknown. Neither are time occurrence and potential inheritance patterns established. Methods To address these questions, we analyzed methylation status in tissue matched white blood cells (WBC) from 408 patients 411 primary cancers, including 66 TNBCs, applying a highly sensitive sequencing...
Tumstatin is an angiogenesis inhibitor that binds to αvβ3 integrin and suppresses tumor growth. Previous deletion mutagenesis studies identified a 25-aa fragment of tumstatin (tumstatin peptide) with in vitro antiangiogenic activity. Here, we demonstrate systemic administration this peptide inhibits growth angiogenesis. Site-directed amino acids L, V, D as essential for the activity tumstatin. The on proliferating endothelial cells localizes select endothelium vivo . Using 3D molecular...
A NOD/Scid mouse expressing enhanced green fluorescent protein (eGFP) is described, in which human and tumors marked with red can be established vivo, both at subcutaneous orthotopic locations. Using light microscopy as well multiphoton confocal techniques, we visualized detail the intricate colocalization of tumor host cells situ. Moreover, using fluorescence-activated cell sorting (FACS), were able to completely separate from cells, thus providing a system for detailed cellular molecular...
VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy patients with metastatic melanoma.Thirty-five melanoma progression were enrolled this phase II, single arm trial. Each patient received 10 mg/kg q14 d until intolerable toxicity or disease occurred. Clinical was evaluated as objective response, control (DC), and survival. observed one complete (3%) 5 partial (14%) responses. In addition, experienced stable >6 months...
Abstract Background Locally advanced breast cancer is a heterogeneous disease with respect to response neoadjuvant chemotherapy (NACT) and survival. It currently not possible accurately predict who will benefit from the specific types of NACT. DNA methylation an epigenetic mechanism known play important role in regulating gene expression may serve as biomarker for treatment We investigated potential prognostic marker long-term survival (> 5 years) after NACT cancer. Methods profiles...
PURPOSE Homologous recombination deficiency (HRD) is highly prevalent in triple-negative breast cancer (TNBC) and associated with response to PARP inhibition (PARPi). Here, we studied the prevalence of HRD non-TNBC assess potential for PARPi a wider group patients cancer. METHODS status was established using targeted gene panel sequencing (360 genes) BRCA1 methylation analysis pretreatment biopsies from 201 primary phase II PETREMAC trial (ClinicalTrials.gov identifier: NCT02624973 )....
Angiogenesis and co-optive vascular remodeling are prerequisites of solid tumor growth. Vascular heterogeneity, notably perivascular composition, may play a critical role in determining the rate cancer progression. The contribution pericyte heterogeneity to progression therapy response is unknown. Here, we show that angiopoietin-2 (Ang2) orchestrates breast with an effect on metastatic disease chemotherapy. Using multispectral imaging human specimens, report as defined by ratio PDGFRβ–...
Abstract Background Current analytical routine methods lack the sensitivity to monitor plasma estrogen levels in breast cancer patients treated with aromatase inhibitors. Such monitoring is warranted for premenopausal an inhibitor and LH-releasing hormone analogue particular. Therefore, we aimed develop a tandem mass spectroscopy combined liquid chromatography (LC-MS/MS) method estradiol (E2) estrone (E1) use sub-picomolar range. Method Calibrators, quality controls (QC), or serum samples...
Transcripts derived from the PTEN pseudogene (PTENP1) function as decoys to adsorb miRNAs targeting tumor suppressor for degradation, and PTENP1 upregulation is known inhibit growth in preclinical cancer models. Here, 3'UTR transduction influences PTEN, AKT/mTOR signaling, progression estrogen receptor (ER)-positive -negative breast cells. decreases gene expression ER-positive MCF7 T47D human carcinoma cells accelerates vivo Of note, significantly ERα (ESR1) mRNA protein levels xenografts...
Abstract Background Subclonal evolution during primary breast cancer treatment is largely unexplored. We aimed to assess the dynamic changes in subclonal composition of treatment-naïve cancers neoadjuvant chemotherapy. Methods performed whole exome sequencing tumor biopsies collected before, at therapy switch, and after with sequential epirubicin docetaxel monotherapy 51 out 109 patients cancer, who were included a prospectively registered, single-arm phase II trial. Results There was...
// Eli Sihn Samdal Steinskog 1 , Solfrid Johanne Sagstad Marek Wagner Tine Veronica Karlsen Ning Yang Carl Erik Markhus Synnøve Yndestad 2, 3 Helge Wiig Hans Petter Eikesdal Department of Biomedicine, University Bergen, Norway 2 Section Oncology, Clinical Science, Haukeland Hospital, Correspondence to: Eikesdal, email: hans.eikesdal@k2.uib.no Keywords: cancer, lymphangiogenesis, Chy mice, tumor associated macrophages, IL-6 Received: January 05, 2016     Accepted:...
PTEN is an important tumor suppressor in breast cancer. Here, we examined the prognostic and predictive value of pseudogene (PTENP1) gene expression patients with locally advanced cancer given neoadjuvant chemotherapy.The association between pretreatment PTENP1 expression, response to chemotherapy, recurrence-free disease-specific survival was assessed 364 doxorubicin, 5-fluorouracil/mitomycin, or epirubicin versus paclitaxel three phase II prospective studies. Further, protein...