A5038714504- Ovarian cancer diagnosis and treatment
- Cancer-related molecular mechanisms research
- Angiogenesis and VEGF in Cancer
- Molecular Biology Techniques and Applications
- Lipid metabolism and disorders
- Virus-based gene therapy research
- Genomics, phytochemicals, and oxidative stress
- Atherosclerosis and Cardiovascular Diseases
- Peroxisome Proliferator-Activated Receptors
- Coronary Interventions and Diagnostics
- Heme Oxygenase-1 and Carbon Monoxide
- RNA Interference and Gene Delivery
- Cholesterol and Lipid Metabolism
- Endoplasmic Reticulum Stress and Disease
- Immune cells in cancer
- RNA Research and Splicing
- CAR-T cell therapy research
- Hippo pathway signaling and YAP/TAZ
- Mitochondrial Function and Pathology
- Lipid Membrane Structure and Behavior
- Autophagy in Disease and Therapy
- Cancer, Lipids, and Metabolism
- CRISPR and Genetic Engineering
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Nuclear Receptors and Signaling
Minerva Foundation
2016-2022
Kuopio University Hospital
2008-2021
University of Eastern Finland
2008-2020
Institute for Molecular Science
2008
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA)
2008
Medical University of Vienna
2008
Tohoku University
2008
Electrophilic fatty acid derivatives, including nitrolinoleic and nitro-oleic (OA-NO2), can mediate anti-inflammatory pro-survival signaling reactions. The transcription factor Nrf2, activated by electrophilic acids, suppresses redox-sensitive pro-inflammatory gene expression protects against vascular endothelial oxidative injury. It was therefore postulated that activation of Nrf2 OA-NO2 accounts in part for its actions, motivating the characterization Nrf2-dependent -independent effects on...
Besides their well-characterized proinflammatory and proatherogenic effects, oxidized phospholipids, such as oxPAPC (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphocholine) have been shown to beneficial responses in vascular cells via induction of antioxidant enzymes heme oxygenase-1. We therefore hypothesized that could evoke a general cytoprotective response activation antioxidative transcription factor Nrf2. Here, we show increases nuclear accumulation Using the small interfering...
Mitochondria are dynamic organelles essential for cell survival whose structural and functional integrity rely on selective regulated transport of lipids from/to the endoplasmic reticulum (ER) across mitochondrial intermembrane space. As they not connected by vesicular transport, exchange between ER mitochondria occurs at membrane contact sites. However, mechanisms proteins involved in these processes only beginning to emerge. Here, we show that main physiological localization lipid transfer...
In many malignancies including ovarian cancer, different angiogenic factors have been related to poor prognosis. However, data on their relations each other or importance as a prognostic factor in cancer is missing. Therefore, we investigated the expressions of VEGF-A, VEGF-C, and VEGF-D, receptors VEGFR1, VEGFR2, VEGFR3 patients with malignant epithelial neoplasms. We further compared expression levels between primary tumors distant omental metastases.This study included 86 16 metastases....
The role of vascular endothelial growth factor (VEGF-A) in atherogenesis has remained controversial. We addressed this by comparing the effects adenoviral VEGF-A gene transfer on atherosclerosis and lipoproteins ApoE−/−, LDLR−/−, LDLR−/−ApoE−/−, LDLR−/−ApoB100/100 mice. After 4 weeks western diet, systemic was performed with hVEGF-A or control vectors. Effects atherosclerotic lesion area composition, lipoprotein profiles, plasma lipase (LPL) activity were examined. On day 4, induced...
Oxidized phospholipids and microRNAs (miRNAs) are increasingly recognized to play a role in endothelial dysfunction driving atherosclerosis. NRF2 transcription factor is one of the key mediators effects oxidized phospholipids, but gene regulatory mechanisms underlying process remain obscure. Here, we investigated genome-wide on transcriptional regulation human umbilical vein cells aortic with special focus miRNAs.We integrated data from HiC, ChIP-seq, ATAC-seq, GRO-seq, miRNA-seq, RNA-seq...
Vascular endothelial growth factor A (VEGF-A) is a master regulator of angiogenesis, vascular development and function. In this study we investigated the transcriptional regulation VEGF-A-responsive genes in primary human aortic cells (HAECs) umbilical vein (HUVECs) using genome-wide global run-on sequencing (GRO-Seq). We demonstrate that half VEGF-A-regulated gene promoters are characterized by transcriptionally competent paused RNA polymerase II (Pol II). show transition into productive...
We aimed to investigate whether apparent diffusion coefficients (ADCs) measured by 3.0T diffusion-weighted magnetic resonance imaging (DWI) associate with histological aggressiveness of ovarian cancer (OC) or predict the clinical outcome. This prospective study enrolled 40 patients primary OC, treated 2011-2014. DWI was performed prior surgery. Two observers used whole lesion single plane region interest (WLsp-ROI) and five small ROIs (S-ROI) analyze ADCs. Samples from tumours metastases...
ORP2 is implicated in cholesterol transport, triglyceride metabolism, and adrenocortical steroid hormone production. We addressed function hepatocytes by generating ORP2-knockout (KO) HuH7 cells CRISPR-Cas9 gene editing, followed analyses of transcriptome, F-actin morphology, migration, adhesion, proliferation. RNA sequencing ORP2-KO revealed >2-fold changes 579 mRNAs. The Ingenuity Pathway Analysis (IPA) uncovered alterations the following functional categories: cellular movement, cell-cell...
Lipolytic modification of LDL particles by SMase generates aggregates with a strong affinity for human arterial proteoglycans and may so enhance retention in the wall. Here, we evaluated effects apoA-I mimetic peptide 4F on structural functional properties SMase-modified particles. without were incubated SMase, after which their aggregation, structure, proteoglycan binding analyzed. At molar ratio L-4F to apoB-100 2.5 20:1, dose-dependently inhibited SMase-induced aggregation. aggregation...
High grade serous ovarian carcinoma (HGSOC) is the most common subtype of epithelial cancers (EOC) with poor prognosis. In cases EOC widely disseminated at time diagnosis. Despite optimal cytoreductive surgery and chemotherapy patients develop chemoresistance, 5-year overall survival being only 25-35%.Here we analyzed gene expression profiles 10 primary HGSOC tumors related omental metastases using RNA sequencing identified 100 differentially expressed genes.The genes were associated...
Oxysterol-binding protein-related protein 2 (ORP2), a cholesterol-PI(4,5)P2 countercurrent transporter, was recently identified as novel regulator of plasma membrane (PM) cholesterol and PI(4,5)P2 content in HeLa cells. Here, we investigate the role ORP2 endothelial cell (EC) distribution, angiogenic signaling, angiogenesis. We show that knock-down modifies distribution accessible to D4H probe, between late endosomes PM. Depletion from ECs inhibits their tube formation capacity, alters gene...
During angiogenesis, endothelial cells form protrusive sprouts and migrate towards the angiogenic stimulus. In this study, we investigate role of endoplasmic reticulum (ER)-anchored protein, Protrudin, in cell protrusion, migration angiogenesis. Our results demonstrate that Protrudin regulates tube formation primary cells, Human umbilical vein (HUVECs). Analysis RNA sequencing data its experimental validation revealed as a prominent cellular function affected HUVECs subjected to knockdown....
Background Antiangiogenic therapy, although part of standard treatment in ovarian cancer, has variable efficacy. Furthermore, little is known about the prognostic biomarkers and factors influencing angiogenesis cancer tissue. We evaluated expression angiopoietin-2 two endothelial tyrosine kinase receptors, Tie-1 Tie-2, assessed their value prediction survival patients with malignant epithelial cancer. also compared these between primary high grade serous tumors distant metastasis. Materials...