A5091450481- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Cells and Metastasis
- CAR-T cell therapy research
- Cancer Research and Treatments
- DNA Repair Mechanisms
- Liver Disease and Transplantation
- Neuropeptides and Animal Physiology
- Liver Disease Diagnosis and Treatment
- Pluripotent Stem Cells Research
- Immunotherapy and Immune Responses
- Neuroendocrine Tumor Research Advances
- Epigenetics and DNA Methylation
- Helicobacter pylori-related gastroenterology studies
- Microtubule and mitosis dynamics
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Tissue Engineering and Regenerative Medicine
- Eosinophilic Esophagitis
- Receptor Mechanisms and Signaling
- Renal and related cancers
- Mast cells and histamine
- Cancer Immunotherapy and Biomarkers
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
Danish Cancer Society
2014-2024
University of Pennsylvania Health System
2018
University of Washington Medical Center
2006-2016
Science for Life Laboratory
2016
Karolinska Institutet
2016
University of Washington
2007-2015
Institute of Molecular and Translational Medicine
2011
Unit of Virus Host Cell Interactions
2011
Palacký University Olomouc
2011
Medical Genetics Center
2006-2009
In our studies of ovarian cancer cells we have identified subpopulations that are in a transitory E/M hybrid stage, i.e. simultaneously express epithelial and mesenchymal markers. not homogenous but, vitro vivo, contain subsets can be distinguished based on number phenotypic features, including the subcellular localization E-cadherin, expression levels Tie2, CD133, CD44. A cellular subset (E/M-MP) (membrane E-cadherinlow/cytoplasmic E-cadherinhigh/CD133high, CD44high, Tie2low) is highly...
Despite significant improvement in modalities for treatment of cancer that led to a longer survival period, the death rate patients with solid tumors has not changed during last decades. Emerging studies have identified several physical barriers limit therapeutic efficacy agents such as monoclonal antibodies, chemotherapeutic agents, anti-tumor immune cells, and gene therapeutics. Most are epithelial origin and, although malignant cells de-differentiated, they maintain intercellular...
A genome-wide screening study for identification of hypermethylated genes in invasive cervical cancer (ICC) was carried out to augment our previously discovered panel three found be useful detection ICC and its precursor neoplasia. Putatively silenced were reactivated four cell lines by treatment with 5-aza-2'-deoxycytidine trichostatin identified on expression microarrays. Thirty-nine the 235 up-regulated multiple further examined determine methylation status associated CpG islands. The...
CD46 is used by human group B adenoviruses (Ads) as a high-affinity attachment receptor. Here we show evidence that several Ads utilize an additional receptor for infection of cells, which different from CD46. We tentatively named this X. Competition studies with unlabeled and labeled Ads, recombinant Ad fiber knobs, soluble antibodies revealed three subgroups in terms their usage. Group I (Ad16, -21, -35, -50) nearly exclusively uses II (Ad3, -7p, -14) utilizes X not III (Ad11p) both the...
Baculovirus vectors are able to transduce a large variety of mammalian cell types and express transgenes placed under the control heterologous promoters. In this study, we evaluated potential baculovirus for malaria vaccination. To induce efficient CD4(+) CD8(+) T-cell responses, produced series that display Plasmodium falciparum circumsporozoite (CS) protein in virion envelope and/or allow CS expression upon transduction cells. We found can professional antigen-presenting cells trigger...
Topoisomerase IIβ-binding protein 1 (TOPBP1) participates in DNA replication and damage response; however, its role repair relevance for human cancer remain unclear. Here, through an unbiased small interfering RNA screen, we identified validated TOPBP1 as a novel determinant whose loss sensitized cells to olaparib, inhibitor of poly(ADP-ribose) polymerase. We show that acts homologous recombination (HR) repair, impacts olaparib response, exhibits aberrant patterns subsets ovarian carcinomas....
Abstract Accumulating data indicate that tumor-infiltrating regulatory T cells (Treg) are present in human tumors and locally suppress antitumor immune cells. In this study, we found an increased Treg/CD8 ratio breast cervical cancers. A similar intratumoral lymphocyte pattern was observed a mouse model for cancer (TC-1 cells). model, systemic Treg depletion inefficient controlling tumor growth. Furthermore, CTL-associated antigen-4 (CTLA-4) blockade, approach can induce immunity other...
Abstract The efficacy of monoclonal antibodies (mAb) used to treat solid tumors is limited by intercellular junctions which tightly link epithelial tumor cells each another. In this study, we define a small, recombinant adenovirus serotype 3-derived protein, termed junction opener 1 (JO-1), binds the protein desmoglein 2 (DSG2). mouse xenograft models employing Her2/neu- and EGFR-positive human cancer cell lines, JO-1 mediated cleavage DSG2 dimers activated intracellular signaling pathways...
We studied the susceptibility of primary ovarian cancer cells to oncolytic adenoviruses. Using gene expression profiling either resistant or susceptible viral oncolysis, we discovered that epithelial phenotype represents a barrier infection by commonly used adenoviruses targeted coxsackie-adenovirus receptor CD46. Specifically, found these adenovirus receptors were trapped in tight junctions and not accessible for virus binding. Accessibility was critically linked depolarization loss...
Recent attempts to circumvent the limitations of adenovirus (Ad) vectors derived from species C serotype Ad5 have focused on use alternative human serotypes. These new serotypes multiple benefits including a low prevalence neutralizing antibodies in humans and alternate tropisms. To investigate characteristics alternatives vectors, we compared biodistribution safety Ads B (Ad3, 11p, 35), (Ad5), E (Ad4), F (Ad41), or chimeric viruses containing Ad11 Ad35 fibers (Ad5/11 Ad5/35), after...
Antihistamines with cationic amphiphilic drug (CAD) characteristics induce cancer-specific cell death in experimental studies. Epidemiologic evidence is, however, limited. In a Danish nationwide cohort of ovarian cancer patients diagnosed during 2000-2015 (n = 5075), we evaluated the association between filled antihistamine prescriptions and mortality. We used Cox regression models to estimate hazard ratios (HRs) 95% confidence intervals (CIs) for an vitro viability assay, three lines after...
In contrast to commonly used serotype 5-based adenovirus (Ad) vectors, Ad's containing fibers derived from B-group 35 (Ad5/35) efficiently transduce human DCs ex vivo and appear target antigen-presenting cells after intravenous injection into baboons. Based on this, Ad5/35 vectors could be valuable tools for immunotherapy vaccination. On the other hand, a number of studies indicate that signaling through Ad receptor, CD46, can cause tolerance or immunosuppression. Since mice do not express...
Caspase-8 is a cysteine protease historically regarded as anti-neoplastic protein, thanks to its role in apoptosis. However, expression retained or even enhanced several tumors, including glioblastoma (GBM), where it plays pro-tumor functions. We previously reported that negative prognostic factor and contributes resistance against DNA damaging agents, such ionizing radiations (IR) Temozolomide, commonly used standard GBM treatment. therefore investigated whether may sustain repair pathways...
Abstract Cancer cells are dependent on cholesterol, and they possess strictly controlled cholesterol homeostasis mechanisms. These allow them to smoothly switch between synthesis uptake fulfill their needs adapt environmental changes. Here we describe a mechanism of how cancer employ oncogenic growth factor signaling promote utilization extracellular via Myeloid Zinc Finger 1 (MZF1)-mediated Niemann Pick C1 (NPC1) expression upregulated macropinocytosis. Expression p95ErbB2, highly...