A5023172362- Enzyme function and inhibition
- Cancer, Hypoxia, and Metabolism
- Amino Acid Enzymes and Metabolism
- Ion Transport and Channel Regulation
- Polyamine Metabolism and Applications
- Nitric Oxide and Endothelin Effects
- Biochemical and Molecular Research
- Nanoplatforms for cancer theranostics
- Ion channel regulation and function
- Sulfur Compounds in Biology
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- 3D Printing in Biomedical Research
- Melanoma and MAPK Pathways
- Synthesis and Catalytic Reactions
- Cancer, Stress, Anesthesia, and Immune Response
- Tryptophan and brain disorders
- Histone Deacetylase Inhibitors Research
- Advanced Biosensing Techniques and Applications
- Epigenetics and DNA Methylation
- Polymer Surface Interaction Studies
- Adenosine and Purinergic Signaling
- Bone Tissue Engineering Materials
- Renal cell carcinoma treatment
- Advanced biosensing and bioanalysis techniques
- Neuroscience and Neuropharmacology Research
Slovak Academy of Sciences
2010-2024
Institute of Virology of the Slovak Academy of Sciences
2015-2024
Biomedical Research Center of the Slovak Academy of Sciences
2016-2024
Centre for Advanced Material Application of the Slovak Academy of Sciences
2023-2024
University of Liège
2011
Gembloux Agro-Bio Tech
2011
University of Florence
2011
University of Glasgow
2006-2010
Comenius University Bratislava
2000
Carbonic anhydrase IX (CA IX) is a hypoxia-induced cell surface enzyme expressed in solid tumors, and functionally involved acidification of extracellular pH destabilization intercellular contacts. Since both acidosis reduced adhesion facilitate invasion metastasis, we investigated the role CA migration, which promotes metastatic cascade. As demonstrated here, ectopically increases scattering, wound healing transwell migration MDCK cells, while an inactive variant lacking catalytic domain...
In the hypoxic regions of a tumor, carbonic anhydrase IX (CA IX) is an important transmembrane component pH regulatory machinery that participates in bicarbonate transport. Because tumor has implications for growth, invasion, and therapy, determining basis contributions CA to microenvironment could lead new fundamental practical insights. Here, we report Thr443 phosphorylation at intracellular domain by protein kinase A (PKA) critical its activation cells, with fullest activity also...
Carbonic anhydrase IX is a hypoxia-induced transmembrane enzyme linked with solid tumors. It catalyzes the reversible hydration of CO2 providing bicarbonate ions for intracellular neutralization and protons extracellular acidosis, thereby supporting tumor cell survival invasiveness. CA only human isoform containing proteoglycan (PG) domain in its part. The PG appears to enhance catalytic activity mediate binding matrix. Moreover, manipulation level by siRNA or overexpression modulates...
Lung cancer represents the leading cause of cancer-related deaths.Non-small cell lung (NSCLC), most common form cancer, is a molecularly heterogeneous disease with intratumoral heterogeneity and significant mutational burden associated clinical outcome.Tumor microenvironment (TME) plays fundamental role in initiation progression primary de novo significantly influences response tumor cells to therapy.Hypoxia, an integral part serious phenomenon, increased genetic instability more aggressive...
Carbonic anhydrase IX (CA IX) is regarded as one of the most prominent markers tumor hypoxia with potential to serve a diagnostic biomarker, prognostic indicator well therapeutic target. The aim present study was perform an in-depth analysis CA expression in blood and tissue samples evaluate significance status for different renal cell carcinomas (RCCs). determined from 74 kidney cancer patients using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay...
Tumor metastasis is tightly linked with invasive membrane protrusions, invadopodia, formed by actively invading tumor cells. Hypoxia and pH modulation play a role in the invadopodia formation their matrix degradation ability. Tumor-associated carbonic anhydrase IX (CAIX), induced hypoxia, essential for regulation migration, predisposing it as an active component of invadopodia. To investigate this assumption, we employed silencing inhibition CA9, isolation assay. Quail chorioallantoic...
Acquired drug resistance and metastasis in breast cancer (BC) are coupled with epigenetic deregulation of gene expression. Epigenetic drugs, aiming to reverse these aberrant transcriptional patterns sensitize cells other therapies, provide a new treatment strategy for drug-resistant tumors. Here we investigated the ability DNA methyltransferase (DNMT) inhibitor decitabine (DAC) increase sensitivity BC anthracycline antibiotic doxorubicin (DOX). Three cell lines representing different...
Hypoxia is a phenomenon often arising in solid tumours, linked to aggressive malignancy, bad prognosis and resistance therapy. Hypoxia-inducible factor-1 has been identified as key mediator of cell tissue adaptation hypoxic conditions through transcriptional activation many genes involved glucose metabolism other cancer-related processes, such angiogenesis, survival invasion. Cyclic adenosine 3'5'-monophosphate one the most ancient evolutionarily conserved signalling molecules cAMP/PKA...
Abstract A biodegradable substrate with a regular array of nanopillars fabricated by electron‐beam lithography and hot embossing is used to address the mechanisms nanotopographical control cell behavior. Two different lines cultured on show striking differences in coverage. These changes are topography‐ cell‐dependent, not mediated air bubbles trapped nanopattern. For first time, strong cell‐selective effect same nanotopography has been clearly demonstrated large area; while fibroblast...
Carbonic anhydrase IX (CA IX) is a transmembrane protein affecting pH regulation, cell migration/invasion, and survival in hypoxic tumors. Although the pathways related to CA have begun emerge, molecular partners mediating its functions remain largely unknown. Here we characterize interactome HEK-293 cells. Most of identified IX-binding contain HEAT/ARM repeat domain belong nuclear transport machinery. We show that interaction with two these proteins, namely XPO1 exportin TNPO1 importin,...
G250 (Girentuximab) is a chimeric IgG1 monoclonal antibody (MAb) currently being evaluated as an immunotherapy for kidney cancer. It targets carbonic anhydrase protein (CA Ⅸ), transmembrane (CA) isoform, which regulated by VHL/HIF pathway and hence expressed in the majority of renal cell carcinomas (RCCs) well hypoxic non‑RCC tumours. CA Ⅸ functions pH regulation migration/invasion, supports tumour survival hypoxia and/or acidosis. contains highly active extracellular catalytic domain...
// Sona Hudecova 1 , Jana Markova Veronika Simko 2 Lucia Csaderova Tibor Stracina 3 Marta Sirova Michaela Fojtu Eliska Svastova Paulina Gronesova 4 Michal Pastorek Marie Novakova Dana Cholujova Juraj Kopacek Silvia Pastorekova Jan Sedlak Olga Krizanova Institute of Clinical and Translational Research, Biomedical Research Center, SAS, Bratislava, Slovakia Virology, Department Physiology, Faculty Medicine, Masaryk University, Brno, Czech Republic Cancer Institute, Correspondence to: Krizanova,...
Hypoxia in the tumor microenvironment (TME) is often main factor cancer progression. Moreover, low levels of oxygen tissue may signal that first- or second-line therapy will not be successful. This knowledge triggers inevitable search for different kinds treatment successfully cure aggressive tumors. Due to its exclusive expression on cells, carbonic anhydrase IX belongs group most precise targets hypoxic CA possesses several exceptional qualities predetermine crucial role targeted therapy....
To investigate an interaction between the calcium and sulphide signalling pathways, particularly effects of slow H2 S release donor morpholin-4-ium-4-methoxyphenyl-(morpholino)-phosphinodithioate (GYY4137) on expression inositol 1,4,5-trisphosphate receptors (IP3 R) with possible impact apoptosis induction in HeLa cells.Gene expression, Western blot analysis, determination by Annexin-V-FLUOS drop mitochondrial membrane potential...
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are specific types of neuroendocrine tumors that originate in the adrenal medulla or sympathetic/parasympathetic paraganglia, respectively. Although these intensively studied, a very effective treatment for metastatic PHEO PGL has not yet been established. Preclinical evaluations novel therapies much required. Therefore, this study we tested effect triptolide (TTL), potent nuclear factor-kappaB (NF-κB) inhibitor, on cell membrane...
Carbonic anhydrase IX (CA IX) is recognized as an excellent marker of hypoxia and adverse prognostic factor in solid tumors, including breast cancer (BC). Clinical studies confirm that soluble CA (sCA IX), shed into body fluids, predicts the response to some therapeutics. However, not included clinical practice guidelines, possibly due a lack validated diagnostic tools. Here, we present two novel tools-a monoclonal antibody for detection by immunohistochemistry ELISA kit sCA plasma-validated...
Resistance to chemotherapy represents a persisting medical problem, ranking among main causes of failure and cancer mortality. There is possibility utilize repurpose already existing therapeutics which were not primarily intended for oncological treatment. Overactivation adrenergic receptors signaling dysregulation promotes tumor progression, metastatic potential, immune system evasion, angiogenesis drug resistance. The non-selective beta-blocker propranolol, approved in infantile...
Photothermal therapy (PTT) mediated at the nanoscale has a unique advantage over currently used cancer treatments, by being spatially highly specific and minimally invasive. Although PTT combats traditional tumor treatment approaches, its clinical implementation not yet been successful. The reasons for disadvantage include an insufficient efficiency or low accumulation. Here, we present promising new platform combining recently emerged two-dimensional (2D) inorganic nanomaterial, MoOx,...
Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that present in many types of solid tumors. Expression CA driven predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain intracellular pH homeostasis under hypoxic conditions, resulting acidification tumor microenvironment. Carnosine (β-alanyl-L-histidine) an anti-tumorigenic agent inhibits proliferation cancer cells. In this study, we investigated role carnosine-mediated antitumor activity whether underlying...
S100P belongs to the S100 family of calcium-binding proteins regulating diverse cellular processes. Certain members (S100A4 and S100B) are associated with cancer used as biomarkers metastatic phenotype. Also is abnormally expressed in tumors implicated migration-invasion, survival, response therapy. Here we show that binds tumor suppressor protein p53 well its negative regulator HDM2, this interaction perturbs p53-HDM2 binding increases level. Paradoxically, S100P-induced unable activate...