TY - JOUR AU - Isotta, Sturniolo AU - Csongor, Váróczy AU - Ákos, Máté Bede AU - Hegedűs, Csaba AU - Demény, Máté Ágoston AU - Virág, László TI - Quantifying antibody-dependent cellular cytotoxicity in a tumor spheroid model : application for drug discovery JF - JOVE-JOURNAL OF VISUALIZED EXPERIMENTS J2 - JOVE-J VIS EXP PY - 2024 SN - 1940-087X UR - https://m2.mtmt.hu/api/publication/34820104 ID - 34820104 LA - English DB - MTMT ER - TY - JOUR AU - Sturniolo, I AU - Váróczy, Cs AU - Regdon, Zsolt AU - Mázló, A AU - Muzsai, Sz AU - Bácsi, A AU - Intili, G AU - Hegedűs, Csaba AU - Boothby, MR AU - Holechek, J AU - Ferraris, D AU - Schüler, H AU - Virág, László TI - PARP14 contributes to the development of the tumor-associated macrophage phenotype JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 7 SP - 1 EP - 21 PG - 21 SN - 1661-6596 DO - 10.3390/ijms25073601 UR - https://m2.mtmt.hu/api/publication/34754751 ID - 34754751 LA - English DB - MTMT ER - TY - JOUR AU - Virág, László AU - Hegedűs, Csaba AU - Kovács, Katalin AU - Polgár, Zsuzsanna AU - Kókai, Endre AU - Sturniolo, Isotta AU - Demény, Máté Ágoston AU - Virág, Bernadett AU - Szabó, Éva TI - Automated high-throughput cell culture scratch assay identifies wound healing promoting and inhibiting compounds from a small compound library of redox active molecules JF - FREE RADICAL BIOLOGY AND MEDICINE J2 - FREE RADICAL BIO MED VL - 208 PY - 2023 SP - S144 EP - S144 PG - 1 SN - 0891-5849 DO - 10.1016/j.freeradbiomed.2023.10.328 UR - https://m2.mtmt.hu/api/publication/34729573 ID - 34729573 LA - English DB - MTMT ER - TY - JOUR AU - Guti, Eliza AU - Bede, Ákos Máté AU - Váróczy, Csongor AU - Hegedűs, Csaba AU - Demény, Máté Ágoston AU - Virág, László TI - High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds JF - JOVE-JOURNAL OF VISUALIZED EXPERIMENTS J2 - JOVE-J VIS EXP PY - 2023 IS - 198 SP - 1 EP - 12 PG - 12 SN - 1940-087X DO - 10.3791/64485 UR - https://m2.mtmt.hu/api/publication/34108111 ID - 34108111 LA - English DB - MTMT ER - TY - JOUR AU - Ujlaki, Gyula AU - Kovács, Tünde AU - Vida, András AU - Kókai, Endre AU - Rauch, Boglárka AU - Schwarcz, Szandra AU - Mikó, Edit AU - Janka, Eszter AU - Sipos, Adrienn AU - Hegedűs, Csaba AU - Uray (Davis), Karen L. AU - Nagy, Péter AU - Bay, Péter TI - Identification of Bacterial Metabolites Modulating Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 15 SN - 1420-3049 DO - 10.3390/molecules28155898 UR - https://m2.mtmt.hu/api/publication/34089348 ID - 34089348 AB - Breast cancer patients are characterized by the oncobiotic transformation of multiple microbiome communities, including the gut microbiome. Oncobiotic transformation of the gut microbiome impairs the production of antineoplastic bacterial metabolites. The goal of this study was to identify bacterial metabolites with antineoplastic properties. We constructed a 30-member bacterial metabolite library and screened the library compounds for effects on cell proliferation and epithelial-mesenchymal transition. The metabolites were applied to 4T1 murine breast cancer cells in concentrations corresponding to the reference serum concentrations. However, yric acid, glycolic acid, d-mannitol, 2,3-butanediol, and trans-ferulic acid exerted cytostatic effects, and 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, and vanillic acid exerted hyperproliferative effects. Furthermore, 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 2,3-butanediol, and hydrocinnamic acid inhibited epithelial-to-mesenchymal (EMT) transition. We identified redox sets among the metabolites (d-mannitol—d-mannose, 1-butanol—butyric acid, ethylene glycol—glycolic acid—oxalic acid), wherein only one partner within the set (d-mannitol, butyric acid, glycolic acid) possessed bioactivity in our system, suggesting that changes to the local redox potential may affect the bacterial secretome. Of the nine bioactive metabolites, 2,3-butanediol was the only compound with both cytostatic and anti-EMT properties. LA - English DB - MTMT ER - TY - JOUR AU - Ráduly, Zsolt AU - Szabó, László AU - Dienes, Beatrix AU - Szentesi, Péter AU - Bana, Ágnes Viktória AU - Hajdú, Tibor AU - Kókai, Endre AU - Hegedűs, Csaba AU - Csernoch, László AU - Gönczi, Mónika TI - Migration of Myogenic Cells Is Highly Influenced by Cytoskeletal Septin7 JF - CELLS J2 - CELLS-BASEL VL - 12 PY - 2023 IS - 14 PG - 17 SN - 2073-4409 DO - 10.3390/cells12141825 UR - https://m2.mtmt.hu/api/publication/34082035 ID - 34082035 AB - Septin7 as a unique member of the GTP binding protein family, is widely expressed in the eukaryotic cells and considered to be essential in the formation of hetero-oligomeric septin complexes. As a cytoskeletal component, Septin7 is involved in many important cellular processes. However, its contribution in striated muscle physiology is poorly described. In skeletal muscle, a highly orchestrated process of migration is crucial in the development of functional fibers and in regeneration. Here, we describe the pronounced appearance of Septin7 filaments and a continuous change of Septin7 protein architecture during the migration of myogenic cells. In Septin7 knockdown C2C12 cultures, the basic parameters of migration are significantly different, and the intracellular calcium concentration change in migrating cells are lower compared to that of scrambled cultures. Using a plant cytokinin, forchlorfenuron, to dampen septin dynamics, the altered behavior of the migrating cells is described, where Septin7-depleted cells are more resistant to the treatment. These results indicate the functional relevance of Septin7 in the migration of myoblasts, implying its contribution to muscle myogenesis and regeneration. LA - English DB - MTMT ER - TY - JOUR AU - Hajnády, Zoltán AU - Nagy-Pénzes, Máté AU - Demény, Máté Ágoston AU - Kovács, Katalin AU - El-Hamoly, Tarek AU - Maléth, József AU - Hegyi, Péter AU - Polgár, Zsuzsanna AU - Hegedűs, Csaba AU - Virág, László TI - OGG1 Inhibition Reduces Acinar Cell Injury in a Mouse Model of Acute Pancreatitis JF - BIOMEDICINES J2 - BIOMEDICINES VL - 10 PY - 2022 IS - 10 PG - 17 SN - 2227-9059 DO - 10.3390/biomedicines10102543 UR - https://m2.mtmt.hu/api/publication/33153168 ID - 33153168 N1 - * Megosztott szerzőség AB - Acute pancreatitis (AP) is a potentially life-threatening gastrointestinal disease with a complex pathology including oxidative stress. Oxidative stress triggers oxidative DNA lesions such as formation of 7,8-dihydro-8-oxo-2′-oxoguanine (8-oxoG) and also causes DNA strand breaks. DNA breaks can activate the nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1) which contributes to AP pathology. 8-oxoG is recognized by 8-oxoG glycosylase 1 (OGG1) resulting in the removal of 8-oxoG from DNA as an initial step of base excision repair. Since OGG1 also possesses a DNA nicking activity, OGG1 activation may also trigger PARP1 activation. In the present study we investigated the role played by OGG1 in AP. We found that the OGG1 inhibitor compound TH5487 reduced edema formation, inflammatory cell migration and necrosis in a cerulein-induced AP model in mice. Moreover, TH5487 caused 8-oxoG accumulation and reduced tissue poly(ADP-ribose) levels. Consistent with the indirect PARP inhibitory effect, TH5487 shifted necrotic cell death (LDH release and Sytox green uptake) towards apoptosis (caspase activity) in isolated pancreatic acinar cells. In the in vivo AP model, TH5487 treatment suppressed the expression of various cytokine and chemokine mRNAs such as those of TNF, IL-1β, IL1ra, IL6, IL16, IL23, CSF, CCL2, CCL4, CCL12, IL10 and TREM as measured with a cytokine array and verified by RT-qPCR. As a potential mechanism underlying the transcriptional inhibitory effect of the OGG1 inhibitor we showed that while 8-oxoG accumulation in the DNA facilitates NF-κB binding to its consensus sequence, when OGG1 is inhibited, target site occupancy of NF-κB is impaired. In summary, OGG1 inhibition provides protection from tissue injury in AP and these effects are likely due to interference with the PARP1 and NF-κB activation pathways. LA - English DB - MTMT ER - TY - JOUR AU - Nagy-Pénzes, Máté AU - Hajnády, Zoltán AU - Regdon, Zsolt AU - Demény, Máté Ágoston AU - Kovács, Katalin AU - El-Hamoly, Tarek AU - Maléth, József AU - Hegyi, Péter AU - Hegedűs, Csaba AU - Virág, László TI - Tricetin Reduces Inflammation and Acinar Cell Injury in Cerulein-Induced Acute Pancreatitis: The Role of Oxidative Stress-Induced DNA Damage Signaling JF - BIOMEDICINES J2 - BIOMEDICINES VL - 10 PY - 2022 IS - 6 PG - 20 SN - 2227-9059 DO - 10.3390/biomedicines10061371 UR - https://m2.mtmt.hu/api/publication/32886684 ID - 32886684 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - JOUR AU - Guti, Eliza AU - Regdon, Zsolt AU - Sturniolo, Isotta AU - Kiss, Alexandra AU - Kovács, Katalin AU - Demény, Máté Ágoston AU - Szöőr, Árpád AU - Vereb, György AU - Szöllősi, János AU - Hegedűs, Csaba AU - Polgár, Zsuzsanna AU - Virág, László TI - The multitargeted receptor tyrosine kinase inhibitor sunitinib induces resistance of HER2 positive breast cancer cells to trastuzumab-mediated ADCC JF - CANCER IMMUNOLOGY IMMUNOTHERAPY J2 - CANCER IMMUNOL IMMUN VL - 71 PY - 2022 IS - 9 SP - 2151 EP - 2168 PG - 18 SN - 1432-0851 DO - 10.1007/s00262-022-03146-z UR - https://m2.mtmt.hu/api/publication/32628668 ID - 32628668 AB - Despite recent advances in the development of novel personalized therapies, breast cancer continues to challenge physicians with resistance to various advanced therapies. The anticancer action of the anti-HER2 antibody, trastuzumab, involves antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells. Here, we report a repurposing screen of 774 clinically used compounds on NK-cell + trastuzumab-induced killing of JIMT-1 breast cancer cells. Using a calcein-based high-content screening (HCS) assay for the image-based quantitation of ADCC that we have developed and optimized for this purpose, we have found that the multitargeted tyrosine kinase inhibitor sunitinib inhibits ADCC in this model. The cytoprotective effect of sunitinib was also confirmed with two other assays (lactate dehydrogenase release, and electric cell substrate impedance sensing, ECIS). The drug suppressed NK cell activation as indicated by reduced granzyme B deposition on to the target cells and inhibition of interferon-γ production by the NK cells. Moreover, sunitinib induced downregulation of HER2 on the target cells' surface, changed the morphology and increased adherence of the target cells. Moreover, sunitinib also triggered the autophagy pathway (speckled LC3b) as an additional potential underlying mechanism of the cytoprotective effect of the drug. Sunitinib-induced ADCC resistance has been confirmed in a 3D tumor model revealing the prevention of apoptotic cell death (Annexin V staining) in JIMT-1 spheroids co-incubated with NK cells and trastuzumab. In summary, our HCS assay may be suitable for the facile identification of ADCC boosting compounds. Our data urge caution concerning potential combinations of ADCC-based immunotherapies and sunitinib. LA - English DB - MTMT ER - TY - JOUR AU - Guti, Eliza AU - Hegedűs, Csaba AU - Regdon, Zsolt AU - Polgár, Zsuzsanna AU - Virág, László TI - The multi-targeted receptor tyrosine kinase inhibitor sunitinib inhibits natural killer cell-mediated antibody-dependent cellular cytotoxicity against JIMT-1 breast carcinoma cells JF - FEBS OPEN BIO J2 - FEBS OPEN BIO VL - 11 PY - 2021 IS - Suppl. 1 SP - 405 EP - 406 PG - 2 SN - 2211-5463 UR - https://m2.mtmt.hu/api/publication/32499240 ID - 32499240 LA - English DB - MTMT ER -