TY - JOUR AU - Korpos, Éva AU - Papp, Ferenc TI - New ‘kids’ on the voltage‐gated proton channel block JF - FEBS JOURNAL J2 - FEBS J VL - 290 PY - 2023 IS - 4 SP - 970 EP - 973 PG - 4 SN - 1742-464X DO - 10.1111/febs.16670 UR - https://m2.mtmt.hu/api/publication/33215047 ID - 33215047 LA - English DB - MTMT ER - TY - JOUR AU - Blokon-Kogan, Dayana AU - Levi-Mann, Maya AU - Malka-Levy, Lior AU - Itzhaki, Orit AU - Besser, Michal J. AU - Shiftan, Yuval AU - Szöőr, Árpád AU - Vereb, György AU - Gross, Gideon AU - Abken, Hinrich AU - Weinstein-Marom, Hadas TI - Membrane anchored IL-18 linked to constitutively active TLR4 and CD40 improves human T cell antitumor capacities for adoptive cell therapy JF - JOURNAL FOR IMMUNOTHERAPY OF CANCER J2 - J IMMUNOTHER CANCER VL - 10 PY - 2022 IS - 9 PG - 12 SN - 2051-1426 DO - 10.1136/jitc-2020-001544 UR - https://m2.mtmt.hu/api/publication/33103806 ID - 33103806 AB - Background Adoptive transfer of tumor-infiltrating lymphocytes (TILs) or blood T cells genetically redirected by an antitumor TCR or CAR induces a strong antitumor response in a proportion of patients with cancer; however, the therapeutic efficacy is often limited by rapid decline in T cell functions. Coadministering supportive cytokines frequently provokes systemic side effects preventing their broad clinical application. We recently showed that cytokines can be anchored to the cell membrane in a functional fashion and that cytokine receptor signaling can synergize with TLR4 and CD40 signaling. Here, we aimed at augmenting T cell activation by simultaneous signaling through the cytokine receptor, toll-like receptor and TNF-type receptor using IL-18, TLR4 and CD40 as prototypes. Methods Genes were expressed on electroporation of in vitro-transcribed mRNA in CD4(+) and CD8(+) T cells from healthy donors redirected against melanoma cells with an anti-melanotransferrin CAR and in TILs derived from melanoma patients. Functional assays included the activation of signaling pathways, expression of activation and differentiation markers, cytokine secretion and killing of melanoma target cells. Results To provide IL-18 costimulation to T cells in-cis while avoiding systemic effects, we genetically anchored IL-18 to the T cell membrane, either alone (memIL-18) or fused with constitutively active (ca)TLR4 and caCD40 signaling domains arranged in tandem, creating a synthetic 'all-in-one' memIL-18-TLR4-CD40 receptor. MemIL-18-TLR4-CD40, but not memIL-18, triggered strong NF-kappa B activation in cells lacking the IL-18 receptor, attesting to functionality of the TLR-CD40 moiety. While the membrane-anchored cytokine was found to act mainly in-cis, some T cell activation in-trans was also observed. The electroporated T cells exhibited spontaneous T-bet upregulation and IFN-gamma and TNF-alpha secretion. Melanoma-induced activation of CAR-T cells and TILs as manifested by cytokine secretion and cytolytic activity was substantially augmented by both constructs, with memIL-18-TLR4-CD40 exerting stronger effects than memIL-18 alone. Conclusions Linking membrane anchored IL-18 with caTLR4 and caCD40 signaling in one hybrid transmembrane protein provides simultaneous activation of three T cell costimulatory pathways through one genetically engineered membrane molecule, strongly amplifying T cell functions for adoptive T cell therapy of cancer. 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 - Pócsi, István AU - Máthéné Szigeti, Zsuzsa AU - Emri, Tamás AU - Boczonádi, Imre AU - Vereb, György AU - Szöllősi, János TI - Use of red, far-red, and near-infrared light in imaging of yeasts and filamentous fungi JF - APPLIED MICROBIOLOGY AND BIOTECHNOLOGY J2 - APPL MICROBIOL BIOT VL - 106 PY - 2022 IS - 11 SP - 3895 EP - 3912 PG - 19 SN - 0175-7598 DO - 10.1007/s00253-022-11967-2 UR - https://m2.mtmt.hu/api/publication/32851076 ID - 32851076 N1 - Department of Molecular Biotechnology and Microbiology, Institute of Biotechnology, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary MTA-DE Cell Biology and Signaling Research Group, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary Faculty of Pharmacy, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary Export Date: 09 January 2024; Cited By: 0; Correspondence Address: I. Pócsi; Department of Molecular Biotechnology and Microbiology, Institute of Biotechnology, Faculty of Science and Technology, University of Debrecen, Debrecen, Egyetem tér 1, 4032, Hungary; email: pocsi.istvan@science.unideb.hu; CODEN: AMBID AB - While phototoxicity can be a useful therapeutic modality not only for eliminating malignant cells but also in treating fungal infections, mycologists aiming to observe morphological changes or molecular events in fungi, especially when long observation periods or high light fluxes are warranted, encounter problems owed to altered regulatory pathways or even cell death caused by various photosensing mechanisms. Consequently, the ever expanding repertoire of visible fluorescent protein toolboxes and high-resolution microscopy methods designed to investigate fungi in vitro and in vivo need to comply with an additional requirement: to decrease the unwanted side effects of illumination. In addition to optimizing exposure, an obvious solution is red-shifted illumination, which, however, does not come without compromises. This review summarizes the interactions of fungi with light and the various molecular biology and technology approaches developed for exploring their functions on the molecular, cellular, and in vivo microscopic levels, and outlines the progress towards reducing phototoxicity through applying far-red and near-infrared light. LA - English DB - MTMT ER - TY - JOUR AU - Bécsi, Bálint AU - Kónya, Zoltán AU - Boratkó, Anita AU - Kovács, Katalin AU - Erdődi, Ferenc TI - Epigallocatechine-3-gallate Inhibits the Adipogenesis of Human Mesenchymal Stem Cells via the Regulation of Protein Phosphatase-2A and Myosin Phosphatase JF - CELLS J2 - CELLS-BASEL VL - 11 PY - 2022 IS - 10 PG - 18 SN - 2073-4409 DO - 10.3390/cells11101704 UR - https://m2.mtmt.hu/api/publication/32837061 ID - 32837061 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 - CHAP AU - Kónya, Gábor AU - Szabó, Zsuzsanna AU - Király, József AU - Dobos, Nikoletta AU - Zsebik, Barbara AU - Szegedi, Krisztián AU - Halmos, Gábor ED - Csiszár, Beáta ED - Hankó, Csilla ED - Kajos, Luca Fanni ED - Mező, Emerencia TI - Expression of indoleamine 2,3-dioxygenase (IDO) and PTEN in human renal carcinoma T2 - Medical Conference for PhD Students and Experts of Clinical Sciences 2021 PB - University of Pécs, Doctoral Student Association CY - Pécs SN - 9789634296539 PY - 2021 SP - 103 UR - https://m2.mtmt.hu/api/publication/32852451 ID - 32852451 LA - English DB - MTMT ER - TY - JOUR AU - Gyongyosi, Adrienn AU - Boldizsar, Eszter AU - Kállai, Judit AU - Czuczku, Daniel AU - Alala, Siham AU - Laoui, Damya AU - Van Ginderachter, Jo A. AU - Lanyi, Arpad TI - The presence of Tks4 augments tumor progression JF - EUROPEAN JOURNAL OF IMMUNOLOGY J2 - EUR J IMMUNOL VL - 51 PY - 2021 IS - Suppl. 1 SP - 324 EP - 324 PG - 1 SN - 0014-2980 UR - https://m2.mtmt.hu/api/publication/32733912 ID - 32733912 LA - English DB - MTMT ER - TY - JOUR AU - Bankó, Csaba AU - Nagy, Zsolt László AU - Nagy, Miklós AU - Szemán-Nagy, Gábor AU - Rebenku, István AU - Imre, László AU - Tiba, Attila AU - Hajdu, András AU - Szöllősi, János AU - Kéki, Sándor AU - Bacsó, Zsolt TI - Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells JF - CANCERS J2 - CANCERS VL - 13 PY - 2021 IS - 22 PG - 24 SN - 2072-6694 DO - 10.3390/cancers13225652 UR - https://m2.mtmt.hu/api/publication/32512952 ID - 32512952 N1 - Department of Biophysics and Cell Biology, Faculty of General Medicine, University of Debrecen, Debrecen, 4032, Hungary Department of Applied Chemistry, Institute of Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen, 4032, Hungary Institute of Chemistry, University of Miskolc, Miskolc, 3515, Hungary Department of Biotechnology and Microbiology, Institute of Biotechnology, Faculty of Science and Technology, University of Debrecen, Debrecen, 4032, Hungary Department of Computer Graphics and Image Processing, Faculty of Informatics, University of Debrecen, Debrecen, 4032, Hungary MTA-DE Cell Biology and Signaling Research Group, Faculty of General Medicine, University of Debrecen, Debrecen, 4032, Hungary Faculty of Pharmacy, University of Debrecen, Debrecen, 4032, Hungary Export Date: 30 November 2021 Correspondence Address: Bacso, Z.; Department of Biophysics and Cell Biology, Hungary; email: bacso@med.unideb.hu LA - English DB - MTMT ER - TY - JOUR AU - Regdon, Zsolt AU - Demény, Máté Ágoston AU - Hegedűs, Csaba AU - Kiss, Alexandra AU - Szabo, E. AU - Virág, László TI - Oxidative stress-induced DNA damage signaling: the role of poly(ADP-ribose) polymerase 1 JF - FEBS OPEN BIO J2 - FEBS OPEN BIO VL - 11 PY - 2021 SP - 61 EP - 61 PG - 1 SN - 2211-5463 UR - https://m2.mtmt.hu/api/publication/32498912 ID - 32498912 LA - English DB - MTMT ER -