TY - JOUR AU - Vajda, Flóra AU - Szepesi, Áron AU - Erdei, Zsuzsa AU - Szabó, Edit Zsuzsanna AU - Várady, György AU - Kiss, Dániel AU - Héja, László AU - Német, Katalin AU - Szakács, Gergely AU - Füredi, András TI - Mesenchymal Stem Cells Increase Drug Tolerance of A431 Cells Only in 3D Spheroids, Not in 2D Co-Cultures JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 PG - 14 SN - 1661-6596 DO - 10.3390/ijms25084515 UR - https://m2.mtmt.hu/api/publication/34805418 ID - 34805418 AB - Mesenchymal stem cells (MSCs) are an integral part of the tumor microenvironment (TME); however, their role is somewhat controversial: conflicting reports suggest that, depending on the stage of tumor development, MSCs can either support or suppress tumor growth and spread. Additionally, the influence of MSCs on drug resistance is also ambiguous. Previously, we showed that, despite MSCs proliferating significantly more slowly than cancer cells, there are chemotherapeutic drugs which proved to be similarly toxic to both cell types. Here we established 2D co-cultures and 3D co-culture spheroids from different ratios of GFP-expressing, adipose tissue-derived MSCs and A431 epidermoid carcinoma cells tagged with mCherry to investigate the effect of MSCs on cancer cell growth, survival, and drug sensitivity. We examined the cytokine secretion profile of mono- and co-cultures, explored the inner structure of the spheroids, applied MSC-(nutlin-3) and cancer cell-targeting (cisplatin) treatments separately, monitored the response with live-cell imaging and identified a new, double-fluorescent cell type emerging from these cultures. In 2D co-cultures, no effect on proliferation or drug sensitivity was observed, regardless of the changes in cytokine secretion induced by the co-culture. Conversely, 3D spheroids developed a unique internal structure consisting of MSCs, which significantly improved cancer cell survival and resilience to treatment, suggesting that physical proximity and cell–cell connections are required for MSCs to considerably affect nearby cancer cells. Our results shed light on MSC–cancer cell interactions and could help design new, better treatment options for tumors. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Levente AU - Ferenci, Tamás AU - Gombos, Balázs AU - Füredi, András AU - Rudas, Imre AU - Szakács, Gergely AU - Drexler, Dániel András TI - Positive Impulsive Control of Tumor Therapy—A Cyber-Medical Approach JF - IEEE TRANSACTIONS ON SYSTEMS MAN AND CYBERNETICS: SYSTEMS J2 - IIEEE TRANS SYST MAN CYBERN SYST VL - 54 PY - 2023 IS - 1 SP - 597 EP - 608 PG - 12 SN - 2168-2216 DO - 10.1109/TSMC.2023.3315637 UR - https://m2.mtmt.hu/api/publication/34168948 ID - 34168948 LA - English DB - MTMT ER - TY - JOUR AU - Szebényi, Kornélia AU - Füredi, András AU - Bajtai, Eszter AU - Sama, Sai Nagender AU - Csiszar, Agnes AU - Gombos, Balázs AU - Szabó, Pál Tamás AU - Grusch, Michael AU - Szakács, Gergely TI - Effective targeting of breast cancer by the inhibition of P-glycoprotein mediated removal of toxic lipid peroxidation byproducts from drug tolerant persister cells JF - DRUG RESISTANCE UPDATES J2 - DRUG RESIST UPDATE VL - 71 PY - 2023 PG - 12 SN - 1368-7646 DO - 10.1016/j.drup.2023.101007 UR - https://m2.mtmt.hu/api/publication/34163799 ID - 34163799 LA - English DB - MTMT ER - TY - CHAP AU - Gergics, Borbála AU - Vajda, Flóra AU - Puskás, Melánia AU - Füredi, András AU - Drexler, Dániel András TI - Mathematical modeling of phototoxicity during fluorescent imaging of tumor spheroids T2 - IEEE 27th International Conference on Intelligent Engineering Systems 2023 (INES 2023) PB - IEEE Hungary Section CY - Budapest SN - 9798350328516 PY - 2023 SP - 291 EP - 296 PG - 6 DO - 10.1109/INES59282.2023.10297657 UR - https://m2.mtmt.hu/api/publication/34081684 ID - 34081684 LA - English DB - MTMT ER - TY - CHAP AU - Puskás, Melánia AU - Gergics, Borbála AU - Gombos, Balázs AU - Füredi, András AU - Szakács, Gergely AU - Kovács, Levente AU - Drexler, Dániel András TI - Noise modeling of tumor size measurements from animal experiments for virtual patient generation T2 - IEEE 27th International Conference on Intelligent Engineering Systems 2023 (INES 2023) PB - IEEE Hungary Section CY - Budapest SN - 9798350328516 PY - 2023 SP - 53 EP - 60 PG - 8 DO - 10.1109/INES59282.2023.10297747 UR - https://m2.mtmt.hu/api/publication/34081565 ID - 34081565 N1 - IEEE Control Systems Chapter; IEEE Hungary Section; IEEE Joint Chapter of IES and RAS; IEEE SMC Chapter Research and Innovation Center of Obuda University Obuda University, Physiological Controls Research Center, Budapest, Hungary Research Center for Natural Sciences, Drug Resistance Research Group, Budapest, Hungary Conference code: 194162 Export Date: 6 May 2024 Correspondence Address: Puskas, M.; Research and Innovation Center of Obuda University Obuda University, Hungary; email: puskas.melania@uni-obuda.hu LA - English DB - MTMT ER - TY - JOUR AU - Vajda, Flóra AU - Szepesi, Áron AU - Várady, György AU - Sessler, Judit AU - Kiss, Dániel AU - Erdei, Zsuzsa AU - Szebényi, Kornélia AU - Német, Katalin AU - Szakács, Gergely AU - Füredi, András TI - Comparison of Different Clinical Chemotherapeutical Agents' Toxicity and Cell Response on Mesenchymal Stem Cells and Cancer Cells JF - CELLS J2 - CELLS-BASEL VL - 11 PY - 2022 IS - 19 PG - 14 SN - 2073-4409 DO - 10.3390/cells11192942 UR - https://m2.mtmt.hu/api/publication/33183423 ID - 33183423 N1 - Institute of Enzymology, Research Centre for Natural Sciences, Budapest, 1117, Hungary Doctoral School of Molecular Medicine, Semmelweis University, Budapest, 1089, Hungary Creative Cell Kft., Budapest, 1119, Hungary Software Engineering Institute, John von Neumann Faculty of Informatics, Óbuda University, Budapest, 1034, Hungary National Laboratory for Drug Research and Development, Budapest, 1117, Hungary Export Date: 15 June 2023 Correspondence Address: Füredi, A.; Institute of Enzymology, Hungary; email: furedi.andras@ttk.hu Chemicals/CAS: bendamustine, 16506-27-7, 3543-75-7; cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; doxorubicin, 23214-92-8, 25316-40-9; irinotecan, 100286-90-6, 97682-44-5; methotrexate, 15475-56-6, 59-05-2, 7413-34-5, 7532-09-4, 6745-93-3, 51865-79-3, 60388-53-6; mitoxantrone, 65271-80-9, 70476-82-3; rebemadlin, 548472-68-0, 675576-97-3, 675576-98-4; vinblastine, 865-21-4; DNA, 9007-49-2; Antineoplastic Agents; DNA Tradenames: 3984, Tocris, United Kingdom; ab 252173, ABCR, Germany; hy 13780, MedChemexpress, United States; m 9929, Sigma Aldrich, United States; nutlin 3, Tocris, United Kingdom; p 4413, Tocris, United Kingdom; vnr 461201, Accord Healthcare, United KingdomEnspire (microplate reader), Perkin Elmer, United States; JuLI Manufacturers: ABCR, Germany; Accord Healthcare, United Kingdom; Tocris, United Kingdom; MedChemexpress, United States; Sigma Aldrich, United StatesCell Signaling Technology, United States; Perkin Elmer, United States Funding details: 2969-1-KÖ-39-2020 Funding details: International Brain Research Organization, IBRO Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, 2019-1.3.1-KK-2019-00007, GINOP-2.1.7-15, K-128011, RRF-2.3.1-21-2022-00015 Funding text 1: This research was funded by the Hungarian National Research, Development and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015 to G.S. and A.F., 2019-1.3.1-KK-2019-00007 to G.S. and A.F., NKFIH K-128011 to G.V., GINOP-2.1.7-15 (Stem Tox) to K.N.), the International Brain Research Organization (IBRO Return Home Fellowship to K.S.) and by the collaboration between the Research Centre for Natural Sciences of the Eötvös Loránd Research Network and the Szentágothai Research Centre of the University of Pécs on internationally recognized medical research projects (2969-1-KÖ-39-2020) to A.F. AB - Mesenchymal stem cells (MSCs) or fibroblasts are one of the most abundant cell types in the tumor microenvironment (TME) exerting various anti- and pro-apoptotic effects during tumorigenesis, invasion, and drug treatment. Despite the recently discovered importance of MSCs in tumor progression and therapy, the response of these cells to chemotherapeutics compared to cancer cells is rarely investigated. A widely accepted view is that these naive MSCs have higher drug tolerance than cancer cells due to a significantly lower proliferation rate. Here, we examine the differences and similarities in the sensitivity of MSCs and cancer cells to nine diverse chemotherapy agents and show that, although MSCs have a slower cell cycle, these cells are still sensitive to various drugs. Surprisingly, MSCs showed similar sensitivity to a panel of compounds, however, suffered fewer DNA double-stranded breaks, did not enter into a senescent state, and was virtually incapable of apoptosis. Our results suggest that MSCs and cancer cells have different cell fates after drug treatment, and this could influence therapy outcome. These findings could help design drug combinations targeting both MSCs and cancer cells in the TME. LA - English DB - MTMT ER - TY - CHAP AU - Gergics, Borbála AU - Gombos, Balázs AU - Vajda, Flóra AU - Füredi, András AU - Gergely, Szakács AU - Drexler, Dániel András TI - Pharmacodynamics modeling based on in vitro 2D cell culture experiments T2 - 2022 IEEE International Conference on Systems, Man, and Cybernetics (SMC) PB - IEEE CY - Piscataway (NJ) SN - 9781665452588 PY - 2022 SP - 2409 EP - 2414 PG - 6 DO - 10.1109/SMC53654.2022.9945355 UR - https://m2.mtmt.hu/api/publication/33138330 ID - 33138330 LA - English DB - MTMT ER - TY - PAT AU - Mező, Gábor AU - Hegedüs, Kristóf AU - Kiss, Krisztina AU - SZAKÁCS, GERGELY AU - Füredi, András AU - VARGA, ZOLTÁN AU - TÓTH, SZILÁRD AU - BARTA, GERGŐ AU - NAGYNÉ, NASZÁLYI LÍVIA AU - GAÁL, ANIKÓ TI - NOVEL ANTICANCER THERAPY PY - 2022 UR - https://m2.mtmt.hu/api/publication/33111421 ID - 33111421 AB - The invention relates to the field of cancer therapy. In particular, a highly effective chemotherapy is provided in the form of liposome-encapsulated 2-deamino-2-pyrrolino-daunorubicin, which has been found to eliminate cancer cells and to support overall survival without causing severe undesired effects in mouse models of different types of cancer. LA - English DB - MTMT ER - TY - JOUR AU - Dékay, Valéria AU - Karai, Edina AU - Füredi, András AU - Szebényi, Kornélia AU - Szakács, Gergely AU - Vajdovich, Péter TI - P-Glycoprotein Activity at Diagnosis Does Not Predict Therapy Outcome and Survival in Canine B-Cell Lymphoma JF - CANCERS J2 - CANCERS VL - 14 PY - 2022 IS - 16 PG - 17 SN - 2072-6694 DO - 10.3390/cancers14163919 UR - https://m2.mtmt.hu/api/publication/33070122 ID - 33070122 N1 - Innovációs szolgáltató bázis létrehozásadiagnosztikai, terápiás és kutatási célú kiberorvosiren...(2019-1-3-1-KK-2019-00007) Támogató: NKFIH AB - Various mechanisms are known to be involved in the development of multidrug resistance during cancer treatment. P-glycoprotein (P-gp) decreases the intracellular concentrations of cytotoxic drugs by an energy-dependent efflux mechanism. The aim of this study was to investigate the predictive value of P-gp function based on the evaluation of P-gp activity in tumor cells obtained from canine B-cell lymphoma patients at diagnosis. P-gp function of 79 immunophenotyped canine lymphoma samples was determined by flow cytometry using the Calcein assay. Dogs were treated with either the CHOP or the L-CHOP protocol, a subset of relapsed patients received L-asparaginase and lomustine rescue treatments. Among the 79 dogs, the median overall survival time was 417 days, and the median relapse-free period was 301 days. 47 percent of the samples showed high P-gp activity, which was significantly higher in Stage IV cancer patients compared to Stage II + III and V. Whereas staging was associated with major differences in survival times, we found that the intrinsic P-gp activity of tumor cells measured at diagnosis is not predictive for therapy outcome. Further studies are needed to identify the intrinsic and acquired resistant mechanisms that shape therapy response and survival in B-cell canine lymphoma patients. LA - English DB - MTMT ER - TY - CHAP AU - Nagy , Erzsébet AU - Czakó, Bence Géza AU - Siket, Máté AU - Gombos, Balázs AU - Füredi, András AU - Szakács, Gergely AU - Kovács, Levente AU - Drexler, Dániel András ED - Szakál, Anikó TI - Tracking parameter changes of an Impulsive Tumor Growth Model T2 - IEEE 10th Jubilee International Conference on Computational Cybernetics and Cyber-Medical Systems ICCC 2022 PB - IEEE Hungary Section CY - Budapest SN - 9781665481762 PY - 2022 SP - 179 EP - 184 PG - 6 DO - 10.1109/ICCC202255925.2022.9922736 UR - https://m2.mtmt.hu/api/publication/33060653 ID - 33060653 LA - English DB - MTMT ER -