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 - Institute of Electrical and Electronics Engineers (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 - JOUR AU - Drexler, Dániel András AU - Ferenci, Tamás AU - Füredi, András AU - Szakács, Gergely AU - Kovács, Levente TI - Experimental data-driven tumor modeling for chemotherapy JF - IFAC PAPERSONLINE J2 - IFACOL VL - 53 PY - 2020 IS - 2 SP - 16245 EP - 16250 PG - 6 SN - 2405-8971 DO - 10.1016/j.ifacol.2020.12.619 UR - https://m2.mtmt.hu/api/publication/31625912 ID - 31625912 AB - Mathematical models of tumor growth in response to chemotherapy are crucial for therapy optimization and outcome. We create a relatively simple tumor growth model describing the antitumor effect of pegylated liposomal doxorubicin (PLD) validated with real experimental data obtained in a genetically engineered mouse model of breast cancer. We use formal reaction kinetics to describe the pathophysiological phenomena using differential equations, and carry out parametric identification based on experiments using a mixed-effect model with stochastic approximation expectation maximization. The model gives a sufficient fit to describe tumor growth and pharmacokinetic data, and a satisfactory fit for the complex case, i.e., tumor response to chemotherapy. The results showed that identification of certain subsystems is easy using experimental data even if it is not specifically designed for identification. However, the identification of the complex pathophysiological phenomena may require experiments specially designed for identification purposes. Copyright (C) 2020 The Authors. LA - English DB - MTMT ER - TY - JOUR AU - Hámori, Lilla AU - Kudlik, Gyöngyi AU - Szebényi, Kornélia AU - Kucsma, Nóra AU - Szeder, Bálint AU - Póti, Ádám AU - Uher, Ferenc AU - Várady, György AU - Szüts, Dávid AU - Tóvári, József AU - Füredi, András AU - Szakács, Gergely TI - Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 4 PG - 19 SN - 1661-6596 DO - 10.3390/ijms21041185 UR - https://m2.mtmt.hu/api/publication/31196937 ID - 31196937 AB - Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. By the age of 80, the estimated risk for breast cancer for women with germline BRCA1 or BRCA2 mutations is around 80%. Genetically engineered BRCA1-deficient mouse models offer a unique opportunity to study the pathogenesis and therapy of triple negative breast cancer. Here we present a newly established Brca1−/−, p53−/− mouse mammary tumor cell line, designated as CST. CST shows prominent features of BRCA1-mutated triple-negative breast cancers including increased motility, high proliferation rate, genome instability and sensitivity to platinum chemotherapy and PARP inhibitors (olaparib, veliparib, rucaparib and talazoparib). Genomic instability of CST cells was confirmed by whole genome sequencing, which also revealed the presence of COSMIC (Catalogue of Somatic Mutations in Cancer) mutation signatures 3 and 8 associated with homologous recombination (HR) deficiency. In vitro sensitivity of CST cells was tested against 11 chemotherapy agents. Tumors derived from orthotopically injected CST-mCherry cells in FVB-GFP mice showed sensitivity to cisplatin, providing a new model to study the cooperation of BRCA1-KO, mCherry-positive tumor cells and the GFP-expressing stromal compartment in therapy resistance and metastasis formation. In summary, we have established CST cells as a new model recapitulating major characteristics of BRCA1-negative breast cancers. LA - English DB - MTMT ER - TY - JOUR AU - Drexler, Dániel András AU - Ferenci, Tamás AU - Lovrics, Anna AU - Kovács, Levente TI - Tumor dynamics modeling based on formal reaction kinetics JF - ACTA POLYTECHNICA HUNGARICA J2 - ACTA POLYTECH HUNG VL - 16 PY - 2019 IS - 10 SP - 31 EP - 44 PG - 14 SN - 1785-8860 DO - 10.12700/APH.16.10.2019.10.3 UR - https://m2.mtmt.hu/api/publication/30864958 ID - 30864958 LA - English DB - MTMT ER - TY - JOUR AU - Füredi, András AU - Szebényi, Kornélia AU - Tóth, Szilárd AU - Cserepes, Tamás Mihály AU - Hámori, Lilla AU - Nagy, Veronika AU - Karai, Edina AU - Vajdovich, Péter AU - Imre, Timea AU - Szabó, Pál Tamás AU - Szüts, Dávid AU - Tóvári, József AU - Szakács, Gergely TI - Pegylated liposomal formulation of doxorubicin overcomes drug resistance in a genetically engineered mouse model of breast cancer. JF - JOURNAL OF CONTROLLED RELEASE J2 - J CONTROL RELEASE VL - 261 ET - 0 PY - 2017 SP - 287 EP - 296 PG - 10 SN - 0168-3659 DO - 10.1016/j.jconrel.2017.07.010 UR - https://m2.mtmt.hu/api/publication/3251042 ID - 3251042 AB - Success of cancer treatment is often hampered by the emergence of multidrug resistance (MDR) mediated by P-glycoprotein (ABCB1/Pgp). Doxorubicin (DOX) is recognized by Pgp and therefore it can induce therapy resistance in breast cancer patients. In this study our aim was to evaluate the susceptibility of the pegylated liposomal formulation of doxorubicin (PLD/Doxil(R)/Caelyx(R)) to MDR. We show that cells selected to be resistant to DOX are cross-resistant to PLD and PLD is also ineffective in an allograft model of doxorubicin-resistant mouse B-cell leukemia. In contrast, PLD was far more efficient than DOX as reflected by a significant increase of both relapse-free and overall survival of Brca1-/-;p53-/- mammary tumor bearing mice. Increased survival could be explained by the delayed onset of drug resistance. Consistent with the higher Pgp levels needed to confer resistance, PLD administration was able to overcome doxorubicin insensitivity of the mouse mammary tumors. Our results indicate that the favorable pharmacokinetics achieved with PLD can effectively overcome Pgp-mediated resistance, suggesting that PLD therapy could be a promising strategy for the treatment of therapy-resistant breast cancer patients. LA - English DB - MTMT ER -