@article{MTMT:34778269, title = {Heat shock factor 1 inhibition enhances the effects of modulated electro hyperthermia in a triple negative breast cancer mouse model}, url = {https://m2.mtmt.hu/api/publication/34778269}, author = {Leroy Viana, Pedro Henrique and Schvarcz, Csaba András and Danics, Lea and Besztercei, Balázs and Aloss, Kenan and Bokhari, Syeda Mahak Zahra and Giunashvili, Nino and Bócsi, Dániel and Koós, Zoltán and Benyó, Zoltán and Hamar, Péter}, doi = {10.1038/s41598-024-57659-x}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {14}, unique-id = {34778269}, issn = {2045-2322}, abstract = {Female breast cancer is the most diagnosed cancer worldwide. Triple negative breast cancer (TNBC) is the most aggressive type and there is no existing endocrine or targeted therapy. Modulated electro-hyperthermia (mEHT) is a non-invasive complementary cancer therapy using an electromagnetic field generated by amplitude modulated 13.56 MHz frequency that induces tumor cell destruction. However, we have demonstrated a strong induction of the heat shock response (HSR) by mEHT, which can result in thermotolerance. We hypothesized that inhibition of the heat shock factor 1 (HSF1) can synergize with mEHT and enhance tumor cell-killing. Thus, we either knocked down the HSF1 gene with a CRISPR/Cas9 lentiviral construct or inhibited HSF1 with a specific small molecule inhibitor: KRIBB11 in vivo. Wild type or HSF1-knockdown 4T1 TNBC cells were inoculated into the mammary gland’s fat pad of BALB/c mice. Four mEHT treatments were performed every second day and the tumor growth was followed by ultrasound and caliper. KRIBB11 was administrated intraperitoneally at 50 mg/kg daily for 8 days. HSF1 and Hsp70 expression were assessed. HSF1 knockdown sensitized transduced cancer cells to mEHT and reduced tumor growth. HSF1 mRNA expression was significantly reduced in the KO group when compared to the empty vector group, and consequently mEHT-induced Hsp70 mRNA upregulation diminished in the KO group. Immunohistochemistry (IHC) confirmed the inhibition of Hsp70 upregulation in mEHT HSF1-KO group. Demonstrating the translational potential of HSF1 inhibition, combined therapy of mEHT with KRIBB11 significantly reduced tumor mass compared to either monotherapy. Inhibition of Hsp70 upregulation by mEHT was also supported by qPCR and IHC. In conclusion, we suggest that mEHT-therapy combined with HSF1 inhibition can be a possible new strategy of TNBC treatment with great translational potential.}, year = {2024}, eissn = {2045-2322}, orcid-numbers = {Schvarcz, Csaba András/0000-0002-2618-1909; Danics, Lea/0000-0001-8568-4074; Besztercei, Balázs/0000-0002-5636-284X; Aloss, Kenan/0000-0003-4806-7477; Giunashvili, Nino/0009-0005-2587-3806; Benyó, Zoltán/0000-0001-6015-0359; Hamar, Péter/0000-0002-1095-3564} } @article{MTMT:34742658, title = {"Digoxin-Mediated Inhibition of Potential Hypoxia-Related Angiogenic Repair in Modulated Electro-Hyperthermia (mEHT)-Treated Murine Triple-Negative Breast Cancer Model" (vol 7, pg 456, 2024)}, url = {https://m2.mtmt.hu/api/publication/34742658}, author = {Bokhari, Syeda Mahak Zahra and Aloss, Kenan and Leroy Viana, Pedro Henrique and Schvarcz, Csaba András and Besztercei, Balázs and Giunashvili, Nino and Bocsi, Daniel and Koos, Zoltan and Balogh, Andrea and Benyó, Zoltán and Hamar, Péter}, doi = {10.1021/acsptsci.4c00094}, journal-iso = {ACS PHARMACOL TRANS SCI}, journal = {ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE}, volume = {7}, unique-id = {34742658}, keywords = {Chemistry, Medicinal}, year = {2024}, eissn = {2575-9108}, pages = {904-904}, orcid-numbers = {Aloss, Kenan/0000-0003-4806-7477; Schvarcz, Csaba András/0000-0002-2618-1909; Besztercei, Balázs/0000-0002-5636-284X; Giunashvili, Nino/0009-0005-2587-3806; Balogh, Andrea/0000-0002-3007-0793; Benyó, Zoltán/0000-0001-6015-0359; Hamar, Péter/0000-0002-1095-3564} } @article{MTMT:34730139, title = {Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice}, url = {https://m2.mtmt.hu/api/publication/34730139}, author = {Aloss, Kenan and Bokhari, Syeda Mahak Zahra and Leroy Viana, Pedro Henrique and Giunashvili, Nino and Schvarcz, Csaba András and Szénási, Gábor and Bócsi, Dániel and Koós, Zoltán and Storm, Gert and Miklós, Zsuzsanna and Benyó, Zoltán and Hamar, Péter}, doi = {10.3390/ijms25063101}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34730139}, issn = {1661-6596}, abstract = {Modulated electro-hyperthermia (mEHT) is an adjuvant cancer therapy that enables tumor-selective heating (+2.5 °C). In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1). The 4T1 cells were orthotopically injected into Balb/C mice, and mEHT was performed on days 9, 12, and 15 after the implantation. DOX, LTLD, or PEGylated liposomal DOX (PLD) were administered for comparison. The tumor size and DOX accumulation in the tumor were measured. The cleaved caspase-3 (cC3) and cell proliferation were evaluated by cC3 or Ki67 immunohistochemistry and Western blot. The LTLD+mEHT combination was more effective at inhibiting tumor growth than the free DOX and PLD, demonstrated by reductions in both the tumor volume and tumor weight. LTLD+mEHT resulted in the highest DOX accumulation in the tumor one hour after treatment. Tumor cell damage was associated with cC3 in the damaged area, and with a reduction in Ki67 in the living area. These changes were significantly the strongest in the LTLD+mEHT-treated tumors. The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Aloss, Kenan/0000-0003-4806-7477; Giunashvili, Nino/0009-0005-2587-3806; Schvarcz, Csaba András/0000-0002-2618-1909; Szénási, Gábor/0000-0002-7350-6091; Storm, Gert/0000-0003-4296-2761; Miklós, Zsuzsanna/0000-0001-8577-4475; Benyó, Zoltán/0000-0001-6015-0359; Hamar, Péter/0000-0002-1095-3564} } @article{MTMT:34533207, title = {Digoxin-Mediated Inhibition of Potential Hypoxia-Related Angiogenic Repair in Modulated Electro-Hyperthermia (mEHT)-Treated Murine Triple-Negative Breast Cancer Model}, url = {https://m2.mtmt.hu/api/publication/34533207}, author = {Bokhari, Syeda Mahak Zahra and Aloss, Kenan and Leroy Viana, Pedro Henrique and Schvarcz, Csaba András and Besztercei, Balázs and Giunashvili, Nino and Bócsi, D. and Koós, Z. and Balogh, Andrea and Benyó, Zoltán and Hamar, Péter}, doi = {10.1021/acsptsci.3c00296}, journal-iso = {ACS PHARMACOL TRANS SCI}, journal = {ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE}, volume = {7}, unique-id = {34533207}, abstract = {Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer type with no targeted therapy and hence limited treatment options. Modulated electrohyperthermia (mEHT) is a novel complementary therapy where a 13.56 MHz radiofrequency current targets cancer cells selectively, inducing tumor damage by thermal and electromagnetic effects. We observed severe vascular damage in mEHT-treated tumors and investigated the potential synergism between mEHT and inhibition of tumor vasculature recovery in our TNBC mouse model. 4T1/4T07 isografts were orthotopically inoculated and treated three to five times with mEHT. mEHT induced vascular damage 4-12 h after treatment, leading to tissue hypoxia detected at 24 h. Hypoxia in treated tumors induced an angiogenic recovery 24 h after the last treatment. Administration of the cardiac glycoside digoxin with the potential hypoxia-inducible factor 1-α (HIF1-α) and angiogenesis inhibitory effects could synergistically augment mEHT-mediated tumor damage and reduce tissue hypoxia signaling and consequent vascular recovery in mEHT-treated TNBC tumors. Conclusively, repeated mEHT induced vascular damage and hypoxic stress in TNBC that promoted vascular recovery. Inhibiting this hypoxic stress signaling enhanced the effectiveness of mEHT and may potentially enhance other forms of cancer treatment. © 2024 The Authors. Published by American Chemical Society.}, keywords = {digoxin; Triple-negative breast cancer; modulated electro-hyperthermia; Hypoxia-inducible factor 1-α}, year = {2024}, eissn = {2575-9108}, pages = {456-466}, orcid-numbers = {Aloss, Kenan/0000-0003-4806-7477; Schvarcz, Csaba András/0000-0002-2618-1909; Besztercei, Balázs/0000-0002-5636-284X; Giunashvili, Nino/0009-0005-2587-3806; Balogh, Andrea/0000-0002-3007-0793; Benyó, Zoltán/0000-0001-6015-0359; Hamar, Péter/0000-0002-1095-3564} } @article{MTMT:34506551, title = {Enhancing therapeutic efficacy in triple-negative breast cancer and melanoma: synergistic effects of modulated electro-hyperthermia (mEHT) with NSAIDs especially COX-2 inhibition in in vivo models}, url = {https://m2.mtmt.hu/api/publication/34506551}, author = {Giunashvili, Nino and Thomas, Mbuotidem Jeremiah and Schvarcz, Csaba András and Leroy Viana, Pedro Henrique and Aloss, Kenan and Bokhari, Syeda Mahak Zahra and Koós, Zoltán and Bócsi, Dániel and Major, Enikő and Balogh, Andrea and Benyó, Zoltán and Hamar, Péter}, doi = {10.1002/1878-0261.13585}, journal-iso = {MOL ONCOL}, journal = {MOLECULAR ONCOLOGY}, volume = {18}, unique-id = {34506551}, issn = {1574-7891}, abstract = {Triple‐negative breast cancer (TNBC) is a leading cause of cancer mortality and lacks modern therapy options. Modulated electro‐hyperthermia (mEHT) is an adjuvant therapy with demonstrated clinical efficacy for the treatment of various cancer types. In this study, we report that mEHT monotherapy stimulated interleukin‐1 beta (IL‐1β) and interleukin‐6 (IL‐6) expression, and consequently cyclooxygenase 2 (COX‐2), which may favor a cancer‐promoting tumor microenvironment. Thus, we combined mEHT with nonsteroid anti‐inflammatory drugs (NSAIDs): a nonselective aspirin, or the selective COX‐2 inhibitor SC236, in vivo . We demonstrate that NSAIDs synergistically increased the effect of mEHT in the 4T1 TNBC model. Moreover, the strongest tumor destruction ratio was observed in the combination SC236 + mEHT groups. Tumor damage was accompanied by a significant increase in cleaved caspase‐3, suggesting that apoptosis played an important role. IL‐1β and COX‐2 expression were significantly reduced by the combination therapies. In addition, a custom‐made nanostring panel demonstrated significant upregulation of genes participating in the formation of the extracellular matrix. Similarly, in the B16F10 melanoma model, mEHT and aspirin synergistically reduced the number of melanoma nodules in the lungs. In conclusion, mEHT combined with a selective COX‐2 inhibitor may offer a new therapeutic option in TNBC.}, year = {2024}, eissn = {1878-0261}, pages = {1012-1030}, orcid-numbers = {Giunashvili, Nino/0009-0005-2587-3806; Schvarcz, Csaba András/0000-0002-2618-1909; Aloss, Kenan/0000-0003-4806-7477; Major, Enikő/0000-0001-5854-9395; Balogh, Andrea/0000-0002-3007-0793; Benyó, Zoltán/0000-0001-6015-0359; Hamar, Péter/0000-0002-1095-3564} } @article{MTMT:34726330, title = {Mutiplex Analysis of Modulated Electro-Hyperthermia-Induced Local Acute Phase Protein Production in Mouse TNBC Model}, url = {https://m2.mtmt.hu/api/publication/34726330}, author = {Hamar, Péter and Schvarcz, Csaba András and Danics, Lea and Krenács, Tibor and Leroy Viana, Pedro Henrique and Nagy, Á. and Szász, A. and Benyó, Zoltán}, journal-iso = {MOL ONCOL}, journal = {MOLECULAR ONCOLOGY}, volume = {17}, unique-id = {34726330}, issn = {1574-7891}, year = {2023}, eissn = {1878-0261}, pages = {468-469}, orcid-numbers = {Hamar, Péter/0000-0002-1095-3564; Schvarcz, Csaba András/0000-0002-2618-1909; Danics, Lea/0000-0001-8568-4074; Krenács, Tibor/0000-0001-9164-065X; Benyó, Zoltán/0000-0001-6015-0359} } @article{MTMT:34726322, title = {Modulated Electro Hyperthermia Enhances the Delivery and Antitumor Effects of Doxorubicin Encapsulated in Lyso-thermosensitive Liposome in 4T1 Mouse Model}, url = {https://m2.mtmt.hu/api/publication/34726322}, author = {Aloss, Kenan and Schvarcz, Csaba András and Leroy Viana, Pedro Henrique and Bokhari, Syeda Mahak Zahra and Guinasvilli, N. and Bocsi, D. and Koós, Z. and Hamar, Péter}, journal-iso = {MOL ONCOL}, journal = {MOLECULAR ONCOLOGY}, volume = {17}, unique-id = {34726322}, issn = {1574-7891}, year = {2023}, eissn = {1878-0261}, pages = {467-468}, orcid-numbers = {Aloss, Kenan/0000-0003-4806-7477; Schvarcz, Csaba András/0000-0002-2618-1909; Hamar, Péter/0000-0002-1095-3564} } @article{MTMT:34726312, title = {Non-steroid anti-inflammatory treatment enhances the efficacy of modulated electro hyperthermia on triple negative breast cancer and melanoma cancer models in vivo}, url = {https://m2.mtmt.hu/api/publication/34726312}, author = {Giunashvili, Nino and Thomas, Mbuotidem Jeremiah and Leroy Viana, Pedro Henrique and Aloss, Kenan and Bokhari, Syeda Mahak Zahra and Koós, Z. and Dániel, B. and Benyó, Zoltán and Schvarcz, Csaba András and Hamar, Péter}, journal-iso = {MOL ONCOL}, journal = {MOLECULAR ONCOLOGY}, volume = {17}, unique-id = {34726312}, issn = {1574-7891}, year = {2023}, eissn = {1878-0261}, pages = {461-461}, orcid-numbers = {Giunashvili, Nino/0009-0005-2587-3806; Aloss, Kenan/0000-0003-4806-7477; Benyó, Zoltán/0000-0001-6015-0359; Schvarcz, Csaba András/0000-0002-2618-1909; Hamar, Péter/0000-0002-1095-3564} } @article{MTMT:34726279, title = {Inhibition of Triple-Negative Breast Cancer Growth in a Mouse Model –Enhancement of Modulated Electro-Hyperthermia (mEHT) Effects by Heat Shock Factor 1 Inhibition}, url = {https://m2.mtmt.hu/api/publication/34726279}, author = {Leroy Viana, Pedro Henrique and Schvarcz, Csaba András and Danics, Lea and Besztercei, Balázs and Aloss, Kenan and Bokhari, Syeda Mahak Zahra and Giunashvili, Nino and Benyó, Zoltán and Hamar, Péter}, journal-iso = {MOL ONCOL}, journal = {MOLECULAR ONCOLOGY}, volume = {17}, unique-id = {34726279}, issn = {1574-7891}, year = {2023}, eissn = {1878-0261}, pages = {460-461}, orcid-numbers = {Schvarcz, Csaba András/0000-0002-2618-1909; Danics, Lea/0000-0001-8568-4074; Besztercei, Balázs/0000-0002-5636-284X; Aloss, Kenan/0000-0003-4806-7477; Giunashvili, Nino/0009-0005-2587-3806; Benyó, Zoltán/0000-0001-6015-0359; Hamar, Péter/0000-0002-1095-3564} } @article{MTMT:34725681, title = {Synergism between methotrexate and modulated electro-hyperthermia is mediated by H19 lnc-RNA}, url = {https://m2.mtmt.hu/api/publication/34725681}, author = {Schvarcz, Csaba András and Danics, Lea and Forika, Gertrud and Leroy Viana, Pedro Henrique and Krenács, Tibor and Benyó, Zoltán and Vancsik, Tamás and Hamar, Péter}, journal-iso = {MOL ONCOL}, journal = {MOLECULAR ONCOLOGY}, volume = {17}, unique-id = {34725681}, issn = {1574-7891}, year = {2023}, eissn = {1878-0261}, pages = {459-460}, orcid-numbers = {Schvarcz, Csaba András/0000-0002-2618-1909; Danics, Lea/0000-0001-8568-4074; Forika, Gertrud/0000-0001-9622-1040; Krenács, Tibor/0000-0001-9164-065X; Benyó, Zoltán/0000-0001-6015-0359; Hamar, Péter/0000-0002-1095-3564} }