@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:34745967,
	title = {Local Production of Acute Phase Proteins: A Defense Reaction of Cancer Cells to Injury with Focus on Fibrinogen},
	url = {https://m2.mtmt.hu/api/publication/34745967},
	author = {Hamar, Péter},
	doi = {10.3390/ijms25063435},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34745967},
	issn = {1661-6596},
	abstract = {This review is intended to demonstrate that the local production of acute phase proteins (termed local acute phase response (lAPR)) and especially fibrin/fibrinogen (FN) is a defense mechanism of cancer cells to therapy, and inhibition of the lAPR can augment the effectiveness of cancer therapy. Previously we detected a lAPR accompanying tumor cell death during the treatment of triple-negative breast cancer (TNBC) with modulated electro-hyperthermia (mEHT) in mice. We observed a similar lAPR in in hypoxic mouse kidneys. In both models, production of FN chains was predominant among the locally produced acute phase proteins. The production and extracellular release of FN into the tumor microenvironment is a known method of self-defense in tumor cells. We propose that the lAPR is a new, novel cellular defense mechanism like the heat shock response (HSR). In this review, we demonstrate a potential synergism between FN inhibition and mEHT in cancer treatment, suggesting that the effectiveness of mEHT and chemotherapy can be enhanced by inhibiting the HSR and/or the lAPR. Non-anticoagulant inhibition of FN offers potential new therapeutic options for cancer treatment.},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {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:34728797,
	title = {Neutrophils and NADPH Oxidases Are Major Contributors to Mild but Not Severe Ischemic Acute Kidney Injury in Mice},
	url = {https://m2.mtmt.hu/api/publication/34728797},
	author = {Révész, Csaba and Kaucsár, Tamás and Godó, Mária and Bocskai, Krisztián and Krenács, Tibor and Mócsai, Attila and Szénási, Gábor and Hamar, Péter},
	doi = {10.3390/ijms25052948},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34728797},
	issn = {1661-6596},
	abstract = {Upregulation of free radical-generating NADPH oxidases (NOX), xanthine oxidoreductase (XOR), and neutrophil infiltration-induced, NOX2-mediated respiratory burst contribute to renal ischemia–reperfusion injury (IRI), but their roles may depend on the severity of IRI. We investigated the role of NOX, XOR, and neutrophils in developing IRI of various severities. C57BL/6 and Mcl-1ΔMyelo neutrophil-deficient mice were used. Oxidases were silenced by RNA interference (RNAi) or pharmacologically inhibited. Kidney function, morphology, immunohistochemistry and mRNA expression were assessed. After reperfusion, the expression of NOX enzymes and XOR increased until 6 h and from 15 h, respectively, while neutrophil infiltration was prominent from 3 h. NOX4 and XOR silencing or pharmacological XOR inhibition did not protect the kidney from IRI. Attenuation of NOX enzyme-induced oxidative stress by apocynin and neutrophil deficiency improved kidney function and ameliorated morphological damage after mild but not moderate/severe IRI. The IR-induced postischemic renal functional impairment (BUN, Lcn-2), tubular necrosis score, inflammation (TNF-α, F4/80), and decreases in the antioxidant enzyme (GPx3) mRNA expression were attenuated by both apocynin and neutrophil deficiency. Inhibition of NOX enzyme-induced oxidative stress or the lack of infiltration by NOX2-expressing neutrophils can attenuate reperfusion injury after mild but not moderate/severe renal IR.},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {Révész, Csaba/0000-0001-6016-526X; Kaucsár, Tamás/0000-0003-4460-1265; Krenács, Tibor/0000-0001-9164-065X; Mócsai, Attila/0000-0002-0512-1157; Szénási, Gábor/0000-0002-7350-6091; 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:34475014,
	title = {Targeting the heat shock response induced by modulated electro-hyperthermia (mEHT) in cancer},
	url = {https://m2.mtmt.hu/api/publication/34475014},
	author = {Leroy Viana, Pedro Henrique and Hamar, Péter},
	doi = {10.1016/j.bbcan.2023.189069},
	journal-iso = {BBA-REV CANCER},
	journal = {BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER},
	volume = {1879},
	unique-id = {34475014},
	issn = {0304-419X},
	abstract = {The Heat Shock Response (HSR) is a cellular stress reaction crucial for cell survival against stressors, including heat, in both healthy and cancer cells. Modulated electro-hyperthermia (mEHT) is an emerging non-invasive cancer therapy utilizing electromagnetic fields to selectively target cancer cells via temperature-dependent and independent mechanisms. However, mEHT triggers HSR in treated cells. Despite demonstrated efficacy in cancer treatment, understanding the underlying molecular mechanisms for improved therapeutic outcomes remains a focus. This review examines the HSR induced by mEHT in cancer cells, discussing potential strategies to modulate it for enhanced tumor-killing effects. Approaches such as HSF1 gene-knockdown and small molecule inhibitors like KRIBB11 are explored to downregulate the HSR and augment tumor destruction. We emphasize the impact of HSR inhibition on cancer cell viability, mEHT sensitivity, and potential synergistic effects, addressing challenges and future directions. This understanding offers opportunities for optimizing treatment strategies and advancing precision medicine in cancer therapy. © 2023},
	year = {2024},
	eissn = {1879-2561},
	orcid-numbers = {Hamar, Péter/0000-0002-1095-3564}
}

@misc{MTMT:34747635,
	title = {COMPARISON OF LIPOSOMAL DRUG-INDUCED BLOOD PRESSURE CHANGES IN MICE AND RATS},
	url = {https://m2.mtmt.hu/api/publication/34747635},
	author = {Szénási, Gábor and Bakos, Tamás and Őrfi, Erik and Mészáros, Tamás and Hricisák, László and Rosivall, László and Hamar, Péter and Benyó, Zoltán and Szebeni, János and Dézsi, László},
	unique-id = {34747635},
	abstract = {Introduction: Liposomal drugs administered intravenously (i.v.) can induce IgEindependent side effects known as infusion reaction, and also termed as complement 
		activation-related pseudoallergy (CARPA).
		Aim: We aimed to reveal the basic mechanisms of blood pressure changes after i.v.
		injection of amphotericin B-containing liposomes (Abelcet, rats: 10 mg/kg; mice: 30 mg/kg).
		Methods: Male NMRI mice, and wild type or thromboxane prostanoid receptor 
		deficient (TP KO) mice on C57Bl/6 background, as well as male Wistar rats (anesthetized with
		pentobarbital) were used (n=6-8/group). Mean arterial blood pressure was continuously 
		monitored. Blood was collected at 0, 1, 3 10 and 30 min in rats, and from separate groups of 
		mice at 3-5 min after treatment. Plasma C3a and thromboxane B2 (TXB2) concentrations were 
		assayed using ELISA. Blood count was obtained using a hematology analyzer (Abacus Vet5).
		Results: Abelcet caused transient hypertension in mice (10-15 min) and transient 
		hypotension in rats (20-40 min). Abelcet resulted in leucopenia and thrombocytopenia, and
		increased plasma complement C3a and TXB2 concentrations in both species. Complement 
		depletion with cobra venom factor (CVF) lengthened the hypertensive effect in mice and 
		abolished the hypotensive effect in rats. Pretreatment with DF2593A (10 mg/kg, i.v.), a C5a 
		receptor (C5aR) antagonist, lengthened the hypertensive effect of Abelcet in mice and elicited
		a small decrease in the hypotensive effect in rats. Inhibition of C3a receptors with SB290157 
		(10 mg/kg) attenuated the hypertension in mice and enhanced the hypotension in rats, but 
		both effects were rather small. Macrophage depletion with clodronate liposomes in mice 
		lengthened the hypertensive effect similarly to CVF. Pre-treatment with GdCl3 to inhibit 
		macrophages slightly attenuated the hypotensive effect of Abelcet in rats. Inhibition of mast 
		cell activation by cromolyn or C48/80, decreased the hypotensive response in rats, but 
		induced delayed hypotension in mice, respectively. Inhibition of platelet activation using 
		eptifibatide, a platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor inhibitor, lengthened the 
		hypertensive effect in mice, but hardly affected the responses in rats. Abelcet did not change 
		blood pressure in TP KO mice and led to a delayed hypertension after pretreatment with CVF. 
		Conclusion: Our results suggest that complement activation has a small contribution 
		to liposomal drug-induced hypotension, and both macrophages and mast cells contribute to 
		the release of vasoactive mediators in rats. The early hypertensive effect of TXA2 release in 
		mice wasindependent from complement activation, and wasreversed with some delay mainly 
		by the activation of C5aR. Both macrophages and platelets are substantially implicated in the 
		latter effect.},
	year = {2023},
	pages = {73-73},
	orcid-numbers = {Szénási, Gábor/0000-0002-7350-6091; Bakos, Tamás/0000-0002-0569-8343; Őrfi, Erik/0000-0002-2190-0708; Hricisák, László/0000-0001-8320-2166; Rosivall, László/0000-0002-9809-3879; Hamar, Péter/0000-0002-1095-3564; Benyó, Zoltán/0000-0001-6015-0359; Dézsi, László/0000-0002-4190-9793}
}

@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}
}