Lea Danics1, Csaba Schvarcz1, Tamás Kaucsár1, Tamás Vancsik2, Tibor Krenács2, Zoltán Benyó1, Péter Hamar1
1 Institute of Clinical Experimental Research / Semmelweis University, Budapest
2 1st Department of Pathology and Experimental Cancer Research / Semmelweis University, Budapest
Introduction: The effective therapy of triple-negative breast cancer (TNBC) has not yet been achieved. Modulated electro-hyperthermia (mEHT) is a novel adjuvant antitumor therapeutic approach, based on the highly selective heating of the tumorous tissue by a 13.56 MHz radiofrequency current promoted electric field.
Aims: Our aim was to investigate the effects of mEHT on a triple-negative mammary carcinoma bearing mouse model.
Method: 4T1 cells transfected with firefly luciferase were inoculated orthotopically in immunocompetent female Blab/c mice. The isografts were treated with mEHT on day 3 and 5 after inoculation. Tumor growth was measured in vivo by IVIS Lumia system (Perkin Elmer), digital caliper and ultrasound (Phillips Sonos 5500) before and after treatments. Mice were euthanized on day 7 after inoculation and the tumors were harvested and processed for histology. The ratio of the damaged area compared to the whole tumor area (Tissue Damage Ratio, TDR) was evaluated on H&E stained sections, while a common damage-associated molecular signal, HSP70 was analyzed on immunohistochemical staining with HistoQuant module of CaseViewer Software (3DHistech).
Results: There was a significant decrease in tumor growth measured by IVIS in the mEHT treated group (mEHT: 7.1*108 p/s vs sham: 13.5*108 p/s, p<0.05), which couldn’t be detected by the less sensitive caliper (mEHT: 51.17±4.86 mm3 vs sham: 52.36±10.25 mm3, p=0.93) and ultrasound (mEHT: 73.29±22.18 mm3 vs sham: 74.87±7.95 mm3, p=0.52) measurements. Furthermore, the tumor damage ratio (fold change: 4.1, p<0.05) and the HSP70 positive signal around the damaged area (fold change: 12.9, p<0.05) was significantly higher in the mEHT treated group compared to the sham group.
Conclusion: Our findings suggest, that mEHT could be a possible alternative adjuvant therapeutic strategy for TNBC cancer patients. We plan next generation sequencing to elucidate the biological mechanism behind the effects of mEHT.
Doctoral School: Basic and Translational Medicine
Program: 02. The Mechanisms of Normal and Pathologic Functions of the Circulatory System
Supervisor: Péter Hamar, Tamás Kaucsár
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