PhD Scientific Days 2022

Translational Medicine II. (Poster discussion will take place in the Aula during the Coffee Break)

Effects of Modulated Electro-Hyperthermia on the vasculature of murine triple negative breast cancer

Text of the abstract

Introduction
Triple negative breast cancer (TNBC) is a highly aggressive breast cancer type with no targeted therapy, hence limited treatment options. Modulated electro-hyperthermia (mEHT) is a novel complementary therapy where a 13.56 MHz radiofrequency current targets cancer cells selectively, inducing tumour damage by thermal and electromagnetic effects. Complementary mEHT treatment can therefore improve the efficacy of available TNBC treatments. inducing tumour damage by thermal and electromagnetic effects. Complementary mEHT treatment can therefore improve the efficacy of available TNBC treatments.
Aims
As we observed vascular damage in treated tumors we aimed to identify the exact pattern and molecular mechanisms of capillary destruction and angiogenesis in our triple negative breast cancer murine model in response to modulated electo-hyperthermia.
Methods
TNBC murine isografts were treated three or five times with an ergonomic pole electrode and LabEHY 200 device at 0.7 ± 0.3 W for 30 min every 48 hours. Tumour growth was monitored with ultrasound and digital callipers. Tumour destruction histology, blood capillary damage and molecular changes were detected using immunohistochemistry, next generation sequencing and RT-qPCR.
Results
mEHT induced capillary damage detected as free red blood cells in the interstitium n TNBC isografts, 24h after 3 mEHT treatments in a time dependent manner starting 4h post treatment. The bleeding peaked at 12h and was significantly reduced by 24h. Similar bleeding was observed after five mEHT treatments and the number of viable blood vessels was significantly reduced.
Significant upregulation of stress related genes in response to mEHT treatment was observed in Multiplex analysis, which may be due to capillary damage mediated hypoxia. Furthermore, angiogenic repair in response to mEHT was detected by a reduction and subsequent continuous upregulation of tumour vasculature marker CD105. Additionally, tumour CD31 staining was reduced at 12h followed by an upregulation after 24 hours.
Conclusion
Our data suggest that mEHT induces blood capillary damage and triggers a stress response that repairs the tumour vasculature 24hour after the last treatment. We aim to further elucidate the mechanistic basis of this stress response, inhibition of which will enhance the effectivity of mEHT.
Funding: EFOP-3.6.3-VEKOP-16-2017-00009