PhD Scientific Days 2025

Poster Session III. - K: Theoretical and Translational Medicine

Effect of Modulated Electro-hyperthermia on Cancer Cell Metabolism in 4T1 Triple Negative Breast Cancer Mouse Model.

Name of the presenter

Abdalla Qusay Osman Mohamed

Institute/workplace of the presenter

Institute of Translational Medicine, Semmelweis University.

Authors

Qusay O. Abdalla¹, Dániel Bócsi¹, Mohamed I. Elsalahaty¹, Hakim Bahlok Jebur¹, Zoltán Koós¹, Eslam Abdalalem¹, Pedro Henrique Leroy Viana¹, Csaba András Schvarcz¹

1: Semmelweis University, Institute of Translational Medicine, 1094 Budapest, Tűzoltó u. 37-47.

Text of the abstract

Introduction:
Modulated electro-hyperthermia (mEHT) is a selective cancer therapy that applies a radiofrequency current of 13.56 MHz resulting in targeted tumor cells destruction. Modulated electro-hyperthermia causes vascular disruption, hypoxia, and consequently induces the transcriptional regulator hypoxia-inducible factor 1 subunit alpha (HIF-1a), furthermore, HIF-1a plays a vital role in cancer metabolism by promoting the expression of several essential genes that collectively help cancer cells to adapt to hypoxia and survive under low oxygen condition, these genes regulate glucose phosphorylation, glycolysis, antioxidant effects, mitochondrial protection, and angiogenesis all of which contribute to tumor proliferation and growth.
Aims:
To determine mEHT treatment effect on genes that regulate cancer metabolism in triple negative breast cancer.
Method:
Murine triple negative breast cancer cells (4T1) were orthotopically inoculated into the mammary fat pads of female BALB/c mice. Following tumor establishment mice were assigned to two groups: mEHT or sham. Then tumors were harvested for transcriptomic profiling via next-generation sequencing (NGS) and validated with Nanostring technology and mass spectrophotometry confirming the transcriptomic alterations associated with mEHT exposure.
Analyses were performed for several key genes in cancer metabolism, particularly those relevant to the mEHT proposed mechanisms of action.
results:
next-generation sequencing analysis revealed a significant upregulation of HIF-1a in mEHT treated tumors compared to sham (p-value =0.0288). In addition, it revealed overexpression which was significant for most genes induced by HIF-1a in mEHT treated group including (SLC2A4) gene that encodes glucose transporter protein, Hexokinase (HK), lactate dehydrogenase A gene (LDHA), a subunit of LDH enzyme, and vascular endothelial growth factor gene (VEGF) which was confirmed by Nanostring.
Conclusion:
mEHT treatment increases HIF-1α expression, indicating tumor hypoxia and vascular disruption. This led to the upregulation of HIF-1α target genes like SLC2A4, HK, LDHA, VEGF which are involved in anaerobic metabolism and survival under low oxygen, suggesting that mEHT alters the tumor microenvironment and metabolic profile of the cancer cell.
Finding:
SE250-2025-108.