PhD Scientific Days 2020

Theoretical and Translational IV. Posters

Effects of Modulated Electro-hyperthermia on Triple Negative Mouse Breast Cancer with Differential Metastatic Potential

Előadó neve

Dr. Schvarcz, Csaba András

Előadó munkahelye

Institute of Translational Medicine

Előadó telefonszáma

+36308439965

Előadó e-mail címe

schvarcz.csaba-andras@med.semmelweis-univ.hu

Az előadás címe

Effects of Modulated Electro-hyperthermia on Triple Negative Mouse Breast Cancer with Differential Metastatic Potential

Szerző(k) neve és munkahelye

Csaba Schvarcz1, Lea Danics1, Tamás Vancsik2, Gertrud Forika2, Tibor Krenács2, Zoltán Benyó1, Tamás Kaucsár1, Péter Hamar1
1 Institute of Translational Medicine, Semmelweis University, Budapest
2 1st Department of Pathology and Experimental Cancer Research

Szekció

Theoretical and Translational IV. Posters

Language of the presentation

Hungarian

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Pathology and Oncology

Összefoglaló szövege

Introduction: Breast cancer is the most common malignancy among women. In triple negative breast cancer (TNBC) lack of receptors excludes hormone- and HER2-targeted-therapies. Modulated electro-hyperthermia (mEHT) is a possible complementary treatment. We investigated two distinctly progressing isogenic mouse TNBC clones.
Aims: Our aim was to investigate the effects of modulated electro-hyperthermia in non-metastatic and highly metastatic triple-negative mammary carcinoma bearing mouse models.
Methods: 4T1 (more aggressive) and 4T07 (less aggressive) cells were inoculated orthotopically into female BALB/c mice. Tumor growth was monitored by caliper and ultrasound (Phillips Sonos 5500). Animals were randomized into sham (n=10) and mEHT (n=11) treated groups 6 days after inoculation. Animals received mEHT treatment 3 times in every 48 hours with Labehy 200 (Oncotherm Ltd.). On day 12, animals were euthanized, tumors were dissected, weighed and processed. Histology slides were digitalized and evaluated with HistoQuant of Caseviewer (3DHistech Ltd.) Tumor Destruction Ratio (TDR) was evaluated on cleaved caspase 3 and H&E stained slides. Heat-shock protein (HSP70) and Ki67 proliferation marker were evaluated (relative mask area). Immune-related markers (T-lymphocyte: CD4, CD8) and immune-checkpoint molecules (PD-1, PD-L1) were measured by quantitative PCR normalized to GAPDH.
Results: mEHT treatment reduced the size and weight (sham: 199.7± 17.35 mg vs mEHT: 139.6 ± 12.07 mg, p<0.001) of 4T1 but not 4T07 tumors (sham: 91 .40± 33.14 mg vs mEHT: 102.3± 39.77 mg, ns). mEHT increased TDR and HSP70 in all treated mice. Ki67 strong positive nuclei were not different from sham mice in either model. Markers of immune infiltration and immune checkpoint inhibitor molecules had an order of magnitude lower expression in the 4T1 model. 24 hours after the last treatment mEHT reduced both tumor cell- and infiltrating lymphocyte-count. However, both infiltrating immune cells and checkpoint molecules increased compared to sham, if tumors were removed 96 hours after the last treatment suggesting a possible immune-stimulatory role of mEHT.
Conclusion: 4T07 tumors grew slower supporting that they have a less aggressive phenotype. The effect of mEHT treatment on TNBC was related to heat-shock response and was more effective against the more aggressive 4T1 type TNBC.

Additional Information

support: NVKP_16-1-2016-0042; Dr. Korányi András az Egészségmegőrzés és Egészségkultúra Fejlesztéséért Alapítvány

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4160

Start

12:49

End

12:52

Authors (legacy)

Csaba Schvarcz1, Lea Danics1, Tamás Vancsik2, Gertrud Forika2, Tibor Krenács2, Zoltán Benyó1, Tamás Kaucsár1, Péter Hamar1
1 Institute of Translational Medicine, Semmelweis University, Budapest
2 1st Department of Pathology and Experimental Cancer Research