PhD Scientific Days 2024

Poster Session K - Theoretical and Translational Medicine 2.

Potential Regulating Mechanisms behind Modulated Electro-hyperthermia and Antifolate Chemotherapy Synergism

Előadó neve

Dr. Schvarcz, Csaba András

Neptun code

TFNW9G

Előadó munkahelye

Institute of Translational Medicine

Előadó telefonszáma

06308439965

Előadó e-mail címe

schvarcz.csaba.andras@semmelweis.hu

Az előadás címe

Potential Regulating Mechanisms behind Modulated Electro-hyperthermia and Antifolate Chemotherapy Synergism

Szerző(k) neve és munkahelye

Csaba András Schvarcz^1,2, Tamás Vancsik³, Lea Danics³, Gertrúd Forika⁴, Pedro Viana³, Zoltán Benyó³, Péter Hamar³

1: Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; HUN-REN-SU Cerebrovascular and Neurocognitive Diseases Research Group, 1094 Budapest, Hungary
2: HUN-REN-SU Cerebrovascular and Neurocognitive Diseases Research Group, 1094 Budapest, Hungary
3: Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary
4: Department of Pathology and Experimental Cancer Research, 1094 Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session K - Theoretical and Translational Medicine 2.

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Triple Negative Breast Cancer (TNBC) has the worst prognosis among breast cancer types, due to the lack of hormone and HER2 targets. Modulated electro-hyperthermia (mEHT) is a local hyperthermia method, able to transfer heat to solid tumors even in deep regions. MEHT is used in the clinics mostly as complementary treatment for chemotherapy. H19 is Long Non-coding RNA (Lnc RNA), promoting various pro-tumoral cellular mechanisms via regulating pathways including Wnt-β-catenin pathway. Inoculation of 4T1/4T07 in the mammary area of Balb/c mice allows to study TNBC.
Aims: to investigate the potential therapeutic effects of MTX and mEHT combination
Method: mEHT treatment of TNB (4T1) spheroids was performed with in vitro applicator. 4T1/4T07 cells were inoculated into BALB/c mice in vivo. Digital caliper and ultrasound measurements were performed repeatedly for tumor growth follow-up. Sham and mEHT+/-Methotrexate (MTX) treated groups were randomized, based on tumor volume. H19 expression was measured with RT-PCR. Hematoxylin-eosin (H&E) and cleaved caspase-3 (cC3) immunohistochemistry stainings were made from the tumors. Mass Spectrometry (MS) was performed from tumor samples.
Results and discussion: 1x repeated mEHT treatment reduced H19 expression in spheroids (ctrl: 0.004±0.0004, mEHT: 0.0006±0.0002, p<0.0001). H19 expression correlated with tumor aggressiveness (4T07:0.006±0.004 vs 4T1:0.4±0.07, p<0.0001). MTX decreased metastatic area in the lungs and combination of mEHT and MTX inhibited tumor growth with synergistic effectiveness. mEHT induced caspase-mediated apoptosis (cC3+ area: sham: 18.8±11.4, mEHT: 50.9±26.2, MTX: 15.4±9.5, mEHT+MTX: 57.6±13.5%, p<0.0001). Tumor size reduction was accompanied by reduction of H19 expression. H19 was overexpressed by MTX, and reversed by mEHT (sham: 0.16±0.07, mEHT: 0.11±0.06, MTX: 0.21±0.08, mEHT+MTX: 0.11±0.05, p<0.05). β-catenin expression was significantly decreased by mEHT (MS: sham: 23,7 ± 0,3, mEHT: 21,9 ± 0,5 LFQ).
Conclusion: MTX treatment’s anti-tumoral effect is synergistically enhanced by mEHT in TNBC preclinical model. MTX-induced Lnc RNA H19 expression is reversed by mEHT. Decreased activation of Wnt-pathway by mEHT may explain the molecular mechanism of synergism between MTX and mEHT.
Funding: NVKP_16-1-2016-0042; ÚNKP-23-4-I-SE-22; OTKA_K 145998; HUN-REN Hungarian Research Network

University

Semmelweis University

Supervisor

Dr. Péter Hamar

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7523

Start

16:45

End

16:48