PhD Scientific Days 2022

Pathology and Oncology III. (Poster discussion will take place in the Aula during the Coffee Break)

Mutiplex Analysis of Modulated Electro-Hyperthermia-Induced Local Acute Phase Protein Production in Mouse TNBC Model

Előadó neve

Dr. Csaba András, Schvarcz

Előadó munkahelye

Institute of Translational Medicine, Semmelweis University

Előadó telefonszáma

+36308439965

Előadó e-mail címe

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

Az előadás címe

Mutiplex Analysis of Modulated Electro-Hyperthermia-Induced Local Acute Phase Protein Production in Mouse TNBC Model

Szerző(k) neve és munkahelye

Csaba András Schvarcz1, Lea Danics1, Tibor Krenács2, Pedro Viana1, Nino Giunashvili1, Mahak Naqvi1, Kenan Aloss1, Rita Béres1, Tamás Vancsik1, Ákos Nagy3, András Szász4, Zoltán Benyó1, Tamás Kaucsár1 and Péter Hamar1
1 Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary;
2 1st Department of Pathology and Experimental Cancer Research, Semmelweis University,
1085 Budapest, Hungary
3 Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary
4 Biotechnics Department, Szent Istvan University, H-2040 Budaors, Hungary

Bemutatás módja

Szóbeli

Szekció

Pathology and Oncology III. (Poster discussion will take place in the Aula during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Pathology and Oncology

Összefoglaló szövege

Introduction: Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer type with no anti-hormone and targeted therapy. Modulated electro-hyperthermia (mEHT) is able to selectively destroy solid tumors without harming healthy tissues, based on bioelectric properties of tumors.

Aims: Investigate tumor growth inhibiting effects of mEHT and reveal most significant molecular pathways, induced by mEHT treatment in a TNBC mouse model.

Methods: 410.4-derived mammary carcinoma TNBC cells were inoculated orthotopically into female BALB/c mice and randomized into sham and mEHT groups by tumor size. 30 minute long treatments were performed with Labehy 200 (Oncotherm Ltd.). Tumors were removed 4/12/24/48/72 hour after last treatment and processed for immunohistochemical (IHC) and molecular analysis. Tumor Destruction Ratio (TDR%) was evaluated on H&E slides. Cleaved caspase 3 (cC3) and heat shock protein 70 (HSP70) stainings were performed. RNA and protein isolated from tumors were investigated with NGS, Nanostring and mass spectrometry. mEHT in combination with heat shock inhibition (KRIBB11) was studied in vitro.

Results: mEHT treatment effectively reduced tumor growth and resulted in significantly smaller tumor size (224±38 mm3 vs. mEHT: 106±25 mm3, ) and weight (sham: 288±6 mg vs mEHT: 98±2 mg, p<0.05) in mEHT treated mice, compared to sham without toxicity. HSP70 expression was 6.1x increased and cC3+ tumor area was also significantly higher in treated tumors (p<0.001 and p<0.01). NGS revealed that upregulation of Acute Phase Protein expression was the most remarkable change in mEHT-treated tumors. Upregulated expression of protease inhibitors, fibrinogens, complement components and haptoglobin was validated on both RNA and protein level. KRIBB11 effectively decreased viability of 4T1 cells in vitro, accompanied with inhibition of HSP70 and C4b expression.

Conclusion: Repeated mEHT treatment efficiently inhibited tumor progression in our TNBC mouse model. The most prominent response is a local Acute Phase Protein production, which may be interpreted as a protective mechanism of cancer cells. APPs can serve as molecular targets for inhibitory therapy to potentiate the efficacy of mEHT and other cellular stress-inducing therapy modalities.

Funding: EFOP-3.6.3-VEKOP-16-2017-00009; ÚNKP-21-3-II-SE-64; Dr. Korányi András Alapítvány

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Supervisor

Dr. Péter Hamar

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4160

Start

10:15

End

10:30

Authors (legacy)

Csaba András Schvarcz1, Lea Danics1, Tibor Krenács2, Pedro Viana1, Nino Giunashvili1, Mahak Naqvi1, Kenan Aloss1, Rita Béres1, Tamás Vancsik1, Ákos Nagy3, András Szász4, Zoltán Benyó1, Tamás Kaucsár1 and Péter Hamar1
1 Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary;
2 1st Department of Pathology and Experimental Cancer Research, Semmelweis University,
1085 Budapest, Hungary
3 Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary
4 Biotechnics Department, Szent Istvan University, H-2040 Budaors, Hungary