PhD Scientific Days 2022
Budapest, 6-7 July 2022
Theoretical Medicine (Poster discussion will take place on the terrace of the room during the Coffee Break)
Inhibition of Triple-Negative Breast Cancer Growth in a Mouse Model – Enhancement of Modulated Electro-Hyperthermia (mEHT) Effects by Heat Shock Factor 1 Inhibition
Előadó neve
Leroy Viana, Pedro Henrique
Előadó munkahelye
Semmelweis University
Előadó telefonszáma
+36702138189
Előadó e-mail címe
pedro.leroy@phd.semmelweis.hu
Az előadás címe
Inhibition of Triple-Negative Breast Cancer Growth in a Mouse Model – Enhancement of Modulated Electro-Hyperthermia (mEHT) Effects by Heat Shock Factor 1 Inhibition
Szerző(k) neve és munkahelye
Viana, Pedro1; Schvarcz, Csaba1; Danics, Lea1; Besztercei, Balázs1; Aloss, Kenan1; Bokhari, Zahra1; Giunashvili, Nino1; Koós, Zoltán1; Hamar, Péter1
1 Semmelweis University, Department of Translational Medicine, Budapest, Hungary
Bemutatás módja
Szóbeli
Szekció
Theoretical Medicine (Poster discussion will take place on the terrace of the room during the Coffee Break)
Language of the presentation
English
Preferred session
Theoretical and Translational Medicine
Összefoglaló szövege
Introduction: Female breast cancer is the most diagnosed cancer worldwide. Triple negative breast cancer (TNBC) is an aggressive type of breast cancer that lacks estrogen receptor, progesterone receptor, and HER2 expression and, therefore, is not sensitive to endocrine therapy. The development of new TNBC treatment strategies has become an urgent clinical need. Modulated electro-hyperthermia (mEHT) is a non-invasive complementary tumor therapy using an electromagnetic field generated by amplitude modulated 13.56 MHz frequency that induces tumor cell destruction.
Aims: We aimed to test the efficiency of mEHT on a murine TNBC cell line in combination with heat shock factor-1 (HSF1) inhibition. It is known that mEHT induces heat shock response (HSR), which can result in thermotolerance. One way to inhibit thermotolerance is knocking out the HSF1 gene. We hypothesized that removal of HSF1 gene sensitizes the transfected tumor cells to mEHT and reduce tumor growth.
Methods: To test this hypothesis, a lentiviral construct to target HSF1 gene was designed. The modified cells were inoculated into the mice mammary gland’s fat pad. Four mEHT treatments were performed every two days and tumor follow-up was done using ultrasound and caliper in the days between treatments. Tumor destruction histology and molecular expression changes were assessed.
Results: In vivo experiments shown reduction of tumor growth and increase of tumor destruction area in HSF1-KO mEHT-treated group (Mean: 28.56 ± 10.71, and Mean: 84.10 ± 10.61, respectively), when compared to Sham group (Mean: 69.80 ± 31.58, and Mean: 23.05 ± 10.4, respectively). Measurement of tumor weight did not show statistical significance, although a tendency in reduction of tumor mass of HSF1-KO mEHT-treated group was observed (Mean: 43.66 ± 20.09, and Sham Mean: 98.02 ± 52.66). The expression of HSF1 RNA level was significantly reduced (Mean: 0.005832 ± 0.001073) and HSP70 RNA expression increased slower in the knockout cells (Mean: 0.01046 ± 0.005662), when compared to Empty Vector Sham (Mean: 0.01330 ± 0.002487) and to Empty Vector mEHT-treated group (0.02273 ± 0.01385), respectively by qPCR.
Conclusion: In conclusion, combined mEHT-therapy with HSF1 inhibition can be a possible new strategy of treating TNBC tumors.
Funding: SE250+ EFOP-3.6.3-VEKOP-16-2017-00009 / SH scholarship - Tempus Public Foundation
University and Doctoral School
Semmelweis University, Doctoral School of Theoretical and Translational Medicine
Supervisor
Prof. Hamar Peter
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
6868
Start
09:15
End
09:30
Authors (legacy)
Viana, Pedro1; Schvarcz, Csaba1; Danics, Lea1; Besztercei, Balázs1; Aloss, Kenan1; Bokhari, Zahra1; Giunashvili, Nino1; Koós, Zoltán1; Hamar, Péter1
1 Semmelweis University, Department of Translational Medicine, Budapest, Hungary