Theoretical and Translational I. Posters
Dr. Forika, Gertrud
1st Department of Pathology and Experimental Cancer Research
003614591500-54432
forika_gertrud@yahoo.com
Apoptosis and DNA Damage Caused by Modulated Electro-Hyperthermia in Preirradiated Pancreas Adenocarcinoma Cell Line
Gertrud Forika1, Andrea Balogh2, Tamás Vancsik2, Zoltán Benyó2, Tibor Krenács1
1Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary
2Semmelweis University, Institute of Translational Medicine, Budapest, Hungary
Theoretical and Translational I. Posters
Hungarian
Theoretical and Translational Medicine
Pathology and Oncology
Aim: Malignant tumors of the pancreas respond very poorly to classical oncotherapy. The survival of patients with inoperable pancreas adenocarcinomas is poor despite the sophisticated guidelines of using newest chemotherapy drugs. The high resistance of tumor cells is attributed mostly to the upregulation of the survival mechanisms.
Modulated electro-hyperthermia (mEHT) is a complementary non-invasive cancer treatment using impedance-coupled radiofrequency to generate selective heat of <42°C. We have tested the effect of mEHT after irradiation on a radioresistant pancreatic adenocarcinoma cell line Panc1.
Method: Panc1 pancreas adenocarcinoma cells grown on coverslips were treated in monotherapy using either mEHT (1 hour mEHT at 42°C) or radiotherapy (2 Gy using 137Cs) and by combining these treatments: irradiation followed by mEHT. The results were compared to each other and to untreated controls concerning viable cell number, cell stress, apoptotic ratio, DNA double-strand breaks and DAMP protein levels and localization. Detection and quantification of changes in various protein expression was done using flow cytometry , digital microscopy.
Results: 24 hours post-mEHT treatment the viable cell number decreased significantly in all treated groups. Hematoxylin-eosin morphology revealed apoptosis specific changes including nuclear shrinkage, chromatin condensation and apoptotic bodies especially in groups treated with mEHT only or in combination therapy. The apoptotic ratio was the highest in groups receiving both mEHT and irradiation and significant increase was measured also after mEHT monotherapy. Also, cleaved/activated caspase 3 positive nuclei increased significantly in these two treatment groups. Furthermore, significantly higher number of H2AX nuclear positive tumor cells were detected indicating DNA double-strand breaks after mEHT treatment after irradiation.
Conclusion: The molecular changes showed efficient tumor destruction of mEHT monotherapy or combined with irradiation. The detected apoptosis was mainly caspase 3 dependent. Though irradiation alone had no major effect on Panc1 cells, its combination with mEHT resolved the irradiation resistance and thus improved the efficiency of radiotherapy.
This study was funded by NKFIH-NVKP_16-1-2016-0042
Szóbeli
Szabad
elfogadva
poszter
nem rendelkezett róla
2211
11:32
11:35
Gertrud Forika1, Andrea Balogh2, Tamás Vancsik2, Zoltán Benyó2, Tibor Krenács1
1Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary
2Semmelweis University, Institute of Translational Medicine, Budapest, Hungary