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Home » Archive » 2019

TDK conference 2019

Investigation of therapy resistance of canine mast cell tumours using flow cytometry functional test
Kórik Csilla - year 5
University of Veterinary Medicine Budapest, Department of Clinical Pathophysiology and Oncology
Supervisors: Dr. Péter Vajdovich, Edina Karai

Abstract:

Mast cell tumors (MCT) are the most common skin tumours in dogs (prevalence 0.27%, 129-265/100.000 dogs). Surgical excision is mostly the first choice of the treatment options. Besides, chemotherapy protocol (vinblastin, prednisolon) can be also used and in case of mutation in the c-kit, the first choice of the treatment is tyrosine kinase inhibitors (TKI). However resistance can occur against drugs used in the therapy. One of the most common reasons of resistance is the overexpression of P170-glycoprotein, also known as MDR1. Some tumour cells with protonpumps use ATP-hydrolysis to release P-gp substrate drugs (for example vinblastin) to the extracellular space.

Our aim was to determine whether parameters calculated from the functional examination of P-gp are reliable prognostic factors of canine mastocytoma.

Tumor cells were extracted from MCT of twenty three dogs and calcein-assay was used. Based on this assay, the numbers of cells with efflux pumps also known calcein negative cells and cells without pumps, calcein positive cells, were counted finally the multidrug resistance activaty factor (MAF) was determined. In this retrospective study several other parameters were compaired to each other for better understanding the MCT mechanisms.

Negative correlation was found between the overall survival time (OST), relaps free period (RFP) of the patients and the chemotherapy pre-treatment (r= -0.53 and r= -0.52, p <0.05). Patients without chemotherapy pre-treatment lived longer and their relaps free period was significantly longer (p= 0.0427). Based on clinical stage category, stage III., IV., histologic (Patnaik) malignant grade, grade III. patients and dogs older than 10 years had significantly shorter OST and RFP value (p <0.05). However, the numbers of calcein positive cells (cells without efflux pumps) showed significantly positive correlation with patients got chemotherapy pre-treatment (r= 0.35), with those who had tumour recurrence (r= 0.41) and with malignant grade (r= 0.38). In case of the MAF values negative correlation was found in the group of chemotherapy pre-treatment (r= -0.47).

Based on our results we can establish that multidrug resistance activaty factor (MAF) can not be used in that way we thought in the prognoses of the canine mastocytoma, because patients with less calcein negativ cells lived longer against their high MAF values. Chemotherapy pre-treatment, such as TKI’s reduce P-gp-mediated resistance and mast cells develop other resistance mechanizms to deactivate the effect of drugs.



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