Conventional-Vincristine Sulfate vs. Modified Protocol of Vincristine Sulfate and L-Asparaginase in Canine Transmissible Venereal Tumor.

Chanokchon Setthawongsin,Anudep Rungsipipat,Somporn Techangamsuwan,Patharakrit Teewasutrakul,Sirikachorn Tangkawattana

doi:10.3389/fvets.2019.00300

Chanokchon Setthawongsin, Anudep Rungsipipat + Show 3 more

Open Access

https://doi.org/10.3389/fvets.2019.00300

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Abstract

Background: Vincristine (VCR) is a mono-chemotherapy for canine transmissible venereal tumor (CTVT). L-asparaginase (LAP) is usually used in combination with other drugs. Previously, LAP-VCR protocol was applied for the CTVT-VCR-resistant cases. However, there were a few reports about using this protocol since the first visit.Aims: To firstly investigate the effectiveness of combining chemotherapy (Vincristine and L-asparaginase, VCR-LAP) in normal CTVT case. Secondly, to compare this protocol with the conventional (Vincristine, VCR) protocol before and during treatment in 24 CTVT dogs.Materials and Methods: Clinical signs, tumor relative volume, and histopathological change [amount of CTVT cells, tumor-infiltrating lymphocytes (TILs), TILs/CTVT ratio, collagen area, and Ki-67 proliferative index (PI)] were the treatment evaluation parameters. Moreover, transcriptome analysis of apoptotic (Bcl-2, Bax), drug-resistant genes (ABCB1, ABCG2), and BCL-2 and BAX expression were also included.Results: Both protocols gave the decreased tumor volume, increased TILs/CTVT ratios and collagen area in the mass. Interestingly, the combination protocol decreased treatment time. There were two resistant cases after treatment with VCR. The expression of Bcl-2 and Bax were decreased, and this may indicate the better response after treatment. Moreover, both drug resistant genes did not increase after treatment.Conclusion: The main finding of this study is that the combination protocol did not only decrease treatment duration time but also gave the effectiveness of treatment outcomes in CTVT cases. Therefore, the application of the new protocol could be used by the field practitioners.

Highlights

Canine transmissible venereal tumor (CTVT) is known as an occurring allograft tumor [1]
All CTVT dogs were based on inclusion criteria: [1] complete blood count (CBC), and serum chemistry profile were in suitable range for chemotherapeutic treatment
The CTVT mass type was anatomically classified into GTVT type for mass, located only in the genital area, ETVT type when the mass is located at other parts of the body within/without involvement of the genital area

Summary

Introduction

Canine transmissible venereal tumor (CTVT) is known as an occurring allograft tumor [1]. P-glycoprotein (P-gp) and multidrug-resistant protein 1 (MDR1) are encoded by the ABCB1 gene. The drug resistance in canine multicentric lymphoma is associated with upregulation of ABCB1 and ABCG2 genes [17]. These genes may be involved in efflux of vinca alkaloid drugs as well as doxorubicin, which is chemotherapeutic drug used for CTVT treatment. Previous studies reported that there was an existing modulator effect of vincristine on MDR-1 gene expression. It was higher in CTVT cells and showed higher survival level after vincristine application [18]. Vincristine (VCR) is a mono-chemotherapy for canine transmissible venereal tumor (CTVT). There were a few reports about using this protocol since the first visit

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Conclusion