<abstract xmlns="http://www.w3.org/1999/xhtml"><p>The main problems that cause unresponsiveness to an anti-neoplastic drug are the overexpression of drug resistant and anti-apoptotic proteins in tumor cells. In a rescue protocol we evaluated the ability of toceranib phosphate concurrent with lomustine (CCNU) or L-asparaginase and vincristine to decrease drug resistant and apoptotic proteins in relapsed and refractory canine lymphomas. The peripheral blood samples were collected before and after the rescue treatment from fourteen dogs that were refractory to cyclophosphamide-vincristine-prednisolone (COP) or COP-doxorubicin (CHOP) treatment and had recurrent multicentric lymphoma. The mRNA expression level of <italic>ABCB1</italic>, <italic>ABCG2</italic>, <italic>Bcl2</italic> and <italic>Bax</italic> were determined by quantitative real-time PCR. The fold-change in <italic>ABCB1</italic>, <italic>ABCG2</italic>, <italic>Bcl2</italic> and <italic>Bax</italic> mRNA levels were analyzed in correlation with the progression-free survival (PFS). After the rescue treatment, the <italic>ABCB1</italic> and <italic>ABCG2</italic> mRNA expression levels were 1.57- and 1.85-fold lower (<italic>p</italic> = 0.4 and <italic>p</italic> = 0.87), respectively, compared to pre-treatment. Bcl2/Bax ratio was numerically but not significantly decreased 1.02-fold (<italic>p</italic> = 0.74). The overall response rate of this protocol was 50% with a median PFS of 79 days (range 14-207 days). The low medians of relative expression levels of <italic>ABCB1</italic>, <italic>ABCG2</italic> and Bcl2/Bax ratio group did not correlate with the clinical outcomes when compared to the high medians of relative expression levels, and likewise with the clinical stage, immunophenotype, histological grade and sub-stage. Therefore, the administration of a rescue drug with toceranib phosphate might be beneficial in refractory and relapsed canine lymphoma.</p></abstract>

The main problems that cause unresponsiveness to an anti-neoplastic drug are the overexpression of drug resistant and anti-apoptotic proteins in tumor cells. In a rescue protocol we evaluated the ability of toceranib phosphate concurrent with lomustine (CCNU) or L-asparaginase and vincristine to decrease drug resistant and apoptotic proteins in relapsed and refractory canine lymphomas. The peripheral blood samples were collected before and after the rescue treatment from fourteen dogs that were refractory to cyclophosphamide-vincristine-prednisolone (COP) or COP-doxorubicin (CHOP) treatment and had recurrent multicentric lymphoma. The mRNA expression level of ABCB1, ABCG2, Bcl2 and Bax were determined by quantitative real-time PCR. The fold-change in ABCB1, ABCG2, Bcl2 and Bax mRNA levels were analyzed in correlation with the progression-free survival (PFS). After the rescue treatment, the ABCB1 and ABCG2 mRNA expression levels were 1.57- and 1.85-fold lower (p = 0.4 and p = 0.87), respectively, compared to pre-treatment. Bcl2/Bax ratio was numerically but not significantly decreased 1.02-fold (p = 0.74). The overall response rate of this protocol was 50% with a median PFS of 79 days (range 14-207 days). The low medians of relative expression levels of ABCB1, ABCG2 and Bcl2/Bax ratio group did not correlate with the clinical outcomes when compared to the high medians of relative expression levels, and likewise with the clinical stage, immunophenotype, histological grade and sub-stage. Therefore, the administration of a rescue drug with toceranib phosphate might be beneficial in refractory and relapsed canine lymphoma.

Transcriptome analysis of <italic>ABCB1</italic>, <italic>ABCG2</italic> and the <italic>BCL2/BAX</italic> ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol

Companion Animal Cancer Research Unit, Department of Pathology, Faculty of Veterinary Science

Oncology Clinic, Small Animal Teaching Hospital, Faculty of Veterinary Science

Department of Veterinary Pathobiology, Faculty of Veterinary Medicine

Acta Veterinaria

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Transcriptome analysis of ,  and the  ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol

The main problems that cause unresponsiveness to an anti-neoplastic drug are the overexpression of drug resistant and anti-apoptotic proteins in tumor cells....

Transcriptome analysis of ABCB1, ABCG2 and the BCL2/BAX ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol

Publié en ligne: 27 mars 2018

Pages: 16 - 31

Reçu: 21 mai 2017

Accepté: 31 oct. 2017

DOI: https://doi.org/10.2478/acve-2018-0002

Mots clés
relapsed/refractory lymphoma

© 2018 Sirintra Sirivisoot et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Transcriptome analysis of ABCB1, ABCG2 and the BCL2/BAX ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol

Publié en ligne: 27 mars 2018

Pages: 16 - 31

Reçu: 21 mai 2017

Accepté: 31 oct. 2017

DOI: https://doi.org/10.2478/acve-2018-0002

Mots clésrelapsed/refractory lymphoma

© 2018 Sirintra Sirivisoot et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mots clés
relapsed/refractory lymphoma