Transcriptome analysis of ABCB1, ABCG2 and the BCL2/BAX 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. In a rescue protocol we evaluated the ability of toceranib phosphate concurrent with lomustine (CCNU) or L-asparaginase and vincristine to dec...

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Autores principales: Sirivisoot Sirintra, Teewasutrakul Patharakrit, Rungsipipat Anudep, Tangkawattana Sirikachorn, Techangamsuwan Somporn
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Publicado: Sciendo 2018
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spelling oai:doaj.org-article:aa8a9d264be6401f91881cf553ba45af2021-11-17T21:27:52ZTranscriptome analysis of ABCB1, ABCG2 and the BCL2/BAX ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol1820-744810.2478/acve-2018-0002https://doaj.org/article/aa8a9d264be6401f91881cf553ba45af2018-03-01T00:00:00Zhttps://doi.org/10.2478/acve-2018-0002https://doaj.org/toc/1820-7448The 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.Sirivisoot SirintraTeewasutrakul PatharakritRungsipipat AnudepTangkawattana SirikachornTechangamsuwan SompornSciendoarticleabcb1abcg2baxbcl2relapsed/refractory lymphomaVeterinary medicineSF600-1100ENActa Veterinaria, Vol 68, Iss 1, Pp 16-31 (2018)
institution DOAJ
collection DOAJ
language EN
topic abcb1
abcg2
bax
bcl2
relapsed/refractory lymphoma
Veterinary medicine
SF600-1100
spellingShingle abcb1
abcg2
bax
bcl2
relapsed/refractory lymphoma
Veterinary medicine
SF600-1100
Sirivisoot Sirintra
Teewasutrakul Patharakrit
Rungsipipat Anudep
Tangkawattana Sirikachorn
Techangamsuwan Somporn
Transcriptome analysis of ABCB1, ABCG2 and the BCL2/BAX ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol
description 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.
format article
author Sirivisoot Sirintra
Teewasutrakul Patharakrit
Rungsipipat Anudep
Tangkawattana Sirikachorn
Techangamsuwan Somporn
author_facet Sirivisoot Sirintra
Teewasutrakul Patharakrit
Rungsipipat Anudep
Tangkawattana Sirikachorn
Techangamsuwan Somporn
author_sort Sirivisoot Sirintra
title Transcriptome analysis of ABCB1, ABCG2 and the BCL2/BAX ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol
title_short Transcriptome analysis of ABCB1, ABCG2 and the BCL2/BAX ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol
title_full Transcriptome analysis of ABCB1, ABCG2 and the BCL2/BAX ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol
title_fullStr Transcriptome analysis of ABCB1, ABCG2 and the BCL2/BAX ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol
title_full_unstemmed Transcriptome analysis of ABCB1, ABCG2 and the BCL2/BAX ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol
title_sort transcriptome analysis of abcb1, abcg2 and the bcl2/bax ratio in refractory and relapsed canine lymphomas under treatment and rescue protocol
publisher Sciendo
publishDate 2018
url https://doaj.org/article/aa8a9d264be6401f91881cf553ba45af
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AT teewasutrakulpatharakrit transcriptomeanalysisofabcb1abcg2andthebcl2baxratioinrefractoryandrelapsedcaninelymphomasundertreatmentandrescueprotocol
AT rungsipipatanudep transcriptomeanalysisofabcb1abcg2andthebcl2baxratioinrefractoryandrelapsedcaninelymphomasundertreatmentandrescueprotocol
AT tangkawattanasirikachorn transcriptomeanalysisofabcb1abcg2andthebcl2baxratioinrefractoryandrelapsedcaninelymphomasundertreatmentandrescueprotocol
AT techangamsuwansomporn transcriptomeanalysisofabcb1abcg2andthebcl2baxratioinrefractoryandrelapsedcaninelymphomasundertreatmentandrescueprotocol
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