The role of the multi-drug resistance 1, p53, b cell lymphoma 2, and bcl 2-associated X genes in the biologic behavior and chemotherapeutic resistance of canine transmissible venereal tumors

Autor: Francisco Pedraza-Ordoñez, Jorge Enrique Pérez, Luis M. Montoya‐Florez, Noeme Sousa Rocha, Juliana M. Alzate
Přispěvatelé: Universidad de Pamplona, Universidad Nacional de Colombia, Pedagogical and Technological University of Colombia, Universidad de Caldas, Universidade Estadual Paulista (Unesp)
Rok vydání: 2018
Předmět:
Male
030213 general clinical medicine
medicine.medical_specialty
Vincristine
Lymphoma
B-Cell
040301 veterinary sciences
medicine.medical_treatment
CTVT chemotherapy
BCL-2
Drug resistance
Real-Time Polymerase Chain Reaction
0403 veterinary science
apoptotic proteins
03 medical and health sciences
0302 clinical medicine
Dogs
Gene expression
medicine
Animals
ATP Binding Cassette Transporter
Subfamily B
Member 1
Dog Diseases
B-cell lymphoma
MDR-1
Venereal Tumors
Veterinary
bcl-2-Associated X Protein
Chemotherapy
General Veterinary
business.industry
04 agricultural and veterinary sciences
medicine.disease
Antineoplastic Agents
Phytogenic
Drug Resistance
Multiple
Lymphoma
Treatment Outcome
Proto-Oncogene Proteins c-bcl-2
Tumor progression
BAX
Cancer research
Disease Progression
Histopathology
Female
Tumor Suppressor Protein p53
business
medicine.drug
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 1939-165X
Popis: Made available in DSpace on 2020-12-12T01:06:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-12-01 Universidad de Caldas Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: Canine transmissible venereal tumors (CTVTs) generally have different cytomorphologic subtypes and phases of progression. Some tumors have variable biologic behavior including a progressive increase in tumor aggressiveness and variable responses to chemotherapy. This behavior is partially due to high p-glycoprotein expression by tumor cells, which leads to the expulsion of chemotherapeutic drugs. Other possible causes include changes in pro- and anti-apoptotic genes from the BCL-2 family and DNA repair systems, which are associated with the p53 gene family. Objectives: We aimed to determine the relative expression of the multi-drug resistance 1 (MDR1), p53, b-cell lymphoma 2 (BCL2), and bcl 2-associated X (BAX) genes in CTVT before and after therapy and establish a relationship with treatment responses, cytomorphologic patterns, and tumor progression identified with histopathology. Methods: RT-qPCR was performed on 21 CTVT tumor samples before and after initiating chemotherapy to determine specific gene expression. Normal canine testicular tissue was used as a negative control for all experiments. Results: MDR1 expression was decreased before and after initiating vincristine therapy in CTVT tumor tissues compared with normal canine testicular tissue; p53 and BAX were overexpressed at both time points compared with normal tissue, and no statistical differences were seen between the different morphologic types. However, BAX expression was decreased in the group with quick therapeutic responses but was still overexpressed compared with normal testicular tissue. In the group with the slowest chemotherapeutic responses, BCL2 was overexpressed. Conclusion: The findings of this study showed a relative increase in MDR1 gene expression in response to chemotherapy and higher expression in plasmacytoid CTVTs compared with the other cytomorphologic patterns. BCL2 overexpression was related to a favorable prognosis, and p53, BAX, and BCL2 were expressed independent of the cytomorphologic CTVT type. All of the genes were expressed independent of tumor progression, as noted on histopathology. Faculty of Agricultural Sciences Veterinary Medicine Department Universidad de Pamplona Faculty of Veterinary Medicine Universidad Nacional de Colombia Research Group in Veterinary Medicine and Husbandry – GIDIMEVETZ Pedagogical and Technological University of Colombia Basic Sciences Department Universidad de Caldas Laboratory of Investigative and Comparative Pathology FMVZ-UNESP Research Group in Veterinary Pathology Animal Health Department Universidad de Caldas Laboratory of Investigative and Comparative Pathology FMVZ-UNESP Universidad de Caldas: 0987014 FAPESP: 2012/19285-2
Databáze: OpenAIRE
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