Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis.

Quantification of Treg cells in peripheral blood and lymph nodes of dogs with multicentric lymphoma / Quantificação de células Treg no sangue periférico e linfonodos de cães com linfoma multicêntrico

Lymphoma is a malignant tumor characterized by cell proliferation of lymphoid origin and corresponds to 90% of all hematopoietic neoplasms of dogs. Regulatory T cells (Tregs) have been the target of many investigations in oncology due to their potential of down-regulating immune responses, as well as ensuring the maintenance of active mechanisms of tumor suppression. The aims of the present study were to compare the percentage of Tregs in peripheral blood between dogs with multicentric lymphoma and healthy animals, together with the percentage of Tregs in peripheral blood and lymph nodes of dogs with multicentric lymphoma. Twenty-six animals were enrolled in the study: 10 healthy dogs comprised the control group (CG) and 16 dogs with multicentric lymphoma comprised the Lymphoma Group (LG). We observed that dogs in the LG showed a significantly higher Tregs expression in peripheral blood compared to the CG. No significant difference was observed between Tregs expression in lymph nodes and peripheral blood of the LG, however. With these results, it is possible to conclude that multicentric lymphoma is a neoplasm with high Tregs expression, which poses this as a condition of interest when investigating treatments that can suppress Regulatory T cells.(AU)

O linfoma é uma neoplasia maligna caracterizada pela proliferação neoplásica de células originadas de tecido linfoide e corresponde a cerca de 90% das neoplasias hematopoiéticas em cães. Células T reguladoras (Tregs) têm sido alvo de diversas investigações na área da oncologia devido ao potencial de regulação negativa da resposta do sistema imune e à manutenção ativa do mecanismo de imunossupressão tumoral. O objetivo do presente estudo foi a comparação da porcentagem de Tregs no sangue periférico entre cães com linfoma multicêntrico e animais saudáveis e a porcentagem de Tregs no sangue periférico e nos linfonodos de cães com linfoma multicêntrico. Foram utilizados 26 animais: 10 cães saudáveis, como grupo controle (CG), e 16 cães com linfoma multicêntrico, como grupo linfoma (LG). Observou-se maior expressão de Tregs no sangue periférico de cães do LG em comparação ao CG. Entretanto, não foi observada diferença significativa entre as expressões de Treg nos linfonodos e no sangue periférico do LG. Com esses resultados, foi possível concluir que o linfoma multicêntrico apresenta alta expressão de Tregs, tornando-se condição interessante para o estudo de tratamentos capazes de suprimir as células T reguladoras.(AU)