ABSTRACT Objective. To describe the prevalence of canine mammary gland tumors (CMT) in females in the municipality of Manizales-Colombia from 2014-2017. Materials and methods. A database of 15961 patients was consolidated. The variables analyzed were, breed, age, reproductive history, weight, diet type and clinical characterization of the tumor with the TNM (tumor-node-metastases) staging system. The statistical analysis include Pearson's chi-squared test with Yates correction for continuity and Fisher's exact test (p<0.05), relative risk and odds ratio (CI95%) and Kaplan-Meier estimator for survival analysis. Results. The incidence in purebred dogs was 79.14%, with a peak at the average age of 9.3 years old. Pearson's chi-squared test and the relative risk and odds ratios indicated a high risk for purebreds (p=0.019, 3.96/100, 1.64, respectively). Females of ages between 9 and 12 years old showed a 74% likelihood of developing a mammary tumor. No found significant relation to weight or reproductive stage but indeed a high association with homemade diet (p<0.001). The inguinal mammary pairs were the most affected (6.9%). The Kaplan-Meier estimate showed a higher survival of surgically-intervened patients, with 2013 days of survival after diagnosis with surgery compared to 1484 days without surgery. Conclusions. The study confirmed the relevance of risk factors, breed type, age, body condition and diet type in the mammary tumor presentation. Furthermore, it highlights the need for improving and integrating the veterinary diagnostic information systems, considering their importance in public health.

RESUMEN Objetivo. Describir la prevalencia del tumor mamario canino (TMC) en hembras en el municipio de Manizales-Colombia durante 2014-2017. Materiales y métodos. Se consolidó una base de datos de 15961 pacientes. Las variables analizadas fueron raza, edad, historia reproductiva, condición corporal, tipo de dieta, y caracterización clínica del tumor mediante el sistema de estadificación tumor-nódulo-metástasis (TNM). El análisis estadístico incluyó prueba de chi-cuadrado de Pearson con corrección de Yates, prueba exacta de Fisher (p<0.05), riesgo relativo, oportunidad relativa (IC95%) y análisis de supervivencia de Kaplan-Meier. Resultados. La incidencia en perros de razas puras fue 79.14%, con un pico promedio a la edad de 9.3 años. La prueba chi-cuadrado de Pearson, el riesgo relativo y las oportunidades relativas mostraron un riesgo alto para razas puras (p=0.019, 3.96/100, 1.64, respectivamente). Hembras entre los 9 y 12 años mostraron una probabilidad del 74% de desarrollo de tumor mamario. No se encontró una relación significativa entre la masa corporal o estado reproductivo pero una elevada asociación con la dita casera (p<0.001). Los pares inguinales mamarios fueron los más afectados (6.9%). La estimación de Kaplan-Meier mostró una alta supervivencia para pacientes intervenidas quirúrgicamente, con 2013 días después del diagnóstico con cirugía en comparación con 1484 días sin cirugía. Conclusiones. El estudio confirma la relevancia de los factores de riesgo: tipo de raza, edad, condición corporal y tipo de dieta en la presentación de tumor mamario. Además, se destaca la necesidad de mejorar e integrar los sistemas de información de diagnóstico veterinario, considerando su importancia en la salud pública.

O objetivo deste trabalho foi avaliar o efeito do tratamento com talidomida no carcinoma mamário murino 4T1. Após a suspensão de células 4T1, estas foram inoculadas no flanco esquerdo para obtenção de tumor sólido. Depois de cinco dias de inoculação, o grupo tratado recebeu, por via oral, 150 mg/kg de talidomida por sete dias. Os tumores foram mensurados a cada 48 horas e ao final do experimento. Sangue total foi coletado para análise hematológica. Os resultados sugerem que a terapêutica com talidomida aumenta o número de leucócitos circulantes no carcinoma mamário murino 4T1. Essa resposta foi acompanhada de uma diminuição do crescimento tumoral.

The aim of this study was to evaluate the therapy effect of thalidomide in the 4T1 murine mammary carcinoma. 4T1 cell suspension was injected into the posterior left flank of all animals to obtain solid tumors. Five days after inoculation, the treatment group was orally administered 150 mg/kg of thalidomide for seven days. Tumors were measured every 48 hours until the end of treatment. Whole blood was collected for hematology analysis. Our results suggest that thalidomide therapy increase the number of circulating leukocytes in the 4T1 murine mammary carcinoma, and this response is accompanied by a decrease in tumor growth.

INTRODUÇÃO E OBJETIVO: A proteína Kint3-4 originou-se a partir de uma recombinação genética dos segmentos K1-3 e K1--4 do plasminogênio humano e é reconhecida por seu potencial anti-inflamatório e antiangiogênico. Este estudo teve como objetivo avaliar o efeito da proteína Kint3-4 no desenvolvimento de tumores em camundongos inoculados com células do tumor de Ehrlich. MÉTODOS: O fragmento de proteína foi obtido por uma técnica de clonagem e transformação de Pichia pastoris. Três diferentes protocolos foram avaliados após a inoculação das células tumorais: no início (0-6 dias), no pico (0-12 dias) e após o pico (0-18 dias) de crescimento do tumor. Foram analisados o crescimento do tumor e as características histomorfológica e imuno-histoquímica com CDC47 (marcador de proliferação celular) e CD31 (marcador de vasos sanguíneos). RESULTADOS: Os animais tratados com a proteína Kint3-4 (150 µg/kg/48 h) nos três diferentes protocolos apresentaram menor crescimento do tumor. Áreas de inflamação e tumor também foram reduzidas, avaliadas por exame histológico. Além disso, a menor taxa de proliferação das células tumorais e a baixa densidade de microvasos foram observadas nos animais tratados com proteína Kint3-4 em comparação com o grupocontrole. CONCLUSÃO: A participação da proteína recombinante Kint3-4 na angiogênese tumoral e no controle da proliferação de células malignas abre perspectivas para seu uso no tratamento clínico como antiangiogênico.

INTRODUCTION AND OBJECTIVE: Kint3-4 protein, originated from a genetic recombination of K1-3 and K1-4 human plasminogen segments, is recognized for its antiangiogenic and anti-inflammatory potential. This study aimed to evaluate the effect of Kint3-4 protein on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. METHODS: The protein fragment was obtained from Pichia pastoris cloning and transformation. After tumor cell inoculation three different protocols were used to assess tumor growth: beginning (0-6 days), peak (0-12 days) and after peak (0-18 days). We analyzed tumor growth, histomorphological characteristics and immunohistochemistry by use of CDC47 (cellular proliferation marker) and CD31 (blood vessel marker). RESULTS: Animals treated with Kint3-4 protein (150 µg/kg/48 h) showed lower tumor growth in all protocols. Based on histological assessment, inflammation and tumor areas were also reduced. Moreover, both the lowest rate of tumor cell proliferation and low microvessel density were observed in animals treated with Kint3-4 protein compared with the untreated control group. CONCLUSION: The effect of Kint3-4 recombinant protein on tumor angiogenesis and control of malignant cell proliferation enhances the prospects of its use in clinical and antiangiogenic treatment.

O objetivo deste estudo foi avaliar a histomorfometria e a taxa de proliferação e apoptose da glândula mamária de ratas tratadas com tiroxina pela imuno-expressão de CDC-47 e caspase-3, respectivamente. Também foi avaliado o desenvolvimento dos filhotes de ratas tratadas com tiroxina. Foram utilizadas 36 ratas distribuídas em dois grupos, tratado com tiroxina e controle. Após 60 dias de tratamento com tiroxina, as ratas foram acasaladas. Seis animais/grupo foram sacrificados no 2º e 21º dias de lactação e no 5º dia após o desmame. Houve diferença significativa entre grupos apenas no quinto dia após o desmame. O tratamento com tiroxina aumentou a taxa de apoptose caracterizada pela maior expressão de caspase-3 nas células do epitélio mamário. As mães tratadas com tiroxina apresentaram comportamento alterado, mas não houve diferença significativa no que se refere aos cuidados com o filhote quanto a higienização e aquecimento. Levando-se em consideração o sexo e o tamanho da ninhada, os filhotes das ratas tratadas com tiroxina e controle não apresentaram diferença significativa de peso ao desmame. Conclui-se que a administração de baixas doses de tiroxina aumenta a taxa de apoptose, caracterizada pelo aumento da expressão de caspase-3 no epitélio mamário cinco dias após o desmame, mas não altera a taxa de proliferação celular e o comportamento materno.

The purpose of this study was to evaluate mammary gland histomorphometry and proliferation rate and apoptosis of thyroxine-treated rats by CDC-47 and caspase-3 immunoexpression. The development of thyroxine-treated rats offspring was also evaluated. Thirty-six female rats were used, distributed in two groups, treated and non-treated with thyroxine. After 60 days of treatment, with thyroxine, rats were mated. Six animals/group were sacrificed on the 2nd and 21st days of lactation and on the 5th day after weaning. A significant difference was observed between groups only on the 5th day after weaning. Thyroxine treatment increased apoptosis rate, which was characterized by a higher caspase-3 expression in mammary epithelial cells. Thyroxine-treated mothers presented changed behavior, but there was no significant difference regarding taking care of offspring, as for cleaning offspring and keeping them warm. Taking into account sex and size of offspring, those from control and thyroxine-treated mothers presented no significant difference of weight and weaning. In conclusion, administering low doses of thyroxine increases apoptosis rate, which is characterized by the increased caspase-3 immunoexpression in mammary epithelial cells 5 days after weaning. But does not affect proliferation rate and development of thyroxine-treated rats offspring.

Foi estudado o efeito do hipotireoidismo, induzido pelo propiltiouracil (PTU), no tumor de Ehrlich sólido, implantado em camundongos fêmeas adultas castradas ou não. Foram utilizados 40 animais distribuídos em quatro grupos: hipotireóideo castrado, hipotireóideo não castrado, eutireóideo castrado e eutireóideo não castrado. Os animais receberam uma injeção de células neoplásicas no coxim plantar esquerdo. A curva de crescimento tumoral foi determinada por mensurações da pata inoculada durante 12 dias quando os animais foram necropsiados. A hipofunção tireoidiana reduziu o tamanho do tumor de Ehrlich nos animais castrados. Embora o crescimento neoplásico tenha sido menor, o diâmetro nuclear médio e o número de regiões organizadoras de nucléolos (NORs) e de mitoses/campo foram maiores. Conclui-se que o hipotireoidismo retarda o crescimento do tumor de Ehrlich sólido, sem alterar as características celulares de malignidade, que o efeito isolado da castração causa alterações discretas e que a associação hipotireoidismo-castração potencializa o retardo do crescimento do tumor de Ehrlich sólido.

The effect of hypothyroidism on the solid form of the Ehrlich tumor in intact or castrated adult female mice was studied. Hypothyroidism was induced by treatment with propylthiouracil (PTU). Forty mice were divided into four groups: castrated hypothyroid, intact hypothyroid, castrated euthyroid, and intact euthyroid. The mice were inoculated with suspension cells into the left footpad. The tumor growth curve was determined by measuring the inoculated footpad during 12 days. At the end of the experimental period the mice were sacrificed. Hypothyroidism was associated with a reduction in size of the tumor only in the castrated animals. Although the neoplastic growth was lower, mean nuclear diameter, number of nucleolar organizer regions (NORs), and area of mitosis were higher. In conclusion, hypothyroidism resulted in a delayed growth of the tumor, but it did not affect the malignant features of the neoplastic cells. In addition, the isolated effect of castration caused only mild alterations, whereas hypothyroidism associated with castration resulted in a more prominent delay in the growth rate of the Ehrlich tumor.