Cytotoxic effects of crotoxin from Crotalus durissus terrificus snake in canine mammary tumor cell lines

Background: Mammary gland tumors are the most prevalent neoplasm in intact female dogs, and they are good natural models to study comparative oncology. Most canine mammary malignancies, as in women, are commonly refractory to conventional therapies and demand continuous new therapeutic approaches. Crotalus durissus terrificus, also called rattlesnake, has more than 60 different proteins in its venom with multiple pharmaceutical uses, such as antitumor, antiviral, and antimicrobial action. Crotoxin, a potent β-neurotoxin formed by the junction of two subunits, a basic subunit (CB-PLA2) and an acidic subunit (crotapotin), has already been reported to have anticancer properties in different types of cancers. Methods: In this work, we describe the cytotoxic potential of crotoxin and its subunits compared to doxorubicin (drug of choice) in two canine mammary carcinoma cell lines. Results: Crotoxin, CB-PLA2, crotalic venom, and doxorubicin decreased cell viability and the ability to migrate in a dose-dependent manner, and crotapotin did not present an antitumoral effect. For all compounds, the predominant cell death mechanism was apoptosis. In addition, crotoxin did not show toxicity in normal canine mammary gland cells. Conclusion: Therefore, this work showed that crotoxin and CB-PLA2 had cytotoxic activity, migration inhibition, and pro-apoptotic potential in canine mammary gland carcinoma cell lines, making their possible use in cancer research.

Infiltrating mammary carcinoma in a cat with a congenital disorder: prognostic interest of histological examination / Carcinoma mamario infiltrante en una gata con un trastorno congénito: interés pronóstico del examen histológico

Resumen En esta publicación se describe el manejo y la evolución clínica de un carcinoma mamario felino (CMF) maligno en una gata mestiza de ocho años de edad con un trastorno congénito. La eficacia de la extirpación de la masa tumoral y el pronóstico del caso se establecieron mediante el examen histológico de rutina postoperatorio. Tras una mastectomía completa se extirpó un bulto de 6 cm de diámetro en la glándula mamaria torácica izquierda de aspecto multinodular y exudado purulento de coloración rojiza. El análisis histopatológico mostró la presencia de numerosos émbolos tumorales linfovasculares y células con alta frecuencia de figuras mitóticas con núcleos hipercromáticos. Estos hallazgos fueron consistentes con una neoplasia agresiva de mal pronóstico, lo que explicaba el fallecimiento de la paciente a las 7 semanas de la cirugía. Los hallazgos histológicos y citológicos son de importancia crítica para los clínicos en el manejo de las neoplasias mamarias más comunes en los gatos, con el fin de aliviar de la mejor manera posible a los animales con cánceres que amenazan su vida. También podría servir como modelo de cáncer para avanzar en el conocimiento de patologías similares en otras especies.

Abstract This report describes the handling and clinical evolution of a malignant feline mammary carcinoma (FMC) in an eight-year-old female crossbred cat with a congenital disorder. Hence, the efficacy of tumor mass removal and the case prognosis was established by postoperative routine histological examination. A 6 cm diameter lump in the left thoracic mammary gland of multinodular appearance and purulent exudate with a reddish hue was excised after the entire mastectomy. The histopathological analysis showed the presence of numerous lymphovascular tumor emboli and frequently mitotic cells with hyperchromatic nuclei. These were consistent with an aggressive malignancy with a poor prognosis explaining the patient's death within 7 weeks after surgery. Histology and cytology findings are of critical importance to clinicians in the management of the most common mammary malignancies in cats, to provide the best possible relief to animals with life-threatening cancer. It could also serve as a cancer model for advancing knowledge in congenitally affected humans.

Evaluation of platelet indices and complete blood count in canine mammary tumors

Malignant mammary tumors in humans and bitches cause hematological disorders such as anemia, erythrocytosis, thrombocytosis, hyperproteinemia, and leucopenia. Novel studies have been conducted on the predictive and prognostic values of platelet (PLT) indices in human breast cancer (HBC). However, there is little information about the alterations in hematological parameters in canine mammary tumors (CMTs). The aims of this study were to evaluate the platelet indices and complete blood count (CBC) parameters in bitches with and without mammary tumor and to assess the above mentioned parameters with regard to histological tumor types and grades. A total of 71 bitches were enrolled in this study. The bitches in the study group were divided into 2 groups which consisted of malignant epithelial mammary tumors (group EMT; n = 43) and malignant mixed mammary tumors (group MMT; n = 12). Control group (group C) consisted of clinically and gynaecologically healthy 16 bitches. Blood samples were obtained to perform the CBC and PLT indices analysis. Histopathological examinations were carried out under a light microscope. Histological tumor types and malignancy grades were classified. The bitches with mammary tumor showed significantly increased PLT values and decreased hematocrit (HCT), hemoglobin (HGB) and mean corpuscular hemoglobin (MCH) values versus the healthy ones, regardless of the tumor type. However, in comparisons with the group C, mean platelet volume (MPV) and mean corpuscular hemoglobin concentration (MCHC) values were different only in the group MMT, while plateletcrit (PCT) and mean corpuscular volume (MCV) values were different only in the group EMT. Also white blood cell (WBC), PLT and PCT values were higher than the referenced laboratory ranges in grade 3 tumors. In the presented study, MPV was considerably correlated with PLT, platelet distribution width (PDW) and PCT. Also, PCT and PLT had high sensitivity and specificity to distinct EMT and MMT from the healthy bitches. Microcytic and hypochromic anemia occurs due to the decrease in the amount of HGB. Levels of MCV, MCH, and MCHC in the HBC group were reported to be significantly lower than in humans without breast cancer. Although anemia did not occur in EMT and MMT groups, obtained significances in the HCT, HGB, MCV, MCH, and MCHC levels between the bitches with and without mammary tumor were in line with the previous reports. In this study, WBC levels in grade 3 tumors were significantly higher than grade1 tumors (P < 0.05). Whereas levels of WBC in grade 1 and grade 2 tumors were in referenced laboratory ranges, it was higher in grade 3. Increased level of WBC in grade 3 was supposed to be due to the rise in malignancy as previously reported. Thrombocytosis was detected in 48.83% and 41.66% of the bitches in EMT and MMT groups, respectively. The higher percentage of CMTs with thrombocytosis in this study might be due to the difference in referenced upper limit of PLT in previous studies. The elapsed time between tumor formation and clinical presentation could be another influencing factor. Although PLT and PCT values were not significant according to the histological grading in this study, both parameters were found to be higher in grade 3 than the normal reference values. Further studies conducted with higher populations may lead the differences in these parameters to significance. With the support of further studies, alterations in the above mentioned parameters in bitches may contribute in the diagnosis process, management of treatment and may constitute an easy way to have an idea about the prognosis of mammary tumors.(AU)

Tumor filodes benigno de la vulva: reporte de un caso / Benign phyllodes tumor of the vulva: Case Report

Resumen: ANTECEDENTES: El tumor filodes de la vulva es una lesión proliferativa, benigna, poco común, que comparte características similares con los tumores mamarios. Aparece en forma de masa unilateral, no dolorosa, localizada en los labios mayores o menores, y en la horquilla posterior de la vulva. Hasta la fecha se han reportado 30 casos de tumor filodes vulvar en todo el mundo. Debido a su baja incidencia no se han estimado los datos epidemiológicos y fisiopatológicos concretos de la enfermedad. CASO CLÍNICO: Paciente de 20 años, que acudió a consulta debido a la aparición de una masa vulvar de aproximadamente 11 cm en el labio mayor izquierdo, no dolorosa, de crecimiento rápido. El tratamiento consistió en resección quirúrgica. El diagnóstico presuntivo fue fibroma vulvar. El servicio de Anatomopatología reportó: tumoración de 280 g, de 12 x 7 x 6 cm, con bordes y formas irregulares, multinodular, cubierta por piel con epidermis; superficie sólida, con bordes irregulares, de aspecto frondoso y consistencia blanda. Se estableció el diagnóstico de tumor filodes de bajo grado (benigno). CONCLUSIÓN: El tumor filodes de la vulva es una alteración excepcional, por lo que es importante conocer sus manifestaciones clínicas, características macro y microscópicas para establecer el diagnóstico y tratamiento certeros.

Abstract: BACKGROUND: Phyllodes tumor of the vulva is a rare, benign, proliferative lesion that shares similar characteristics with mammary tumors. It appears as a unilateral, non-painful mass located on the labia majora or majora, and on the posterior fork of the vulva. To date, 30 cases of phyllodes tumor have been reported worldwide. Due to its low incidence, the specific epidemiological and pathophysiological data of the disease have not been estimated. CLINICAL CASE: A 20-year-old patient, who came to the clinic for a vulvar mass of approximately 11 cm in the left, non-painful, rapidly growing lip. Treatment consisted of surgical resection. The presumptive diagnosis was vulvar fibroma. The pathology service reported: a 280 g mass, 12 x 7 x 6 cm, with irregular edges and shapes, multinodular, covered by skin with epidermis; Solid cutting surface with uneven edges, leafy appearance and soft consistency. The diagnosis of low-grade phyllodes (benign) tumor was established. CONCLUSION: The phyllodes tumor of the vulva is an exceptional alteration, so it is important to know its clinical manifestations, in addition to the macro and microscopic characteristics to establish the accurate diagnosis and treatment.

Perfil de tutores de cadelas portadoras de tumor de mama / Profile of tutors of dogs with mammary tumor / Perfil de tutores de perras portadoras de tumor mama

É importante que se obtenha informações sobre tutores de cadelas portadoras de tumor de mama, pois o tutor precisa cuidar do animal principalmente no pós-operatório já que o tratamento é mastectomia. Foram entrevistados 11 tutores de cadelas submetidas à mastectomia. A maioria dos entrevistados tem ensino médio e superior, morando em casa própria com renda de um a cinco salários mínimos. Apenas uma pessoa disse que não sabia que cadelas podem ter câncer de mama. Entretanto, a maioria não sabe como prevenir o câncer de mama em cadelas, demonstrando que são necessárias campanhas educacionais sobre a doença para tutores de cadelas. A maneira mais frequente de aquisição do animal foi a adoção, o que demonstra o crescimento da posse responsável entre os tutores brasileiros. Três tutores afirmaram que aplicaram anticoncepcional nas suas cadelas várias vezes. Este fato é bastante preocupante porque tais fármacos possuem diversos efeitos colaterais adversos, inclusive tumor de mama. Oito tutores informaram que nunca haviam consultado um médico veterinário antes sobre o tumor, embora o mesmo fosse evidente. A maioria dos tutores só procurou ajuda para a cadela porque a participação no projeto era gratuita. Dificuldades financeiras é um dos principais motivos para que os tutores retardem as consultas. Entretanto, quando questionados por qual motivo as cadelas não tinham sido tratadas antes, nenhum tutor citou dificuldades financeiras. Concluiu-se que alguns tumores de mama foram causados por aplicação de anticoncepcional e que o desconhecimento sobre a doença ainda é grande entre os tutores entrevistados.(AU)

It is important to collect information about owners of dogs with mammary tumor, since the owner must take care of the animal after surgery, given that the treatment of choice is a mastectomy. This study interviewed eleven owners of female dogs submitted to mastectomy. Most respondents have high school and/or college education, live in their own homes with incomes between one to five minimum salaries. Only one person said they did not know that dogs could have mammary cancer. However, most do not know how to prevent mammary cancer in dogs, demonstrating the need for educational campaigns on the disease. The most frequent way of acquiring the animal was adoption, which demonstrates the growth of responsible ownership among Brazilian owners. Three owners stated that they used contraceptive drugs on their dogs several times. This fact is quite worrisome since such drugs have several adverse effects, including mammary tumor. Eight owners reported that they had never been to a veterinarian before about the tumor, although the tumor was evident. Most owners only sought help for the dog because participation in the project was free of charge. Financial difficulties are one of the main reasons for owners to delay consultations. However, when asked why the dogs had not been treated before, no owner mentioned financial difficulties. It can be concluded that some breast tumors were caused by the use of contraceptive drugs and that ignorance regarding the disease is still high among the interviewed tutorsd.(AU)

Es importante que se obtenga informaciones sobre los tutores de perras portadoras de tumor de mama, pues el tutor necesita cuidar del animal principalmente en el postoperatorio, ya que el tratamiento es la mastectomía. Se han entrevistado a once tutores de perras sometidas a la mastectomía. La mayoría de los encuestados tienen educación secundaria y universitaria, y viven en sus propios hogares con ingresos de uno a cinco sueldos mínimos. Solo una persona dijo que no sabía que las perras pueden tener cáncer de mama. Sin embargo, la mayoría no sabe cómo prevenir el cáncer de mama en perras, demostrando que son necesarias campañas educativas sobre la enfermedad para dueños de perras. La forma más frecuente de adquirir el animal es la adopción, lo que demuestra el crecimiento de la posesión responsable entre los tutores brasileños. Tres tutores declararon que aplicaron anticonceptivos a sus perras varias veces. Este hecho es bastante preocupante porque estos medicamentos tienen varios efectos secundarios adversos, incluso el tumor de mama. Ocho tutores informaron que nunca antes habían consultado a un médico veterinario sobre el tumor, aunque el mismo era evidente. La mayoría de los tutores solo buscaron ayuda para la perra porque la participación en el proyecto era gratuita. Las dificultades financieras es una de las principales razones por las cuales los tutores retrasan las consultas. Sin embargo, cuando cuestionados por cuál motivo las perras no habían sido tratadas antes, ningún tutor mencionó dificultades financieras. Se concluyó que algunos tumores de mama fueron causados por la aplicación de anticonceptivos y que el desconocimiento sobre la enfermedad aún es alta entre los tutores encuestados.(AU)

Dampness-Heat Accelerates DMBA-Induced Mammary Tumors in Rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the impact of dampness-heat (DH) on the development of mammary tumors in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats.</p><p><b>METHODS</b>Forty rats were randomly divided into 3 groups in a randomized block design, including the control group (n=13), DMBA group (n=14), and DMBA plus DH group (n=13). Rats in the DMBA group and DMBA plus DH group were intragastrically administrated with DMBA (100 mg/kg) for twice, once per week, while rats in the control group were treated with equivalent volumes of sesame oil. After DMBA administration, rats in the DMBA plus DH group were exposed to a simulated climate chamber with ambient temperature (33.0±0.5°C) and humidity (90%±5%) for 8 weeks, 8 h per day. The body weight, time of tumor formation, and number of tumors were measured weekly to calculate tumor incidence, average latency period, average number of tumors, and average tumor weight. At the end of the experiment, the levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in serum, and the contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β in serum and tumor tissue were measured, respectively. Some tumor tissues were processed for hematoxylin-eosin staining to determine the histopathological changes.</p><p><b>RESULTS</b>Compared with DMBA, DMBA plus DH significantly increased the average number of tumors, average tumor weight, levels of serum MMP-9, TIMP-1, TNF-α and IL-1β, and contents of tumor tissue TNF-α and IL-1β (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>DH could accelerate the development of mammary tumors through increasing the expressions of MMP-9, TIMP-1, TNF-α and IL-1β in DMBA-induced rats.</p>

Metástasis mamaria de linfoma de células del manto / Mammary metastasis of mantle cell lymphoma

Resumen ANTECEDENTES: Los linfomas mamarios primarios constituyen menos de 1% de todos los linfomas no-Hodgkin, 1.7-2.2% de todos los linfomas no-Hodgkin nodales adicionales y 0.04-0.5% de todas las neoplasias malignas de la mama. El linfoma de células del manto representa 4% de los linfomas en Estados Unidos, y entre 7-9% en Europa y se diagnostica en pacientes con una mediana de edad de 60 años. Aparece en mujeres posmenopáusicas en forma de masa mamaria indolora, unilateral. El linfoma de mama secundario es sistémico, con afectación simultánea o posterior en otro sitio. CASO CLÍNICO: Paciente con una tumoración mamaria, inicialmente postraumática, que en el contexto de plaquetopenia se catalogó clínica y radiológicamente como hematoma y que, más tarde, el diagnóstico fue: linfoma de células del manto secundario a linfoma previo nodal inguinal en segunda línea de tratamiento con quimioterapia. CONCLUSIONES: La persistencia o el rápido crecimiento de un hematoma mamario o de una lesión con apariencia radiológica benigna, sobre todo con antecedente de linfoma previo, puede resultar maligna. La biopsia mediante aguja gruesa es decisiva en el diagnóstico porque permite el estudio histológico e inmunohistoquímico para la confirmación molecular. El tratamiento se basa, sobre todo, en quimio y radioterapia, opciones que mejoran la supervivencia y disminuyen la recurrencia.

Abstract BACKGROUND: Primary mammary lymphomas represent less than 1% of all Non Hodgking Lymphomas (NHL). Mantle cell lymphoma (MCL) represents 4% of lymphomas in the United States, and 7-9% in Europe and is diagnosed in patients with a median age of 60 years. Unilateral painless mammary mass in postmenopausal women use to be the clinical presentation. Secondary breast lymphoma is defined as the presence of systemic lymphoma with breast involvement, as the patient below. CLINICAL CASE: 57-year-old female patient with post-traumatic mammary tumor, with history of thrombocytopenia, first-time diagnosed of hematoma, with breast enlargement and later diagnosed as lymphoma of mantle cells with pathology test and classified as secondary to previous inguinal nodal lymphoma. CONCLUSIONS: It is important to keep in mind this diagnosis in view of the persistence or rapid growth of a mammary hematoma or other lesion with benign radiological appearance. The biopsy is the gold standard for diagnosis, since it allows the histological and immunohistochemical study, for molecular confirmation. The treatment is mainly based on chemo / radiotherapy, which improves survival and decreases recurrence.

Paraneoplastic hematological, biochemical, and hemostatic abnormalities in female dogs with mammary neoplasms / Anormalidades hematológicas, bioquímicas e hemostáticas de origem paraneoplásica em fêmeas caninas com neoplasia mamária

Paraneoplastic laboratory abnormalities are identified in several types of cancers in dogs and cats. In veterinary medicine, particularly in mammary cancer, there are few studies that correlate abnormal laboratory findings with tumor type and staging. The aim of this study was to evaluate hematological, biochemical, and hemostatic abnormalities and correlate them with mammary tumor staging in female dogs with mammary cancer. Blood samples from 24 female dogs were evaluated, and the hematological, biochemical, and hemostatic parameters were correlated with tumor staging obtained by physical examination, imaging exams, and histopathological surgical biopsies. The groups were organized according to tumor staging: group 1 (stages I and II), group 2 (stage III), and group 3 (stages IV and V). Anemia, neutrophilic leukocytosis, monocytosis, eosinophilia, thrombocytosis, hypoalbuminemia, hypocalcemia, hypoglycemia, and low blood urea were observed. The variables MCHC, TPP, and RDW were correlated with tumor staging with no clinical relevance. Thrombin time and fibrinogen were significant between the groups in the coagulation test, being associated with tumor staging. The findings suggest influence of the proinflammatory cytokines released during tumor growth.(AU)

Alterações laboratoriais de origem paraneoplásica são identificadas em diversos tipos de câncer de cães e gatos. Na medicina veterinária, existem poucos estudos que correlacionam os achados laboratoriais anormais com o tipo e estadiamento tumorais, principalmente em cadelas com neoplasia mamária. O objetivo deste estudo foi avaliar as alterações hematológicas, bioquímicas e hemostáticas em cadelas com neoplasia mamária e relacioná-las com o estadiamento tumoral. Foram coletadas amostras de sangue de 24 fêmeas caninas, e os parâmetros hematológicos, bioquímicos e hemostáticos obtidos foram relacionados com o estadiamento tumoral, realizado através do exame físico, exames de imagem e avaliação histopatológica após remoção cirúrgica. Os grupos foram organizados de acordo com o estadiamento tumoral em: Grupo 1 (estádios I e II), grupo 2 (estádio III) e grupo 3 (estádios IV e V). Observou-se anemia, leucocitose neutrofílica, monocitose, eosinofilia, trombocitose, hipoalbuminemia, hipocalcemia, hipoglicemia e diminuição de ureia sanguínea. As variáveis CHCM, PPT e RDW foram relacionadas com o estadiamento tumoral, porém sem relevância clínica. Nos testes de coagulação, o TT e o fibrinogênio apresentaram diferença significativa entre os grupos, sendo associado com estadiamento tumoral. Os resultados sugerem influência das citocinas pró-inflamatórias liberadas durante o crescimento do tumor.(AU)

Suplementação com imunoestimulante em cadelas com neoplasia mamária maligna: aspectos hematológicos e bioquímicos / Immunostimulant supplementation for bitches with malignant mammary tumor: hematological and biochemical aspects

Os alimentos funcionais têm sido empregados como adjuvantes no tratamento do câncer de mama. Neste estudo avaliaram-se as respostas hematológicas e bioquímicas clínicas à ação de um alimento funcional administrado a cadelas com diagnóstico de neoplasia mamária maligna. Após a mastectomia, 16 cadelas foram divididas em dois grupos: suplementadas (S) e não suplementadas (NS) com um composto comercial contendo Saccharomyces cerevisiae, mananoligossacarídeos e nutracêuticos. Ambos grupos receberam tratamento quimioterápico com doxorrubicina e carboplatina, alternadamente, em intervalos de 21 dias, por oito sessões, totalizando 168 dias de tratamento. As avaliações clínicas e laboratoriais foram realizadas nos momentos de aplicação do tratamento. Os resultados dos perfis hematológico (hemograma, leucograma e plaquetograma) e bioquímico sérico (ureia, creatinina, albumina, bilirrubina total e direta, alanina aminotransferase, fosfatase alcalina e gama glutamiltransferase - GGT) foram analisados pelo teste de Kruskall Wallis. No grupo S comprovou-se elevação do peso corporal e não foram observados transtornos gastrointestinais ou outros sinais de alteração clínica ao longo do tratamento. Diferentemente no grupo NS, ocorreu perda de peso e alterações clínicas, como diarreia e vômito. No quadro hematológico, constatou-se leucopenia por linfopenia no grupo de cadelas NS e preservação do valores dentro dos parâmetros considerados normais para a espécie no grupo S. Dentre todas as variáveis da bioquímica clínica, constatou-se apenas a elevação da atividade sérica da GGT nos animais do grupo NS, sem alterações no grupo S. Conclui-se que cadelas com neoplasia mamária quando suplementadas com com alimento funcional imunoestimulante apresentam melhor condição clínica, hematológica e dos níveis bioquímicos, particularmente da GGT.(AU)

Functional foods have been used as adjuvant for breast cancer treatment of bitches. The aim of the present study was to evaluate hematological and clinical biochemistry response in female dogs diagnosed with malignant mammary tumors and supplemented with functional food. After the mastectomy, 16 bitches were divided into two groups: supplemented (S) and none supplemented (NS) with a commercial product of Saccharomyces cerevisiae, mannanoligosaccharides and nutraceuticals. Chemotherapy with doxorubicin and carboplatin was performed alternately at intervals of 21 days for eight sessions during 168 days of treatment. Clinical and laboratorial assessments was made at the treatment moments. The results of the hemogram (erythrogram, leukogram and platelet count) and serum biochemistry (urea, creatinine, albumin, total and direct bilirubin, alanine aminotransferase, alkaline phosphatase and gamma glutamyltransferase - GGT) were analyzed by Kruskal Wallis test. In the S group, increase body weight was observed, but gastrointestinal disorders or other clinical disorders were not detected over the treatment. In the NS group, loss of weight and clinical disorders were observed. All hematology parameters were normal in the S group; however, leukopenia and lymphopenia were detected in the bitches of the NS group. Among all the clinical biochemistry parameters tested, only serum GGT was increased in the NS group, with no changes in the S group. In conclusion, female dogs with mammary tumor supplemented with immunostimulant functional food have better clinical condition, they demonstrate normal levels of hematological and biochemical exams, particularly GGT.(AU)

Evaluation of expression of the Wnt signaling components in canine mammary tumors via RT² Profiler PCR Array and immunochemistry assays

The Wnt signaling pathway and its key component β-catenin have critical roles in the development of diseases such as tumors in mammals. However, little has been reported about involvement of the Wnt/β-catenin signaling pathway in canine mammary tumors (CMTs). The present study detected expression of 30 Wnt signaling pathway-related genes in CMTs; the results are potentially useful for molecular-based diagnosis of CMTs and the development of new targeted therapies. Significant upregulations of dickkopf-1 protein, secreted frizzled-related sequence protein 1 (SFRP1), frizzled 3, β-catenin, and lymphoid enhancer-binding factor 1 (LEF1) were detected in highly malignant CMTs compared to levels in normal mammary gland tissues; moreover, highly significant upregulation of WNT5A was observed in low malignancy CMTs. Downregulation was only detected for SFRP4 in malignant CMT samples. The subcellular location of β-catenin and cyclin D1 in 100 CMT samples was investigated via immunohistochemical analysis, and significantly increased expressions of β-catenin in cytoplasm and cyclin D1 in nuclei were revealed. Western blotting analysis revealed that the expression of β-catenin and LEF1 increased in in the majority of CMT samples. Taken together, the results provide important evidence of the activation status of the Wnt pathway in CMTs and valuable clues to identifying biomarkers for molecular-based diagnosis of CMT.

Infecciones virales, posible factor de riesgo en cáncer de mama / Viral infection as a potential risk factor for breast cancer

Introducción: los factores de riesgo convencionales solo pueden explicar una parte del cáncer de mama esporádico. Se ha propuesto que las infecciones causadas por el virus del tumor mamario en ratón, el virus de Epstein Barr y el virus del papiloma humano constituyen un factor de riesgo potencial para el desarrollo de esta enfermedad. Objetivo: realizar una actualización acerca del papel de algunas infecciones virales en el desarrollo del cáncer de mama. Métodos: se realizó una revisión de los artículos publicados sobre este tema en algunas bases de datos (PubMed, Medline, BioMed Central y SciELO). Conclusiones: aunque existen criterios controversiales sobre el tema, algunos resultados sugieren que la acción de estos virus puede contribuir al desarrollo de las enfermedades malignas de la mama(AU)

Introduction: conventional risk factors cannot explain all cases of sporadic breast cancer. Infections caused by the mouse mammary tumor virus, Epstein-Barr virus and human papillomavirus have been suggested to be potential risk factors for this condition. Objective: to update the information on the role of some viral infections in the development of breast cancer. Methods: a review was conducted of papers about the subject published in several databases (PubMed, Medline, BioMed Central and SciELO). Conclusions: despite the fact that criteria on the subject are controversial, some results suggest that the action of these viruses may contribute to the development of malignant breast disease(AU)

Estadiamento do câncer de mama em mulheres atendidas em um centro de referência em oncologia / Staging of breast cancer in women admitted for care in an oncology reference center

O objetivo do estudo foi avaliar a possível associação entre as características sociodemográficas e o estádio clínico do câncer de mama em mulheres, admitidas para atendimento em um centro de referência em oncologia. Os prontuários de 257 pacientes com diagnóstico de câncer de mama e atendidas entre novembro de 2009 a novembro de 2010 foram revisados. Os dados de interesse foram extraídos para um banco de dados e analisados por meio de regressão logística para identificação das variáveis associadas com o estádio clínico. As pacientes tinham em média 54,5 anos de idade e a maioria eram pardas (62,8%), sem história familiar de câncer de mama (78,2%) e com índice de massa corporal acima do ideal (57,2%). O diagnóstico do câncer foi tardio (estádio III e IV) em 32,7% das pacientes. Não houve associação significativa entre o estádio clínico e a idade, cor da pele, estado civil, índice de massa corpórea ou história familiar de câncer de mama. O percentual de casos diagnosticados em estádio tardio ainda é elevado, quando comparado com o encontrado em países desenvolvidos, o que aponta para necessidade de políticas que facilitem a detecção precoce da doença na região.

The aim of the study was to evaluate the possible association between sociodemographic characteristics and the clinical stage of breast cancer in women admitted for care at an oncology reference center. The medical records of 257 patients treated between November 2009 and November 2010 were reviewed. The data of interest were extracted onto a database and analyzed using logistic regression to identify the variables associated with the clinical stage. The patients were on average 54.5 years of age, primarily Caucasian (62.8%), with no family history of breast cancer (78.2%) and above the ideal body mass index (57.7%). Cancer diagnosis was late (stage II and IV) in 32.7% of patients. There was no significant relationship between the initial or early stages and age, skin color, marital status, body mass index and family history of breast cancer. The percentage of cases diagnosed in a late stage is still high when compared to what is found in developed countries, which points to the need for policies that facilitate the early detection of the disease in the region.

Pathological analysis of the induced breast tumor models in tree shrew / 中国比较医学杂志

Objective To establish a tree shrew mode of breast tumor.Method Forty-five 3 to 4 month-old female tree shrews were orally gavaged with 20 mg 7,12-dimethylbenz(a)anthracene (DMBA) or peanut oil per animal for three times.Following that, fifteen DMBA administrated tree shrews were implanted 90 day-release medroxyprogesterone acetate ( MPA) pellets.The tree shrews were palpated once weekly to detect mammary tumors for 45 weeks after first DMBA administration.Results DMBA were able to induce breast tumors (12.5%) in tree shrews, and MPA increased the tumor incidence (50%) while no breast tumors were observed in the control group.Three induced breast tumors were intraductal papillary carcinomas and one was IDC by H&E stain.Conclusion All induced tumors are similar with spontaneous tumors in structure and molecular markers.

Immunodetection of myeloid and plasmacytoid dendritic cells in mammary carcinomas of female dogs / Imunodetecção de células dendríticas mieloides e plasmocitoides nos carcinomas mamários em cadelas

Dendritic cells have attracted great interest from researchers as they may be used as targets of tumor immune evasion mechanisms. The main objective of this study was to evaluate the relationship between the dendritic cells (DCs) subpopulation in simple type mammary carcinomas in female dogs. Two groups of samples were used: the control group consisted of 18 samples of mammary tissue without changes and the tumor group with 26 simple type mammary carcinomas. In these groups, we evaluated the immunodetection of immature and mature myeloid DCs, plasmacytoid DCs and MHC-II. In mammary tumor, mature myeloid DCs predominated in the peritumoral region, while immature myeloid DCs and plasmacytoid DCs were evident in the intratumoral region. Immunostaining of MHC-II was visualized in mammary acini (control group), in tumor cells and inflammatory infiltration associated with tumors. The comparison between the control and tumor groups showed a statistically significant difference between immature myeloid DCs, mature myeloid DCs and plasmacytoid DCs. The immunodetection of MHC-II was not significant when comparing the groups. The predominance of immature DCs in the tumor group is possibly related to an inefficient immune response, promoting the development and survival of tumor cells. The presence of plasmacytoid DCs in the same group suggests a worse prognosis for female dogs with mammary tumors. Therefore, the ability of differentiation of canine dendritic cells could be influenced by neoplastic cells and by the tumor microenvironment...

As células dendríticas têm despertado grande interesse dos pesquisadores, pois podem ser alvo dos mecanismos de evasão imune do tumor. O objetivo principal deste estudo foi avaliar a relação entre as subpopulações de células dendríticas (DCs) nos carcinomas mamários do tipo simples em cadelas. Dois grupos de amostras foram utilizados, o grupo controle composto por 18 amostras de tecido mamário sem alterações e o grupo tumor com 26 carcinomas mamários do tipo simples. Nestes grupos foram avaliadas a imunodetecção de DCs mieloides imaturas e maduras, DCs plasmocitoides e de MHC-II. Nas mamas com tumor, as DCs mieloides maduras predominaram na região peritumoral, enquanto que as DCs mieloides imaturas e as DCs plasmocitoides foram evidentes na região intratumoral. A imunomarcação do MHC-II foi visualizada nos ácinos mamários (grupo controle), nas células tumorais e no infiltrado inflamatório associado aos tumores. Na comparação entre os grupos controle e tumor houve diferença estatística significativa entre as DCs mieloides imaturas, DCs mieloides maduras e DCs plasmocitoides. A imunodetecção de MHC-II não foi significativa na comparação entre os grupos. A predominância de DCs imaturas no grupo tumor, possivelmente, está relacionada com uma resposta imune ineficiente, favorecendo o desenvolvimento e a sobrevivência das células tumorais. A presença das DCs plasmocitoides no mesmo grupo sugere um prognóstico pior para cadelas com tumores de mama. Portanto, a capacidade de diferenciação das células dendríticas caninas poderia ser influenciada pelas células neoplásicas e pelo microambiente tumoral...

The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study

Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs.

Anestesia convencional e técnica de tumescência em cadelas submetidas à mastectomia. Avaliação da dor pós-operatória / Conventional anesthesia and tumescent technique in bitches which underwent mastectomy. Evaluation of postoperative pain

As neoplasias mamárias são as mais comuns em cadelas e geralmente acometem fêmeas de meia-idade a idosas, não castradas ou que foram submetidas ao procedimento de ovario-histerectomia tardiamente. A principal forma de tratamento é a excisão cirúrgica, sendo a ressecção unilateral das glândulas mamárias o procedimento mais realizado na prática veterinária. O objetivo do presente estudo foi comparar a dor pós-operatória em cadelas submetidas ao procedimento de mastectomia unilateral sob efeito das técnicas anestésicas de tumescência ou convencional. Foram utilizadas 20 cadelas, divididas em dois grupos: um grupo recebeu apenas a anestesia geral inalatória (grupo convencional), e o outro recebeu adicionalmente a anestesia infiltrativa por tumescência (grupo tumescência). Elas foram avaliadas nas primeiras 24 horas do período pós-operatório, e o processo álgico foi avaliado pela escala de dor da Universidade de Melbourne. As médias dos escores obtidos ao longo do tempo foram submetidas ao teste de Tukey a um nível de 5 por cento de significância (p<0,05). Não foram observadas diferenças significativas entre os grupos com relação à dor pós-operatória. A técnica anestésica infiltrativa por tumescência apresentou a vantagem da redução do sangramento transoperatório e mostrou-se exequível em pequenos animais, entretanto seu uso está relacionado à experiência e à preferência do cirurgião e do anestesista...

Mammary tumors are the most common neoplasm in bitches. Intact, mild to advanced aged female dogs are generally more affected. The main treatment is surgical excision and unilateral mastectomy is the most performed procedure in veterinary practice. The aim of this study was to compare the postoperative pain in dogs which underwent unilateral mastectomy and were anesthetized with tumescence and conventional anesthesia. Twenty bitches were randomly divided into two groups: Conventional Group (GC), which received only general inhalational anesthesia and Tumescence Group (GT), which also received tumescence anesthesia. All dogs were evaluated during the first 24 hours postoperatively. The scale of Pain from the University of Melbourne was used for the evaluation. The tukey test at a 5 percent level of significance (p <0.05) was used. There were no significant differences between groups related to postoperative pain. The technique of tumescent anesthesia reduced bleeding during surgery and is feasible in dogs. Its use is related to the surgeon and anesthesiologist's experience and preferences...

Establishment of linear accelerator-based image guided radiotherapy for orthotopic 4T1 mouse mammary tumor model / 한국실험동물학회지

This study was conducted to assess the feasibility of image guided radiotherapy (IGRT) for orthotopic 4T1 mouse mammary tumor using linear accelerator (LINAC). Eighteen Balb/C mice were inoculated with 4T1 cells on left mammary fat pad and nine of them were irradiated using LINAC. Tumors, planning target volumes (PTV), bowels adjacent to tumors, bones and lungs were delineated on planning CT images. IGRT plans were generated to irradiate prescription dose to at least 90% of the PTV and then compared with conventional 2-dimensional plans with anterior-posterior and posterior-anterior beams with 5 mm margins (2D AP/PA plan). Homemade dose-build-up-cradle was designed to encompass mouse bed for homogeneous dose build up. To confirm the irradiated dose, tumor doses were measured using diode detector placed on the surface of tumors. Plan comparison demonstrated equivalent doses to PTV while sparing more doses to normal tissues including bowel (from 90.9% to 40.5%, median value of mean doses) and bone marrow (from 12.9% to 4.7%, median value of mean doses) than 2D AP/PA plan. Quality assurance using diode detector confirmed that IGRT could deliver 95.3-105.3% of the planned doses to PTV. Tumors grew 505.2-1185.8% (mean 873.3%) in the control group and 436.1-771.8% (mean 615.5%) in the irradiated group. These results demonstrate that LINAC-based IGRT provides a reliable approach with accurate dose delivery in the radiobiological study for orthotropic tumor model maintaining tumor microenvironment.

Carcinoma mamário pouco diferenciado em macaco-prego, Cebus sp. (Cebidae) / Mammary high-grade carcinoma in a monkey, Cebus sp. (Cebidae)

As neoplasias mamárias são raras em primatas não humanos, enquanto que nas mulheres apresentam alta incidência. O objetivo deste trabalho foi relatar a ocorrência e os resultados do tratamento de um Cebus sp. (fam. Cebidae) fêmea, com carcinoma mamário pouco diferenciado encaminhado ao Serviço de Atendimento de Animais Selvagens da Universidade Estadual do Centro-Oeste. À inspeção o animal apresentava aumento de volume em região mamária direita e ao exame radiográfico foram observados três pontos de radiopacidade, característicos de projétil balístico de arma de pressão, com um deles alojado ao centro da massa de tecido mamário Após estabilização, a paciente foi submetida à exérese cirúrgica de aumento de volume e o material foi encaminhado para análise histopatológica. O diagnóstico obtido foi de carcinoma de alto grau, compatível com carcinoma adenoescamoso. Após a retirada dos pontos a paciente foi encaminhada ao convívio de outros animais. Mais de 20 meses após a terapia cirúrgica não há sinais de recidiva. A paciente alimenta-se bem, convive normalmente com o grupo, sugerindo que a terapia adotada foi eficiente até o momento em alcançar qualidade de vida e aumento de sobrevida do animal.

Mammary tumors in non-human primates are rare. The aim of this paper is to report the occurrence and treatment outcomes of a female Cebus sp. (fam. Cebidae) with high-grade mammary carcinoma received at the Serviço de Atendimento de Animais Selvagens (SAAS), Universidade Estadual do Centro-Oeste. A right mammary gland nodule was identified and at radiographic examination a point of radiopacity due to gun projectile entrapped within the mammary mass was seen. After the patient stabilization, the mass was excised and submitted to histopathological examination. The diagnosis was of high-grade carcinoma, compatible with adenosquamous carcinoma. The monkey was transported to Wild Animals Treat and Receiving Center (CETAS) and introduced into a colony. More than 20 months after surgery no evidence of relapse was seen and the patient is living with the group. That suggests that the adopted therapy was effective, achieving quality of life and increased survival.

Mammary gland radius measurement and its application in female adults / 中华内分泌外科杂志

Objective We invented mammary lump skin-positioning membrane (named scare membrane) to facilitate localization of mammary lump during ultrasound scan.This study is to measure the radius of mammary of Chinese adult women for designing different types of skin-positioning membrane.MethodsThe radius of mammary glands in 236 cases of adult females was detected with color Doppler ultrasound at 5 different clock positions:12:00,3:00,6:00,9:00 and 10:30 or 1:30.SPSS 16.0 statistical software was used to analyze the data.The cut-off values of mammary glands radius at 99％,95％,75％ and 50％ were calculated.Paired t tests or nonparametric tests (relative sample rank sum tests) were used to verify the consistency of mammary gland radius between left and right sides.ResultsThe cut-off value of 95％ mammary gland radius was:7.700cm at 12:00,7.810 cm at 13:00,8.100 cm at 3:00,5.330 cm at 6:00 and 6.300 cm at 9:00 for left mammary gland ; 7.500 cm at 12:00,6.015 cm at 3:00,5.500 cm at 6:00,8.510 cm at 9:00 and 7.930 cm at 10:30 for right mammary gland.In comparison of left and right mammary gland radius,the difference had statistical significance between the group of left side at 1:30 and right side at 10:30,the group of left side at 3:00 and right side at 9:00(P ＜0.05).The right mamma was relatively larger.The cut-off values of the right mamma at the above two clock points were taken as radius of scale membranes while the average of percentage cut-off values at 12:00,3:00 of both mammas,left side at 9:00 and right side at 3:00 are taken as radius of scale membranes.ConclusionsAccording to the cut-off values of 99％,95％,75％ and 50％ radius of adult female mammary glands,mammary lump skin-positioning membrane radius can be classified into 4 size-types:extra large,large,medium and small.The precise classification of radius of mammary scale membranes according to mammary glands of adult females provides convenience for production,manufacture and clinical application of mammary lump skin-positioning membrane.

Detecção de aglomerados espaciais de casos de neoplasia mamária em cães no município de Salvador, Bahia / Detection of spatial clusters for breast cancer in canines in the city of Salvador, Bahia

Os tumores mamários espontâneos representam a neoplasia mais frequente em fêmeas caninas, correspondendo aproximadamente a 50 por cento de todas as neoplasias. A maioria dos estudos científicos restringe-se a dados pontuais sobre a doença, sem a preocupação com sua distribuição geográfica ou mesmo com a possibilidade da geração de agregados desses eventos em uma determinada área. Levando-se em consideração a lacuna de informações na literatura, o presente trabalho teve como objetivo a criação de mapas temáticos da distribuição espacial das neoplasias mamárias em cadelas e a identificação de aglomerados de risco para a doença no município de Salvador, Bahia. Pela análise espacial de varredura, verificou-se que os casos de neoplasia mamária não estão homogeneamente distribuídos no município. Foi detectado um aglomerado primário estatisticamente significante (P<0,001), abrangendo 67,3 por cento dos casos estudados. Espera-se que estes resultados contribuam principalmente na elaboração de novos estudos, nos quais devem ser analisadas variáveis de caráter intrínseco e extrínseco ao animal para a identificação dos fatores de risco e elaboração de planos educacionais direcionados à promoção da saúde animal.

Spontaneous mammary tumors represent the most frequent type of cancer in canines, accounting for approximately 50 percent of all neoplasms. The majority of scientific papers cited in the literature are limited to non refined epidemiological data, without mentioning the trend of this disease in generating clusters in a given geographical area. In this context, this research aimed to create thematic maps of spatial distribution of mammary neoplasms in bitches and to identify disease clusters for the city of Salvador, Bahia. Trough the spatial analysis scanning, it was found that cases of breast cancer is not evenly distributed in the municipality. A significant primary cluster was detected (P>0,001) covering 67.3 percent of the studied cases. Considering the gap in literature available in this field, it is believed that such results will become very important, especially in leading to new studies, where intrinsic and extrinsic variables regarding the animal must be taken into consideration and analyzed for factors risk identification to formulate educational plans targeting the promotion of animal welfare.