Abstract 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. Background dogs oncology malignancies women approaches terrificus rattlesnake 6 uses antitumor antiviral action Crotoxin βneurotoxin β neurotoxin CBPLA2 CBPLA CB PLA2 PLA (CB-PLA2 crotapotin, , (crotapotin) cancers Methods drug choice lines Results CBPLA2, PLA2, dosedependent dose dependent manner effect compounds apoptosis addition cells Conclusion Therefore CB-PLA activity inhibition proapoptotic pro apoptotic research (CB-PLA (crotapotin

Resumo A ação do sistema imunológico contra as enfermidades neoplásicas tem se tornado uma das principais fontes de pesquisa na atualidade. As vias biológicas desse sistema são conhecidas por contribuir na limitação da progressão e na eliminação do tumor, e são delineadas por conceitos e mecanismos de imunovigilância e imunoedição. A imunovigilância é considerada o processo pelo qual o sistema imunológico reconhece e inibe o processo neoplásico. O conceito de imunoedição tem origem no sentido de que o sistema imune é capaz de moldar o perfil antigênico do tumor devido à pressão seletiva, baseada nas etapas de eliminação, equilíbrio e evasão tumoral. A resposta imunológica ocorre contra antígenos tumorais e modificações do microambiente tumoral, envolvendo diferentes componentes do sistema imune inato, como células T, células natural Killer, linfócitos B e macrófagos. Nesse sentido, conhecer esses conceitos e compreender seus respectivos mecanismos torna-se essencial na investigação de novas estratégias de prevenção e combate ao câncer. Dessa forma, esta revisão apresenta aspectos históricos e definições de imunovigilância e imunoedição tumoral, com ênfase em sua importância e aplicabilidade, assim como aos diferentes métodos utilizados em imunoterapia.

Abstract The action of the immune system against neoplastic diseases has become one of the main sources of research. The biological pathways of this system are known to contribute in limiting the progression and elimination of the tumor, and are delineated by concepts and mechanisms of immunosurveillance and immunoediting. Immunosurveillance is considered the process by which the immune system recognizes and inhibits the neoplastic process. The concept of immunoediting arises in the sense that immune system is able to shape the antigenic profile of the tumor due to selective pressure, based on the stages of tumor elimination, balance and evasion. The immune response occurs against tumor antigens and changes in the tumor microenvironment, involving different components of the innate immune system, such as T cells, natural Killer cells, B lymphocytes and macrophages. In this sense, knowing these concepts and understanding their respective mechanisms becomes essential in the investigation of new strategies for cancer prevention and cure. Thus, this review presents historical aspects and definitions of immunosurveillance and tumor immunoediting, with emphasis on its importance and applicability, such as on the different methods used in immunotherapy.

RESUMO: A brucelose é uma das zoonoses bacterianas mais importantes e difundidas no mundo. São poucos os estudos epidemiológicos sobre a doença em bovinos na região produtiva do Oeste de Santa Catarina. Desta forma, o objetivo deste estudo foi caracterizar os aspectos epidemiológicos da brucelose bovina notificados nesta região entre os anos de 2013 a 2018. Os dados sobre os bovinos foram fornecidos pela Companhia Integrada de Desenvolvimento Agrícola de Santa Catarina (CIDASC). Foram avaliadas as prevalências da doença nos bovinos e rebanhos, por meio de análise de tendência temporal e distribuição espacial. Os bovinos, cujo exame confirmatório mostrou positividade para brucelose, foram analisados quanto à localização (município) e o ano de confirmação do diagnóstico. No período de estudo (2013-2018) foram realizados 686.086 testes para brucelose, encontrando-se prevalência de 1,11% (7.586/686.086) de animais positivos, enquanto a prevalência de rebanhos positivos, dentre os 80.171 testados, foi de 0,95% (764/80171). As razões de chances de ocorrência de brucelose nos bovinos aumentaram significativamente nos anos de 2015 (OR= 1,55) e 2016 (OR= 1,97) e diminuíram em 2014 (OR= 0,47) e 2017 (OR= 0,97). A doença está presente nos bovinos em 61,07% (80/131) dos municípios em que foram realizados os testes. Os resultados demonstram que a brucelose é endêmica na região.

ABSTRACT: Brucellosis is one of the most important and widespread bacterial zoonoses in the world. There are few epidemiological studies on brucellosis in cattle in the productive region of western Santa Catarina. Thus, the objective of this study was to characterize the epidemiological aspects of bovine brucellosis reported in this region from 2013 to 2018. Cattle data were provided by the Integrated Company for Agricultural Development of Santa Catarina (Companhia Integrada de Desenvolvimento Agrícola de Santa Catarina - CIDASC). The prevalence of the disease was evaluated in cattle and herds by means of temporal trend analysis and spatial distribution. Bovines with tests showing positive for brucellosis were analyzed for location (municipality) and year of confirmation of diagnosis. In the study period (2013-2018), 686,086 tests were performed for brucellosis, with a prevalence rate of 1.11% (7,586/686,086). Among the 80,171 herds tested, 0.95% were found to be positive (764/80171). The odds ratio of brucellosis occurrence in cattle increased significantly in 2015 (OR = 1.55) and 2016 (OR = 1.97) and decreased in 2014 (OR = 0.47) and 2017 (OR = 0.97). The disease is present in cattle in 61.07% (80/131) of the municipalities where the tests were performed. Results showed that brucellosis is endemic in the region.