Carcinogenese quimica por DMBA (7,12-dimethylbenzanthracene) em camundongos femeas BALB/c: novos fatos

Polycyclic aromatic hydrocarbons are known carcinogens used in rodent experimental models. In this study, the carcinogen DMBA (7,12-dimethylbenzanthracene) was administered by gavage, diluted in corn oil, to female BALB / c mice at hebdomadary doses of 1 mg per animal for 1, 3, 6 or 9 weeks. Animals were weighed and monitored weekly until death. Remaining animals were euthanized at the age of 53 weeks. At necropsy, representative fragments of neoplasms were collected and routinely processed for histopathological analysis. Of all mice that received DMBA, 68.57% developed some type of tumor. Of the 70 mice treated with various doses of DMBA, 22 (31.43%) developed mammary tumors. The adenoacanthoma was the most commonly (18.75%) diagnosed histological type of breast cancer. Lung (15.71%), lymphoid tissue (11.43%), stomach (7.14%) and skin (2.86%) were also primary sites of tumor development. One third (33.33%) of the mice receiving 1 mg of DMBA developed lung cancer. Therefore, the administration of DMBA was shown to be an efficient model of carcinogenesis in mice, especially for the study of breast cancer, when using the highest dose, and lung, when using the lowest dose. Carcinogenesis models have been used for several purposes in cancer research. These results represent new facts for a classic carcinogenesis model.Hidrocarbonetos policíclicos e aromáticos são carcinógenos usados em modelos experimentais em roedores. Neste estudo, o carcinógeno DMBA (7,12-dimetilbenzantraceno) foi administrado por gavagem, diluído em óleo de milho, para camundongos BALB/c em doses hebdomadárias de 1 mg por animal por 1, 3, 6 ou 9 semanas. Os animais foram pesados e monitorados semanalmente até a morte. Os animais remanescentes foram eutanasiados com a idade de 53 semanas. Na necroscopia, fragmentos representativos das neoplasias foram colhidos e rotineiramente processados para exame histopatológico. De todos os animais que receberam DMBA, 68,57% desenvolveram algum tipo de tumor. Entre os 70 camundongos tratados com diferentes doses de DMBA, 22 (31,43%) desenvolveram neoplasias mamárias. O adenoacantoma foi o tumor mamário mais comumente diagnosticado (18,75%). Pulmões (15,71%), tecido linfoide (11,43%), estômago (7,14%) e pele (2,86%) foram também locais primários de desenvolvimento de neoplasias. Um terço (33,33%) dos camundongos que receberam 1 mg de DMBA desenvolveram neoplasias pulmonares. Portanto, a administração de DMBA foi considerada um modelo eficiente de carcinogênese em camundongos, especialmente para o estudo de neoplasias mamárias, quando a maior dose é utilizada, e de neoplasias pulmonares, quando utilizada a menor dose. Os modelos de carcinogênese química têm sido usados para diversos estudos na pesquisa em câncer, os resultados aqui apresentados mostram novos fatos para um modelo clássico de carcinogênese

Chemical carcinogenesis by 7,12-dimethylbenzanthracene in balb/c mice

FAPES

Cartography of neoplasms in dogs from different regions of the city of São Paulo, SP, Brazil: a survey (2002-2003) of data from the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil

Avanços na medicina veterinária resultaram em benefícios significativos na vida de animais de estimação nos últimos 20 anos, e o aumento da expectativa de vida para animais levou a uma maior prevalência de neoplasias em cães. A Epidemiologia do Câncer e as ferramentas de análise espacial, embora bem desenvolvidas na pesquisa oncológica humana, estão começando a serem exploradas na Oncologia Veterinária. A cidade de São Paulo, capital do estado de São Paulo, Brasil, é dividida em cinco regiões: Norte, Sul, Leste, Oeste e centro. O Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo (HOVET-SVMAS-USP) está localizado na região Oeste de São Paulo, Brasil, e admite casos de pequenos e grandes animais. Tumores mamários caninos são tão numerosos que não são tratados na rotina do HOVET. O objetivo deste trabalho foi realizar um estudo cartográfico para descrever a distribuição espacial dos casos prevalentes de neoplasias em cães a partir do HOVET. Dos 3.620 casos atendidos em 2002 e 2003, 380 (10,5%) casos eram de cães acometidos por tumores benignos e malignos. Não foi encontrada diferença estatística entre a distribuição dos 380 endereços entre as cinco regiões da cidade. Os resultados mostraram que o HOVET atende pacientes caninos de todas as regiões de São Paulo e que há uma distribuição espacial homogênea das neoplasias. Os autores incentivam estudos mais amplos, envolvendo vários hospitais veterinários, clínicas e laboratórios, a fim de obter dados mais precisos sobre a distribuição das neoplasias caninas em São Paulo, SP, Brasil.Improvements in veterinary medicine have resulted in a significant benefit in the life of pets in the last 20 years, and increased pet life expectancy led to an increased prevalence of canine neoplasia. Cancer epidemiology and spatial analysis tools, although well developed for human oncology research, is just beginning to be explored in veterinary oncology. São Paulo city, capital of the state of São Paulo, Brazil, is divided into five regions: North, South, East, West and downtown. The Veterinary Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo (HOVET-SVMAS-USP), is located in the West region of São Paulo, Brazil, and admits cases of small and large animals. Canine mammary tumors are so numerous that they are not routinely treated at the HOVET. The aim of this work was to perform a cartographic study to describe the spatial distribution of prevalent cases of neoplasms in dogs from the HOVET. Of the 3,620 cases seen in 2002 and 2003, 380 cases (10.5%) were of dogs affected with benign and malignant neoplasms. No statistical difference was found for the 380 addresses distributed among the five regions of the city. These results showed that the HOVET receives canine patients from all regions of São Paulo and there is a homogeneous spatial distribution of neoplasms. Authors encourage additional broader studies, involving several veterinary hospitals, clinics or laboratories in order to obtain more accurate data on distribution of canine neoplasms in São Paulo, SP, Brazil

Feasibility study of the implantation of an animal cancer registry in Sao Paulo, SP, Brazil

Registros de Câncer são sistemas padronizados, flexíveis e multicêntricos para coleta de dados de pacientes com neoplasias, permitindo a obtenção de dados epidemiológicos de alta qualidade a um baixo custo. Eles podem ser de base populacional, abrangendo todos os casos de uma área geográfica delimitada, possibilitando calcular sua incidência e sobrevida, quanto de base hospitalar, coletando dados sobre o paciente para uso em pesquisa, educação continuada e melhoria dos atendimentos. Essas abordagens, na Medicina Veterinária, tiveram início na década de 60 com o Kansas Animal Tumor Registry (1961) e com o California Animal Tumor Registry (1963). Desde então, outras iniciativas similares surgiram nos Estados Unidos, Canadá, Noruega, Dinamarca, Suécia e Reino Unido. Esses registros, concentrados no Hemisfério Norte, não existem ainda na América Latina. Este trabalho teve como objetivo avaliar a viabilidade de implantação de um Registro de Câncer Animal na cidade de São Paulo, SP, Brasil. Elaborou-se um registro piloto para permitir entender a sua viabilidade em larga escala quanto Sistema de Informação em Saúde. Foram desenvolvidos identidade, logotipo, formulários de admissão e seguimento, e um software especializado, o SIRCA-SP, para o funcionamento do Registro de Câncer Animal de São Paulo (RCA-SP). O fluxo de informação foi planejado para que a coleta pudesse ser realizada de forma multicêntrica, padronizada e sigilosa. A análise preliminar dos dados permite entender as características da distribuição local do câncer e o potencial do RCA-SP. O estudo de viabilidade foi realizado através de parâmetros definidos pelo Center for Diseases Control, Atlanta, EUA. O RCA-SP foi criado, em 2013, como um registro de base hospitalar que coleta informações sobre cães e gatos diagnosticados com câncer a partir de janeiro de 2012 em hospitais, clínicas e serviços autônomos veterinários sediados na cidade de São Paulo. O software SIRCA-SP foi desenvolvido para otimizar e garantir a qualidade dos dados coletados, consolidados e armazenados pelo RCA-SP. O sistema possui interface amigável e pode ser acessado via internet. Os formulários foram padronizados e geram dados comparáveis aos outros Registros de Câncer em animais e humanos. Avaliação preliminar dos dados demonstra predomínio, nos 645 casos registrados de cães (96,58%) e de fêmeas (80,15%). As localizações de câncer mais comuns foram em glândula mamária (63,88%), pele (17,98%) e em órgãos genitais (5,43%). O sistema demonstrou ser simples, flexível, bem aceito, oportuno e útil. A sua representatividade, por ser projeto piloto, é pequena, mas tenderá a aumentar com adesão de novas fontes notificadoras. O sistema não possui mecanismos de garantia de sua exaustividade. Algumas soluções como o sistema de pré-verificação de inclusão, projetado para evitar entrada duplicada de dados, e a integração entre prontuário eletrônico e os campos de interesse epidemiológico auxiliam na distribuição de responsabilidades do registro aos usuários e, consequente, diminuição de custos operacionais. A implantação de um Registro de Câncer Animal na cidade de São Paulo mostrou-se viável e a coleta multicêntrica é realizada de forma contínua e ininterruptaCancer Registries are flexible, multicentric and standardized systems to collect data from patients with neoplasia, allowing the epidemiological registry of high quality data, at low cost. They can be classified as population-based, covering all cases in a defined geographical area, allowing incidence and survival calculation, or, hospital-based, collecting data about the patient for research, continuing education and improvement of care. Those approaches started in Veterinary Medicine in the 60’s, with the Kansas Animal Tumor Registry (1961) and the California Animal Tumor Registry (1963). Since then, other similar initiatives have emerged in United States, Canada, Norway, Denmark, Sweden, Italy and United Kingdom. Those registries, concentrated in North Hemisphere, were absent in Latin America up to now. This study aimed to assess the feasibility of implementing an Animal Cancer Registry in Sao Paulo, SP, Brazil. A pilot cancer registry system was developed to allow understanding its feasibility, in large scale, as a Health Information System. An identity, logo, admission and follow-up forms were developed, and a specialized software, the SIRCA-SP, for Sao Paulo Animal Cancer Registry (RCA-SP) operation was standardized. An information flow was planned, so that the collection could be performed in a multicentric, standardized and confidential way. Preliminary analysis of the data allowed the understanding of local cancer distribution characteristics and the RCA-SP potential. The feasibility study was perform using parameters defined by the Centers for Disease Control, Atlanta, USA. The RCA-SP, created in 2013, is a hospital-based cancer registry, which collects information about dogs and cats diagnosed with cancer since January 2012 in hospitals, clinics and veterinary autonomous services in Sao Paulo, SP, Brazil. The SIRCA-SP was designed to optimize and ensure the quality of data collection, consolidation and storing by RCA-SP. The system has a friendly interface and can be access via Internet. The forms were standardized and generate data comparable to other cancer registries in animals and humans. Preliminary survey data shows predominance, in the 645 cases, of dogs (96.58%) and females (80.15%). The most common cancer location were mammary gland (63.88%), skin (17.98%) and genitals (5.43%). The system proved to be simple, flexible, well accepted, timely and useful. As a pilot study, its representativeness is still small, but tends to increase with the accession of new reporting sources. The system has no assurance mechanisms of their completeness. Some solutions such, as the pre-verification tool, designed to avoid duplicated entries, and the electronic medical records integration with the standard epidemiological fields, share the fields to assist in the distribution of registry responsibilities to users and, consequently, decrease operating costs. The implementation of an Animal Cancer Registry in São Paulo proved to be feasible, and the multicentric collection is ready to be carried out continuously and uninterruptedl

Higher Incidence of Lung Adenocarcinomas Induced by DMBA in Connexin 43 Heterozygous Knockout Mice

Gap junctions are communicating junctions which are important for tissue homeostasis, and their disruption is involved in carcinogenic processes. This study aimed to verify the influence of deletion of one allele of the Connexin 43 gene on cancer incidence in different organs. The 7, 12-dimethylbenzanthracene (DMBA) carcinogenic model, using hebdomadary doses by gavage of 9 mg per animal, was used to induce tumors in Connexin 43 heterozygous or wild-type mice. The experiment began in the eighth week of the mice life, and all of them were euthanized when reaching inadequate physical condition, or at the end of 53 weeks. No statistical differences occurred for weight gain and cancer survival time (P=0.9853) between heterozygous and wild-type mice. Cx43+/− mice presented significantly higher susceptibility to lung cancer (P=0.0200) which was not evidenced for benign neoplasms (P=0.3449). In addition, incidence of ovarian neoplasms was 2.5-fold higher in Cx43+/− mice, although not statistically significant. Other organs showed a very similar cancer occurrence between Cx43 groups. The experiment strengthens the evidence of the relationship between Connexin 43 deficiency and carcinogenesis

Comparative Aspects of Canine Melanoma

Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas

Global DNA methylation of peripheral blood leukocytes from dogs bearing multicentric non-Hodgkin lymphomas and healthy dogs: A comparative study.

Non-Hodgkin lymphomas are among the most common types of tumors in dogs, and they are currently accepted as comparative models of the disease in humans. Aberrant patterns of DNA methylation seem to play a key role in the development of hematopoietic neoplasms in humans, constitute a special mechanism of transcriptional control, and may be influenced by genetic and environmental factors. Blood leukocyte DNA global methylation has been poorly investigated in dogs. The aim of this study is to examine whether peripheral blood global DNA methylation is associated with canine multicentric lymphomas. Peripheral venous blood samples from ten healthy dogs and nine dogs bearing multicentric lymphomas were collected, and the buffy coat was separated. Global DNA methylation was analyzed by High Performance Liquid Chromatography (HPLC) and immunocytochemistry (ICC). In both analyses, leukocytes from dogs with lymphoma presented lower global DNA methylation than in healthy dogs (HPLC: p = 0.027/ 5MeCyt immunoreactivity scores: p = 0.015). Moderate correlation was observed between the results obtained by HPLC and ICC (correlation coefficient = 0.50). For the identification of differently methylated genes between both groups, the Infinium Human Methylation (HM) EPIC BeadChip (850K) was used. Of the 853,307 CpGs investigated in the microarray, there were 34,574 probes hybridized in the canine samples. From this total, significant difference was observed in the methylation level of 8433 regions, and through the homologous and orthologous similarities 525 differently methylated genes were identified between the two groups. This study is pioneer in suggesting that dogs bearing non-Hodgkin lymphoma presented DNA global hypomethylation of circulating leukocytes compared with healthy dogs. Although canine samples were used in an assay developed specifically for human DNA, it was possible to identify differently methylated genes and our results reiterate the importance of the use of peripheral blood leukocytes in cancer research and possible new biomarkers targets

Cartography of neoplasms in dogs from different regions of the city of São Paulo, SP, Brazil: a survey (2002-2003) of data from the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil

Improvements in veterinary medicine have resulted in a significant benefit in the life of pets in the last 20 years, and increased pet life expectancy led to an increased prevalence of canine neoplasia. Cancer epidemiology and spatial analysis tools, although well developed for human oncology research, is just beginning to be explored in veterinary oncology. São Paulo city, capital of the state of São Paulo, Brazil, is divided into five regions: North, South, East, West and downtown. The Veterinary Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo (HOVET-SVMAS-USP), is located in the West region of São Paulo, Brazil, and admits cases of small and large animals. Canine mammary tumors are so numerous that they are not routinely treated at the HOVET. The aim of this work was to perform a cartographic study to describe the spatial distribution of prevalent cases of neoplasms in dogs from the HOVET. Of the 3,620 cases seen in 2002 and 2003, 380 cases (10.5%) were of dogs affected with benign and malignant neoplasms. No statistical difference was found for the 380 addresses distributed among the five regions of the city. These results showed that the HOVET receives canine patients from all regions of São Paulo and there is a homogeneous spatial distribution of neoplasms. Authors encourage additional broader studies, involving several veterinary hospitals, clinics or laboratories in order to obtain more accurate data on distribution of canine neoplasms in São Paulo, SP, Brazil