RESUMO

Mammary cancer is the most frequently diagnosed neoplasia in women and non-spayed female dogs and is one of the leading causes of death in both species. Canines develop spontaneous mammary tumors that share a significant number of biological, clinical, pathological and molecular characteristics with human breast cancers. This review provides a detailed description of the histological, molecular and clinical aspects of mammary cancer in canines; it discusses risk factors and currently available diagnostic and treatment options, as well as remaining challenges and unanswered questions. The incidence of mammary tumors is highly variable and is impacted by biological, pathological, cultural and socioeconomic factors, including hormonal status, breed, advanced age, obesity and diet. Diagnosis is mainly based on histopathology, although several efforts have been made to establish a molecular classification of canine mammary tumors to widen the spectrum of treatment options, which today rely heavily on surgical removal of tumors. Lastly, standardization of clinical study protocols, development of canine-specific biological tools, establishment of adequate dog-specific disease biomarkers and identification of targets for the development of new therapies that could improve survival and have less adverse effects than chemotherapy are among the remaining challenges.

RESUMO

ABSTRACT: Sapajus libidinosus is a New World primate belonging to the Cebidae family that lives in the caatinga and cerrado, which are known Brazilian biomes. It is currently classified as near threatened, almost endangered, by the main animal protection organizations. Knowledge of biochemistry, the C-reactive protein, and the proteinogram are important for the preservation of this species. Our study established reference intervals for several biochemical variables and the proteinogram. For this purpose, blood samples were collected from 50 S. libidinosus monkeys (25 males and 25 females) kept in captivity at the Brazilian state of Paraíba. Descriptive analysis and reference intervals were estimated following the guidelines of the American Society of Veterinary Clinical Pathology, using the Reference Value Advisor 2.1 software. In the overall population (n=50), significant differences (P < 0.05) were noted for creatinine and total proteins when considering the age factor (higher in adults), as well as for albumin and indirect bilirubin (higher in juveniles). Sex-associated differences (females versus males, P < 0.05) were reported for serum urea and creatinine (higher in males), as well as for albumin and Beta-Globulins (higher in females). In conclusion, to the authors' best knowledge, the present results are innovative and can be used as reference intervals for assessing the animals' health status. Moreover, it is also pioneer in determining the C-reactive protein in this species. It is important to emphasize that gender and age categories can have an influence and should be considered when interpreting the tests results.

RESUMO: O Sapajus libidinosus é um primata do novo mundo pertencente à família Cebidae que habita os biomas da caatinga e cerrado do Brasil. Atualmente esta classificado como quase ameaçado pelos principais orgãos de proteção animal. O conhecimento da bioquímica sérica, proteína C reativa e proteinograma são importantes na preservação desta espécie. O nosso estudo tem como objetivo determinar os intervalos de referência para várias variáveis bioquímicas e proteinograma. Para isso, foram colhidas amostras de sangue de 50 macacos da espécie S. libidinosus (25 machos e 25 fêmeas) mantidos em cativeiro no estado da Paraíba, Brasil. A análise descritiva e os cálculos dos intervalos de referência foram estimados segundo as diretrizes da Sociedade Americana de Patologia Clínica Veterinária com o uso do software Reference Value Advisor 2.1. Na população total (n=50), considerando o factor idade, foram observadas diferenças significativas (P < 0,05) para a creatinina e proteínas totais (valores superiores nos adultos) e para a albumina e bilirrubina indirecta (valores superiores nos jovens). Foram encontradas diferenças associadas ao sexo (fêmeas versus machos, P < 0,05) para a ureia e creatinina séricas (valores superiores nos machos) e albumina e Beta-Globulinas (valores superiores nas fêmeas). Conclui-se que, tanto quanto é do conhecimento dos autores, os resultados deste estudo são inovadores e podem ser utilizados como intervalos de referência para avaliação do estado de higidez dos animais e é pioneiro na determinação da proteína C reativa nesta espécie. É importante salientar que o sexo e a faixa etária podem ter influência e devem ser levados em consideração pelos profissionais na interpretação dos exames.

RESUMO

Sapajus libidinosus is a New World primate belonging to the Cebidae family that lives in the caatinga and cerrado, which are known Brazilian biomes. It is currently classified as near threatened, almost endangered, by the main animal protection organizations. Knowledge of biochemistry, the C-reactive protein, and the proteinogram are important for the preservation of this species. Our study established reference intervals for several biochemical variables and the proteinogram. For this purpose, blood samples were collected from 50 S. libidinosus monkeys (25 males and 25 females) kept in captivity at the Brazilian state of Paraíba. Descriptive analysis and reference intervals were estimated following the guidelines of the American Society of Veterinary Clinical Pathology, using the Reference Value Advisor 2.1 software. In the overall population (n=50), significant differences (P < 0.05) were noted for creatinine and total proteins when considering the age factor (higher in adults), as well as for albumin and indirect bilirubin (higher in juveniles). Sex-associated differences (females versus males, P < 0.05) were reported for serum urea and creatinine (higher in males), as well as for albumin and Beta-Globulins (higher in females). In conclusion, to the authors' best knowledge, the present results are innovative and can be used as reference intervals for assessing the animals' health status. Moreover, it is also pioneer in determining the C-reactive protein in this species. It is important to emphasize that gender and age categories can have an influence and should be considered when interpreting the tests results.

O Sapajus libidinosus é um primata do novo mundo pertencente à família Cebidae que habita os biomas da caatinga e cerrado do Brasil. Atualmente esta classificado como quase ameaçado pelos principais orgãos de proteção animal. O conhecimento da bioquímica sérica, proteína C reativa e proteinograma são importantes na preservação desta espécie. O nosso estudo tem como objetivo determinar os intervalos de referência para várias variáveis bioquímicas e proteinograma. Para isso, foram colhidas amostras de sangue de 50 macacos da espécie S. libidinosus (25 machos e 25 fêmeas) mantidos em cativeiro no estado da Paraíba, Brasil. A análise descritiva e os cálculos dos intervalos de referência foram estimados segundo as diretrizes da Sociedade Americana de Patologia Clínica Veterinária com o uso do software Reference Value Advisor 2.1. Na população total (n=50), considerando o factor idade, foram observadas diferenças significativas (P < 0,05) para a creatinina e proteínas totais (valores superiores nos adultos) e para a albumina e bilirrubina indirecta (valores superiores nos jovens). Foram encontradas diferenças associadas ao sexo (fêmeas versus machos, P < 0,05) para a ureia e creatinina séricas (valores superiores nos machos) e albumina e Beta-Globulinas (valores superiores nas fêmeas). Conclui-se que, tanto quanto é do conhecimento dos autores, os resultados deste estudo são inovadores e podem ser utilizados como intervalos de referência para avaliação do estado de higidez dos animais e é pioneiro na determinação da proteína C reativa nesta espécie. É importante salientar que o sexo e a faixa etária podem ter influência e devem ser levados em consideração pelos profissionais na interpretação dos exames.

Assuntos

RESUMO

The involvement of the nervous system in the development of cancer is controversial. Several authors have shown opinions and conflicting evidence that support the early effect of the nervous system on the carcinogenic process. For about a century, research has not been enough, questions remain open, ideas are not discarded, and although more research is still needed to answer all the questions, there is now enough evidence to support the theories and give hope of finding one more possible form of treatment. It is clear that malignant neoplasms have endogenous characteristics that allow them to establish and progress. Some of these characteristics known as hallmarks of cancer, are damage mechanisms in the pathology but necessary during other physiological processes which show some nerve dependence. The nervous system communicates with the whole organism, regulating physiological processes necessary to respond to external stimuli and for the maintenance of homeostasis. The modification of nerve activity could generate an overload and deregulate the state of cellular and tissue homeostasis; this could drive cancer development. In this review, we will address the issue in an evidence-oriented manner that supports that the nervous system is able to participate in the initial and progressive process of carcinogenesis by inducing biochemical, physiological, and cellular modifications involved in the hallmarks of cancer.

RESUMO

Histological grading systems remain cornerstones in the prognosis of canine cutaneous mast cell tumours (MCTs), but the distinct biological behaviour of each tumour often necessitates the use of complementary markers. Although a plethora of immunohistochemical markers have been proposed as prognostic factors, few are presently applied in routine diagnosis. This systematic review and meta-analysis was designed to establish which immunohistochemical markers have verifiable prognostic value for cutaneous MCTs in dogs. A Boolean search of five databases identified 200 articles for screening, of which 73 were selected for full-text assessment and 24 ultimately included in the systematic review. Odds Ratio (OR) was adopted as the summary measure for subsequent meta-analysis but only 15 articles, relating to the immunomarkers Ki-67 (9), KIT (5), and BAX (2), provided either a value for OR or sufficient data to calculate this statistic. Meta-analysis verified that canine cutaneous MCTs with elevated expression of Ki-67 or BAX, as well aberrant immuno-expression of KIT, showed an increased odds of death, with respective OR values of 11.2 (95% CI 6.3-20.0; p < .01), 9.9 (95% CI 1.3-73.6; p = .03), and 4.1 (95% CI 1.1-15.3; p = .03). Despite KIT, Ki67, and BAX arise as suitable prognostic factor for canine MCTs, this study highlighted the lack of important clinical and statistical data in many published articles, rendering it impossible to complete the meta-analysis of several potentially valuable immunohistochemical markers.

Assuntos

RESUMO

Feline mammary carcinomas (FMCs) are commonly characterized by high clinical aggressiveness and poor prognosis. FMCs share many features with the corresponding human disease, allowing the comparative investigation of tumour biology and therapeutic strategies, including multidrug resistance (MDR) mechanisms. Although transporting/binding proteins, including permeability glycoprotein (P-gp), lung resistance protein (LRP) and metallothionein (MT), are frequently associated with tumour aggressiveness and unresponsiveness to chemotherapy in human breast cancer, they have not been analysed in FMCs. We investigated the immunoexpression of P-gp, LRP and MT in FMCs and their correlation with clinicopathological parameters and overall survival (OS) time in 46 FMCs, with a median follow-up period of 289 days. These markers were co-expressed in 85% of tumours. P-gp was expressed in 93.4% of FMCs and was positively associated with tumour grade (P = 0.049). While unequivocally observed in all FMCs, LRP immunoexpression did not correlate with any clinicopathological parameters or OS. Expression of MT was significant in triple-negative basal- and normal-like molecular subtypes of FMCs (P = 0.023). The concurrent expression of MDR proteins indicates the potential existence of chemotherapy resistance-related mechanisms in FMCs. The positive association between P-gp and MT immunoexpression and aggressive phenotypes could open new therapeutic and translational strategies for FMCs.

Assuntos

RESUMO

Mammary tumours are the first and third most incident neoplasm in women and cats, respectively. Approximately 85% of feline mammary gland tumours are malignant and aggressive, especially the triple-negative and HER-2+ molecular subtypes. Triple-negative basal-like feline mammary carcinomas (FMCs) are considered suitable models due to the clinical and morphological similarities with human basal-like triple-negative breast cancer (TNBC). In women, TNBC has a poor prognosis and is often associated with mutations in the tumour suppressor genes BRCA1 and BRCA2. In light of this, the aim of the present investigation was to screen somatic and germline variants of BRCA1 and BRCA2 in nine female cats bearing FMCs. Matched whole blood and FMC samples were obtained for genetic analysis. Additional tumour samples were obtained for histopathological and immunohistochemical evaluation. Genomic DNA was isolated and 27 exonic regions of BRCA1 and BRCA2 genes were amplified and screened by next-generation sequencing. A somatic variant with high functional impact was found in exon 11 of BRCA2 at a frequency of 4.34% in one FMC-bearing cat. Four germline variants with moderate impact were detected in three of the nine FMC-bearing cats and were restricted to exon 9 of BRCA1. It is concluded that the germline genetic variants found in one-third of FMC-bearing animals might be associated with a higher risk of hereditary mammary carcinogenesis.

Assuntos

RESUMO

ABAutosomal dominant polycystic kidney disease (ADPKD) has been related to left ventricular structural and functional abnormalities in human patients. The present study aimed to evaluate the cardiac structural and functional findings in Persian cats with ADPKD. Client-owned ADPKD (n=12) and non-ADPKD (n=12) Persian cats were enrolled in this study. The animals underwent echo- and electrocardiographic (ECG) examinations, and non-invasive measurements of systolic blood pressure (SBP) were obtained. Both groups were similar regarding hematological and biochemical parameters, including white blood cell count and levels of blood urea nitrogen, creatinine, total protein and thyroxine. There were no differences related to ECG parameters between ADPKD and non-ADPKD cats. Left ventricular hypertrophy (LVH) was demonstrated in 6/12 (50%) normotensive ADPKD cats with preserved renal function. There were no differences between animal groups regarding the echocardiographic parameters, including left ventricular ejection fraction and shortening fraction; however, basal interventricular septal thickness at end-diastole near the left ventricular outflow tract and aortic artery flow velocity showed slightly elevated values in ADPKD-cats. Our study revealed that Persian cats with ADPKD do not reproduce the functional and structural cardiac phenotype reported in human patients; however, large-scale cohort studies are necessary to distinguish the possibilities of a true linkage between ventricular myocardial hypertrophy and ADPKD in this breed.(AU)

A doença renal policística autossômica dominante (DRPAD) tem sido relacionada a anormalidades estruturais e funcionais de ventrículo esquerdo em pacientes humanos. O objetivo do presente estudo foi avaliar os achados estruturais e funcionais cardíacos em gatos persas com DRPAD. Gatos persas pertencentes à clientes com DRPAD (n=12) e sem DRPAD (n=12) foram envolvidos neste trabalho. Os animais foram submetidos aos exames de eco e eletrocardiografia (ECG) e foram obtidas medições não-invasivas da pressão arterial sistólica (PAS). Ambos os grupos apresentaram valores semelhantes em relação aos parâmetros hematológicos e bioquímicos, incluindo contagem de glóbulos brancos e níveis séricos de ureia, creatinina, proteína total e tiroxina. Não houve diferença em relação aos parâmetros do ECG entre os gatos com ou sem DRPAD. A hipertrofia ventricular esquerda foi demonstrada em 6/12 (50%) dos gatos normotensos com DRPAD e função renal preservada. Não houve diferenças entre os grupos em relação aos parâmetros ecocardiográficos, incluindo fração de ejeção e fração de encurtamento do ventrículo esquerdo, entretanto a espessura septal interventricular basal na diástole na via de saída do ventrículo esquerdo e a velocidade do fluxo da artéria aórtica mostraram valores ligeiramente elevados em gatos com DRPAD. Nosso estudo revelou que gatos persas com DRPAD não reproduzem o fenótipo cardíaco funcional e estrutural encontrado em pacientes humanos. No entanto, estudos de coorte em larga escala são necessários para distinguir as possibilidades de uma verdadeira ligação entre a hipertrofia ventricular do miocárdio e a DRPAD nesta raça.(AU)

Assuntos

RESUMO

ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) has been related to left ventricular structural and functional abnormalities in human patients. The present study aimed to evaluate the cardiac structural and functional findings in Persian cats with ADPKD. Client-owned ADPKD (n=12) and non-ADPKD (n=12) Persian cats were enrolled in this study. The animals underwent echo- and electrocardiographic (ECG) examinations, and non-invasive measurements of systolic blood pressure (SBP) were obtained. Both groups were similar regarding hematological and biochemical parameters, including white blood cell count and levels of blood urea nitrogen, creatinine, total protein and thyroxine. There were no differences related to ECG parameters between ADPKD and non-ADPKD cats. Left ventricular hypertrophy (LVH) was demonstrated in 6/12 (50%) normotensive ADPKD cats with preserved renal function. There were no differences between animal groups regarding the echocardiographic parameters, including left ventricular ejection fraction and shortening fraction; however, basal interventricular septal thickness at end-diastole near the left ventricular outflow tract and aortic artery flow velocity showed slightly elevated values in ADPKD-cats. Our study revealed that Persian cats with ADPKD do not reproduce the functional and structural cardiac phenotype reported in human patients; however, large-scale cohort studies are necessary to distinguish the possibilities of a true linkage between ventricular myocardial hypertrophy and ADPKD in this breed.

RESUMO: A doença renal policística autossômica dominante (DRPAD) tem sido relacionada a anormalidades estruturais e funcionais de ventrículo esquerdo em pacientes humanos. O objetivo do presente estudo foi avaliar os achados estruturais e funcionais cardíacos em gatos persas com DRPAD. Gatos persas pertencentes à clientes com DRPAD (n=12) e sem DRPAD (n=12) foram envolvidos neste trabalho. Os animais foram submetidos aos exames de eco e eletrocardiografia (ECG) e foram obtidas medições não-invasivas da pressão arterial sistólica (PAS). Ambos os grupos apresentaram valores semelhantes em relação aos parâmetros hematológicos e bioquímicos, incluindo contagem de glóbulos brancos e níveis séricos de ureia, creatinina, proteína total e tiroxina. Não houve diferença em relação aos parâmetros do ECG entre os gatos com ou sem DRPAD. A hipertrofia ventricular esquerda foi demonstrada em 6/12 (50%) dos gatos normotensos com DRPAD e função renal preservada. Não houve diferenças entre os grupos em relação aos parâmetros ecocardiográficos, incluindo fração de ejeção e fração de encurtamento do ventrículo esquerdo, entretanto a espessura septal interventricular basal na diástole na via de saída do ventrículo esquerdo e a velocidade do fluxo da artéria aórtica mostraram valores ligeiramente elevados em gatos com DRPAD. Nosso estudo revelou que gatos persas com DRPAD não reproduzem o fenótipo cardíaco funcional e estrutural encontrado em pacientes humanos. No entanto, estudos de coorte em larga escala são necessários para distinguir as possibilidades de uma verdadeira ligação entre a hipertrofia ventricular do miocárdio e a DRPAD nesta raça.