Histone epigenetic modifications and their relationship with cancer: a comparative medicine view / Modificações epigenéticas de histonas e sua relação com o câncer: uma visão da medicina comparada

ABSTRACT: Epigenetic modifications have become highly important in the study of cancer pathogenesis due to research showing that changes in the expression of DNA-associated proteins can affect gene expression but may be reversible after treatment. The changing histones are being studied on a large scale in medicine while recent studies also show this relationship in veterinary medicine. Histone deacetylation is related to tumor progression and overexpression of histone deacetylases (HDACs) is responsible for these changes. The silencing of tumor suppressor genes related to epigenetic changes favors tumor progression; however, using HDAC inhibitors has been shown to effectively reverse these histone changes while having anticancer effects. This research provided an overview of comparative medicine between humans and dogs concerning epigenetic changes while showing the physiological mechanisms and the relationship between cancer and epigenetics, specifically regarding histone acetylation and deacetylation. This overview should contribute to a better understanding of epigenetics and cancer and their relationship with new target-molecular therapies in veterinary medicine and the importance of such studies.

RESUMO: Mudanças epigenéticas assumiram importância na patogênese do câncer a partir de pesquisas que mostraram que mudanças na expressão de proteínas associadas ao DNA podem afetar a expressão gênica e podem ser reversíveis após o tratamento. As alterações nas histonas têm sido estudadas em larga escala na medicina, particularmente no câncer de mama, e estudos recentes mostram essa relação também na medicina veterinária. A desacetilação das histonas está relacionada à progressão tumoral e a superexpressão de histonas desacetilases (HDACs) é responsável por essas alterações. O silenciamento de genes supressores de tumor relacionados a alterações epigenéticas favorece a progressão tumoral, entretanto, o uso de inibidores de HDAC é eficaz em reverter as alterações nas histonas e tem efeitos anticâncer. Uma visão da medicina comparada entre humanos e cães em relação às alterações epigenéticas, será o objetivo deste trabalho, mostrando os mecanismos fisiológicos e a relação entre o câncer e a epigenética, especificamente com a acetilação e desacetilação de histonas. Essa visão contribuirá para um melhor entendimento da epigenética e do câncer, bem como a relação com as novas terapias moleculares-alvo na medicina veterinária e a importância dos estudos neste contexto.

MicroRNA and cancer: a focus on mammary tumors in female dogs / MicroRNA e o câncer: um enfoque em tumores mamários de cadelas

Mammary tumors are the most frequent tumors reported in female dogs and have great relevance in veterinary oncology; however, little is known about the molecular mechanisms involved in the development of metastasis. An increasing number of human studies have suggested that epigenetic alterations, such as DNA methylation, miRNA, and histone modifications, are the predominant events leading to the metastatic phenotype in tumor cells and participate in regulating oncogenic signals associated with tumor spread. Among these epigenetic alterations, miRNAs have stood out in recent years, presenting a fundamental role in tumorigenesis. There are still few studies evaluating the role of miRNAs in canine mammary tissues. Thus, this paper aims to review the role of miRNAs in cancer with a special focus on canine mammary tumors.(AU)

Os tumores mamários caninos são considerados os mais frequentes em cadelas, além de apresentarem grande relevância na oncologia veterinária, porém a doença metastática ainda é um desafio que compreende mecanismos moleculares não totalmente esclarecidos. Um número crescente de estudos na medicina humana tem sugerido que alterações epigenéticas, tais como metilação do DNA e modificação das histonas são eventos predominantes na célula tumoral para aquisição do fenótipo metastático, participando da regulação de sinais oncogênicos associados com a disseminação do tumor. Dentre as alterações epigenéticas, os miRNAs se destacaram nos últimos anos apresentando um papel fundamental na tumorigênese. Ainda existem poucos estudos avaliando o papel dos miRNAs em tecidos mamários caninos. Assim, com este trabalho objetiva-se revisar o papel dos miRNAs no câncer com foco especial nos tumores de mama de cadelas.(AU)

Evaluation of serum concentrations of cortisol and thyroxine in bitches with early-stage mammary carcinoma / Concentrações séricas de cortisol e tiroxina em cadelas com carcinoma mamário em estádio inicial

In view of the fact that cancer is considered a chronic disease that can interfere with hormonal homeostasis by means of cytokines, we hypothesized that, even at early stages, mammary carcinoma is able to alter the balance of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. To test this hypothesis, the serum concentrations of basal cortisol, thyroxine (T4), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated in 20 unspayed bitches that had a histopathological diagnosis of grade 1 mammary carcinoma at clinical stage I according to the World Health Organization (WHO) classification (T1N0M0). The control animals comprised 10 unspayed bitches in perfect health conditions that were matched with those with mammary carcinoma by age. No significant differences regarding the concentrations of basal cortisol, TSH, t4, and fT4 were found between the bitches carrying early stage mammary carcinoma when compared to the control group. This suggests that, even if malignant, early-stage mammary carcinomas do not exhibit the ability to alter the concentrations of hormones produced by the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-thyroid axes.(AU)

Em vista do fato de neoplasias serem consideradas doenças crônicas que por meio de citocinas podem interferir na homeostase hormonal, hipotetizou-se que o carcinoma mamário, mesmo nos seus estádios iniciais, fosse capaz de alterar o equilíbrio dos eixos hipotalâmico-hipofisário-tireóideo e hipotalâmico-hipofisário-adrenal. Para tal, foram avaliadas as concentrações séricas de cortisol basal, tiroxina (T4), tiroxina livre (fT4) e tireotrofina (TSH) de 20 fêmeas caninas, inteiras, com diagnóstico histopatológico de carcinoma mamário grau 1 e estadiamento clínico I segundo a classificação da Organização Mundial da Saúde - OMS (T1N0M0). Os animais controle constituíram-se por 10 fêmeas caninas inteiras, em perfeitas condições de higidez, as quais foram pareadas, por idade, com aquelas portadoras de carcinoma mamário. Não foram encontradas diferenças significativas nas concentrações de cortisol basal, TSH, T4 e fT4 das cadelas portadoras de carcinoma mamário em estádio inicial quando comparadas às controles sugerindo que, mesmo considerados malignos, ainda não apresentam a capacidade de alterar as concentrações dos hormônios produzidos pelos eixos hipotalâmico-hipofisário-adrenal e tireóideo.(AU)

Evaluation of serum concentrations of cortisol and thyroxine in bitches with early-stage mammary carcinoma / Concentrações séricas de cortisol e tiroxina em cadelas com carcinoma mamário em estádio inicial

In view of the fact that cancer is considered a chronic disease that can interfere with hormonal homeostasis by means of cytokines, we hypothesized that, even at early stages, mammary carcinoma is able to alter the balance of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. To test this hypothesis, the serum concentrations of basal cortisol, thyroxine (T4), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated in 20 unspayed bitches that had a histopathological diagnosis of grade 1 mammary carcinoma at clinical stage I according to the World Health Organization (WHO) classification (T1N0M0). The control animals comprised 10 unspayed bitches in perfect health conditions that were matched with those with mammary carcinoma by age. No significant differences regarding the concentrations of basal cortisol, TSH, t4, and fT4 were found between the bitches carrying early stage mammary carcinoma when compared to the control group. This suggests that, even if malignant, early-stage mammary carcinomas do not exhibit the ability to alter the concentrations of hormones produced by the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-thyroid axes.(AU)

Em vista do fato de neoplasias serem consideradas doenças crônicas que por meio de citocinas podem interferir na homeostase hormonal, hipotetizou-se que o carcinoma mamário, mesmo nos seus estádios iniciais, fosse capaz de alterar o equilíbrio dos eixos hipotalâmico-hipofisário-tireóideo e hipotalâmico-hipofisário-adrenal. Para tal, foram avaliadas as concentrações séricas de cortisol basal, tiroxina (T4), tiroxina livre (fT4) e tireotrofina (TSH) de 20 fêmeas caninas, inteiras, com diagnóstico histopatológico de carcinoma mamário grau 1 e estadiamento clínico I segundo a classificação da Organização Mundial da Saúde - OMS (T1N0M0). Os animais controle constituíram-se por 10 fêmeas caninas inteiras, em perfeitas condições de higidez, as quais foram pareadas, por idade, com aquelas portadoras de carcinoma mamário. Não foram encontradas diferenças significativas nas concentrações de cortisol basal, TSH, T4 e fT4 das cadelas portadoras de carcinoma mamário em estádio inicial quando comparadas às controles sugerindo que, mesmo considerados malignos, ainda não apresentam a capacidade de alterar as concentrações dos hormônios produzidos pelos eixos hipotalâmico-hipofisário-adrenal e tireóideo.(AU)

Molecular detection of Anaplasma species in dogs in Colombia / Detecção molecular de espécies de Anaplasma em cães na Colômbia

Abstract Anaplasma platys and A. phagocytophilum are tick-borne pathogens that parasitize platelets and neutrophils, respectively, of humans and animals. The former is the etiological agent of canine cyclic thrombocytopenia, while the latter is that of canine granulocytic anaplasmosis. This work involved the detection and identification of Anaplasma species in blood samples from dogs in Colombia, using molecular techniques. Between December 2008 and April 2009, blood samples were drawn from the cephalic vein of 91 dogs in the central-western region of Colombia (cities of Bogota, Villavicencio and Bucaramanga) and stored in tubes containing EDTA. These samples were used in 16S rRNA-Anaplasma spp. nPCR and the preparation of blood smears. One (1.1%) of the 91 sampled dogs showed inclusions suggestive of Anaplasmataceae agents in the cytoplasm of platelets. Based on PCR followed by sequencing and phylogenetic analysis, A. platys and Anaplasma sp. closed related to A. phagocytophilum were detected in two and one dog, respectively. Interestingly, all the samples were negative for specific msp-2-A. phagocytophilum real-time qPCR, suggesting the circulation of an Anaplasma species phylogenetically related to A. phagocytophilum in dogs in the aforementioned region. Hence, Anaplasma spp. circulates among dogs in Colombia, albeit with low frequency. To the best of authors' knowledge, this is the first molecular detection of Anaplasma spp. in dogs in Colombia.(AU)

Resumo Anaplasma platys e A. phagocytophilum são patógenos transmitidos por carrapatos que parasitam plaquetas e neutrófilos, respectivamente, de humanos e animais. Enquanto o primeiro é agente etiológico da trombocitopenia cíclica canina, o último é o agente responsável pela anaplasmose granulocítica canina. O presente trabalho objetivou detectar e caracterizar, utiizando técnicas moleculares, a presença de espécies de Anaplasma em amostras de sague de cães na Colômbia. Entre Dezembro de 2008 e Abril de 2009, amostras de sangue colhidas em tubos contendo EDTA da veia cefálica de 91 cães da região centro-oeste da Colômbia (cidades de Bogotá, Villavicencio e Bucaramanga). As amostras de sangue foram utilizadas em reações de nPCR para 16S rRNA-Anaplasma spp. e confecção de esfregaços sanguíneos. Um (1,1%) dos 91 cães amostrados mostraram inclusões sugestivas de agentes Anaplasmataceae no citoplasma de plaquetas. Baseada na PCR seguida de sequenciamento e análise filogenética, A. platys and Anaplasma sp. relacionado a A. phagocytophilum foram detectados em dois e um cão, respectivamente. Interessantemente, todas as amostras mostraram-se negativas na PCR em tempo real quantitativa específica para msp-2-A. phagocytophilum, sugerindo a circulação de uma espécie de Anaplasma sp. filogeneticamente relacionado ao A. phagocytophilum em cães na região estudada. Embora em uma baixa freqüência, Anaplasma spp. circula entre cães na Colômbia. O presente trabalho representa a primeira detecção de Anaplasma spp. em cães na Colômbia.(AU)

Paraneoplastic hypercalcemia secondary to canine mammary tumors

Background: Paraneoplastic syndromes are complexes symptom that occur at a distinct site from the primary tumor or its metastasis by the production of hormone by the tissue in which the tumor appears. Paraneoplastic hypercalcemia is associated with an abnormal elevation of serum calcium levels and the mainly tumor related to this syndrome in canine is lymphoma, anal sac apocrine gland adenocarcinoma and multiple myeloma. In mammary tumors, the most frequent tumor that affect female dogs, this syndrome was also observed. The aims of this study were to evaluate serum calcium levels in female dogs with malignant mammary tumors and correlate calcium levels with clinicopathological parameters. Materials, Methods & Results: It was evaluated fifty-one female dogs with mammary carcinomas (simple carcinomas and carcinoma in mixed tumors) for serum calcium levels using colorimetric test. Clinical-histopathological data as spray status, pseudopregnancy, tumor size, ulceration, clinical staging, histopathological type and tumor grade were also evaluated in association with serum calcium levels. All dogs were treated with unilateral mastectomy. It was observed that 18 animals (35%) had calcium serum levels increased (>11.5 mg/dL) and 56% (10/18 cases) of these animals had serum calcium levels higher than 12 mg/dL. All dogs with hypercalcemia were asymptomatic, including two female [...](AU)

Paraneoplastic hypercalcemia secondary to canine mammary tumors

Background: Paraneoplastic syndromes are complexes symptom that occur at a distinct site from the primary tumor or its metastasis by the production of hormone by the tissue in which the tumor appears. Paraneoplastic hypercalcemia is associated with an abnormal elevation of serum calcium levels and the mainly tumor related to this syndrome in canine is lymphoma, anal sac apocrine gland adenocarcinoma and multiple myeloma. In mammary tumors, the most frequent tumor that affect female dogs, this syndrome was also observed. The aims of this study were to evaluate serum calcium levels in female dogs with malignant mammary tumors and correlate calcium levels with clinicopathological parameters. Materials, Methods & Results: It was evaluated fifty-one female dogs with mammary carcinomas (simple carcinomas and carcinoma in mixed tumors) for serum calcium levels using colorimetric test. Clinical-histopathological data as spray status, pseudopregnancy, tumor size, ulceration, clinical staging, histopathological type and tumor grade were also evaluated in association with serum calcium levels. All dogs were treated with unilateral mastectomy. It was observed that 18 animals (35%) had calcium serum levels increased (>11.5 mg/dL) and 56% (10/18 cases) of these animals had serum calcium levels higher than 12 mg/dL. All dogs with hypercalcemia were asymptomatic, including two female [...]

A retrospective study of canine cutaneous food allergy at a Veterinary Teaching Hospital from Jaboticabal, São Paulo, Brazil / Estudo retrospectivo da dermatite trofoalérgica canina em um Hospital Veterinário de Jaboticabal, São Paulo, Brasil

Cutaneous food allergy is an adverse immunological response, triggered by antigenic dietary components that may escape the digestion process and are absorbed intact through the gastrointestinal mucosa. In Brazil, there are only a few reports on cutaneous food allergy and antigenicity of food components used in pet food production. Thus, the aim of this report was to assess and describe data from medical records of canine patients diagnosed with cutaneous food allergy at a Veterinary Teaching Hospital from Jaboticabal, SP, Brazil, in order to evaluate epidemiological and clinical aspects related to this skin problem. From 2007 to 2012, 29 dogs received the diagnosis of cutaneous food allergy after an eight-week hypoallergenic elimination trial. Among them, purebred dogs were more frequent, as well as females, and their mean age was 50.4 months old. Pruritus was reported in all cases, especially in interdigital areas. In order to establish the diagnosis, most patients received home-cooked elimination diet, based on potato and lamb in approximately 80% of the cases. Besides, it was highlighted the importance of the hypoallergenic elimination diet being rigorously followed by dogs' owners, aiming the adequate control of the clinical signs related to cutaneous food allergy.(AU)

A dermatite trofoalérgica é uma resposta imunológica adversa, desencadeada por componentes dietéticos antigênicos, que escapam do processo de digestão e são absorvidos intactos pela mucosa gastrointestinal. No Brasil, há poucos relatos acerca da dermatite trofoalérgica e da antigenicidade dos componentes utilizados na produção de alimentos para animais. Assim, o objetivo deste trabalho foi avaliar e relatar dados de prontuários de pacientes caninos diagnosticados com dermatite trofoalérgica em um Hospital Veterinário de Jaboticabal, SP, Brasil, a fim de analisar os aspectos epidemiológicos e clínicos relacionados a este problema de pele. De 2007 a 2012, 29 cães receberam o diagnóstico de dermatite trofoalérgica após oito semanas de dieta de eliminação hipoalergênica. Dentre eles, destacam-se os cães de raça definida e as fêmeas como mais frequentes, com idade média de 50,4 meses. Prurido foi a queixa relatada em todos os casos, especialmente na região interdigital. Para fins diagnósticos, a maioria dos animais recebeu dieta caseira de eliminação, a base de batata e carneiro em aproximadamente 80% dos casos. Ademais, destaca-se a importância de que a dieta de eliminação hipoalergênica seja criteriosamente seguida pelo proprietário, a fim de controlar adequadamente os sinais clínicos da dermatite trofoalérgica.(AU)

Acute and subclinical Ehrlichia canis infection and cortisol response to ACTH stimulation test

Adrenocortical disturbances are associated with canine ehrlichiosis due to the immunological changes caused by infection and consequent inflammation. Thus, this study aimed to evaluate the occurrence of adrenocortical hormonal changes in dogs naturally infected with Ehrlichia canis (n=21) as confirmed by the presence of anti-E. canis antibodies (Dot-ELISA) and nested PCR (nPCR). Serum cortisol concentrations were assessed by radioimmunoassay before and one hour after ACTH stimulation. Ten healthy dogs were subjected to the same stimulation protocol and used as controls. The results revealed that the dogs with naturally acquired acute and subclinical ehrlichiosis secreted cortisol following ACTH stimulation in similar concentrations to those of healthy dogs.

Acute and subclinical Ehrlichia canis infection and cortisol response to ACTH stimulation test

Adrenocortical disturbances are associated with canine ehrlichiosis due to the immunological changes caused by infection and consequent inflammation. Thus, this study aimed to evaluate the occurrence of adrenocortical hormonal changes in dogs naturally infected with Ehrlichia canis (n=21) as confirmed by the presence of anti-E. canis antibodies (Dot-ELISA) and nested PCR (nPCR). Serum cortisol concentrations were assessed by radioimmunoassay before and one hour after ACTH stimulation. Ten healthy dogs were subjected to the same stimulation protocol and used as controls. The results revealed that the dogs with naturally acquired acute and subclinical ehrlichiosis secreted cortisol following ACTH stimulation in similar concentrations to those of healthy dogs.(AU)

Nitric oxide, protein oxidation and total antioxidant levels in serum of dogs naturally infected by Ehrlichia canis, Leishmania infantum and Babesia vogeli

Background: Ehrlichia canis and Babesia vogeli comprise a group of globally distributed pathogens transmitted by ticks. Leishmania infantum is transmitted by Lutzomyia longipalpis, etiological agent of leishmaniasis. The pathogens affect the animals; and can also affect the human. An imbalance between oxidants and antioxidants compounds causes an increase in free radicals, and other reactive oxygen species (ROS) has play an important role in tissue damage in a variety of pathological processes, as parasitic disease. The objective of this study was to evaluate the nitric oxide levels, protein oxidation and total antioxidant status in serum of dogs infected by L. infantum, E. canis and B. vogeli.Materials, Methods & Results: Blood samples from dogs originating from the city of Campo Grande, Mato Grosso do Sul state, Brazil were collected to research hemoparasites by polymerase chain reaction (PCR) using specific primers for each parasite. Serum samples obtained from 54 dogs with single and co-infection were used this study: L. infantum (n = 19), E. canis (n = 8), B. vogeli (n = 5), L. infantum and E. canis (n = 12), L. infantum and B. vogeli (n = 4), and E. canis and B. vogeli (n = 6), as well as 17 normal controls (uninfected). Samples were stored at -80ºC for further evaluation of NOx , AOPP, and FRAP levels using Cobas Mira automated analyzer, and results were expressed as µmol/L. NOx , AOPP and FRAP levels were increased (P < 0.01) in dogs infected by parasites when compared to uninfected animals. Levels of NO· and AOPP in dogs naturally infected by Babesia vogeli and Ehrlichia canis, respectively, did not differ from the control group (uninfected). The higher NOx levels were observed in the serum of dogs with co-infection by L. infantum and E. canis, and L. infantum and B. vogeli (P < 0.01). Altogether, our results indicate that dogs naturally infected by L. infantum, E. canis and B. vogeli developed a state of redox imbalance.[...](AU)

Nitric oxide, protein oxidation and total antioxidant levels in serum of dogs naturally infected by Ehrlichia canis, Leishmania infantum and Babesia vogeli

Background: Ehrlichia canis and Babesia vogeli comprise a group of globally distributed pathogens transmitted by ticks. Leishmania infantum is transmitted by Lutzomyia longipalpis, etiological agent of leishmaniasis. The pathogens affect the animals; and can also affect the human. An imbalance between oxidants and antioxidants compounds causes an increase in free radicals, and other reactive oxygen species (ROS) has play an important role in tissue damage in a variety of pathological processes, as parasitic disease. The objective of this study was to evaluate the nitric oxide levels, protein oxidation and total antioxidant status in serum of dogs infected by L. infantum, E. canis and B. vogeli.Materials, Methods & Results: Blood samples from dogs originating from the city of Campo Grande, Mato Grosso do Sul state, Brazil were collected to research hemoparasites by polymerase chain reaction (PCR) using specific primers for each parasite. Serum samples obtained from 54 dogs with single and co-infection were used this study: L. infantum (n = 19), E. canis (n = 8), B. vogeli (n = 5), L. infantum and E. canis (n = 12), L. infantum and B. vogeli (n = 4), and E. canis and B. vogeli (n = 6), as well as 17 normal controls (uninfected). Samples were stored at -80ºC for further evaluation of NOx , AOPP, and FRAP levels using Cobas Mira automated analyzer, and results were expressed as µmol/L. NOx , AOPP and FRAP levels were increased (P < 0.01) in dogs infected by parasites when compared to uninfected animals. Levels of NO· and AOPP in dogs naturally infected by Babesia vogeli and Ehrlichia canis, respectively, did not differ from the control group (uninfected). The higher NOx levels were observed in the serum of dogs with co-infection by L. infantum and E. canis, and L. infantum and B. vogeli (P < 0.01). Altogether, our results indicate that dogs naturally infected by L. infantum, E. canis and B. vogeli developed a state of redox imbalance.[...]

Endoscopic approach for a laryngeal neoplasm in a dog

Laryngeal and tracheal tumors are rare in pets; some piece of information on their disease behavior, therapy and evolution are limited. Neoplasms in this area are a diagnostic challenge. In many cases, they can be biopsied and excised using endoscopic instruments, but there is no report of this in canines. The goal of this study is to report a successful case of a laryngeal neoplasm removal through endoscopy. A head and neck radiogram revealed a mass in the laryngeal lumen protruding into the trachea. The patient then underwent an endoscopy to confirm the radiographic diagnosis and to surgically remove the tumor. The histopathological diagnosis was poorly differentiated carcinoma. The most appropriate treatment for laryngeal tumors is the resection of the submucosa or a partial laryngectomy however, partial and total laryngectomies are associated with many postoperative complications. In contrast, the endoscopic approach allows for highly magnified visualization of the lesion in situ, which facilitates the surgical removal of the mass through videosurgery. With little manipulation of the affected area, the chances of postoperative complications are reduced, leading to a more rapid recovery.

Tumores de laringe e traqueia são raros em animais de estimação e as informações sobre o comportamento, terapia e evolução destas neoplasias são limitadas. Neoplasias nesta área são desafios diagnósticos. Em muitos casos, pode ser feita a biópsia e excisão da massa utilizando instrumentos endoscópicos, mas não existe relato deste tipo de procedimento em caninos. O objetivo deste estudo foi relatar um caso de sucesso da remoção endoscópica de um tumor de laringe. A radiografia da região cervical revelou uma massa na luz da laringe invadindo a traqueia. O paciente foi então submetido a uma endoscopia para confirmar o diagnóstico radiográfico e remover cirurgicamente o tumor. O diagnóstico histopatológico foi de carcinoma pouco diferenciado. O tratamento mais adequado para os tumores da laringe é a ressecção da submucosa ou uma laringectomia parcial, no entanto, estas estão associadas a muitas complicações pós-operatórias. Em contraste, a abordagem endoscópica permite a visualização da lesão in situ, o que facilita a remoção cirúrgica da massa através de videocirurgia. Com pouca manipulação da área afetada, as chances de complicações pós-operatórias são reduzidas, levando a uma recuperação mais rápida.

Endoscopic approach for a laryngeal neoplasm in a dog

Laryngeal and tracheal tumors are rare in pets; some piece of information on their disease behavior, therapy and evolution are limited. Neoplasms in this area are a diagnostic challenge. In many cases, they can be biopsied and excised using endoscopic instruments, but there is no report of this in canines. The goal of this study is to report a successful case of a laryngeal neoplasm removal through endoscopy. A head and neck radiogram revealed a mass in the laryngeal lumen protruding into the trachea. The patient then underwent an endoscopy to confirm the radiographic diagnosis and to surgically remove the tumor. The histopathological diagnosis was poorly differentiated carcinoma. The most appropriate treatment for laryngeal tumors is the resection of the submucosa or a partial laryngectomy however, partial and total laryngectomies are associated with many postoperative complications. In contrast, the endoscopic approach allows for highly magnified visualization of the lesion in situ, which facilitates the surgical removal of the mass through videosurgery. With little manipulation of the affected area, the chances of postoperative complications are reduced, leading to a more rapid recovery.

Tumores de laringe e traqueia são raros em animais de estimação e as informações sobre o comportamento, terapia e evolução destas neoplasias são limitadas. Neoplasias nesta área são desafios diagnósticos. Em muitos casos, pode ser feita a biópsia e excisão da massa utilizando instrumentos endoscópicos, mas não existe relato deste tipo de procedimento em caninos. O objetivo deste estudo foi relatar um caso de sucesso da remoção endoscópica de um tumor de laringe. A radiografia da região cervical revelou uma massa na luz da laringe invadindo a traqueia. O paciente foi então submetido a uma endoscopia para confirmar o diagnóstico radiográfico e remover cirurgicamente o tumor. O diagnóstico histopatológico foi de carcinoma pouco diferenciado. O tratamento mais adequado para os tumores da laringe é a ressecção da submucosa ou uma laringectomia parcial, no entanto, estas estão associadas a muitas complicações pós-operatórias. Em contraste, a abordagem endoscópica permite a visualização da lesão in situ, o que facilita a remoção cirúrgica da massa através de videocirurgia. Com pouca manipulação da área afetada, as chances de complicações pós-operatórias são reduzidas, levando a uma recuperação mais rápida.

Endoscopic approach for a laryngeal neoplasm in a dog / Abordagem endoscópica de neoplasia em laringe em um cão

Laryngeal and tracheal tumors are rare in pets; some piece of information on their disease behavior, therapy and evolution are limited. Neoplasms in this area are a diagnostic challenge. In many cases, they can be biopsied and excised using endoscopic instruments, but there is no report of this in canines. The goal of this study is to report a successful case of a laryngeal neoplasm removal through endoscopy. A head and neck radiogram revealed a mass in the laryngeal lumen protruding into the trachea. The patient then underwent an endoscopy to confirm the radiographic diagnosis and to surgically remove the tumor. The histopathological diagnosis was poorly differentiated carcinoma. The most appropriate treatment for laryngeal tumors is the resection of the submucosa or a partial laryngectomy however, partial and total laryngectomies are associated with many postoperative complications. In contrast, the endoscopic approach allows for highly magnified visualization of the lesion in situ, which facilitates the surgical removal of the mass through videosurgery. With little manipulation of the affected area, the chances of postoperative complications are reduced, leading to a more rapid recovery. .(AU)

Tumores de laringe e traqueia são raros em animais de estimação e as informações sobre o comportamento, terapia e evolução destas neoplasias são limitadas. Neoplasias nesta área são desafios diagnósticos. Em muitos casos, pode ser feita a biópsia e excisão da massa utilizando instrumentos endoscópicos, mas não existe relato deste tipo de procedimento em caninos. O objetivo deste estudo foi relatar um caso de sucesso da remoção endoscópica de um tumor de laringe. A radiografia da região cervical revelou uma massa na luz da laringe invadindo a traqueia. O paciente foi então submetido a uma endoscopia para confirmar o diagnóstico radiográfico e remover cirurgicamente o tumor. O diagnóstico histopatológico foi de carcinoma pouco diferenciado. O tratamento mais adequado para os tumores da laringe é a ressecção da submucosa ou uma laringectomia parcial, no entanto, estas estão associadas a muitas complicações pós-operatórias. Em contraste, a abordagem endoscópica permite a visualização da lesão in situ, o que facilita a remoção cirúrgica da massa através de videocirurgia. Com pouca manipulação da área afetada, as chances de complicações pós-operatórias são reduzidas, levando a uma recuperação mais rápida. .(AU)

P-glycoprotein and MRP1 expression in tissues from dogs with visceral leishmaniasis / Expressão da glicoproteína-P e MRP1 em tecidos de cães com leishmaniose visceral

P-Glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are efflux pumps responsible for the MDR phenotype (multidrug resistance). In this work, we will investigate the immunohistochemical expression of P-gp and MRP1 in 24 tissue samples from dogs with Leishmania infantum (syn. L. chagasi) and evaluate whether canine visceral leishmaniasis (CVL) induces MDR in dogs. The expectation is that the results obtained from this research may offer prospects for a safer and more effective therapeutic approach for this disease. Findings illustrated that the expression of P-gp in CVL affected tissue samples (p<0.05) was greater than those of the control group, with the exception of skin tissue samples which did not differ. However, only the adrenal gland samples affected by LVC expressed significantly more MRP1 (p<0.05) than the control group. The expressions of P-gp and MRP1 were lower (p<0.05) in LVC positive spleen and skin samples in comparison with other tissues. These results suggest that the lack of a parasitological cure could be due to the high expression of P-gp and MRP1 in the liver, adrenal glands, and kidneys, which block the action of parasitacidal drugs recommended in treatment.

Glicoproteína-P (gp-P) e proteína de resistência a múltiplas drogas (MRP1) são bombas de efluxo responsáveis pelo fenótipo MDR (resistência a múltiplas drogas). Neste trabalho, investigamos a expressão por imuno-histoquímica da gp-P e MRP1 em amostras de tecidos de 24 cães com Leishmania infantum (syn. L. chagasi), e avaliamos se a leishmaniose visceral canina (LVC) induz a MDR em cães, tendo a expectativa de que os resultados obtidos possam oferecer perspectivas de uma abordagem terapêutica mais segura e eficaz nesta doença. Os resultados mostraram que a expressão da gp-P nas amostras de cães com LVC foi maior (p<0,05) em todos os tecidos em comparação ao grupo controle, com exceção da pele, que não diferiu. Entretanto, apenas as glândulas adrenais nas amostras LVC, em comparação as controle, expressaram significativamente mais MRP1 (p<0,05). As expressões de gp-P e MRP1 foram menores (p<0,05) no baço e pele das amostras LVC positivas, em comparação aos demais tecidos. Os resultados sugerem que a falha da cura parasitológica poderia ser devido à alta expressão da gp-P e MRP1 no fígado, adrenal e rins, por impedir a ação parasiticida dos fármacos recomendados no tratamento.

P-glycoprotein and MRP1 expression in tissues from dogs with visceral leishmaniasis / Expressão da glicoproteína-P e MRP1 em tecidos de cães com leishmaniose visceral

P-Glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are efflux pumps responsible for the MDR phenotype (multidrug resistance). In this work, we will investigate the immunohistochemical expression of P-gp and MRP1 in 24 tissue samples from dogs with Leishmania infantum (syn. L. chagasi) and evaluate whether canine visceral leishmaniasis (CVL) induces MDR in dogs. The expectation is that the results obtained from this research may offer prospects for a safer and more effective therapeutic approach for this disease. Findings illustrated that the expression of P-gp in CVL affected tissue samples (p<0.05) was greater than those of the control group, with the exception of skin tissue samples which did not differ. However, only the adrenal gland samples affected by LVC expressed significantly more MRP1 (p<0.05) than the control group. The expressions of P-gp and MRP1 were lower (p<0.05) in LVC positive spleen and skin samples in comparison with other tissues. These results suggest that the lack of a parasitological cure could be due to the high expression of P-gp and MRP1 in the liver, adrenal glands, and kidneys, which block the action of parasitacidal drugs recommended in treatment.(AU)

Glicoproteína-P (gp-P) e proteína de resistência a múltiplas drogas (MRP1) são bombas de efluxo responsáveis pelo fenótipo MDR (resistência a múltiplas drogas). Neste trabalho, investigamos a expressão por imuno-histoquímica da gp-P e MRP1 em amostras de tecidos de 24 cães com Leishmania infantum (syn. L. chagasi), e avaliamos se a leishmaniose visceral canina (LVC) induz a MDR em cães, tendo a expectativa de que os resultados obtidos possam oferecer perspectivas de uma abordagem terapêutica mais segura e eficaz nesta doença. Os resultados mostraram que a expressão da gp-P nas amostras de cães com LVC foi maior (p<0,05) em todos os tecidos em comparação ao grupo controle, com exceção da pele, que não diferiu. Entretanto, apenas as glândulas adrenais nas amostras LVC, em comparação as controle, expressaram significativamente mais MRP1 (p<0,05). As expressões de gp-P e MRP1 foram menores (p<0,05) no baço e pele das amostras LVC positivas, em comparação aos demais tecidos. Os resultados sugerem que a falha da cura parasitológica poderia ser devido à alta expressão da gp-P e MRP1 no fígado, adrenal e rins, por impedir a ação parasiticida dos fármacos recomendados no tratamento.(AU)

Expression of P-glycoprotein, multidrug resistance-associated protein, glutathione-S-transferase pi and p53 in canine transmissible venereal tumor / Expressão da glicoproteína-P, proteína associada à múltiplas drogas, glutationa-S-transferase pi e p53 no tumor venéreo transmissível canino

The overexpression of proteins P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP1), mutant p53, and the enzyme glutathione-S-transferase (GSTpi) are related to resistance to chemotherapy in neoplasms. This study evaluated the expression of these markers by immunohistochemistry in two groups of canine TVT, without history of prior chemotherapy (TVT1, n=9) and in TVTs presented unsatisfactory clinical response to vincristine sulfate (TVT2, n=5). The percentage of specimens positively stained for P-gp, MRP1, GSTpi and p53 were, respectively 88.8%, 0%, 44.5% and 22.2% in TVT1 and 80%, 0%, 80% and 0% in TVT2. In TVT1, one specimen presented positive expression for three markers and four specimens for two markers. In TVT2, three specimens expressed P-gp and GSTpi. In conclusion, the canine TVTs studied expressed the four markers evaluated, but just P-gp and GSTpi were significantly expressed, mainly at cytoplasm and cytoplasm and nuclei, respectively, either before chemotherapy as after vincristine sulfate exposure. Future studies are needed to demonstrate the function of these two markers in conferring multidrug resistance (MDR) or predict the response to chemotherapy in canine TVT.(AU)

A superexpressão das proteínas glicoproteína-P (Gp-P), proteína associada à resistência à múltiplas drogas 1 (MRP1) e p53 mutante e a enzima glutationa-S-transferase pi (GSTpi) está relacionada com resistência à quimioterapia em neoplasias humanas e caninas. Este estudo avaliou a expressão, por meio da imuno-histoquímica desses marcadores em espécimes de TVT caninos sem histórico de quimioterapia prévia (TVT1, n=9) e em TVT caninos que apresentaram resposta clínica insatisfatória ao sulfato de vincristina (TVT2, n=5). A porcentagem de espécimes positivos para Gp-P, MRP1, GSTpi e p53 foram, respectivamente 88,8%, 0%, 44,5% e 22,2% no grupo TVT1 e 80%, 0%, 80% e 0% no grupo TVT2. No TVT1, um espécime apresentou expressão positiva para três marcadores e quatro para dois marcadores. No TVT2, três espécimes expressaram a Gp-P e GSTpi. Em conclusão, os TVTs caninos estudados expressaram os quatro marcadores avaliados, no entanto apenas a Gp-P e GSTpi foram significativamente expressas, principalmente no citoplasmas e no citoplasma e no núcleo, respectivamente, tanto antes da quimioterapia quanto após à exposição ao sulfato de vincristina. Estudos futuros são necessários para demonstrar a função desses dois marcadores em conferir resistência à multiplas drogas (RMD) ou predizer a resposta a quimioterapia no TVT canino.(AU)

Penfigo foliaceo em um felino: relato de caso / Pemphigus foliaceus in a cat: case report / Pénfigo foliáceo en un gato: reporte de un caso

O pênfigo foliáceo é uma das formas mais importantes de dermatoses imunomediadas vesico-pustulosas em cães e gatos. A patogênese da doença está bem documentada em humanos e cães e sugere-se que em felinos o comportamento seja similar, caracterizado pela produção de anticorpos direcionados contra estruturas responsáveis pela manutenção da adesão intercelular. Embora haja relatos de diversas opções de tratamento descritos na literatura para esta dermatopatia, a maioria não foi utilizada em estudos envolvendo um grande número de animais. Descreve-se um caso de pênfigo foliáceo em um gato que respondeu satisfatoriamente apenas à corticoterapia e sem apresentar efeitos adversos.

Pemphigus foliaceus is one of the most important immune-mediated dermatoses in dogs and cats. The pathogenesis of the disease is well documented in humans and dogs and it is suggested its behavior in felines is similar, characterized by the production of antibodies directed against structures responsible for the maintenance of intercellular adhesion. Although there are reports of several treatment options described in literature for this dermatopathy, most have not been used in studies involving an increased number of animals. Here, we report a case of pemphigus foliaceus in a cat which responded favorably only to corticosteroids and without presenting adverse effects.

Pénfigo foliáceo es una de las formas más importantes de dermatosis mediada por la inmunidad en perros y gatos. La patogénesis de la enfermedad está bien documentada en seres humanos y perros, y se sugiere que el comportamiento en los gatos es similar, caracterizada por la producción de anticuerpos dirigidos contra las estructuras responsables del mantenimiento de la adesión intercelular. Aunque hay informes de diversas opciones de tratamiento descritos en la literatura para este dermatopatía más, no se han utilizado en estudios que implican un gran número de animales. Se describe un caso de pénfigo foliáceo en un gato que respondió satisfactoriamente sólo a los corticosteroides y sin presentar efectos adversos.

T-cell lymphoma in the tongue of a dog with cutaneous and striated forelimb muscle involvement / Linfoma de células T em língua de cão com envolvimento cutâneo e de musculatura estriada de membro torácico

Background: Primary tongue tumors rarely affect dogs and correspond to 4% of tumors involving the oropharynx. Until now, primary tongue lymphoma had not been reported. However, lymphoma involvement in the skeletal muscle, although quite unusual, was described in the literature in four cases. Cutaneous lymphoma is another rare extranodal manifestation. The objective of this report is to describe a case of T immunophenotype lymphoma occurrence, whose manifestation is atypical, not only because it is situated in the tongue muscle but also because of the subsequent involvement of the striated musculature of the left forelimb and the skin, which showed unfavorable evolution. Case: A female seven-year-old mongrel was seen showing a regular lump in the base of the tongue, 3 cm in diameter, not ulcerated and of firm consistency, with halitosis as the only clinical sign of the disease. Incisional biopsy of the lump was performed and histopathology verified that it was large cell lymphoma. The material was sent for immunohistochemical evaluation and was characterized as T immunophenotype lymphoma by positive CD3 and negative CD79a marking. The CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy protocol was established as treatment and after the first chemotherapy session there was partial remission of the mass, measuring 2 cm in diameter. The lump, however...(AU)