Doxorubicin nephrotoxicity in cats (Felis catus) with malignant mammary neoplasms / Nefrotoxicidade da doxorrubicina em gatas (Felis catus) com neoplasias mamárias malignas

The aim of the study was to investigate the nephrotoxicity of doxorubicin in cats with malignant neoplasms of the mammary gland. All selected cats did not present comorbidities such as nephropathies and/or cardiomyopathies, confirmed by physical and laboratory tests, underwent radical mastectomy associated with regional lymph node excision and were treated with a protocol based on doxorubicin. Renal markers of urea, creatinine, symmetrical dimethylarginine were evaluated during all the treatment, and two months after the end. Abdominal ultrasound, urinalysis and biochemical analysis of protein, urinary creatinine and urinary GGT were performed in the beginning and two months after the end of the treatment, to evaluate possible renal alterations. Six cats did not present renal alterations in any exams performed during the study. Two cats presented azotemia during this study, and one of them stopped the treatment early, because of the intense azotemia. Clinical imaging and laboratory monitoring of patients throughout the treatment is essential, including the measurement of analytes that detect kidney changes early. Thus, it is emphasized that doxorubicin is a safe drug for use in non-nephropathic cats.

O objetivo do estudo foi investigar a nefrotoxicidade da doxorrubicina em gatas com neoplasias malignas da glândula mamária. Todas as gatas selecionadas não apresentaram comorbidades como nefropatias e/ou cardiomiopatias, comprovadas por exames físicos e laboratoriais, foram submetidas à mastectomia radical associada à exérese de linfonodos regionais e tratadas com protocolo baseado em doxorrubicina. Os marcadores renais ureia, creatinina, dimetilarginina simétrica foram avaliados durante todo o tratamento e dois meses após o término. Ultrassonografia abdominal, urinálise e análise bioquímica de proteínas, creatinina urinária e GGT urinária foram realizadas no início e dois meses após o término do tratamento, para avaliar possíveis alterações renais. Seis gatas não apresentaram alterações renais em nenhum dos exames realizados durante o estudo. Duas gatas apresentaram azotemia durante este estudo, e uma delas interrompeu o tratamento precocemente, devido à intensa azotemia. A individualidade de cada paciente deve ser sempre considerada, pois são muitas as variáveis. O monitoramento clínico, com exames complementares, tais como bioquímicos séricos e de imagem dos pacientes durante todo o tratamento, é essencial, especialmente a mensuração de analitos que detectam alterações renais precocemente. Diante disso, ressalta-se que a doxorrubicina é um medicamento seguro para utilização em gatas não nefropatas.

Hematological and biochemical alterations in female dogs with mammary cancer and inflammatory carcinoma / Alterações hematológicas e bioquímicas em cadelas com neoplasias mamárias e carcinoma inflamatório

Hematological and biochemical alterations in animals with neoplasms may result from the direct effects of tumor growth or paraneoplastic syndromes. The objective of this study was to evaluate these hematological and biochemical alterations in female dogs with mammary tumors and with inflammatory carcinoma (IC). Blood samples were collected from 43 female dogs divided into three groups according to clinical staging: Group 1 (G1) - animals in initial stage (T1,2,3N0M0, N=17), Group 2 (G2) - animals in advanced stage (T1,2,3N1M0,1, N=15) and Group 3 (G3) - animals presenting IC (N=11). Hematological and biochemical parameters obtained were related to patients' clinical staging. Among alterations, the most common were anemia, neutrophilic leukocytosis, monocytosis, increased ALT, AST, and hypoalbuminemia, mainly in dogs in advanced clinical staging and with inflammatory carcinoma.

Aterações hematológicas e bioquímicas em animais portadores de neoplasias podem resultar dos efeitos diretos do crescimento tumoral ou de síndromes paraneoplásicas. O objetivo deste estudo foi avaliar as alterações hematológicas e bioquímicas em cadelas com neoplasias mamárias e carcinoma inflamatório (IC). Foram coletadas amostras de sangue de 43 cadelas divididas em três grupos de acordo com o estadiamento clínico: grupo 1 (G1) - cadelas em estádio inicial (T1,2,3N0M0, N=17), grupo 2 (G2) - cadelas em estádio avançado (T1,2,3N1M0,1, N=15) e grupo 3 (G3) - cadelas que apresentaram IC (N=11). Os parâmetros hematológicos e bioquímicos obtidos foram relacionados com o estadiamento clínico das pacientes. Entre as alterações, as mais comuns foram anemia, leucocitose neutrofílica, monocitose, aumento de ALT, AST e hipoalbuminemia, principalmente em cadelas em estadiamento clínico avançado e com carcinoma inflamatório.

The prognostic significance of immunophenotypes in canine malignant mammary tumors / [Significância prognóstica dos imunofenótipos em tumores mamários malignos caninos]

Canine malignant mammary neoplasms (CMMN) exhibit behavioral variability with the patient survival time depending on several prognostic factors. In the present study, 134 CMMN were selected and different immunophenotypes and their associations with clinical and pathological parameters were identified. The tumors were classified as follows: 46% of luminal B HER2-, 34% of luminal A, 13% of triple-negative, and 7% of luminal B HER2+. Shorter specific survival time were associated with larger tumor sizes (>3.0 cm, HR=1.94; P=0.0209), lymph node metastasis or distant metastasis (HR= 2.82; P <.0001), more aggressive histological types (HR= 7.15, P<0.0001), higher histological grades (HR= 12.97 P=0.011), angiolymphatic invasion (HR=4.68, P<0.0001) and luminal B HER2 - (HR= 3.27, P<0.0001) and luminal B HER2 + (HR= 7.14 P<0.0001) immunophenotypes. In patients with lymph nodal metastasis, shorter survival times were associated with luminal immunophenotype B HER2 + (P=0.003). However, in patients without metastasis, an increased risk of death was associated with the aggressive histological type. In conclusion, the classification in our study allowed us to identify subtypes with different prognoses in canine malignant mammary tumors. Factors such as clinical stage, histological type, luminal B HER2+ subtype, and angiolymphatic invasion were the most important prognostic factors.

Neoplasias mamárias malignas caninas (CMMN) apresentam variável comportamento biológico e o tempo de sobrevida depende de diversos fatores prognósticos. Neste estudo, foram selecionadas 134 CMMN, bem como identificados diferentes imunofenótipos e suas associações com parâmetros clínicos e patológicos. Os tumores foram classificados em: 46% luminal B HER2-, 34% luminal A, 13% triplo negativo e 7% luminal B HER2+. Menores taxas de sobrevida específica foram associadas a tamanhos de tumor maiores (> 3,0cm; HR = 1,94; P = 0,0209), metástases em nodais ou a distância (HR = 2,82; P <0,0001), tipos histológicos mais agressivos (HR = 7,15; P <0,0001), graus histológicos mais elevados (HR = 12,97; P = 0,011), invasão angiolinfática (HR = 4,68; P <0,0001) e aos imunofenótipos luminal B HER2- (HR = 3,27; P <0,0001) e luminal B HER2+ ( HR = 7,14; P <0,0001). Em pacientes com estágio avançado, menor sobrevida específica foi associada ao imunofenótipo luminal B HER2+ (P = 0,003). Entretanto, em estágio inicial, um risco aumentado de óbito foi associado a tipos histológicos agressivos. Em conclusão, a classificação utilizada no presente estudo permitiu identificar subtipos com diferentes prognósticos em CMMN. Estágio clínico, tipo histológico, subtipo luminal B HER2+ e invasão angiolinfática foram os fatores prognósticos mais importantes.

Evaluation of the immunomodulatory activity of thalidomide on tumor-associated macrophages in the 4T1 murine metastatic breast cancer model / [Avaliação do efeito imunomodulador da talidomida em macrófagos associados a tumores no modelo murino de câncer de mama metastático 4T1]

The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.(AU)

No presente trabalho, foi avaliado o efeito imunomodulador de diferentes doses de talidomida em macrófagos associados ao tumor (TAMs), em um modelo murino de câncer de mama. Camundongos foram inoculados com células 4T1, na região do flanco esquerdo, e tratados com talidomida, uma vez ao dia, nas doses de 50, 100 e 150mg/k, por massa corporal, do quinto dia ao 28º dia de inoculação tumoral. Os tumores foram medidos, o índice de proliferação celular e a contagem de TAMs foram avaliados nos tumores primários e nos pulmões com metástases. Além disso, a taxa de metástases pulmonares também foi avaliada. A talidomida na dose de 150mg/kg diminuiu significativamente o crescimento tumoral, o índice de proliferação celular e a infiltração de TAMs nos tumores primários. Por outro lado, maior número de TAMs e menor índice de proliferação celular foram observados nos pulmões metastáticos, em camundongos tratados com 150mg/kg de talidomida. Ademais, a talidomida na dose de 150mg/kg diminuiu significativamente os nódulos metastáticos nos pulmões. Os resultados demonstraram que o tratamento com talidomida diminuiu o crescimento tumoral e as metástases pulmonares em camundongos, associado com diferentes efeitos na infiltração de TAMs nesses locais.(AU)

Histopathological and immunohistochemical characteristics of malignant adenomyoepithelioma in a cat: case report / [Características histopatológicas e imuno-histoquímicas do adenomioepitelioma maligno em gata: relato de caso]

The malignant adenomyoepithelioma is a rare mammary tumor in women and uncommon in cats with only one report in this species. In this case report, the histopathological and immunohistochemical characteristics of six cases of malignant adenomyopithelioma in the feline mammary gland are described. Microscopic evaluation of tumors showed dense cellular neoplastic proliferation, composed of malignant myoepithelial and epithelial cells, formed by varied arrangements and presenting papillary, tubular and solid nest proliferation. Immunohistochemistry was performed for markers Ki67, Cox-2, RE, RP, p63 and HER-2. All cases were positive for p63, confirming the myoepithelial nature of neoplastic cells. The diagnosis of malignant adenomyopithelioma was made possible through the association between histopathological characteristics and immunohistochemical results.(AU)

O adenomioepitelioma maligno é uma neoplasia mamária rara em mulheres e incomum em gatas, possuindo apenas uma descrição nessa espécie. Neste relato de caso, são descritas as características histopatológicas e imuno-histoquímicas de seis casos de adenomioepitelioma maligno na glândula mamária felina. A avaliação microscópica dos tumores demonstrou proliferação neoplásica densamente celular, composta por células mioepiteliais e epiteliais malignas dispostas em padrão papilar, tubular e ninhos sólidos. Foi realizada técnica de imuno-histoquímica para os marcadores Ki67, Cox-2, RE, RP, p63 e HER-2. Todos os casos foram positivos para p63, confirmando a natureza mioepitelial das células neoplásicas. O diagnóstico de adenomioepitelioma maligno foi possível por meio da associação entre as características histopatológicas e os resultados de imuno-histoquímica.(AU)

Expression of VCAN and its receptors in canine mammary carcinomas with or without myoepithelial proliferation.

The proteoglycan versican (VCAN) plays a complex role in cancer. The expression of this molecule has been related to invasion and progression in malignant mixed tumors, such as carcinoma in mixed tumors (CMT) of the canine mammary gland. In addition, its interaction with surface cell receptors EGFR, HER-2 and CD44 in malignant epithelial cells may be responsible for proliferation and cellular motility in early stages of cancer. We comparatively evaluated the expression of this proteoglycan and its receptors in in situ and invasive areas of simple carcinomas (SC) and CMT to investigate similarities and differences between these histological types. Immunohistochemistry was performed with anti-VCAN, anti-CD44, anti-EGFR and anti-HER-2 antibodies in 32 cases of SC or CMT. VCAN was highly expressed in stroma adjacent to invasive areas in SC and CMT. CMTs presented comparatively higher expression of VCAN in stroma adjacent to in situ and in invasive areas than in corresponding areas in SCs. In CMT, EGFR and HER-2 expressions were higher in situ compared to invasive areas. In contrast, increased CD44 and EGFR expression was found in invasive areas in SC compared to CMT. These results indicate that versican expression is similarly associated with invasiveness in SC and CMT, however higher levels were seen in CMT suggesting that the presence of myoepithelial proliferation in this tumor type participates in stromal composition and promoting an increase in the expression of versican.

Extracapsular extension and tumor implants in lymph nodes with canine mammary carcinoma metastasis: Study of the impact on survival.

Regional lymph node status impacts survival in dogs with malignant mammary tumors. However, few studies have evaluated extracapsular extension and tumor implants in regional lymph node metastases in dogs with mammary carcinoma. Therefore, 84 cases of mammary carcinomas with metastases in inguinal and/or axillary lymph nodes from female dogs of different breeds and a total of 139 metastatic lymph nodes were evaluated by routine histological staining. Clinical and pathological characteristics of primary tumors as well as the presence of extracapsular extension and tumor implants in the lymph nodes were analyzed, in addition to survival. One to 5 lymph nodes were evaluated in each case. Extracapsular extension and tumor implants were present in 17.9% and 39.3% of cases, respectively. The simultaneous presence of extracapsular extension and tumor implants were associated with an increased risk of death (hazard ratio 10.46). In addition, "special type carcinomas", high histological grade (grade III), and presence of extracapsular extension associated with tumor implants were related to a worse prognosis and shorter survival times (p < 0.05). Based on these results, we highlight the importance of identifying extracapsular extension and tumor implants in dogs with metastatic mammary carcinomas, as they are associated with a higher risk of death and shorter survival.

Osteosarcoma of the hard palate in a dog - case report / [Osteossarcoma em palato duro de cão - relato de caso]

The osteosarcoma (OSA) is the most diagnosed primary bone cancer in canine patients. This work reports a case of a canine, six years old, mongrel, female, intact, with an OSA in the hard palate. Physical examination detected a firm mass in the palate. Thoracic radiographs, hematological and biochemical exams, histopathological exams and computed tomography were requested. A chondroblastic OSA was diagnosed and the tumor was characterized by immunohistochemistry. There was never evidence of metastasis in this case. The treatment consisted of the combination of conventional chemotherapy, metronomic chemotherapy, and palliative care, aiming at greater survival and well-being of the patient since surgical excision was not possible due to the location and extension of the tumor. Osteogenic sarcomas of the hard palate are rarely seen and described in the literature. In this article we present a characterization of the osteosarcoma with uncommon localization in the hard palate.(AU)

O osteossarcoma (OSA) é a neoplasia óssea primária mais diagnosticada em pacientes caninos. Este trabalho relata o caso de um canino, com seis anos de idade, sem raça definida, fêmea, não castrado, apresentando OSA em região de palato duro. Ao exame clínico, constatou-se uma massa de consistência firme em região palatina. Além do exame clínico, foram solicitadas radiografias torácicas, exames hematológicos e bioquímicos, exames histopatológicos e tomografia computadorizada. Fora então dado o diagnóstico de OSA condroblástico, e o tumor foi caracterizado pela imuno-histoquímica. Não foram observadas evidências de metástases nesse caso. O tratamento instituído consistiu na combinação de quimioterapia convencional, quimioterapia metronômica e cuidados paliativos, almejando maior sobrevida e bem-estar do paciente, uma vez que a excisão cirúrgica não foi possível devido à localização e à extensão do tumor. Neste artigo, apresentou-se uma caracterização do osteossarcoma com localização incomum no palato duro.(AU)

Beneficial effects resulting from oral administration of Escherichia coli Nissle 1917 on a chronic colitis model.

Inflammatory bowel diseases (IBD) are chronic processes involving a deregulated immune response against intestinal microbiota in genetically susceptible individuals. Ulcerative colitis (UC) is an IBD restricted to colonic mucosa and its chronicity is a predisposing factor for colorectal cancer (CRC). Probiotics have been investigated as an adjuvant treatment for UC, and Escherichia coli Nissle 1917 (EcN) was the focus of our investigation. The aim of this study was to investigate the preventive effect of the EcN probiotic in an experimental model of chronic colitis in germ-free (GF) and conventional (CV) mice. CV female mice were used for clinical, immunological and permeability experiments. GF mice were used for a faecal microbiota transplantation assay. To induce colitis, three cycles of 3.0% dextran sulphate sodium (DSS) were administered to the animals. For probiotic treatment, the mice received a daily intragastric gavage of 9.0 log10 cfu of EcN, beginning 10 days before colitis induction and continuing until the end of the experiment. EcN presented beneficial effects when administered preventively. Daily Disease Activity Index (DAI) evolution demonstrated significant difference in remission periods after the first two DSS cycles and during the third one. Reduction in bacterial translocation after probiotic treatment indicated protection of the intestinal barrier. Associated with mucosal preservation, restoration of secretory immunoglobulin A levels and reduction of interleukin (IL)-5, IL-13, tumour necrosis factor and interferon-γ levels were observed in EcN treatment. Finally, when microbiota modification was verified, 16S rRNA-based compositional analysis showed variation of intestinal microbiota between the control and colitis groups. After faecal transplantation using GF mice, it was observed that EcN treatment in CV mice might result in modulated intestinal microbiota. This was observed indirectly in the reduced daily DAI, when colitis was compared with treated group. In conclusion, EcN presented beneficial effects in this model, suggesting its usefulness for treating UC.

Azithromycin for chronic eosinophilic rhinosinusitis with nasal polyp: a placebo-controlled trial.

BACKGROUND: Chronic eosinophilic rhinosinusitis with nasal polyps (CRSwNP eosinophilic) is characterised by the formation of benign and bilateral nasal polyps. We aimed to compare the effectiveness of azithromycin as an immunomodulator with the use of a placebo in patients presenting with CRSwNP concomitant with asthma and aspirin intolerance after 3 months of treatment and at a 1-year follow-up. METHODOLOGY: We performed a randomised, double-blind, placebo-controlled trial. Patients received 500 mg azithromycin orally three times/week for 12 weeks. Improvement was evaluated by staging, the Sino-Nasal Outcome Test (SNOT-22), and nasal polyp biopsy. Data collected at pretreatment and 3 months posttreatment were compared. Quality of life was evaluated at the 1-year follow-up. RESULTS: Twenty-seven and 21 patients were treated with azithromycin and a placebo, respectively. The medication was well tolerated overall. Twenty patients (74%) in the azithromycin group and three patients (14%) in the placebo group were not refer- red for surgery at the end of the 3-month treatment. Regarding subjective improvement, there was a median decrease only in the azithromycin group, and the between-group difference was significant. SNOT-22 improvement was maintained in the azithromy- cin group at the 1-year follow-up. CONCLUSIONS: Azithromycin could be considered a therapeutic option for patients presenting with CRSwNP concomitant with asthma and aspirin intolerance.

Extragonadal malignant teratoma in a dog - case report / Teratoma extragonodal maligno em cão - relato de caso

Teratomas are neoplasms thought to arise from germ cells which usually occur within gonads and are rarely described on extragonadal sites. The present study reports a case of a 15 year old female mongrel dog with a lumbosacral tumor. The tumor was microscopically composed of embryonic tissues with areas containing atypical undifferentiated cells, leading to the diagnosis of a malignant teratoma. Malignant teratomas are uncommon tumors in domestic animals.(AU)

Os teratomas são neoplasias originárias das células germinativas que têm como sítio principal as gônadas; raramente ocorrem em sítios extragonodais. O presente estudo relata um caso de uma cadela de 15 anos de idade, sem raça definida, apresentando aumento de volume na região lombossacral que ao exame microscópico revelou neoformação composta por tecidos de origem embrionária, com áreas indiferenciadas exibindo atipia celular, características compatíveis com teratoma maligno. Teratomas malignos são incomuns em animais domésticos.(AU)

Extragonadal malignant teratoma in a dog - case report / Teratoma extragonodal maligno em cão - relato de caso

Teratomas are neoplasms thought to arise from germ cells which usually occur within gonads and are rarely described on extragonadal sites. The present study reports a case of a 15 year old female mongrel dog with a lumbosacral tumor. The tumor was microscopically composed of embryonic tissues with areas containing atypical undifferentiated cells, leading to the diagnosis of a malignant teratoma. Malignant teratomas are uncommon tumors in domestic animals.(AU)

Os teratomas são neoplasias originárias das células germinativas que têm como sítio principal as gônadas; raramente ocorrem em sítios extragonodais. O presente estudo relata um caso de uma cadela de 15 anos de idade, sem raça definida, apresentando aumento de volume na região lombossacral que ao exame microscópico revelou neoformação composta por tecidos de origem embrionária, com áreas indiferenciadas exibindo atipia celular, características compatíveis com teratoma maligno. Teratomas malignos são incomuns em animais domésticos.(AU)

Alpha-tocopheryl succinate improves encapsulation, pH-sensitivity, antitumor activity and reduces toxicity of doxorubicin-loaded liposomes.

Doxorubicin (DOX) plays an important role in cancer treatment; however, high cardiotoxicity and low penetration in solid tumors are the main limitations of its use. Liposomal formulations have been developed to attenuate the DOX toxicity, but the technological enhancement of the liposomal formulation as well as the addition of another agent with antitumor properties, like alpha-tocopheryl succinate (TS), a semi-synthetic analog of vitamin E, could certainly bring benefits. Thus, in this study, it was proposed the development of liposomes composed of DOX and TS (pHSL-TS-DOX). A new DOX encapsulation method, without using the classic ammonium sulfate gradient with high encapsulation percentage was developed. Analysis of Small Angle X-ray Scattering (SAXS) and release study proved the pH-sensitivity of the developed formulation. It was observed stabilization of tumor growth using pHSL-TS-DOX when compared to free DOX. The toxicity tests showed the safety of this formulation since it allowed body weight initial recovery after the treatment and harmless to heart and liver, main target organs of DOX toxicity. The developed formulation also avoided the occurrence of myelosuppression, a typical adverse effect of DOX. Therefore, pHSL-TS-DOX is a promising alternative for the treatment of breast cancer since it has adequate antitumor activity and a safe toxicity profile.

Histological and immunohistochemical evaluation of two cell therapy protocols in equine suspensory ligament repair / Avaliação histológica e imunoistoquímica do reparo do ligamento suspensório equino tratado com dois protocolos de terapia celular

This study aimed to histologically evaluate the quality of tissue repair in equine suspensory ligament treated with two cell therapy protocols. All four limbs of six animals were operated simultaneously to remove a fragment in each ligament using a skin biopsy punch. Two days later, intralesional injections were performed using bone marrow mononuclear fraction (BM group), cultivated cells derived from adipose tissue (AT group), saline (positive control group), or no treatment (negative control group), in such way that each horse received all treatments. After sixty days biopsies were performed for histological analysis (H & E, Masson's trichrome and picrosirius red) and immunohistochemistry analysis (collagen type III). Histological findings (H & E and Masson's trichrome), birefringence intensity (through picrosirius) and collagen type III expression (through immunohistochemistry) were analyzed. Samples from treated groups had better birefringence intensity (P=0.007) and fiber alignment scores were superior compared to controls, though not statistically significant (P=0.08). Presence of inflammatory cells and intense staining for collagen type III occurred in all groups demonstrating an active healing process. In conclusion, both protocols resulted in improvement of tissue repair indicating their potential to be used as an adjuvant treatment of equine suspensory ligament disorders.(AU)

Este estudo teve como objetivo a avaliação histológica e imunoistoquímica do reparo do ligamento suspensório equino tratado com dois protocolos de terapia celular. Os quatro membros dos seis animais do experimento foram submetidos a procedimento cirúrgico em que um fragmento de cada ligamento foi retirado, utilizando-se punch de biópsia. Dois dias após o procedimento, aplicações intralesionais foram realizadas, por meio de aspirado de medula óssea (bone marrow-BM), células mesenquimais derivadas de tecido adiposo (adipose tissue-AT), solução salina (positive control group-PC) ou controle (negative control-NC). Após 60 dias, biópsias foram retiradas da região de reparo dos ligamentos e foram submetidas à análise histológica (HE, tricrômio de Masson, picrosírius red) e imunoistoquímica (colágeno tipo III). Diferentes variáveis histológicas (HE e tricrômio de Masson), a intensidade de birrefringência das fibras colágenas (picrosírius red) e a expressão de colágeno tipo III foram avaliadas. Os grupos tratados apresentaram maior birrefringência (P=0,007) e alinhamento de fibras (P=0,08) comparados ao controle, para o qual o resultado não se mostrou estatisticamente significativo. Achados histológicos e imunoistoquímicos demonstraram um processo ativo de reparo tecidual em todos os grupos. Concluiu-se que os dois protocolos de terapia celular apresentaram melhora no reparo tecidual, demonstrando potencial terapêutico adjuvante no tratamento de afecções do ligamento suspensório equino.(AU)

Histological and immunohistochemical evaluation of two cell therapy protocols in equine suspensory ligament repair / Avaliação histológica e imunoistoquímica do reparo do ligamento suspensório equino tratado com dois protocolos de terapia celular

This study aimed to histologically evaluate the quality of tissue repair in equine suspensory ligament treated with two cell therapy protocols. All four limbs of six animals were operated simultaneously to remove a fragment in each ligament using a skin biopsy punch. Two days later, intralesional injections were performed using bone marrow mononuclear fraction (BM group), cultivated cells derived from adipose tissue (AT group), saline (positive control group), or no treatment (negative control group), in such way that each horse received all treatments. After sixty days biopsies were performed for histological analysis (H & E, Masson's trichrome and picrosirius red) and immunohistochemistry analysis (collagen type III). Histological findings (H & E and Masson's trichrome), birefringence intensity (through picrosirius) and collagen type III expression (through immunohistochemistry) were analyzed. Samples from treated groups had better birefringence intensity (P=0.007) and fiber alignment scores were superior compared to controls, though not statistically significant (P=0.08). Presence of inflammatory cells and intense staining for collagen type III occurred in all groups demonstrating an active healing process. In conclusion, both protocols resulted in improvement of tissue repair indicating their potential to be used as an adjuvant treatment of equine suspensory ligament disorders.(AU)

Este estudo teve como objetivo a avaliação histológica e imunoistoquímica do reparo do ligamento suspensório equino tratado com dois protocolos de terapia celular. Os quatro membros dos seis animais do experimento foram submetidos a procedimento cirúrgico em que um fragmento de cada ligamento foi retirado, utilizando-se punch de biópsia. Dois dias após o procedimento, aplicações intralesionais foram realizadas, por meio de aspirado de medula óssea (bone marrow-BM), células mesenquimais derivadas de tecido adiposo (adipose tissue-AT), solução salina (positive control group-PC) ou controle (negative control-NC). Após 60 dias, biópsias foram retiradas da região de reparo dos ligamentos e foram submetidas à análise histológica (HE, tricrômio de Masson, picrosírius red) e imunoistoquímica (colágeno tipo III). Diferentes variáveis histológicas (HE e tricrômio de Masson), a intensidade de birrefringência das fibras colágenas (picrosírius red) e a expressão de colágeno tipo III foram avaliadas. Os grupos tratados apresentaram maior birrefringência (P=0,007) e alinhamento de fibras (P=0,08) comparados ao controle, para o qual o resultado não se mostrou estatisticamente significativo. Achados histológicos e imunoistoquímicos demonstraram um processo ativo de reparo tecidual em todos os grupos. Concluiu-se que os dois protocolos de terapia celular apresentaram melhora no reparo tecidual, demonstrando potencial terapêutico adjuvante no tratamento de afecções do ligamento suspensório equino.(AU)

First description of basaloid carcinoma of the canine mammary gland: case report / Primeira descrição do carcinoma basaloide da glândula mamária canina: relato de caso

The objective of this case report was to describe histopathological and immunohistochemical characteristics of the first reported basaloid carcinomas in the canine mammary gland. Two bitches were treated for tumors in the mammary gland and underwent mastectomy. Microscopic evaluation of these tumors revealed epithelial cells arranged in a predominantly solid pattern with hyperchromatic peripheral cells arranged in a palisade pattern. Metastases in regional lymph nodes were found in both animals, and one bitch exhibited pulmonary metastasis. Immunohistochemistry revealed positive labeling for the basal cell markers cytokeratin 14 and p63. Histopathological and immunohistochemical findings led to diagnoses of basaloid carcinoma of the canine mammary gland with regional and distant metastasis.(AU)

O objetivo deste relato de caso é descrever as características histopatológicas e imuno-histoquímicas do primeiro relato de carcinoma basaloide na glândula mamária canina. Duas cadelas foram atendidas com tumores na glândula mamária e foram submetidas à mastectomia. A avaliação microscópica demonstrou células epiteliais arranjadas em um padrão predominantemente sólido, com células periféricas hipercromáticas, dispostas em paliçada. As duas apresentaram metástase em linfonodos regionais e uma delas metástase pulmonar. A imuno-histoquímica revelou marcação positiva para citoqueratina 14 e p63, marcadores de células basais. Achados histopatológicos e imuno-histoquímicos levaram ao diagnóstico de carcinoma basaloide da glândula mamária canina com metástase regional e a distância.(AU)

First description of basaloid carcinoma of the canine mammary gland: case report / Primeira descrição do carcinoma basaloide da glândula mamária canina: relato de caso

The objective of this case report was to describe histopathological and immunohistochemical characteristics of the first reported basaloid carcinomas in the canine mammary gland. Two bitches were treated for tumors in the mammary gland and underwent mastectomy. Microscopic evaluation of these tumors revealed epithelial cells arranged in a predominantly solid pattern with hyperchromatic peripheral cells arranged in a palisade pattern. Metastases in regional lymph nodes were found in both animals, and one bitch exhibited pulmonary metastasis. Immunohistochemistry revealed positive labeling for the basal cell markers cytokeratin 14 and p63. Histopathological and immunohistochemical findings led to diagnoses of basaloid carcinoma of the canine mammary gland with regional and distant metastasis.(AU)

O objetivo deste relato de caso é descrever as características histopatológicas e imuno-histoquímicas do primeiro relato de carcinoma basaloide na glândula mamária canina. Duas cadelas foram atendidas com tumores na glândula mamária e foram submetidas à mastectomia. A avaliação microscópica demonstrou células epiteliais arranjadas em um padrão predominantemente sólido, com células periféricas hipercromáticas, dispostas em paliçada. As duas apresentaram metástase em linfonodos regionais e uma delas metástase pulmonar. A imuno-histoquímica revelou marcação positiva para citoqueratina 14 e p63, marcadores de células basais. Achados histopatológicos e imuno-histoquímicos levaram ao diagnóstico de carcinoma basaloide da glândula mamária canina com metástase regional e a distância.(AU)

Serum evaluation of leptin, IL-6, IGF-1 and estrogen in obese bitches with early stages of mammary carcinoma / Avaliação sérica de leptina, IL-6, IGF-1 e estrógeno em cadelas com excesso de peso e portadoras de carcinomas mamários em estágio inicial

The aim of this study was to relate the serum concentration IL-6, IGF-1, leptin and estrogen in non-castrated bitches with or without overweight and early stage mammary carcinomas. Forty-three bitches were divided into four groups, two groups without mammary carcinomas with and without overweight, and two groups with mammary carcinomas with and without overweight. Overweight bitches, with or without mammary carcinomas, were statistically different from bitches by ideal weight, in relation to ECC, IMCC and body fat percentages (P< 0.0001). There was a positive correlation between ECC and IMCC (P< 0.0001), ECC and % GC (P< 0.0001), and IMCC and % GC (P< 0.0001). A positive correlation was found between serum leptin and IL-6 (P= 0.0451) and leptin and IGF-1 (P= 0.05). A positive correlation (P= 0.0053) between ECC and leptin was found in the analysis of body evaluation methods and serum concentrations, and a negative correlation between ECC and IL-6 (P= 0.0435). Among the fat percentage and the leptin concentration, there was a positive correlation (P= 0.0016), as found between the IMCC and leptin (P= 0, 0209). In this study, no association was observed between excessive weight and the presence of early stage mammary carcinomas.(AU)

Este estudo teve por objetivo relacionar a concentração sérica de IL-6, IGF-1, leptina e estrógeno, em cadelas não castradas com ou sem excesso de peso, e carcinomas mamários em estágio inicial. Quarenta e três cadelas foram divididas em quatro grupos, sendo dois de cadelas sem carcinomas mamários, com e sem excesso de peso, e dois de cadelas com carcinomas mamários, com e sem excesso de peso. Cadelas com excesso de peso, com ou sem carcinomas mamários, foram estatisticamente diferentes de cadelas em peso ideal, em relação às avaliações corporais de ECC, IMCC e percentual de gordura corpórea (P<0,0001). Foi observada uma correlação positiva entre ECC e IMCC (P<0,0001), ECC e %GC (P<0,0001), e IMCC e %GC (P<0,0001). As análises de estrógeno, leptina, IL-6 e IGF-1 não apresentaram diferenças estatísticas entre os grupos. Demonstrou-se correlação positiva entre as concentrações séricas de leptina e IL-6 (P=0,0451) e leptina e IGF-1 (P=0,05). Encontrou-se correlação positiva entre ECC e leptina (P=0,0053) e negativa entre ECC e IL-6 (P=0,0435). Entre o percentual de gordura e leptina encontrou-se correlação positiva (P=0,0016), assim como entre IMCC e leptina (P=0,0209). Neste estudo, não se observou associação entre excesso de peso e a presença de carcinomas mamários em estadio inicial.(AU)

Serum evaluation of leptin, IL-6, IGF-1 and estrogen in obese bitches with early stages of mammary carcinoma / Avaliação sérica de leptina, IL-6, IGF-1 e estrógeno em cadelas com excesso de peso e portadoras de carcinomas mamários em estágio inicial

The aim of this study was to relate the serum concentration IL-6, IGF-1, leptin and estrogen in non-castrated bitches with or without overweight and early stage mammary carcinomas. Forty-three bitches were divided into four groups, two groups without mammary carcinomas with and without overweight, and two groups with mammary carcinomas with and without overweight. Overweight bitches, with or without mammary carcinomas, were statistically different from bitches by ideal weight, in relation to ECC, IMCC and body fat percentages (P< 0.0001). There was a positive correlation between ECC and IMCC (P< 0.0001), ECC and % GC (P< 0.0001), and IMCC and % GC (P< 0.0001). A positive correlation was found between serum leptin and IL-6 (P= 0.0451) and leptin and IGF-1 (P= 0.05). A positive correlation (P= 0.0053) between ECC and leptin was found in the analysis of body evaluation methods and serum concentrations, and a negative correlation between ECC and IL-6 (P= 0.0435). Among the fat percentage and the leptin concentration, there was a positive correlation (P= 0.0016), as found between the IMCC and leptin (P= 0, 0209). In this study, no association was observed between excessive weight and the presence of early stage mammary carcinomas.(AU)

Este estudo teve por objetivo relacionar a concentração sérica de IL-6, IGF-1, leptina e estrógeno, em cadelas não castradas com ou sem excesso de peso, e carcinomas mamários em estágio inicial. Quarenta e três cadelas foram divididas em quatro grupos, sendo dois de cadelas sem carcinomas mamários, com e sem excesso de peso, e dois de cadelas com carcinomas mamários, com e sem excesso de peso. Cadelas com excesso de peso, com ou sem carcinomas mamários, foram estatisticamente diferentes de cadelas em peso ideal, em relação às avaliações corporais de ECC, IMCC e percentual de gordura corpórea (P<0,0001). Foi observada uma correlação positiva entre ECC e IMCC (P<0,0001), ECC e %GC (P<0,0001), e IMCC e %GC (P<0,0001). As análises de estrógeno, leptina, IL-6 e IGF-1 não apresentaram diferenças estatísticas entre os grupos. Demonstrou-se correlação positiva entre as concentrações séricas de leptina e IL-6 (P=0,0451) e leptina e IGF-1 (P=0,05). Encontrou-se correlação positiva entre ECC e leptina (P=0,0053) e negativa entre ECC e IL-6 (P=0,0435). Entre o percentual de gordura e leptina encontrou-se correlação positiva (P=0,0016), assim como entre IMCC e leptina (P=0,0209). Neste estudo, não se observou associação entre excesso de peso e a presença de carcinomas mamários em estadio inicial.(AU)

Long-circulating and fusogenic liposomes loaded with a glucoevatromonoside derivative induce potent antitumor response.

Cancer is an important public health problem, being one of the leading causes of death worldwide. Most antineoplastic agents cause severe toxic effects and some types of cancer do not respond or are resistant to the existing pharmacotherapy, necessitating the research and development of new therapeutic strategies. Cardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells. Glucoevatromonoside containing peracetylated glucose hydroxyl groups (GEVPG) is a cardenolide derivative that has low solubility in aqueous media, which constitutes a barrier to its potential biological applications. In this context, the use of liposomes represents a promising strategy to deliver GEVPG, thus allowing its intravenous administration. In this study, long-circulating and fusogenic liposomes containing GEVPG (SpHL-GEVPG) were developed, and their chemical and physicochemical properties were evaluated. SpHL-GEVPG presented adequate properties, including a mean diameter of 182.2 ± 2.7 nm, a polydispersity index equal to 0.36 ± 0.03, a zeta potential of -2.37 ± 0.31 mV, and a GEVPG entrapment of 0.38 ± 0.04 mg/mL. Moreover, this formulation showed a good stability after having been stored for 30 days at 4 °C. The cytotoxic studies against breast (MDA-MB-231, MCF-7, and SKBR-3) and lung (A549) cancer cell lines demonstrated that SpHL-GEVPG treatment significantly reduced the cell viability. In addition, the SpHL-GEVPG formulation presented a good selectivity toward these cancer cells. The evaluation of the therapeutic efficacy of the treatment with SpHL-GEVPG showed a potent anticancer effect in an A549 human lung cancer xenograft model. SpHL-GEVPG administered at doses of 1.0 and 2.0 mg/kg (i.v.) induced antitumor effect comparable to paclitaxel given at dose of 10 mg/kg (i.v.) to mice. Therefore, the results of the present work indicate the potential applicability of SpHL-GEVPG as a new anticancer formulation.