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1.
Vet Comp Oncol ; 19(3): 529-540, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33724647

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
Doenças do Cão , Mastocitoma Cutâneo , Mastocitose Cutânea , Neoplasias Cutâneas , Animais , Doenças do Cão/diagnóstico , Cães , Imuno-Histoquímica , Antígeno Ki-67 , Mastócitos , Mastocitoma Cutâneo/diagnóstico , Mastocitoma Cutâneo/veterinária , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/veterinária , Prognóstico , Proteínas Proto-Oncogênicas c-kit , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/veterinária , Proteína X Associada a bcl-2
2.
Vet Comp Oncol ; 19(2): 404-408, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33576549

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
Neoplasias da Mama , Carcinoma , Doenças do Gato , Neoplasias Mamárias Animais , Neoplasias de Mama Triplo Negativas , Animais , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/veterinária , Carcinoma/veterinária , Doenças do Gato/genética , Gatos , Feminino , Genes BRCA2 , Predisposição Genética para Doença , Humanos , Neoplasias Mamárias Animais/genética , Mutação , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/veterinária
3.
Clin Exp Pharmacol Physiol ; 44(2): 197-206, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27859493

RESUMO

Non-alcoholic steatohepatitis is a highly prevalent liver pathology featured by hepatocellular fat deposition and inflammation. Connexin32, which is the major building block of hepatocellular gap junctions, has a protective role in hepatocarcinogenesis and is downregulated in chronic liver diseases. However, the role of connexin32 in non-alcoholic steatohepatitis remains unclear. Connexin32-/- mice and their wild-type littermates were fed a choline-deficient high-fat diet. The manifestation of non-alcoholic steatohepatitis was evaluated based on a battery of clinically relevant read-outs, including histopathological examination, diverse indicators of inflammation and liver damage, in-depth lipid analysis, assessment of oxidative stress, insulin and glucose tolerance, liver regeneration and lipid-related biomarkers. Overall, more pronounced liver damage, inflammation and oxidative stress were observed in connexin32-/- mice compared to wild-type animals. No differences were found in insulin and glucose tolerance measurements and liver regeneration. However, two lipid-related genes, srebf1 and fabp3, were upregulated in Cx32-/- mice in comparison with wild-type animals. These findings suggest that connexin32-based signalling is not directly involved in steatosis as such, but rather in the sequelae of this process, which underlie progression of non-alcoholic steatohepatitis.


Assuntos
Conexinas/deficiência , Citocinas/metabolismo , Fígado , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Animais , Conexinas/genética , Citocinas/sangue , Proteína 3 Ligante de Ácido Graxo , Proteínas de Ligação a Ácido Graxo/genética , Junções Comunicantes/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Fígado/imunologia , Fígado/metabolismo , Fígado/ultraestrutura , Regeneração Hepática , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Regulação para Cima , Proteína beta-1 de Junções Comunicantes
4.
Methods Mol Biol ; 1437: 55-70, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27207286

RESUMO

Immunohistochemistry (IHC) is a ubiquitous used technique to identify and analyze protein expression in the context of tissue and cell morphology. In the connexin research field, IHC is applied to identify the subcellular location of connexin proteins, as this can be directly linked to their functionality. The present chapter describes a protocol for fluorescent IHC to detect connexin proteins in tissues slices and cells, with slight modifications depending on the nature of biological sample, histological processing, and/or protein expression level. Basically, fluorescent IHC is a short, simple, and cost-effective technique, which allows the visualization of proteins based on fluorescent-labeled antibody-antigen recognition.


Assuntos
Conexinas/metabolismo , Imunofluorescência/métodos , Junções Comunicantes/metabolismo , Histocitoquímica/métodos , Imuno-Histoquímica/métodos , Animais , Imunofluorescência/economia , Humanos , Imuno-Histoquímica/economia , Fígado/metabolismo , Camundongos , Miocárdio/metabolismo
5.
J Membr Biol ; 249(3): 199-213, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26914707

RESUMO

Cellular and molecular mechanisms of wound healing, tissue repair, and fibrogenesis are established in different organs and are essential for the maintenance of function and tissue integrity after cell injury. These mechanisms are also involved in a plethora of fibroproliferative diseases or organ-specific fibrotic disorders, all of which are associated with the excessive deposition of extracellular matrix components. Fibroblasts, which are key cells in tissue repair and fibrogenesis, rely on communicative cellular networks to ensure efficient control of these processes and to prevent abnormal accumulation of extracellular matrix into the tissue. Despite the significant impact on human health, and thus the epidemiologic relevance, there is still no effective treatment for most fibrosis-related diseases. This paper provides an overview of current concepts and mechanisms involved in the participation of cellular communication via connexin-based pores as well as pannexin-based channels in the processes of tissue repair and fibrogenesis in chronic diseases. Understanding these mechanisms may contribute to the development of new therapeutic strategies to clinically manage fibroproliferative diseases and organ-specific fibrotic disorders.


Assuntos
Conexinas/genética , Conexinas/metabolismo , Fibrose/genética , Fibrose/metabolismo , Junções Comunicantes/metabolismo , Animais , Comunicação Celular , Conexinas/química , Suscetibilidade a Doenças , Fibroblastos , Regulação da Expressão Gênica , Humanos , Fígado/metabolismo , Fígado/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Especificidade de Órgãos/genética , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Cicatrização
6.
São Paulo; s.n; 2014. [66] p. ilus, mapas, graf.
Tese em Português | LILACS | ID: lil-750130

RESUMO

Estima-se que 170 milhões de pessoas no mundo estejam infectadas com o vírus da hepatite C (VHC), o que está altamente relacionado à ocorrência de hepatite crônica e carcinoma hepatocelular. A prevalência de esteatose hepática em doentes com hepatite C crônica é muito maior do que na população geral variando entre 40 a 75%. A associação entre a infecção pelo VHC e esteatose hepática é multifatorial. Duas formas de esteatose hepática são encontradas em pacientes com hepatite C crônica: esteatose metabólica (fatores de risco) e citopática relacionada ao genótipo 3a. Os lipídios são essenciais para o ciclo de replicação do VHC, eles podem exercer seu efeito em diferentes níveis como: grupos prostéticos em proteínas virais e/ou cofatores celulares na replicação de VHC, componentes especializados na estrutura do VHC onde ocorre a replicação ou como constituinte das partículas lipovirais. Trabalhos experimentais realizados anteriormente por nosso grupo relataram que a administração do composto natural Yo Jyo Hen Shi Ko (YHK) promove a inibição do desenvolvimento da esteatose, redução dos marcadores de estresse oxidativo, menor escore de inflamação, melhora nas concentrações de aminotransferases e diminuição da gordura visceral em um modelo animal de esteato-hepatite não alcoólica. A terapia padrão da hepatite C consiste em uma combinação de interferon peguilado alfa (PEG-IFN-alfa) que estimula o sistema imunológico do hospedeiro para combater a infecção e o composto antiviral ribavirina. Atualmente foram aprovados pelas agências de saúde os inibidores de protease Boceprevir, Telaprevir, Daclatasvir e Simeprevir. No entanto, sua eficiência varia entre os genótipos e as constantes mutações do vírus podem levar a resistência. A falta de uma vacina ou uma terapia definitiva faz com que diversos compostos com diferentes mecanismos de ação sejam testados como possíveis alternativas de tratamento. Tendo em vista a capacidade do YHK de reduzir a esteatose e a importância...


Worldwide is estimated that nearly 170 million people are infected with hepatitis C virus (HCV), highly correlated with the occurrence of chronic hepatitis and hepatocellular carcinoma. Hepatitis C patients present higher prevalence of steatosis when compared with the general population, ranging between 40% and 75%. There are two forms of steatosis in HCV infected patients: metabolic steatosis (risk factors) and cytopathic associated with genotype 3. Lipids are essential for the HCV replication cycle. It acts on different functions: as prosthetic groups into viral proteins and / or cellular cofactors in the HCV replication, as specific HCV components or as a constituent of lipovirals particles. Our group previously reported that the administration of the natural compound Yo Jyo Hen Shi Ko (YHK) inhibits steatosis development, decreases markers of oxidative stress and inflammation, improves aminotransferases concentration and decreases the visceral fat. Standard therapy for hepatitis C is a combination of pegylated interferon alpha (PEG-IFN-alfa), stimulating the host immune system to fight infection and the antiviral compound named ribavirin. Nowadays, Telaprevir, Boceprevir, Sofosbovir and Simeprevir are approved as new anti-HCV drugs; they act as protease inhibitors. Its efficiency, however, varies between genotypes, and the constant mutations of the virus can lead to resistance. The lack of vaccines, or a definitive therapy, stimulates the research of new compounds and alternative treatments. In this study, we evaluated the effect of YHK in HCV replication cycle due to the effect of YHK and the importance of lipid metabolism for HCV. For this purpose we used cell culture techniques allowing the study of different stages of HCV replication cycle: entry (HCVpp), replication - replicons JFH1 NS3-5B and Con1, also replication and infection-JC1-Fluc. We also used active compounds of its ingredients: Panax pseudo ginseng - Notoginsenoside R1...


Assuntos
Antivirais , Técnicas de Cultura de Células , Medicamentos de Ervas Chinesas , Hepacivirus , Hepatite C , Reguladores do Metabolismo de Lipídeos , Replicação Viral
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