ABSTRACT
Background & objectives: To examine ?-D-mannuronic acid (M2000) effects on L-selectin shedding and leucocyte function-associated antigen-1 (LFA-1) expression as mechanisms of action of this drug in patients with ankylosing spondylitis (AS). Methods: To investigate the molecular consequences of ?-D-mannuronic acid on L-selectin shedding, flow cytometry method was used. Furthermore, the effect of it on LFA-1 gene expression was analyzed by using quantitative real time (qRT)-PCR technique. Results: The LFA-1 expression in patients with AS was higher than controls (P=0.046). The LFA-1 expression after 12 wk therapy with ?-D-mannuronic acid was meaningfully decreased (P=0.01). After 12 wk treatment with ?-D-mannuronic acid, the frequency of CD62L-expressing CD4+ T cells in patients with AS, was not considerably altered, compared to the patients before therapy (P=0.5). Furthermore, after 12 wk therapy with ?-D-mannuronic acid, L-selectin expression levels on CD4+ T-cells in patients with AS, were not remarkably changed, compared to the expression levels of these in patients before treatment (P=0.2). Interpretation & conclusions: The results of this study for the first time showed that ?-D-mannuronic acid can affect events of adhesion cascade in patients with AS. Moreover, ?-D-mannuronic acid presented as an acceptable benefit to AS patients and could aid in the process of disease management
ABSTRACT
Introduction: Vascular endothelial growth factor is thought to be an important angiogenic factor involved in tumor growth, progression, and metastasis. Objective: The present study evaluated the relation between tissue expression, serum and salivary levels of vascular endothelial growth factor in head and neck squamous cell carcinomas, and their correlation with clinicopathologic features. Methods: Samples were collected from 30 patients with head and neck squamous cell carcinomas and 24 healthy volunteers. Immunohistochemical analysis was used for tissue expression and enzyme-linked immunosorbent assay was employed to measure serum and salivary levels. Results: No vascular endothelial growth factor staining was observed in normal tissues, whereas vascular endothelial growth factor expression was seen in 6 patients (20%). Mean serum level of VEGF was 83.7 ± 104.47 in patients and 50.04 ± 32.94 in controls. Mean salivary level of vascular endothelial growth factor was 174.41 ± 115.07 in patients and 149.58 ± 101.88 in controls. No significant difference was found by Mann-Whitney test between controls and patients (p = 0.411, p = 0.944, respectively). No correlation was found between vascular endothelial growth factor tissue expression and its serum and salivary level. Conclusion: Overexpression of vascular endothelial growth factor was found in head and neck squamous cell carcinoma patients, suggesting its role in the pathogenesis of head and neck squamous cell carcinoma, but no relation was found between tissue expression, serum levels, and salivary levels of this marker. .
Introdução: Acredita-se que o fator de crescimento vascular endotelial (FCEV) seja um importante fator angiogênico envolvido no crescimento, na progressão e na metástase tumoral. Objetivo: O presente estudo avalia a relacão entre a expressão tecidual e os níveis séricos e salivares do FCEV em carcinomas de células escamosas da cabeca e pescoco (CCECPs) e sua correlacão com aspectos clinicopatológicos. Método: Foram coletadas amostras de 30 pacientes com CCECP e de 24 voluntários saudáveis. Utilizamos análise imuno-histoquímica para a expressão tecidual e ELISA para determinação dos níveis séricos e salivares. Resultados: Não foi observada coloração para FCEV nos tecidos normais, enquanto que foi observada expressão de FCEV em seis pacientes (20%). O nível sérico médio de FCEV foi 83,7 ± 104,47 em pacientes e 50,04 ± 32,94 em controles. O nível salivar médio de FCEV foi de 174,41 ± 115,07 em pacientes e 149,58 ± 101,88 em controles. Não foi observada diferenca significativa pelo teste de Mann-Whitney entre controles e pacientes (respectivamente, p = 0,411, p = 0,944). Não foi observada relacão entre a expressão tecidual de FCEV e seus níveis séricos e salivares. Conclusão: A expressão elevada de FCEV foi observada em pacientes com CCECP, e isso sugere seu papel na patogênese de CCECP, mas não foi observada relacão entre a expressão tecidual e os níveis séricos e salivares desse marcador. .
Subject(s)
Female , Humans , Male , Middle Aged , Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Neoplasm Proteins/metabolism , Saliva/chemistry , Vascular Endothelial Growth Factor A/metabolism , Case-Control Studies , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Neoplasm Staging , Neoplasm Proteins/analysis , Vascular Endothelial Growth Factor A/analysisABSTRACT
P53 tumoral suppressor gene harbors a functional polymorphism which codes either arginine (Arg) or proline (Pro) in the protein p53 of codon 72. Such polymorphism has been associated with the development or prognosis of head and neck squamous cell carcinoma (HNSCC). AIM: we assessed codon 72 p53 allelic frequencies and genotypes in HNSCC Iranian patients. STUDY DESIGN: Case Study. MATERIALS AND METHODS: a total of 132 HNSCC patients and 123 healthy controls were genotyped. DNA source was from mononuclear cells of the peripheral blood. DNA amplification was done by means of the allele-specific polymerase chain reaction. RESULTS: genotypes and allele distribution were not significantly different between patients and controls. Moreover, no statistically significant association was found between the 72 and p53 codon tumor location, gender or age at the time of diagnosis. However, the Pro/Pro genotype was significantly increase in stage IV patients (30.8 percent) when compared to stages I-III of the disease (11.1 percent) (p=0.03), and a significantly higher percentage of patients with the Pro allele had and a risk increase in stage IV disease (OR=2.2, 95 percent CI=1.2-4.2, p=0.01). CONCLUSION: data revealed that the p53 polymorphism do not impact the risk of HNSCC in Iranians, nonetheless, it can affect tumor progression to a higher tumor stage.
O gene supressor tumoral p53 abriga um polimorfismo funcional que codifica ou arginina (Arg) ou prolina (Pro) no códon 72 da proteína p53. Este polimorfismo tem sido considerado associado com o desenvolvimento e prognóstico do carcinoma espinocelular de cabeça e pescoço (CECP). OBJETIVO: Foram avaliados genótipo e freqüências alélicas do códon 72 do p53 em pacientes iranianos com CECP. TIPO DE ESTUDO: Estudo de Caso. MATERIAIS E MÉTODOS: Um total de 132 pacientes com CECP e 123 controles saudáveis foram genotipados. A fonte de DNA foi composta de células mononucleares do sangue periférico. A amplificação do DNA foi realizada através da reação em cadeia da polimerase específica para alelos. RESULTADOS: A distribuição dos alelos e genótipos não foi significativamente diferente entre os pacientes e controles. Além disso, nenhuma associação estatisticamente significativa foi encontrada entre o polimorfismo do códon 72 do p53 e localização, sexo ou idade no momento do diagnóstico. No entanto, o genótipo Pro/Pro estava significativamente aumentado em pacientes no estágio IV (30,8 por cento) quando comparado ao estágio I-III da doença (11,1 por cento) (p=0,03), e um número significativamente maior de doentes com o alelo Pro teve um aumento no risco de desenvolver doença no estágio IV (OR=2,2, IC= 95 por cento =1.2-4.2, p=0,01). CONCLUSÃO: Os dados revelaram que o polimorfismo do p53 não afeta o risco de CECP em iranianos; porém, pode afetar a progressão para um estágio superior tumor.