ABSTRACT
BACKGROUND: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs. MATERIAL AND METHODS: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. RESULTS: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cystic carcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. CONCLUSIONS: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST.
Subject(s)
Carcinoma, Adenoid Cystic , Salivary Gland Neoplasms , Humans , Carcinoma, Adenoid Cystic/drug therapy , Salivary Gland Neoplasms/drug therapy , Databases, Factual , Salivary GlandsABSTRACT
The most important role played by the enzyme Glucose-6-Phosphate Dehydrogenase (G6PD) in erythrocyte metabolism is in generating energy and reducing power used to protect the cell against oxidative attack. G6PD deficiency is the erythroenzymopathy that most frequently causes hemolytic anemia, and more than 130 molecular variants have already been identified. The aim of this study was to analyze the genetic mutations in the G6PD-deficient adult males in the population of the region of Araraquara, São Paulo State. Out of 5087 male blood donors, 89 were deficient for G6PD, as confirmed by assaying the enzyme activity and electrophoresis on cellulose acetate. Thus, a frequency of 1.75% of G6PD-deficient patients was found, this value being similar to other investigations in São Paulo state. Molecular analysis was performed by amplification of genomic DNA with specific primers and digestion with restriction enzymes. In 96.6% of the patients, the G6PD A¯ variant was observed, with mutations at residues 376(A-G) and 202(G-A). Mean G6PD specific activity among the patients was 1.31 IU.g Hb-1.min-1 at 37ºC, that is 10.8% of the normal activity of the G6PD B enzyme. The variant forms G6PD A¯680(G-T) and 968(T-C) were not found. In 3.4% of the deficient individuals, the G6PD Mediterranean variant was found, with a mutation at 563(C-T). In these cases,mean enzymatic activity was 0.25 IU.g Hb-1.min-1 at 37ºC, or 2.1% of the enzymatic activity of G6PD B. Theuse of traditional techniques, allied to the identification of the different molecular variants, is important for the understanding of the structural and functional properties and hemolytic behavior of the red blood cells of the patient...
A importância da enzima Glicose-6-fosfato desidrogenase (G6PD) no metabolismo eritrocitário está na obtenção de energia calórica e redutora para a proteção celular contra agressões oxidativas. A deficiência de G6PD é a eritroenzimopatia que causa mais frequentemente anemia hemolítica, com mais de 130 variantes moleculares identificadas. O objetivo deste estudo foi realizar a análise molecular da deficiência de G6PD em uma população masculina adulta da região de Araraquara, SP, para a identificação das mutações genéticas. Nos 5087 doadores de sangue do sexo masculino pesquisados, foram encontrados 89 deficientes de G6PD, confirmados pela determinação da atividade enzimática e eletroforese em acetato de celulose, com frequência de 1,75%, valores semelhantes aos encontrados por outros pesquisadores no Estado de São Paulo. A análise molecular realizada pela amplificação do DNA genômico com iniciadores específicos e digestão com enzimas de restrição, demonstrou que 96,6% dos deficientes apresentaram a variante G6PD A¯, com as mutações 376(A-G) e 202(G-A) e atividade enzimática média de 1,31 UI.g de Hb-1.min-1 a 37ºC, correspondendo a 10,8% da atividade enzimática da enzima normal G6PD B. Não foram encontradas as formas variantes G6PD A¯ 680(G-T) e 968(T-C). Em 3,4% dos indivíduos deficientes, foi encontrada a variante G6PD Mediterrânea, mutação 563(C-T) e atividade enzimática média de 0,25 UI.g de Hb-1.min-1 a 37ºC, correspondendo a 2,1% da atividade enzimática da G6PD B. A utilização das técnicas tradicionais, aliadas à identificação da variante molecular, são importantes na compreensão das propriedades estruturais, funcionais e comportamento hemolítico dos glóbulos vermelhos do paciente...
Subject(s)
Humans , Male , Adolescent , Adult , Middle Aged , Anemia, Hemolytic , Glucosephosphate Dehydrogenase Deficiency/complications , Glucosephosphate Dehydrogenase Deficiency/epidemiology , Polymorphism, Genetic , Electrophoresis, Cellulose AcetateABSTRACT
O objetivo deste estudo foi analisar os fatores de risco relacionados às doenças cardiovasculares (FRDCV), em idosos diabéticos do tipo 2, através de um estudo observacional com delineamento transversal, tendo sido realizado com 100 idosos atendidos no Centro Regional de Reabilitação de Araraquara (CRRA), São Paulo, Brasil, de março a dezembro de 2004. Houve predominância de indivíduos casados, sexo feminino, brancos, com baixa renda e baixa escolaridade. Quanto aos hábitos e estilo de vida, predominaram os que mantinham dietas adequadas, sedentários, não fumantes e não etilistas. Entre os 100 indivíduos estudados, 42% apresentaram sobrepeso, 42% obesidade, 71% valores inadequados de circunferência abdominal e 84% de relação cintura-quadril de acordo com o sexo. Em relação aos FRDCV, 54,0% apresentaram hipertensão arterial sistêmica (HAS), 54,0% com hipercolesterolemia, 51,0% de hipertrigliceridemia, 84% com valores elevados de LDL-colesterol, 59% com níveis reduzidos de HDL-colesterol, 78,0% com níveis elevados de glicemia de jejum, 76,0% com níveis elevados de hemoglobina glicada e 57,0% de fibrinogênio. Os resultados demonstraram uma frequência elevada de FRDCV com diferenças em relação ao sexo e a idade.
The aim of this study was to analyze the risk factors related to the cardiovascular diseases (CVRF) in elderly type 2 diabetics. A cross-sectional observational study was carried out on 100 elderly patients attending the Rehabilitation Center of Araraquara (CRRA), São Paulo State, Brazil, from March to December, 2004. The majority were married, female, white, with a low income and low educational level. Regarding habits and style of life, the subjects had an adequate diet, were sedentary, non-smoking and non-drinking. In the population of 100, 42% were overweight, 42% obese, 71% had abovenormal waist measurements and 84% high waist-to-hip ratios. Concerning the CVRF, it was observed that more than half had hypertension, hypercholesterolaemia and hypertriglyceridaemia. 84% had high values of LDLcholesterol and 59% HDL-cholesterol levels below the reference values, 78% high levels of fasting glycemia, 76% glycohemoglobin and 57% fibrinogen and thus subject to cardiovascular risk. The results showed a highfrequency of cardiovascular risk factors, differing according to sex and the age.
Subject(s)
Male , Female , Middle Aged , Aged , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Brazil , Risk FactorsABSTRACT
Glucose-6-phosphate dehydrogenase (G6PD) activity and the affinity for its substrate glucose-6-phosphate were investigated under conditions similar to the physiological environment in terms of ionic strength (I: 0.188), cation concentration, pH 7.34, and temperature (37oC). A 12.4, 10.4 and 21.4 percent decrease was observed in G6PD B, G6PD A+ and G6PD A- activities, respectively. A Km increase of 95.1, 94.4 and 95.4 percent was observed in G6PD B, G6PD A+ and G6PD A-, respectively, leading to a marked decrease in affinity. In conclusion, the observation of the reduced activity and affinity for its natural substrate reflects the actual pentose pathway rate. It also suggests a much lower NADPH generation, which is crucial mostly in G6PD-deficient individuals, whose NADPH availability is poor