RESUMO
BACKGROUND: Thymidylate synthase (TYMS) expression in lung cancer tissue affects the therapeutic efficacy of pemetrexed (PMT). TYMS protein expression is primarily assessed using immunohistochemistry (IHC), but this method is not suitable for accurate quantitative analysis. It is not known whether the analysis of TYMS gene copy number using fluorescence in situ hybridization (FISH) is a useful method for assessment of TYMS expression. PATIENTS AND METHODS: The participants were patients with chemo-naïve advanced NSCLC treated with PMT plus carboplatin (CBDCA) in prospective clinical phase II study. TYMS expression was evaluated in 40 patients by gene copy number and protein expression using FISH and IHC. Therapeutic efficacy was evaluated by investigating the response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: TYMS gene amplification was detected in 8 patients (32 %) among 25 patients who could be evaluated for TYMS gene copy number. There were no patients with complete or partial response in the TYMS amplified group. RR and DCR were lower in the TYMS amplified group compared with the TYMS unamplified group (0 versus 35.3 %, p = 0.0539, 62.5 versus 94.1 %, p = 0.0443). PFS and OS were reduced in the TYMS amplified group. The analysis of TYMS gene copy number had higher sensitivity and specificity compared with TYMS protein expression (76.2 versus 50.0 %, 75.0 versus 66.7 %). CONCLUSION: The analysis of TYMS gene copy number is more suitable than TYMS protein expression for assessment of TYMS expression. TYMS gene amplification predicts outcome of patients receiving PMT with advanced NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Amplificação de Genes , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/administração & dosagem , Timidilato Sintase/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
Os autores registram o terceiro caso de eumicetoma podal de graos pretos, por Madurella grisea, observado no Brasil, com duracao aproximada de 22 anos. Extensas lesoes osseas estavam presentes. O exame histopatologico e as caracteristicas macroscopicas e micromorfologicas da amostra isolada permitiram identifica-la como Madurella grisea, especie criada em 1949 por Mackinnon & col. Apos varias tentativas de tratamento clinico (ketoconazol),termoterapia local e medicacao anti-inflamatoria) foi indicada amputacao, devido a cronicidade do processo e presenca de extensas lesoes osteo-articulares. Os autores fazem comentarios sobre a distribuicao dos eumicetomas no Brasil,em especial os que produzem graos pretos ou fuliginosos.Sobre a Madurella grisea, referem sua ampla distribuicao geografica
Assuntos
Dermatoses do Pé , Fungos Mitospóricos , MicetomaRESUMO
Free amino acid concentration in the plasma of rats fed on different diets were compared. The diets contained 7 g protein/100 g furnished by: casein, or common corn, or opaque 2 corn, or eggalbumin, or gelatin. A protein free diet was also included. The results showed that imbalance of the protein diet influenced the appetite; whenever the NE/E aminoacid ratio increased, body development, appetite and plasma albumin decreased. An inverse correlation between the NE/E of free aminoacids of the plasma and voluntary intake was observed. The results also show that the plasma aminogram did not reflect the composition of the protein in the diet. The results obtained are discussed.