RESUMO
BACKGROUND: TGF-ß-activated kinase-1 (TAK1) has been found to be over-expressed in a variety of solid malignancies and related to tumor growth. The aim of this study was to evaluate the expression level of TAK1 in clear cell renal cell carcinoma (ccRCC) and assess its value as a novel prognostic marker. METHODS: TAK1 mRNA was assessed in 51 paired ccRCC tissues and adjacent normal tissues (ADTs) by real-time PCR. Tissue TAK1 protein was also assessed in 91 ADTs and 177 samples of ccRCC immunohistochemically for evaluation of relationships with clinical characteristics. RESULTS: RT-PCR showed that TAK1 RNA level was significantly higher in ccRCC tissues than in the paired ADTs and immunohistochemistry confirmed higher expression of TAK1 protein in ccRCC samples compared with ADTs. TAK1 protein expression in 177 ccRCC samples was significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, but not age and gender. Patients with low TAK1 levels had a better survival outcome. TAK1 expression and N stage were independent prognosis factors for the overall survival of ccRCC patients. CONCLUSIONS: Overexpression of TAK1 predicts a poor prognosis in patients with ccRCC, so that TAK1 may serve as a novel prognostic marker.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , MAP Quinase Quinase Quinases/metabolismo , Recidiva Local de Neoplasia/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/secundário , Feminino , Humanos , Estimativa de Kaplan-Meier , Rim/metabolismo , Neoplasias Renais/genética , MAP Quinase Quinase Quinases/genética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , RNA MensageiroRESUMO
AIM: To investigate the stepwise development and germ cell gene expression in allografted neonatal mouse testes and the differentiation of immature human testicular cells in xenografted human testes. METHODS: Immunodeficient nude mice were used as hosts for allografting of neonatal mouse testes and xenografting of human fetal testicular tissues. Stepwise development and stage-specific gene expression of germ cells in allografts were systematically evaluated and parallel compared with those in intact mice by periodically monitoring the graft status with measurement of graft weight, histological analysis and determination of five stage-specific genes. Human testicular tissues from 20 and 26 weeks fetuses were used for the xenografting study. Histological analysis of xenografts was performed 116 and 135 d after the grafting procedure. RESULTS: In the allografting study, progressive increase in tissue volume and weight as well as in tubule diameter in grafts was observed; the appearance time of various germ cells in seminiferous tubules, including spermatogonia, spermatocytes, round and elongate spermatids and sperm, was comparable with that in intact donors; the initiation of gene transcription in grafts showed a similar trend as in normal mice. Graft weight ceased to increase after 7-8 weeks and degradation of grafts was observed after 5 weeks with progressive damage to seminiferous epithelium. In the xenografting study using immature human testicular tissues, graft survival and development was indicated by increasing graft weight, Sertoli cells differentiation into advanced stage, germ cells migration and location to the basal lamina and formation of a niche-like structure. CONCLUSION: The developmental course and gene expression pattern of germ cells in allografts were similar to those in intact mice. The best time point for retrieval of mouse sperm from grafts was 5-7 weeks after grafting procedure. An accelerated development of immature human testicular cells could be achieved by ectopic xenografting of human testes.