RESUMO
Tropomyosin-1 (TPM1), a widely expressed actin-binding protein, is downregulated in many tumors and associated with cancer progression. A previous study from our group suggested that TPM1 could be involved in renal cell carcinoma (RCC) apoptosis, but the mechanisms and details remained unknown. The present study aimed to further examine the proapoptotic effects of TPM1 and investigate the underlying mechanisms in RCC cell lines. Results from cell viability, DAPI staining and apoptosis assays demonstrated that TPM1 upregulation inhibited cell proliferation and promoted cell apoptosis in both 786-O and ACHN RCC cell lines. However, TPM1 knockdown in the two RCC cell lines did not result in the opposite effects on cell proliferation or cell apoptosis. Comet assay and western blotting results demonstrated that TPM1 overexpression induced DNA damage and decreased the expression levels of the antiapoptotic factor BCL2 apoptosis regulator, while increasing the expression levels of the proapoptotic factors BCL2 associated X, Caspase-3 and p53 in 786-O and ACHN cells. The present findings suggest that TPM1 overexpression in RCC cell lines can induce tumor cell apoptosis via the p53-mediated mitochondrial pathway. Further studies are needed to fully elucidate the potential of TPM1 as a candidate for RCC targeted therapy in the future.
RESUMO
OBJECTIVE: We compared long-term clinical outcomes of upper urinary tract transitional cell carcinoma (TCC) patients treated by retroperitoneoscopic nephroureterectomy (RNU) or open radical nephroureterectomy (ONU). METHODS: Upper urinary tract TCC patients were treated with RNU (n = 86) or ONU (n = 72) and followed-up for more than three years. Demographic and clinical data, including preoperative indexes, intraoperative indexes and long-term clinical outcomes, were retrospectively compared to determine long-term efficacy of the two procedures. RESULTS: The RNU and ONU groups were statistically similar in age, gender, previous bladder cancer history, tumour location, pathologic tumour stage, pathologic node metastasis or tumour pathologic grade. The original surgery time required for both RNU and ONU was statistically similar, but RNU was associated with a significantly smaller volume of intraoperative estimated blood loss and shorter length of postoperative hospital stay. Follow-up (average: 42.4 months, range: 3-57) revealed that the RNU 3-year recurrence-free survival rate was 62.8% and the 3-year cancer specific survival rate was 80.7%. In the ONU group, the 3-year recurrence-free survival and the three-year cancer-specific survival rates were 59.2% and 80.3%, respectively. Neither of the survival rates were statistically different between the two groups. T stage, grade, lymph node metastasis and bladder tumour history were risk factors for tumour recurrence; the operation mode and the bladder cuff incision mode had no correlation with the recurrence-free survival. CONCLUSION: The open surgery strategy and the retroperitoneoscopic nephroureterectomy strategy are equally effective for treating upper urinary tract TCC. However, the RNU procedure is less invasive, and requires a shorter duration of postoperative hospitalized care; thus, RNU is recommended as the preferred strategy.
