Bladder cancer and apoptosis: matters of life and death.

摘要

Urothelial-cell carcinoma, the most common tumour type of the bladder, includes a wide variety of neoplasms. Some of these are no more dangerous than a skin wart while others recur repeatedly and generate inconvenience and high-health care expenses for the patient-few of these, however, cause patient death. In contrast, the muscle-invasive tumours are aggressive and require cystectomy, with a mortality rate of about 50%. For patients with these types of tumour, it is a matter of life and death. In this issue of The Lancet Oncology, Karam and co-workers report the results of an immunohistochemical study of four proteins involved in apoptosis (P53, Bcl-2, survivin, and caspase-3) in 226 patients undergoing radical cystectomy. This is the first study in which multiple apoptosis markers have been used together to assess their value in improving the accuracy of predicting outcome for patients with bladder cancer. Apoptosis is crucial for tissue homeostasis during development and adulthood, and evading apoptosis is one of the six changes of cell behaviour proposed by researchers to be essential for malignantgrowth. An apoptotic response results from the integration of extracellular and intracellular proapoptotic and antiapoptotic signals that converge to change mitochondrial function, to release cytochrome C, and to activate apoptotic effectors. P53 can induce apoptosis in response to a range of stress signals. Genes activated by P53 (ie, PMAIP1 and BBC3) or repressed by P53 (ie, BIRC5) have important roles in the apoptotic response. Bcl-2, and its related proapoptotic and antiapoptotic proteins, control the release of cytochrome C, which activates effector caspases. Diverse genetic and biochemical mechanisms contribute to change the expression of the proteins from the Bcl-2 family and to tumour progression, as elegantly shown using mouse cancer models. Additionally, the resistance of tumour cells to apoptosis is associated with the extent to which a disease becomes refractory to treatment. Therefore, information about tumour biology and response to treatment could be gained by knowledge of how changes in markers for apoptosis are associated with disease outcome.