Cathepsin L is associated with proliferation and clinical outcome of urothelial carcinoma of the bladder.

Increasing evidence suggests that the activity of cysteine proteases, including cathepsin L, is important in cancer cell invasion and metastasis. This study was designed to investigate the clinicopathological and prognostic significance of cathepsin L in human urothelial carcinoma of the bladder (UCB). Standard immunohistochemistry was used to determine the presence of cathepsin L and Ki-67 (a marker of proliferation) in paraffin-embedded specimens of 82 human UCB cases. Cathepsin L protein was localized in the cytoplasm of the malignant UCB cells, and was significantly associated with the pathological tumour stage (invasiveness), tumour grade, survival, local tumour recurrence during follow-up, the occurrence of distant metastasis during follow-up and the presence of Ki-67 protein. Multivariate analysis using the Cox proportional hazards model revealed that cathepsin L immunopositivity and pathological tumour stage (invasiveness) were independent significant prognostic factors for overall survival. This study showed that cathepsin L provides significant prognostic information and that it might be a useful therapeutic target in the future.

Orexin affects dorsal root ganglion neurons: a mechanism for regulating the spinal nociceptive processing.

Orexins (orexin A and B) are initially known to be a hypothalamic peptide critical for feeding and normal wakefulness. In addition, emerging evidence from behavioral tests suggests that orexins are also involved in the regulation of nociceptive processing, suggesting a novel potential therapeutic approach for pain treatment. Both spinal and supraspinal mechanisms appear to contribute to the role of orexin in nociception. In the spinal cord, dorsal root ganglion (DRG) neurons are primary afferent neurons that transmit peripheral stimuli to the pain-processing areas. Morphological results show that both orexin A and orexin-1 receptor are distributed in DRG neurons. Moreover, by using whole-cell patch-clamp recordings and calcium imaging measurements we found that orexin A induced excitability and intracellular calcium concentration elevation in the isolated rat DRG neurons, which was mainly dependent on the activation of spinal orexin-1 receptor. Based on these findings, we propose a hypothesis that the direct effect of orexin A on DRG neurons would represent a possible mechanism for the orexinergic modulation of spinal nociceptive transmission.