Active Surveillance in Non-Muscle Invasive Bladder Cancer, the Potential Role of Biomarkers: A Systematic Review.

Bladder cancer (BC) is the tenth most common cause of cancer worldwide and is the thirteenth leading cause of cancer mortality. The non-muscle invasive (NMI) variant represents 75% of cases and has a mortality rate of less than 1%; however, it has a high recurrence rate. The gold standard of management is transurethral resection in the case of new lesions. However, this is associated with significant morbidity and costs, so the reduction of these procedures would contribute to reducing complications, morbidity, and the burden to the health system associated with therapy. In this clinical scenario, strategies such as active surveillance have emerged that propose to manage low-risk BC with follow-up; however, due to the low evidence available, this is a strategy that is underutilized by clinicians. On the other hand, in the era of biomarkers, it is increasingly known how to use them as a tool in BC. Therefore, the aim of this review is to provide to clinical practitioners the evidence available to date on AS and the potential role of biomarkers in this therapeutic strategy in patients with low-grade/risk NMIBC. This is the first review linking use of biomarkers and active surveillance, including 29 articles.

Wnt Signaling Pathway Dysregulation in the Aging Brain: Lessons From the Octodon degus.

Wnt signaling constitutes a fundamental cellular and molecular pathway, necessary from proper embryogenesis to function-maintenance of fully developed complex organisms. In this regard, Wnt pathway plays a crucial role in both the development of the central nervous system and in maintaining the structure and function of the neuronal circuits, and it has been suggested that its dysregulation is critical in the onset of several pathologies including cancer and neurodegenerative disorders, such as Alzheimer's disease (AD). Due to its relevance in the maintenance of the neuronal activity and its involvement in the outbreak of devastating diseases, we explored the age-related changes in the expression of Wnt key components in the cortex and hippocampus of 7 to 72-months-old Octodon degus (O. degus), a Chilean long-living endemic rodent that has been proposed and used as a natural model for AD. We found a down-regulation in the expression of different Wnt ligands (Wnt3a, Wnt7a, and Wnt5a), as well as in the Wnt co-receptor LRP6. We also observed an increase in the activity of GSK-3ß related to the down-regulation of Wnt activity, a fact that was confirmed by a decreased expression of Wnt target genes. Relevantly, an important increase was found in secreted endogenous Wnt inhibitors, including the secreted-frizzled-related protein 1 and 2 (SFRP-1 and SFRP-2) and Dickkopf-1 (Dkk-1), all them antagonists at the cell surface. Furthermore, treatment with Andrographolide, a labdane diterpene obtained from Andrographis paniculata, prevents Wnt signaling loss in aging degus. Taken together, these results suggest that during the aging process Wnt signaling activity decreases in the brain of O. degus.

Is L-methionine a trigger factor for Alzheimer's-like neurodegeneration?: Changes in Aß oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice.

BACKGROUND: L-methionine, the principal sulfur-containing amino acid in proteins, plays critical roles in cell physiology as an antioxidant and in the breakdown of fats and heavy metals. Previous studies suggesting the use of L-methionine as a treatment for depression and other diseases indicate that it might also improve memory and propose a role in brain function. However, some evidence indicates that an excess of methionine can be harmful and can increase the risk of developing Type-2 diabetes, heart diseases, certain types of cancer, brain alterations such as schizophrenia, and memory impairment. RESULTS: Here, we report the effects of an L-methionine-enriched diet in wild-type mice and emphasize changes in brain structure and function. The animals in our study presented 1) higher levels of phosphorylated tau protein, 2) increased levels of amyloid-ß (Aß)-peptides, including the formation of Aß oligomers, 3) increased levels of inflammatory response,4) increased oxidative stress, 5) decreased level of synaptic proteins, and 6) memory impairment and loss. We also observed dysfunction of the Wnt signaling pathway. CONCLUSION: Taken together, the results of our study indicate that an L-methionine-enriched diet causes neurotoxic effects in vivo and might contribute to the appearance of Alzheimer's-like neurodegeneration.