Autophagy in tumor suppression and cancer therapy.

Autophagy is a stress-induced cell survival program whereby cells under metabolic, proteotoxic, or other stress remove dysfunctional organelles and/or misfolded/polyubiquitylated proteins by shuttling them via specialized structures called autophagosomes to the lysosome for degradation. The end result is the release of free amino acids and metabolites for use in cell survival. For tumor cells, autophagy is a double-edged sword: autophagy genes are frequently mono-allelically deleted, silenced, or mutated in human tumors, resulting in an environment of increased oxidative stress that is conducive to DNA damage, genomic instability, and tumor progression. As such, autophagy is tumor suppressive. In contrast, it is important to note that although tumor cells have reduced levels of autophagy, they do not eliminate this pathway completely. Furthermore, the exposure of tumor cells to an environment of increased metabolic and other stresses renders them reliant on basal autophagy for survival. Therefore, autophagy inhibition is an active avenue for the identification of novel anti-cancer therapies. Not surprisingly, the field of autophagy and cancer has experienced an explosion of research in the past 10 years. This review covers the basic mechanisms of autophagy, discusses its role in tumor suppression and cancer therapy, and posits emerging questions for the future.

Safety and Efficacy of Nitazoxanide-Based Regimen for the Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Helicobacter pylori (HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy or bismuth-based quadruple therapy is usually considered the first-line treatment, however with around 30% failure rate for both regimens. Drug resistance of clarithromycin and metronidazole is a growing concern in some parts of the world. Therefore, there is a need for effective eradication regimen for HP. Nitazoxanide, a bactericidal thiazolide antibiotic, has been shown to be effective in HP infection. We conducted a systematic review and meta-analysis to evaluate the efficacy of nitazoxanide-based regimen for the eradication of HP. METHODS: We have searched PubMed, Embase, Ovid Medline and Cochrane library database from inception to December 9, 2020 to identify studies that utilized nitazoxanide in the treatment regimen for HP eradication. Our primary outcome was pooled eradication rate of HP. RESULTS: Thirteen studies including 1,028 patients met our inclusion criteria and were analyzed in a meta-analysis. HP eradication was successful in 867 patients with a pooled eradication rate of 86% (95% confidence interval (CI): 79-90%) with 84% heterogeneity. A subgroup analysis that included 230 patients who failed other prior eradication regimens revealed a pooled eradication rate of 85% (95% CI: 69-94%) without heterogeneity. In a subgroup analysis, highest eradication rates were achieved with levofloxacin, doxycycline, nitazoxanide and proton pump inhibitor with a pooled eradication rate of 92% (88-95%). CONCLUSION: Nitazoxanide-based regimen is safe and effective in the eradication of HP infection. It is also successful as a salvage therapy in patients who have failed prior treatments.

Parathyroid hormone stimulation of noncanonical Wnt signaling in bone.

In bone, parathyroid hormone (PTH) exerts either a catabolic or an anabolic effect depending on its method of administration. This paradoxical action has led to the use of PTH as an effective treatment for osteoporosis. The Wnt family of signaling proteins has a critical role in multiple events, which are necessary for proper animal development and survival, yet their exact method of action in bone remains elusive. We have uncovered a novel link between Wnt-4 and PTH. We think that, in bone, Wnt-4 signaling in response to PTH implicates cross-talk of multiple signaling pathways. This work hopes to further elucidate Wnt signaling in bone and provide greater understanding of PTH's anabolic effects in bone.