RESUMEN
E3 ubiquitin ligases comprise a family of ubiquitination-catalyzing enzymes that have been extensively researched and are considered crucial components of the ubiquitin-proteasome system involved in various diseases. The ubiquitin-protein ligase E3 component n-recognition 5 (UBR5) is an E3 ubiquitin-protein ligase that has garnered considerable interest of late. Recent studies demonstrate that UBR5 undergoes high-frequency mutations, chromosomal amplification, and/or abnormalities during expression of various malignant tumors. These alterations correlate with the biological behaviors and prognoses of malignancies, such as tumor invasion, metastasis, and resistance to chemotherapeutic agents. This study aimed to comprehensively elucidate the biological functions of UBR5, and its role and relevance in the context of gastrointestinal cancers. Furthermore, this article expounds a scientific basis to explore the molecular mechanisms underlying gastrointestinal cancers and developing targeted therapeutic strategies for their remediation.
RESUMEN
BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).