RESUMO
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).
Assuntos
Amoxicilina , Antibacterianos , Bismuto , Claritromicina , Esquema de Medicação , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Sulfonamidas , Tetraciclina , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/efeitos dos fármacos , Pessoa de Meia-Idade , Masculino , Feminino , Tetraciclina/administração & dosagem , Tetraciclina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Bismuto/administração & dosagem , Bismuto/uso terapêutico , Bismuto/efeitos adversos , Adulto , Claritromicina/administração & dosagem , Amoxicilina/administração & dosagem , Sulfonamidas/administração & dosagem , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Testes Respiratórios , Resultado do Tratamento , Idoso , ChinaRESUMO
Cancer cells generally have reprogrammed gene expression profiles to meet the requirements of survival, continuous division, and metastasis. An interesting question is whether the cancer cells will be affected by interfering their global RNA metabolism. In this research, we found that human Ccr4a/b (hCcr4a/b) and Caf1a/b (hCaf1a/b) deadenylases, the catalytic components of the Ccr4-Not complex, were dysregulated in several types of cancers including stomach adenocarcinoma. The impacts of the four deadenylases on cancer cell growth were studied by the establishment of four stable MKN28 cell lines with the knockdown of hCcr4a/b or hCaf1a/b or transient knockdown in several cell lines. Depletion of hCcr4a/b or hCaf1a/b significantly inhibited cell proliferation and tumorigenicity. Mechanistic studies indicated that the cells were arrested at the G2/M phase by knocking down hCaf1a, while arrested at the G0/G1 phase by depleting hCaf1b or hCcr4a/b. The four enzymes did not affect the levels of CDKs and cyclins but modulated the levels of CDK-cyclin inhibitors. We identified that hCcr4a/b, but not hCaf1a/b, targeted the p21 mRNA in the MKN28 cells. Furthermore, depletion of any one of the four deadenylases dramatically impaired processing-body formation in the MKN28 and HEK-293T cells. Our results highlight that perturbating global RNA metabolism may severely affect cancer cell proliferation, which provides a potential novel strategy for cancer treatment.
RESUMO
OBJECTIVE: This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin (ADR) in treating proliferative vitreoretinopathy (PVR) using ARPE-19 cells. METHODS: The growth inhibitory effects of ADR on ARPE-19 cells were assessed by sulforhodamine B (SRB) assay and propidium iodide (PI) staining using flow cytometry. The differentially expressed genes between ADR-treated ARPE-19 cells and normal ARPE-19 cells and the signaling pathways involved were investigated by microarray analysis. Mitochondrial function was detected by JC-1 staining using flow cytometry and the Bcl-2/Bax protein family. The phosphorylated histone H2AX (γ-H2AX), phosphorylated checkpoint kinase 1 (p-CHK1), and phosphorylated checkpoint kinase 2 (p-CHK2) were assessed to detect DNA damage and repair. RESULTS: ADR could significantly inhibit ARPE-19 cell proliferation and induce caspase-dependent apoptosis in vitro. In total, 4479 differentially expressed genes were found, and gene ontology items and the p53 signaling pathway were enriched. A protein-protein interaction analysis indicated that the TP53 protein molecules regulated by ADR were related to DNA damage and oxidative stress. ADR reduced mitochondrial membrane potential and the Bcl-2/Bax ratio. p53-knockdown restored the activation of c-caspase-3 activity induced by ADR by regulating Bax expression, and it inhibited ADR-induced ARPE-19 cell apoptosis. Finally, the levels of the γ-H2AX, p-CHK1, and p-CHK2 proteins were up-regulated after ADR exposure. CONCLUSIONS: The mechanism of ARPE-19 cell death induced by ADR may be caspase-dependent apoptosis, and it may be regulated by the p53-dependent mitochondrial dysfunction, activating the p53 signaling pathway through DNA damage.