RESUMEN
BACKGROUND: Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. METHODS: In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. RESULTS: Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Biomarcadores de Tumor/metabolismo , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Adolescente , Adulto , Anciano , Aminopiridinas/administración & dosificación , Animales , Antraciclinas/administración & dosificación , Apoptosis , Benzamidas/administración & dosificación , Biomarcadores de Tumor/genética , Ciclo Celular , Proliferación Celular , Niño , Quinasa 2 Dependiente de la Ciclina/genética , Quinasa 2 Dependiente de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Femenino , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto JovenRESUMEN
OBJECTIVE: We aimed to identify the differences in symptoms, high-resolution manometry (HRM) characteristics, and the efficacy of peroral endoscopic myotomy (POEM) regarding patients' sex in achalasia. METHODS: All patients diagnosed with achalasia by HRM who underwent POEM and were followed up for more than 6 months were included. The individual characteristics, symptoms and signs, POEM findings, HRM results and potentially related complications in male and female patients were reviewed. RESULTS: Prior to POEM, dysphagia was more severe in female than male patients (P = 0.044), while regurgitation was more severe (P = 0.013) and heartburn was more common in male patients (P = 0.003). Regarding HRM characteristics, the lower esophageal sphincter pressure (LESP) was higher (P = 0.01) and length of esophagus was shorter in female patients than in male patients. Eckardt scores, LESP and integrated relaxation pressure were significantly improved after the POEM procedure (P < 0.001). No significant difference was observed between the sexes regarding the efficacy of POEM, reflux symptoms, HRM data and complications after POEM. CONCLUSIONS: Before they seek treatment, female patients with achalasia may experience severe dysphagia and male patients are more likely to experience heartburn and more severe regurgitation. POEM is a safe and effective option for treating both male and female patients with achalasia.
