Oxymatrine reduces expression of programmed death-ligand 1 by promoting DNA demethylation in colorectal cancer cells

Background Colorectal cancer (CRC) represents an important neoplasm with high mortality. Although PD-L1/PD-1 system-based immunotherapy has benefits for a certain type of CRC, many efforts should be made to enhance the responses to anti-PD-1/PD-L1 drugs. DNA methylation has been critically implicated in the regulation of tumor immunity. Here, we examined the effects of the natural alkaloid oxymatrine on PD-L1 expression in CRC cells and to elucidate the underlying mechanism. Methods Human CRC SW620 and HCT116 cells were treated with interferon γ (IFNγ) and/or oxymatrine. Cell viability was determined using MTT assays. PD-L1 expression was detected by real-time PCR and Western blot analyses. DNA demethylase activity was measured using kits. Results Oxymatrine did not apparently affect the viability of normal human intestinal epithelial cells. IFNγ at 20 ng/ml increased the viability of CRC cells, but oxymatrine concentration-dependently reduced the viability in the absence or presence of IFNγ. IFNγ increased the mRNA and protein expression of PD-L1 in the two cell lines, but oxymatrine significantly abolished IFNγ-elevated PD-L1 levels at both mRNA and protein levels. Furthermore, DNA demethylase activity was remarkably increased in IFNγ-treated CRC cells, which was abolished by oxymatrine concentration-dependently. In addition, DNA methyltransferase inhibitor 5-azacytidine considerably abrogated oxymatrine-induced downregulation of PD-L1 mRNA and protein levels in IFNγ-stimulated CRC cells. Conclusion Oxymatrine suppressed viability and reduced PD-L1 expression in IFNγ-stimulated CRC cells, which was attributed to enhanced DNA demethylation. Our current discoveries suggested oxymatrine as an epigenetic modulatory agent for immunotherapy against CRC via PD-1/PD-L1 blockade (AU)

Anemia hemolítica autoinmune, reacción adversa a venetoclax / Autoimmune hemolytic anemia, adverse event to venetoclax

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Aplicabilidad y coste-efectividad de la administración de azacitidina en régimen domiciliario / Feasibility and cost-effectiveness of at home azacitidine administration

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Independencia transfusional en un paciente con anemia refractaria con exceso de blastos tipo 2 refractario a 5-azacitidina tratado con deferasirox y agentes estimuladores de colonias / Transfusional independence in a patient with refractory anemia with excess blasts-2 refractory to 5-azacitidine treated with deferasirox and colony stimulating factors

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Efectividad y seguridad de 5-azacitidina en tres pacientes con síndrome mielodisplásico / Effectiveness and safety of 5-azacitidine in three patients with myelodysplastic syndromes

Objetivo Evaluar la efectividad y seguridad del tratamiento con 5-azacitidina en síndrome mielodisplásico. Métodos Revisión de historias clínicas de pacientes que recibieron 5-azacitidina 75mg/m2 subcutánea durante 7 días, cada 28 días en 12 ciclos. Se valoró la respuesta objetiva, mejoría clínica y tiempo hasta la progresión de la enfermedad. Se recogieron las reacciones adversas descritas en la historia clínica. Resultados Seis pacientes fueron candidatos a tratamiento con 5-azacitidina. Tres casos fueron evaluables tras el período considerado. La mayoría permanecieron en respuesta parcial o mejor al finalizar el estudio, dejando de precisar transfusiones. En una paciente se retrasó la progresión a leucemia.Conclusiones5-Azacitidina podría considerarse un fármaco relativamente efectivo y seguro, pudiendo haber contribuido al control de citopenias periféricas, a mejorar la calidad de vida y a retrasar la progresión a leucemia. Serían necesarios estudios con mayor número de pacientes que corroborasen estos resultados (AU)

Objective To assess the effectiveness and safety of using 5-azacitidine to treat myelodysplastic syndromes. Methods Review of medical records of patients who received 5-azacitidine 75mg/m2 subcutaneously for during 7 days every 28 days in twelve cycles as compassionate use. We evaluated the objective response, clinical improvement and time to disease progression. We recorded adverse reactions described in the medical history. Results Six patients were candidates for treatment with 5-azacitidine. Three cases were evaluated over the study period. Most remained in partial response or better after the study, and no longer needed transfusions. In one patient, the treatment appeared to delay progression to leukaemia.Conclusions5-Azacitidine might be considered an effective and relatively safe drug, and may have contributed to controlling peripheral cytopenias, improving the quality of life and delaying progression to leukaemia. Additional studies with more patients are needed to support these results (AU)