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1.
Mol Ther ; 30(2): 644-661, 2022 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-34547462

RESUMEN

Preclinical and clinical studies have validated the antitumor effects of several oncolytic viruses (OVs). However, the efficacy of OVs is limited when they are administered as monotherapies. Combination therapy is a promising direction for oncolytic virotherapy in the future. A high dose of vitamin C (VitC) exerts anticancer effects by triggering the accretion of substantial amounts of reactive oxygen species (ROS). OVs can induce immunogenic tumor cell death and elicit an antitumor immune response. ROS play an important role in immunogenic cell death (ICD). This study aimed to explore whether high-dose VitC in combination with oncolytic adenoviruses (oAds) exhibited a synergistic antitumor effect. High-dose VitC synergized with oAds against tumor by enhancing immunogenic tumor cell death. Combination therapy with high-dose VitC and oAds significantly increased the number of T cells in the tumor microenvironment (TME) and promoted the activation of T cells. Furthermore, the antitumor effect of the combination therapy was CD8+ T cell dependent. In addition, combination therapy with high-dose VitC and oAds reprogramed the immunosuppressive TME. Our study provides a new strategy for combination therapy of OVs.


Asunto(s)
Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Adenoviridae/genética , Humanos , Muerte Celular Inmunogénica , Neoplasias/terapia , Virus Oncolíticos/fisiología , Microambiente Tumoral
2.
J Ocul Pharmacol Ther ; 36(5): 304-310, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32186940

RESUMEN

Purpose: To assess the clinical effects of preoperative, intraoperative, or preoperative combined with intraoperative intravitreal conbercept (IVC) injection in vitrectomy with silicone oil tamponade for severe proliferative diabetic retinopathy (PDR). Methods: Ninety-eight eyes of 98 severe PDR patients undergoing vitrectomy with silicone oil tamponade were randomly assigned to 3 groups: Group 1 (34 eyes) received IVC injections 3 to 5 days before surgery; Group 2 (35 eyes) received IVC injections at the end of surgery; and Group 3 (29 eyes) received IVC injections 3 to 5 days before and at the end of operation. Follow-up examinations were performed for 6 months. Results: The incidence and severity of intraoperative bleeding were not significantly different (P = 0.233). However, the duration of surgery was significantly shorter in Group 1 and Group 3 compared with Group 2 (P < 0.001). The incidences of early and late recurrent vitreous hemorrhage (VH) were 32.35%, 28.57%, and 13.80%, respectively. At 6-month follow-up, mean best-corrected visual acuity had significantly increased to 1.25 ± 0.45 logMAR in Group 1, 1.29 ± 0.46 logMAR in Group 2, 1.16 ± 0.44 logMAR in Group 3 (all P < 0.001). The incidence of postoperative VH, neovascular glaucoma, and retinal detachment in Group 3 was slightly lower, however, no significant differences were observed (all P > 0.05). In young patients, similar results were observed and Group 3 had better visual improvements (P = 0.037). Conclusions: Preoperative IVC injection could be a safe and effective adjunct in pars plana vitrectomy with silicone oil tamponade for severe PDR. Preoperative combined with intraoperative IVC are promising, especially in young patients.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Quimioterapia Adyuvante/métodos , Retinopatía Diabética/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Vitrectomía/métodos , Adulto , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Quimioterapia Adyuvante/estadística & datos numéricos , Terapia Combinada , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/cirugía , Femenino , Estudios de Seguimiento , Glaucoma Neovascular/epidemiología , Hemorragia/epidemiología , Humanos , Incidencia , Cuidados Intraoperatorios/estadística & datos numéricos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Cuidados Preoperatorios/estadística & datos numéricos , Estudios Prospectivos , Proteínas Recombinantes de Fusión/administración & dosificación , Desprendimiento de Retina/epidemiología , Índice de Severidad de la Enfermedad , Aceites de Silicona/administración & dosificación , Aceites de Silicona/uso terapéutico , Agudeza Visual/fisiología , Hemorragia Vítrea/epidemiología
3.
Int J Chron Obstruct Pulmon Dis ; 13: 3107-3114, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30323581

RESUMEN

PURPOSE: Recurrence of acute exacerbations has a major impact on patients with COPD. Therefore, effective prevention and treatment of exacerbation is crucial in the management of COPD, especially for patients with moderate to severe disease. This study evaluated the effectiveness of YuPingFeng granule administration in preventing exacerbation and improving symptom score, as well as its long-term (1 year) safety profile, in patients with COPD. PATIENTS AND METHODS: This was a randomized, double-blind, parallel, placebo-controlled study of 240 patients from eight centers in China. Participants were eligible if they had mild to severe COPD as defined by Global Initiative for Chronic Obstructive Lung Disease, had a history of at least two COPD exacerbations or one hospitalization within the previous year, and had remained clinically stable for over 4 weeks before the study. They were randomly assigned to receive 5 g of YuPingFeng or placebo, three times per day, for 1 year. The primary end point was the exacerbation rate over 1 year, and the analysis was by intention to treat. Secondary end points included symptom score, which was assessed by COPD assessment test (CAT) score and safety profiles. This trial was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn; registration number: ChiCTR-IPR-15007023). RESULTS: The YuPingFeng group had a significantly lower exacerbation rate than the placebo group (1.15 vs 1.55; risk ratio=0.677 [95% CI 0.531-0.863]; P=0.002) and a significantly reduced risk of second exacerbation (95% CI 0.326-0.772; P=0.002). After treatment, the mean change in the CAT score in the YuPingFeng group (-4.41±7.01) differed significantly from that in the placebo group (-2.49±5.31; P=0.001). YuPingFeng was well tolerated. CONCLUSION: YuPingFeng granules can be considered as a treatment option for COPD; this treatment prevents acute exacerbations of COPD and has a good safety profile.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Enfermedad Pulmonar Obstructiva Crónica , Brote de los Síntomas , Anciano , Progresión de la Enfermedad , Método Doble Ciego , Monitoreo de Drogas/métodos , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Manejo de Atención al Paciente/métodos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Fármacos del Sistema Respiratorio/farmacología , Tiempo , Resultado del Tratamiento
4.
Mol Med Rep ; 12(2): 2735-40, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25954855

RESUMEN

Paeoniflorin is one of the active ingredients of the commonly used herbal medicine derived from Paeonia, which exhibits anticancer properties. MicroRNA-16 (miR-16) is upregulated in CD133(-) cells, but downregulated in CD133(+) cells from glioma tissue. Matrix metalloproteinase-9 (MMP-9) expression in glioma tissue samples is significantly higher than that in healthy brain tissue samples. Therefore, miR-16 and MMP-9 expression may be associated with glioma pathogenesis. In the present study, the effects of paeoniflorin on glioma were analyzed. U87 cells were treated with paeoniflorin at 0, 5, 10 and 20 µΜ concentrations. The results suggested that paeoniflorin inhibited U87 cell proliferation and accelerated cell apoptosis. In the present study paeoniflorin treatment increased miR-16 expression and reduced MMP-9 protein expression in U87 cells. Additionally, the results of the present study suggested that miR-16 may regulate MMP-9 expression in miR-16-transfected U87 cells. Furthermore, anti-miR-16 antibodies were used in order to investigate the apoptotic effects of paeoniflorin on U87 cells. The results demonstrated that paeoniflorin inhibits proliferation and induces apoptosis of human glial cells, via miR-16 upregulation and MMP-9 downregulation.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioma/tratamiento farmacológico , Glucósidos/farmacología , Metaloproteinasa 9 de la Matriz/genética , MicroARNs/genética , Monoterpenos/farmacología , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Glioma/genética , Glioma/patología , Glucósidos/química , Humanos , Monoterpenos/química , Paeonia/química , Regulación hacia Arriba/efectos de los fármacos
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