RESUMEN
The substance P/neurokinin-1 receptor system has been implicated in tumor cell proliferation. Neurokinin-1 receptor has been identified in different solid tumors but not frequently in hematopoietic malignant cells. We investigated the presence of the Neurokinin-1 receptor in acute myeloid leukemia cell lines (KG-1 and HL-60), demonstrating that acute myeloid leukemia cell lines overexpress the truncated Neurokinin-1 receptor isoform compared with lymphocytes from healthy donors. Using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) method, we demonstrated that substance P induced cell proliferation in both acute myeloid leukemia cell lines. We also observed that four different Neurokinin-1 receptor antagonists (L-733,060, L-732,138, CP 96-345 and aprepitant) elicited inhibition of acute myeloid leukemia cell growth lines in a concentration-dependent manner, while growth inhibition was only marginal in lymphocytes; the specific antitumor action of Neurokinin-1 receptor antagonists occurs via the Neurokinin-1 receptor, and leukemia cell death is due to apoptosis. Finally, administration of high doses of daily intraperitoneal fosaprepitant to NOD scid gamma mice previously xenografted with the HL60 cell line increased the median survival from 4 days (control group) to 7 days (treated group) (p = 0.059). Taken together, these findings suggest that Neurokinin-1 receptor antagonists suppress leukemic cell growth and may be considered to be potential antitumor drugs for the treatment of human acute myeloid leukemia.
Asunto(s)
Leucemia Mieloide Aguda/tratamiento farmacológico , Antagonistas del Receptor de Neuroquinina-1/farmacología , Receptores de Neuroquinina-1/química , Animales , Apoptosis , Proliferación Celular , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Receptores de Neuroquinina-1/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Respiratory syncytial virus (RSV) is a potential cause of serious morbidity and even mortality among children undergoing hematopoietic SCT (HSCT). Contrary to the available information regarding the aerosolized formulation of ribavirin, there is a paucity of published studies using i.v. ribavirin in adults, and very few single reports on pediatric patients. Aerosolized drug administration has been limited by potential toxicity and special air-flow requirements. In this regard, i.v. ribavirin could prevent these disadvantages, but its efficacy and safety remain controversial in the pediatric HSCT setting. The present study describes the outcome of six pediatric patients undergoing HSCT with nine episodes of proven RSV. Four episodes corresponded to lower respiratory tract infection (LRTI) and five presented with upper respiratory tract infection (URTI). All LRTI patients showed favorable clinical responses, with 100% survival and no progression to LRTI in the remaining five URTI. No side effects were documented during ribavirin administration. We conclude that ribavirin was well tolerated intravenously, without associated side effects, and was effective in the treatment of RSV in this limited number of pediatric HSCT patients. The role and efficacy of i.v. ribavirin needs to be further clarified by prospective controlled trials in pediatric populations.
Asunto(s)
Antivirales/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Ribavirina/administración & dosificación , Administración Intravenosa , Niño , Preescolar , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Lactante , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/virología , Estudios RetrospectivosRESUMEN
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