ABSTRACT
Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.
Subject(s)
Antineoplastic Agents/pharmacology , Gene Expression Regulation, Neoplastic , Niacinamide/analogs & derivatives , Phenylurea Compounds/pharmacology , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Receptors, Tumor Necrosis Factor, Type I/metabolism , Signal Transduction , Caspase 3/genetics , Caspase 3/metabolism , Caspase 8/genetics , Caspase 8/metabolism , Caspase 9/genetics , Caspase 9/metabolism , Cell Death/drug effects , Cysteine/analogs & derivatives , Cysteine/chemistry , Cysteine/pharmacology , Hep G2 Cells , Humans , Niacinamide/pharmacology , Nitric Oxide/chemistry , Nitric Oxide/pharmacology , Nitric Oxide Donors/chemistry , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , Receptors, Tumor Necrosis Factor, Type I/genetics , S-Nitrosothiols/chemistry , S-Nitrosothiols/pharmacology , SorafenibABSTRACT
Objetivo. Analizar las variables que influyen en los pacientes transfundidosy sometidos a cirugía oncológica.Material y método. Se han revisado y analizado los datos de 44 pacientes intervenidosquirúrgicamente de neoplasia, a los que se les ha practicado transfusiónsanguínea peri operatoria, evaluando: edad, sexo, localización de la lesión,código de diagnostico, tratamiento realizado, hematocrito preoperatorio,hemoglobina preoperatoria y hemoglobina pretransfusional, numero de unidadestransfundidas, estadio TNM, riesgo ASA y tiempo quirúrgico.Resultados. 44 pacientes fueron transfundidos, 32 varones, con una mediade edad de 65 años y con localización lingual en un 36,36%. La cirugía masfrecuente fue la exéresis tumoral asociándose resecciòn ósea y vaciamientocervical en el 56,82% y con reconstrucción simple en el 63% de los casos.La duración media fue 5,7 horas, con un riesgo ASA medio de 3 y con unamedia de 2,9 unidades transfundidas. Un 70% se encontraban en estadio IV.La Hb pretransfusional fue de media 7,71 g/dl. El tiempo quirúrgico, la Hbpreoperatoria y el HTC preoperatorio son las variables que ha resultado estadísticamentesignificativas en el análisis multivariante.Conclusiones. La transfusión sanguínea alogénica presenta una serie de efectosadversos que pueden condicionar la evolución del paciente oncológico,para evitar o disminuir estos efectos deletéreos se debe mantener criteriostransfusionales restrictivos con Hb<8 g/dl, debemos actuar sobre la Hb preoperatoria,como única variable en la que podemos incidir para disminuir elvolumen transfundido y promover programas de ahorro de hemoderivados(AU)
Objective. Analyze the variables that influence bloodtransfusion in patients undergoing surgery for cancer.Material and method. Data from 44 patients who underwentsurgery for neoplasms and required perioperative blood transfusionwas analyzed to evaluate: age, sex, tumor location, diagnostic code,treatment, preoperative hematocrit, preoperative hemoglobin andpretransfusion hemoglobin, number of units transfused, TNM stage,ASA risk, and surgical time.Results. Forty-four patients received transfusions (32 men). Themean age of patients was 65 years and the tumor was lingual in36.36%. The most frequent intervention was tumor exeresis, whichwas associated with bone resection and cervical lymph nodeclearance in 56.82% of cases and with simple reconstruction in 63%of cases. The mean duration of the intervention was 5.7 hours,mean ASA risk was 3, and mean transfusion volume was 2.9 units.Seventy percent of patients had stage IV tumors. Mean hemoglobinconcentration before transfusion was 7.71 g/dl. Surgical time,preoperative hemoglobin concentration, and preoperative hematocritwere statistically significant in multivariate analysis.Conclusions. Allogeneic blood transfusions originate adverse effectsthat can condition the evolution of patients with cancer. Stricttransfusion criteria should be followed (Hb < 8g/dl) to prevent ordiminish these deleterious effects. Preoperative Hb is the only variablethat we can act on to reduce transfusion volume. Blood-sparingprograms should be implemented(AU)
Subject(s)
Humans , Oral Surgical Procedures/methods , Blood Transfusion, Autologous , Mouth Neoplasms/surgery , Blood Transfusion, Autologous/adverse effects , Retrospective Studies , Risk FactorsABSTRACT
No disponible
Subject(s)
Humans , Antibodies, Antiphospholipid , Myocardial Ischemia , Thrombophilia , Blood Cells , HemostasisABSTRACT
The localized Castleman's disease (CD) seemingly has a different clinical behaviour depending on whether the pathologic study is consistent with the plasma cell (PC) or with the hyaline-vascular types. We report here two cases of localized CD with associated analytical changes, although only the PC modality was associated with symptoms. Surgery proved effective, and the systemic picture disappeared in both cases, as well as clinical manifestations in the PC variant.
Subject(s)
Castleman Disease/pathology , Adult , Aged , Castleman Disease/classification , Castleman Disease/surgery , Diagnosis, Differential , Humans , Lymph Node Excision , Lymph Nodes/pathology , Male , Remission InductionABSTRACT
La enfermedad de Castleman localizada posee, al parecer, un diferente comportamiento clínico en función de que su estudio anatomopatológico sea compatible con la modalidad plasmocelular (PC) o con la hialino-vascular. Describimos dos casos de enfermedad de Castleman unicéntrica con alteraciones analíticas acompañantes, si bien sólo la forma PC fue sintomática. El tratamiento quirúrgico fue efectivo, constatándose en ambos la desaparición del cuadro sistémico y de la clínica en la variante PC (AU)
