RESUMO
The 5-year relative survival rate estimate of treated patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is â¼50% since they generally present with tumor progression, relapse, metastasis, and/or chemoresistance. The expression of cytochrome P450 (CYP) enzymes in malignancies can affect the pharmacology of drugs commonly used in chemotherapy or confer susceptibility to development of chemical carcinogenesis; in addition, their specific tumor expression can be used as a therapeutic target. Using qPCR and Western blot assays, the expression of CYP1B1, CYP2E1, CYP3A4, and CYP3A5 were analyzed in a cohort of tumor tissue paired with non-malignant adjacent tissue of patients with NRSTS. The mRNA and protein expression of CYP1B1, CYP2E1, and CYP3A4 were significantly increased in tumor tissue. We propose that the expression of these isoforms is related to carcinogenesis and chemoresistance frequently observed in these neoplasms.
Assuntos
Citocromo P-450 CYP3A , Sarcoma , Carcinogênese , Criança , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP3A/genética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Sarcoma/tratamento farmacológico , Sarcoma/genética , Sarcoma/patologiaRESUMO
BACKGROUND: Intratumoral up-regulation of genes coding for drug transporters and metabolizing enzymes, such as MDR1 and CYP3A4, after chemotherapy are linked to cancer drug resistance. However their expression in primary soft tissue sarcomas (STS) prior to drug treatment and their role in innate resistance remain unclear. OBJECTIVE: The aim of this study was characterize MDR1 and CYP3A4 expression pattern before to chemotherapy and its clinical implication in pediatric STS. METHODS: In this prospective study we analyzed MDR1 and CYP3A4 mRNA expression in both normal and tumor tissues from 28 newly diagnosed STS pediatric and then compared with patients' clinical-pathological data, including chemotherapy response. RESULTS: Our data showed that the expression of the MDR1 gene was significantly higher in malignant tissue than in the normal tissues of patients with STS. In addition, high MDR1 expression was significantly associated with local advances, as well as poor response to treatment. In contrast, CYP3A4 expression level was negligible in both tumoral and non-tumoral tissues. CONCLUSIONS: These results suggest that a significant mRNA level of MDR1 gene was intrinsically present in STS before exposure to chemotherapeutic drugs, suggesting that MDR1 may be important contributors of innate chemoresistance of this tumor type.
Assuntos
Citocromo P-450 CYP3A/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Sarcoma/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adolescente , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , Sarcoma/mortalidade , Sarcoma/patologia , Sarcoma/terapiaRESUMO
Los tumores malignos de ovario son raros en la edad pediátrica y pueden originarse de los componentes del tejido ovárico; el tumor más frecuente es el de células germinales. La variedad de tumores del estroma incluye los tumores de células de la granulosa (teca y los tumores de células de Sertoli-Leydig); este grupo de tumores son raros; sin embargo, son propensos a presentarse con pubertad precoz. Se presentan tres casos clínicos de pacientes que cursaron con manifestaciones clínicas de pubertad precoz y tumoración abdominal. Se estableció un protocolo de estudio para su abordaje y, finalmente, se realizó resección quirúrgica, con evolución satisfactoria.
Malignant ovarian tumors are rare in children. They may originate from components of the ovarian tissue; the germ cell tumor is the most common. The variety of stromal tumors include granulosa cell tumors (theca and Sertoli-Leydig cell tumors); this group of tumors is rare but they are likely to present with precocious puberty. We report three cases of patients with clinical manifestations of an abdominal tumor in association with precocious puberty; we also describe the way they were approached, until final surgical resection. We had excellent results.
RESUMO
El dolor por cáncer es un problema frecuente en nuestro medio, se presenta en 80 a 90 % de los pacientes y en aproximadamente 90 % de ellos se resuelve con medidas relativamente sencillas. No obstante, aproximadamente 40 % de los pacientes se encuentra insatisfecho con el médico o la enfermera respecto al manejo de su dolor. Por tal motivo, se convocó a un grupo de consenso con la finalidad de generar parámetros de práctica clínica fundamentados en la evidencia publicada y en la opinión de los expertos. Este grupo estuvo integrado por 31 médicos líderes de opinión es este campo, quienes con base en 599 documentos emitieron esta serie de recomendaciones, identificadas cada una según su nivel de evidencia.
Cancer pain is a frequent medical problem in our society. This syndrome affects from 80 to 90% of cancer patients and can be solved with relatively simple measures in 90% of the cases. Approximately 40% of cancer patients reported to be unsatisfied with the physician or nurse about their pain management. For these reasons, we gathered a task force in order to generate practice guidelines based on medical evidence and on the opinion of experts in this area. These guidelines were generated by a task force of 31 physicians who were leaders in this field and based on 599 papers selected by a previous literature search. This group evaluated the results of this search in three work sessions, during which a level of evidence was assigned to each recommendation.
