RESUMO
Pericardial effusion and cardiac tamponade is a rarely reported complication following stem cell transplant (SCT). The incidence among pediatric SCT recipients is not well defined. To assess the frequency of clinically significant pericardial effusions, we retrospectively examined clinically significant cardiac effusions at our center. Between January of 1993 and August 2004, clinically significant pericardial effusions were identified in nine of 205 patients (4.4%). The median age at the time of transplant was 9 years (range 0.6-18 years) and seven received an allogeneic transplant. All nine had normal cardiac function prior to transplant. The effusion developed at a median of 30 days (range 18-210 days). All allogeneic recipients had acute or clinically extensive graft-versus-host disease (GVHD) at the time the effusion was diagnosed. Seven patients (78%) required pericardiocentesis or surgical creation of a pericardial window. No patient died as a complication of the effusion or the therapeutic procedures. Clinically significant pericardial effusions are more common than previously reported in pediatric SCT recipients. Acute and chronic GVHD is an associated factor.
Assuntos
Tamponamento Cardíaco , Transplante de Células-Tronco Hematopoéticas , Derrame Pericárdico , Adolescente , Tamponamento Cardíaco/epidemiologia , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/mortalidade , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Incidência , Lactente , Masculino , Derrame Pericárdico/epidemiologia , Derrame Pericárdico/etiologia , Derrame Pericárdico/mortalidade , Estudos Retrospectivos , Transplante HomólogoRESUMO
Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients.
Assuntos
Doxorrubicina/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neuroblastoma/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neuroblastoma/metabolismo , Neuroblastoma/patologia , VorinostatRESUMO
An association between oxcarbazepine therapy and hepatic adenoma (HA) has been documented in animal models but not observed in humans. The authors report a case of a 16-year-old girl on oxcarbazepine therapy for seizure disorder who presented with a giant HA. Pathology of the HA was notable for marked periductal fibrosis and glycoprotein inclusions in the nontumor liver. The patient was not on oral contraceptives and has no other known risk factors for HA.