RESUMO
BACKGROUND: Single nucleotide polymorphisms (SNPs) in double-strand break repair genes may alter DNA repair capacity and, in turn, confer predisposition to leukemia. We analyzed polymorphic variants of DNA repair and detoxification genes in patients with multiple sclerosis (MS) who developed secondary acute promyelocytic leukemia (sAPL), in most cases after treatment with mitoxantrone (MTZ). METHODS: Using MassARRAY high-throughput DNA analysis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we genotyped patients with sAPL (n=20) developed after treatment of MS (18 out 20 treated with MTZ) for the presence of 210 SNPs of 22 genes mostly involved in DNA repair and drug detoxification. Patients with MS who did not develop sAPL including 41 treated with MTZ (n=253 and 41, respectively) and healthy blood donors (n=310) were also genotyped as controls. RESULTS: We observed risk allele frequency between MS and sAPL for BRCA2 (rs1801406): 6% and 26%, p=0.007; XRCC5 (rs207906): 2.5% and 15%, p=0.016; CYP3A4 (rs2740574): 4.5% and 25%, p=0.0035. The association of homozygous variants of BRCA2 and XRCC5 yielded higher risk of sAPL (MS vs sAPL: 0.4% and 18%, p=0.001). We also observed a significant association between a SNP in the promoter region (rs2740574) of CYP3A4, an enzyme involved in the metabolism of chemotherapeutic agents and development of sAPL. CONCLUSIONS: Increased susceptibility to develop sAPL in patients with MS receiving MTZ may be linked to genetic variants in DNA repair and drug-metabolizing enzymes that result in impaired detoxification of chemotherapy or inefficient repair of drug-induced genetic damage.
Assuntos
Enzimas Reparadoras do DNA/genética , Predisposição Genética para Doença , Leucemia Promielocítica Aguda/genética , Esclerose Múltipla/genética , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Humanos , Leucemia Promielocítica Aguda/induzido quimicamente , Leucemia Promielocítica Aguda/complicações , Masculino , Mitoxantrona/efeitos adversos , Mitoxantrona/uso terapêutico , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Fatores de RiscoAssuntos
Osteossarcoma/diagnóstico , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias Torácicas , Adulto , Humanos , Masculino , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Cintilografia , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias Torácicas/diagnóstico por imagem , Neoplasias Torácicas/patologia , Tomografia Computadorizada por Raios XRESUMO
The treatment of three cases of aneurysmal bone cyst by selective arterial embolism is described. Two cases had involvement of the pelvis and one of the knee. The 2-year follow up has been promising. Radiologically the lesion has been arrested with increased density of the cyst wall and intra-cystic trabecular new bone formation. Pain relief has been complete and up to now no surgical treatment has been required.
Assuntos
Cistos Ósseos/terapia , Embolização Terapêutica , Articulação do Quadril , Articulação do Joelho , Neoplasias Pélvicas/terapia , Adulto , Criança , Feminino , Seguimentos , Humanos , Ílio , Ísquio , Masculino , Ossos Pélvicos , Articulação SacroilíacaAssuntos
Cistos Ósseos/terapia , Embolização Terapêutica/métodos , Ossos Pélvicos , Adulto , Criança , Feminino , Humanos , MasculinoRESUMO
Norepinephrine (NE) concentrations were measured in the olfactory bulbs and olfactory cortex of male albino rats and golden hamsters sacrificed 13-16 days after castration or sham surgery. Castration significantly decreased NE concentrations in the olfactory bulbs of rats but not hamsters. Castration had no significant influence on NE levels in the olfactory cortex of either species. Regional brain weights were not influenced by surgery, and previous olfactory exposure had no significant effect on any variable measured. The decrease in rat olfactory bulb NE levels may be involved in castration-induced changes in preferences for conspecific odors.