RESUMO
High-risk neuroblastoma is an aggressive malignancy, with high rates of treatment failure. We evaluated genetic variants associated with in vitro sensitivity to two derivatives of cyclophosphamide for association with clinical response in a separate replication cohort of neuroblastoma patients (n = 2,709). To determine sensitivity, lymphoblastoid cell lines (LCLs) were exposed to increasing concentrations of 4-hydroperoxycyclophosphamide (4HC; n = 422) and phosphoramide mustard (PM; n = 428). Genome-wide association studies were performed to identify single-nucleotide polymorphisms (SNPs) associated with sensitivity to 4HC and PM. SNPs consistently associated with LCL sensitivity were analyzed for associations with event-free survival (EFS) in patients. Two linked SNPs, rs9908694 and rs1453560, were found to be associated with (i) sensitivity to PM in LCLs across populations and (ii) EFS in all patients (P = 0.01) and within the high-risk subset (P = 0.05). Our study highlights the value of cell-based models to identify candidate variants that may predict response to treatment in patients with cancer.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Estudo de Associação Genômica Ampla , Neuroblastoma/genética , Neuroblastoma/patologia , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Criança , Estudos de Coortes , Cicloexilaminas/metabolismo , Ciclofosfamida/análogos & derivados , Ciclofosfamida/metabolismo , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Predisposição Genética para Doença , Variação Genética , Humanos , Neuroblastoma/tratamento farmacológico , Fenótipo , Polimorfismo de Nucleotídeo Único , Controle de Qualidade , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Medição de Risco , Falha de TratamentoRESUMO
Myositis in the hip joint is a rare entity in sportsmen. Repeated trauma or massage can be detrimental. Successful outcome depends upon the recognition of mature, well-organized new bone, and full excision. Best results can be obtained by performing surgery on a biologically sound joint which contains no trace of active or latent inflammation. The joint should be immobilized till the soft tissue trauma has completely healed. Rehabilitation must be in stages.