RESUMEN
Genome-wide association mapping for complex traits in cattle populations is a powerful, but expensive, selection tool. The DNA pooling technique can potentially reduce the cost of genome-wide association studies. However, in DNA pooling design, the additional variance generated by pooling-specific errors must be taken into account. Therefore, this study aimed to investigate factors such as: (i) the accuracy of allele frequency estimation; (ii) the magnitude of errors in pooling construction and in the array; and (iii) the effect of the number of replicate arrays on P-values estimated by a genome-wide association study. Results showed that the Illumina correction method is the most effective method to correct the allele frequency estimation; pooling errors, especially array variance, should be taken into account in DNA pooling design; and the risk of a type I error can be reduced by using at least two replicate arrays. These results indicate the practical capability and cost-effectiveness of pool-based genome-wide association studies using the BovineSNP50 array in a cattle population.
Asunto(s)
Bovinos/genética , ADN/genética , Pool de Genes , Estudio de Asociación del Genoma Completo/economía , Estudio de Asociación del Genoma Completo/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Polimorfismo de Nucleótido Simple/genética , Animales , Análisis Costo-Beneficio , Frecuencia de los GenesRESUMEN
We aim to maintain the registered pemetrexed (PEM) monotherapy regimen from the standpoint of its frequency of use, patient adherence and compliance to treatment its toxicity and efficacy. With the development and expanded indication of PEM for non-small cell lung cancer (NSCLC), we registered the PEM monotherapy regimen for pretreated NSCLC. In order to investigate the validity of this approach, we retrospectively collected and analyzed data on the background, administration status, and toxicity of PEM from medical records of the initial consecutive 21 cases who received PEM monotherapy. Excluding only one case of grade 3 neutropenia (leucopenia), hematological toxicities were not significant. Common non-hematological toxicities were grade 1-2 nausea, fatigue, rash, and liver dysfunction, while grade 3 pneumonitis was observed in one case, and grade 3 hyponatremia was observed in two. Co-medication with non-steroidal anti-inflammatory drugs (NSAIDs) did not increase toxicity. PEM is tolerable for pretreated NSCLC, but continual problems with non-significant common toxicities may arise.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Glutamatos/uso terapéutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Femenino , Glutamatos/efectos adversos , Guanina/efectos adversos , Guanina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pemetrexed , Estudios RetrospectivosRESUMEN
Although amrubicin hydrochloride (AMR) has promising activity against pretreated lung cancer, there are few reports on the adverse events of this agent in a clinical practice setting. We analyzed the adverse events experienced in 27 hospitalized patients who had received AMR monotherapy by collecting data from the pharmaceutical management records. Neutropenia was the main hematological toxicity, and 77.8% of patients developed grade 3/4 neutropenia. Neutrophil counts reached the nadir in 9 to 21 (median 14) days and recovered to normal in 14 to 27 (median 20) days. Seven cases experienced febrile neutropenia without any serious sequelae. Grade 2 or worse non-hematological toxicities were fatigue, constipation, nausea, vomiting, anorexia, and pneumonitis. In comparison with the data of pre-marketing clinical trials, constipation was more commonly observed, while nausea/vomiting was less frequent probably due to appropriate preventive antiemetics. Based on these findings, we have created a novel drug information chart for patients and utilized it in pharmaceutical care in our hospital.