RESUMEN
A 23-year-old woman who had experienced repeated stillbirths, was found to carry an additional segment on the long arm of the X chromosome. Array comparative genomic hybridization (aCGH) confirmed the origin of the 2 duplications (about 17.11 Mb). Thus, her karyotype was 46, X, dup (X) (q13.2-q21.1), dup(X) (q21.32-q22.1). We demonstrate that aCGH is a useful complementary tool to cytogenetic analysis for accurately determining banding. To our knowledge, this is the first case with normal apparently phenotype who inherited 2 duplications on Xq. Notably, after 2 stillbirths, she bore a healthy, normal female infant via natural pregnancy. Thus, a carrier of this karyotype can birth a phenotypically normal child.
Asunto(s)
Duplicación Cromosómica , Cromosomas Humanos X , Hibridación Genómica Comparativa/métodos , Aberraciones Cromosómicas Sexuales , Femenino , Tamización de Portadores Genéticos , Humanos , Masculino , Fenotipo , Mortinato , Adulto JovenRESUMEN
The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 >10 microg/mL), while MCF-7 cells were sensitive to ADM (IC50 <10 microg/mL). A subtoxic concentration of ADM (0.5 microg/mL) combined with 0.1, 1, or 10 microg/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 microg/mL) and ADM (0.5 microg/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8% (TRAIL) or 17% (ADM) to 38.7%, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Doxorrubicina/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Western Blotting , Caspasa 9/análisis , Línea Celular Tumoral , Sinergismo Farmacológico , Citometría de Flujo , Humanos , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína X Asociada a bcl-2/análisisRESUMEN
The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 >10 µg/mL), while MCF-7 cells were sensitive to ADM (IC50 <10 µg/mL). A subtoxic concentration of ADM (0.5 µg/mL) combined with 0.1, 1, or 10 µg/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 µg/mL) and ADM (0.5 µg/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8 percent (TRAIL) or 17 percent (ADM) to 38.7 percent, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.