RESUMEN
The aim of this study was to evaluate the efficacy and safety of the combination of docetaxel (TXT) plus tamoxifen (TAM) in advanced non-small-cell lung cancer (NSCLC) patients who had received platinum-based first-line chemotherapy. A total of 120 advanced NSCLC patients pretreated with platinum-based chemotherapy were randomized into two treatment groups (the TXT and TXT+TAM groups) in a 1 : 1 ratio. Reversal of P-glycoprotein (P-gp) expression, tumor response, progression-free survival, overall survival, and safety were evaluated on an intention-to-treat basis. The median number of cycles of allocated chemotherapy was four in each treatment group (range: 2-6 cycles). The overall response rate and disease control rate in the TXT+TAM group were significantly higher than those in the TXT group (36.7 vs. 15.0% for overall response rate, P=0.007; 85.0 vs. 68.3% for disease control rate, P=0.031). The combination of TXT and TAM could effectively reverse P-gp expression in tumor tissues and provide a significant survival benefit for advanced NSCLC patients compared with TXT alone (11.6 vs. 9.1 months, P=0.030). In addition, in the TXT+TAM group, patients achieving P-gp reversal had a significantly greater median progression-free survival and overall survival than nonreversal patients. Furthermore, the combined therapy showed a safety profile comparable to that of TXT. The combination of TXT and TAM may be an effective and safe treatment option for advanced NSCLC patients who have already developed P-gp-mediated multidrug resistance.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Docetaxel , Resistencia a Antineoplásicos , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tamoxifeno/administración & dosificación , Taxoides/administración & dosificaciónRESUMEN
Human osteosarcoma is the most frequent malignant primary bone tumor that mainly occurs in young adults and children. MicroRNAs (miRNAs/miRs) are abnormally expressed in human osteosarcoma and contribute to osteosarcoma initiation and development. The present study aimed to investigate the role of miR-382-5p in the nosogenesis of osteosarcoma and to identify a novel target for osteosarcoma treatment. miR-382-5p expression was detected in human osteosarcoma clinical tissues and cell lines, including 143B, U2OS and MG63, via reverse transcription-quantitative PCR analysis. Multiple bioinformatic prediction toowe used to identify the potential target genes of miR-382-5p and vascular endothelial zinc finger 1 (VEZF1), which were validated via the dual-luciferase reporter assay. MG63 and U2OS cells were transfected with miR-382-5p mimics. The Cell Counting Kit-8 assay was performed to assess cell proliferation, while the Transwell assay was performed to assess migration and invasion. Cell colony formation was measured via crystal violet staining, and apoptosis was assessed via Annexin V/propidium iodide staining. The wound healing assay was performed to assess the migratory ability of U2OS and MG63 cells. Antitumor effects of miR-382-5p were evaluated in nude mice xenografts using U2OS cells. The results demonstrated that miR-382-5p expression was markedly downregulated in human osteosarcoma tissues and cell lines compared with adjacent normal tissues. Transfection of miR-382-5p mimics into MG63 and U2OS cells significantly inhibited the malignant behaviors of cells, including decreased proliferation, migration, diminished colony formation and invasion, and promoted osteosarcoma cell apoptosis. Bioinformatics prediction indicated that VEZF1 is a direct target gene of miR-382-5p. Overexpression of VEZF1 restored osteosarcoma tumor development inhibited by miR-382-5p in vivo. In addition, overexpression of miR-382-5p restrained the growth of xenograft osteosarcoma in nude mice following co-transfection, and overexpression of VEZF1 attenuated the inhibitory effect of miR-382-5p in nude mice. miR-382-5p acted as a tumor suppressor gene and inhibited the malignant biological behaviors of human osteosarcoma cells and functions associated with directly targeting VEZF1. Taken together, these results suggest that the miR-382-5p/VEZF1 interaction has an important role in osteosarcoma development and progression, and thus may be used as a diagnostic and therapeutic target for osteosarcoma.
RESUMEN
The aim of the study was to investigate the effect of three-dimensional conformal radiation therapy (3D-CRT) on nasopharyngeal carcinoma (NPC) and the incidence of complications. Between May 2010 and June 2012, 141 patients diagnosed with local recurrence of NPC due to cranial base lesions or cranial nerve symptoms, confirmed by pathology biopsy and/or by CT/MRI, were included in the present study. In accordance with the principle of randomized control, the patients were divided into three groups and treated with three different doses of 3D-CRT. The planned radiotherapy doses of 3D-CRT were 58/1.8-2 Gy, 62/1.8-2 Gy and 68/1.8-2 Gy, respectively. The survival rate, disease-free survival (DFS) rate and local control rate of the three groups of patients were compared as well as the adverse reactions observed after radiotherapy. The prognoses of NPC patients were analyzed by univariate and multivariate analyses. The follow-up rate of the study was 100%. The 5-year overall survival, DFS, and locoregional recurrence-free survival rates were: 43.2 vs. 64.53 vs. 75%, 29.13 vs. 42.82 vs. 39.7% and 30.76 vs. 44.19 vs. 45.4%, respectively. In addition, 62/1.8-2 Gy was similar in treatment effects to 68/1.8-2 Gy, but 68/1.8-2 Gy showed more adverse reactions than 62/1.8-2 Gy. Thus, 62/1.8-2 Gy can be used as a safe and effective dose for 3D-CRT treatment of NPC. Univariate and multivariate analyses showed that age may be the main prognostic factor of patients with NPC. In conclusion, 3D-CRT with a dose of 62/1.8-2 Gy is a safe, effective and tolerable treatment for NPC patients with good clinical value.