RESUMEN
To elucidate the mechanism of action of HOXA11-AS in modulating the cisplatin resistance of nasopharyngeal carcinoma (NPC) cells. HOXA11-AS and miR-454-3p expression in NPC tissue and cisplatin-resistant NPC cells were measured via quantitative reverse transcriptase polymerase chain reaction. NPC parental cells (C666-1 and HNE1) and cisplatin-resistant cells (C666-1/DDP and HNE1/DDP) were transfected and divided into different groups, after which the MTT method was used to determine the inhibitory concentration 50 (IC50) of cells treated with different concentrations of cisplatin. Additionally, a clone formation assay, flow cytometry and Western blotting were used to detect DDP-induced changes. Thereafter, xenograft mouse models were constructed to verify the in vitro results. Obviously elevated HOXA11-AS and reduced miR-454-3p were found in NPC tissue and cisplatin-resistant NPC cells. Compared to the control cells, cells in the si-HOXA11-AS group showed sharp decreases in cell viability and IC50, and these results were reversed in the miR-454-3p inhibitor group. Furthermore, HOXA11-AS targeted miR-454-3p, which further targeted c-Met. In comparison with cells in the control group, HNE1/DDP and C666-1/DDP cells in the si-HOXA11-AS group demonstrated fewer colonies, with an increase in the apoptotic rate, while the expression levels of c-Met, p-Akt/Akt and p-mTOR/mTOR decreased. Moreover, the si-HOXA11-AS-induced enhancement in sensitivity to cisplatin was abolished by miR-454-3p inhibitor transfection. The in vivo experiment showed that DDP in combination with si-HOXA11-AS treatment could inhibit the growth of xenograft tumors. Silencing HOXA11-AS can inhibit the c-Met/AKT/mTOR pathway by specifically upregulating miR-454-3p, thus promoting cell apoptosis and enhancing the sensitivity of cisplatin-resistant NPC cells to cisplatin.
Asunto(s)
Cisplatino/farmacología , Resistencia a Antineoplásicos , MicroARNs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogénicas c-met/genética , ARN Largo no Codificante/genética , Adulto , Anciano , Animales , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Persona de Mediana Edad , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Trasplante de Neoplasias , Proteínas Proto-Oncogénicas c-met/metabolismoRESUMEN
OBJECTIVE: To study the clinical characteristics, diagnosis, treatment and prognostic factors of patients with postradiation nasopharyngeal necrosis (PRNN) in nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with PRNN were studied retrospectively, 50 males and 10 females, age ranging from 30 - 70 years of (median 51.5 years). All patients were treated with endoscopic debridement and systemic or local anti-inflammatory treatment. Kruskal-Wallis H test was used to assess the interval time between irradiation completion and necrosis onset and related factors of treatment outcome. Multivariate Cox proportional hazards regression survival analysis was performed to analyze risk factors. RESULTS: The latent period between the last irradiation and the onset of the symptom ranged from 1 to 156 months, with a median of 5 months. The median interval time was 7.0 months in 1 course group and 4.5 months in ≥2 courses group (χ2=5.527, P=0.031), and 7.5 months in T2 group and 5.0 months in ≥T3 group (χ2=4.330, P=0.037), respectively. Forty-one patients of them had nasopharyngeal infection, and the difference in curative effect between infection group and non-infection group was significantly (χ2=14.775, P<0.001). Symptoms were alleviated in all patients after endoscopic debridement and systemic or local anti-inflammatory treatment. Follow-up for all patients ranged from 2 to 46 months (median 12.5 months). Seven patients with internal carotid artery exposure died of sudden nasopharyngeal massive bleeding and fifteen patients died of tumor or systemic exhaustion; five cases were lost, and the rest were all in survival. Inter carotid artery erosion was an independent prognostic risk factor according to multivariate Cox proportional hazards regression survival analysis (P<0.05). CONCLUSIONS: Endoscopic debridement is effective in treating irradiation-related nasopharyngeal necrosis. The occurrence of nasopharyngeal necrosis is related to infection, irradiation dose and course, and T stage. Internal carotid artery erosion is a severe situation and also an independent prognostic factor for the patients. The most common causes of death were nasopharyngeal bleeding and systemic exhaustion.
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Neoplasias Nasofaríngeas/patología , Nasofaringe/patología , Adulto , Anciano , Carcinoma , Desbridamiento , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/radioterapia , Necrosis , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: To identify new plasma proteomic markers before radiotherapy start to predict later grade ≥2 radiation-induced lung toxicity (RILT2). METHODS: Fifty-seven patients with non-small cell lung cancer received radiotherapy (RT) were eligible. Forty-eight patients with minimum follow-up of 1 year, nine with RILT2 with tumor stage matched to 39 without RILT2, were enrolled for this analysis. Platelet-poor plasma was obtained within 2 weeks before radiotherapy. The plasma proteomes were compared using a multiplexed quantitative proteomics approach involving ExacTag labeling, reverse-phase high-performance liquid chromatography, and nano liquid chromatography electrospray ionization tandem mass spectrometry. Z scores and Bonferroni-adjusted p values for the two-sample mean comparison were used to identify the differential protein expression between patients with and without RILT2. RESULTS: More than 200 proteins were identified and quantified. After excluding proteins that were not detected in at least 40% of the 48 patient samples, C4b-binding protein alpha chain and vitronectin had significantly higher (p < 0.001 and p = 0.02) expression levels in patients with RILT2 compared with patients without RILT2. These two proteins were validated by Western blot. Ingenuity pathway analysis revealed that they both play important roles in the inflammatory response and are associated with the known pathways of radiation-induced lung damage. CONCLUSIONS: This proteomic approach demonstrates new plasma protein biomarkers before treatment for future studies on RILT2 prediction.
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Carcinoma de Pulmón de Células no Pequeñas/sangre , Neoplasias Pulmonares/sangre , Pulmón/efectos de la radiación , Proteínas/análisis , Proteómica/métodos , Traumatismos por Radiación/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Proteína de Unión al Complemento C4b/análisis , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Traumatismos por Radiación/diagnóstico , Reproducibilidad de los Resultados , Vitronectina/sangreRESUMEN
PURPOSE: To compare the survival of postresection recurrent vs. newly diagnosed non-small-cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. METHODS AND MATERIALS: The study population consisted of 661 consecutive patients with NSCLC registered in the radiation oncology databases at two medical centers in the United States between 1992 and 2004. Of the 661 patients, 54 had postresection recurrent NSCLC and 607 had newly diagnosed NSCLC. Kaplan-Meier and Cox regression models were used for the survival analyses. RESULTS: The distribution of relevant clinical factors between these two groups was similar. The median survival time and 5-year overall survival rates were 19.8 months (95% confidence interval [CI], 13.9-25.7) and 14.8% (95% confidence interval, 5.4-24.2%) vs. 12.2 months (95% CI, 10.8-13.6) and 11.0% (95% CI, 8.5-13.5%) for recurrent vs. newly diagnosed patients, respectively (p = .037). For Stage I-III patients, no significant difference was observed in the 5-year overall survival (p = .297) or progression-free survival (p = .935) between recurrent and newly diagnosed patients. For the 46 patients with Stage I-III recurrent disease, multivariate analysis showed that chemotherapy was a significant prognostic factor for 5-year progression-free survival (hazard ratio, 0.45; 95% CI, 0.224-0.914; p = .027). CONCLUSION: Our institutional data have shown that patients with postresection recurrent NSCLC achieved survival comparable to that of newly diagnosed NSCLC patients when they were both treated with radiotherapy or chemoradiotherapy. These findings suggest that patients with postresection recurrent NSCLC should be treated as aggressively as those with newly diagnosed disease.
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Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Terapia Recuperativa/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Terapia Combinada/métodos , Intervalos de Confianza , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Modelos de Riesgos Proporcionales , Radioterapia Conformacional/métodos , Radioterapia Conformacional/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To evaluate the efficacy and toxicity of recombinant adenovirus p53 agent (SBN-1) combined with radiotherapy in treatment of nasopharyngeal carcinoma. METHODS: Twenty-nine cases with nasopharyngeal carcinoma were randomly divided into two groups: gene therapy + radiotherapy group (GTRT group, n = 16, SBN-1 was injected intratumorally once a week for 8 weeks, and radiotherapy with the dosage of 60-70 Gy was given 3 days after the first injection of SBN-1) and radiotherapy group (RT group, n = 213, the same regimen of radiotherapy was given only). CT and MRI were conducted 4, 8, and 12 weeks after to evaluate the size of tumor. Then the patients were followed-up every month. Toxicity was evaluated by physical examination, KPS scoring, blood, urine, and feces routines, serum BUN, creatine, AST, ALT, LDH, and AKP, electrocardiography, and X-ray. RESULTS: The tumors of the patients group were reduced by 70.9 +/- 18.1% and 49.4 +/- 22.8% in the GTRT group and the RT group respectively (P < 0.001) 4 weeks after treatment; and were reduced by 94.9 +/- 10.2% and 80.4 +/- 17.0% in the GTRT group and RT group respectively (P < 0.001) 8 weeks after treatment. The rates of complete regression of tumor 12 weeks after the treatment were 75% and 15% in the GTRT group and RT group respectively (P < 0.005). 3 cases presented mild, self-limited fever and no other side effects were noted. CONCLUSION: Local injection of SBN-1 combined with radiotherapy to treat nasopharyngeal carcinoma is safe and significantly more effective than single radiotherapy.