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1.
BMC Cancer ; 17(1): 501, 2017 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-28743242

RESUMEN

BACKGROUND: Base excision repair (BER) pathway is a DNA repair pathway that is important in carcinogenesis and in response to DNA-damaging chemotherapy. XRCC1 is one of important molecular markers for BER. So far, the role of XRCC1 polymorphisms with clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy is inconclusive. To explore the relationship between XRCC1 polymorphisms and platinum-based chemotherapy in advanced NSCLC patients, we performed this meta-analysis. METHODS: Crude odds ratios (ORs), Cox proportional hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were adopted to assess the strength of association between XRCC1 polymorphisms and response rate, Overall survival (OS) and progression free survival (PFS) of advanced NSCLC treated with platinum-based chemotherapy. Q test and I 2 test were used for the assessment of heterogeneity. Subgroup analyses were conducted when heterogeneity exists. Begg's funnel plots and Egger's linear regression test were used to estimate publication bias. Sensitivity analysis was performed to evaluate the stability of the result. RESULTS: A total of 19 studies including 2815 individuals were eligible for the analysis, results showed XRCC1 194Arg allele was negatively associated with the objective response rate relative to 194Trp, and results of homozygous model, dominant model and heterozygous model suggested a gene dosage effect negative correlation between 194Arg allele and objective response rate(ArgArg vs TrpTrp: OR = 0.64(95%CI: 0.44-0.91); ArgArg + TrpArg vs TrpTrp: OR = 0.79(95%CI: 0.57-1.11); TrpArg vs TrpTrp: OR = 1.05(95%CI: 0.73-1.51)). XRCC1 399Gln may indicate favorable overall survival (GlnGln + GlnArg vs ArgArg: HR = 0.65(95%CI: 0.43-0.98)) and favorable PFS (GlnGln vs ArgArg: HR = 0.72(95%CI: 0.48-0.97)) in Asian patients; while in Caucasian patients, XRCC1 399Gln indicated poorer overall survival (GlnGln vs ArgArg: HR = 2.29(95%CI: 1.25-3.33)). CONCLUSIONS: Our results indicated that in NSCLC patients treated with platinum-based regimen, XRCC1 194Arg allele suggest poor objective response rate, the GlnGln genotype of XRCC1 399 suggest poorer overall survival in Caucasian patients, and longer PFS in Asian patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Compuestos de Platino/uso terapéutico , Polimorfismo Genético , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genética , Antineoplásicos/uso terapéutico , Pueblo Asiatico/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Población Blanca/genética
2.
Lab Invest ; 95(9): 1056-70, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26098000

RESUMEN

The miR-19 family (miR-19a and miR-19b-1) are key oncogenic components of the miR-17-92 cluster. Overexpression of miR-19 is strongly associated with cancer invasion and metastasis, and poor prognosis of cancer patients. However, the underlying mechanisms remain largely unknown. In the present study, we found that enforced expression of miR-19 including miR-19a and miR-19b-1 triggered epithelial-mesenchymal transition (EMT) of lung cancer cells A549 and HCC827 as shown by mesenchymal-like morphological conversion, downregulation of epithelial proteins (e.g., E-cadherin, ZO-1 (zona occludens 1), and α-catenin), upregulation of mesenchymal proteins (e.g., vimentin, fibronectin 1, N-cadherin, and snail1), formation of stress fibers, and reduced cell adhesion. In addition, enhanced migration and invasion were observed in the cancer cells A549 and HCC827 undergoing EMT. In contrast, silencing of endogenous miR-19 reversed EMT and reduced the migration and invasion abilities of A549 and HCC827 cells. DNA microarray results revealed significant changes of the expression of genes related to EMT, migration, and metastasis of miR-19-expressing A549 cells. Moreover, siRNA-mediated knockdown of PTEN, a target of miR-19, also resulted in EMT, migration, and invasion of A549 and HCC827 cells, suggesting that PTEN is involved in miR-19-induced EMT, migration and invasion of lung cancer cells. Furthermore, lung cancer cells undergoing EMT induced by miR-19 demonstrated reduced proliferation in vitro and in vivo, and enhanced resistance to apoptosis caused by TNF-α. Taken together, these findings suggest that miR-19 triggers EMT, which has an important role in the invasion and migration of lung cancer cells, accompanied by the reduced proliferation of cells.


Asunto(s)
Transición Epitelial-Mesenquimal/fisiología , Regulación Neoplásica de la Expresión Génica/fisiología , Neoplasias Pulmonares/fisiopatología , MicroARNs/metabolismo , Animales , Antígenos CD/metabolismo , Western Blotting , Cadherinas/metabolismo , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibronectinas/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Luciferasas , Ratones , Ratones Endogámicos BALB C , MicroARNs/farmacología , Análisis de Secuencia por Matrices de Oligonucleótidos , Interferencia de ARN , Factores de Transcripción de la Familia Snail , Sales de Tetrazolio , Tiazoles , Factores de Transcripción/metabolismo , Ensayo de Tumor de Célula Madre , Vimentina/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , alfa Catenina/metabolismo
3.
Cancer Sci ; 100(12): 2396-401, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19737146

RESUMEN

There is currently substantial interest in the identification of human tumor antigens for the diagnosis and immunotherapy of cancer. In our previous study, secretion character and up-regulation of triosephosphate isomerase were observed in lung squamous cell carcinoma, and autoantibodies against triosephosphate isomerase and peroxiredoxin 6 were detected in the sera from over 25% of patients, but in none of the healthy controls. In this study, peroxiredoxin 6 was also found at higher levels in the sera of the patients. Up-regulated triosephosphate isomerase and peroxiredoxin 6 were further validated by enzyme-linked immunosorbent assay in an additional 61 lung squamous cell carcinoma patients, 23 lung adenocarcinoma patients, 56 other types of carcinoma patients, 12 benign lung disease patients, and 59 healthy controls. We found that both triosephosphate isomerase and peroxiredoxin 6 were specifically elevated in lung squamous cell carcinoma sera compared with other groups, with the exception of peroxiredoxin 6 in lung adenocarcinoma patients. Positive correlation between triosephosphate isomerase and distant metastasis was found. At the cut-off point 0.221 (optical density value) on the receiver operating characteristic curve, triosephosphate isomerase could comparatively discriminate lung squamous cell carcinoma from healthy controls with a sensitivity of 65.6%, specificity 84.7%, and total accuracy 75%. For peroxiredoxin 6, at the cut-off point 0.151, it could discriminate the two groups with a sensitivity of 70.5%, specificity 62.7%, and total accuracy 65.8%. With both triosephosphate isomerase and peroxiredoxin 6, discriminant analysis results showed that 68.9% of the lung squamous cell carcinoma and 83.1% of healthy controls were correctly classified. We concluded that triosephosphate isomerase and peroxiredoxin 6 could be markers for lung squamous cell carcinoma.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Neoplasias Pulmonares/sangre , Peroxiredoxina VI/sangre , Triosa-Fosfato Isomerasa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad
4.
Med Oncol ; 27(1): 134-44, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19242827

RESUMEN

The stroma surrounding cancer cell population is increasingly recognized as playing an important role in cancer proliferation, invasion, and metastasis. To identify the stromal proteins involved in nasopharyngeal carcinoma (NPC) carcinogenesis, differences in protein expression of the stroma from NPC and normal nasopharyngeal epithelium tissues (NNET) were assessed using a comparative proteomic approach combined with laser capture microdissection (LCM). LCM was performed to purify stromal cells from NPC and NNET, respectively. Proteins between the pooled microdissected tumor and normal stroma were separated by two-dimensional electrophoresis (2-DE) and differential proteins were identified by mass spectrometry (MS). Sixty differential proteins between normal stroma (NS) and tumor stroma (TS) were identified, and the expression of CapG protein was further confirmed by western blotting and immunohistochemical analysis. Our results will be helpful to study the role of stroma in the NPC carcinogenesis and may provide helpful clues for pathogenesis, early diagnosis, and progression of NPC.


Asunto(s)
Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Neoplasias Nasofaríngeas/química , Neoplasias Nasofaríngeas/patología , Nasofaringe/química , Nasofaringe/citología , Proteoma/análisis , Adulto , Anciano , Secuencia de Aminoácidos , Carcinoma de Células Escamosas/metabolismo , Electroforesis en Gel Bidimensional , Epitelio/química , Epitelio/metabolismo , Femenino , Humanos , Masculino , Espectrometría de Masas , Microdisección , Proteínas de Microfilamentos/análisis , Proteínas de Microfilamentos/biosíntesis , Persona de Mediana Edad , Datos de Secuencia Molecular , Neoplasias Nasofaríngeas/metabolismo , Nasofaringe/metabolismo , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/biosíntesis , Proteínas Nucleares/análisis , Proteínas Nucleares/biosíntesis , Proteoma/biosíntesis , Células del Estroma/química , Células del Estroma/metabolismo
5.
Cancer Lett ; 279(1): 65-73, 2009 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-19231067

RESUMEN

In this study, we aim to screen metastasis-related proteins in human lung squamous carcinoma (LSC) using laser capture microdissection and a proteomic approach. Twenty two differential proteins were identified from pooled microdissected primary LSC and matched lymph node (LN) metastatic tissues. Expression of the differential protein 14-3-3 sigma was determined by Western blotting and immunohistochemistry. In cell invasion assay, down-regulated 14-3-3 sigma by siRNA increased in vitro invasive ability of HTB-182 and A549 cells, up-regulation of 14-3-3 sigma by pcDNA3.0/14-3-3 sigma decreased in vitro invasive ability of HTB-182 and A549 cells. The data suggest that 14-3-3 sigma is a potential LN metastasis-related protein in LSC, and its dysregulation might play an important role in the LN metastatic process of LSC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Exonucleasas/metabolismo , Neoplasias Pulmonares/metabolismo , Ganglios Linfáticos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas 14-3-3 , Anciano , Secuencia de Aminoácidos , Biomarcadores de Tumor/genética , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular , Bases de Datos de Proteínas , Regulación hacia Abajo , Electroforesis en Gel Bidimensional , Exonucleasas/genética , Exorribonucleasas , Humanos , Inmunohistoquímica , Rayos Láser , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Microdisección/instrumentación , Persona de Mediana Edad , Datos de Secuencia Molecular , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Proteómica/métodos , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
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