RESUMEN
HPV 16 E6 upregulates hTERT expression in lung cancer cells. However, the underlying molecular mechanism is unclear. In this paper, E6, LKB1, SP1, and hTERT mRNA expression levels were detected in brushing cells of patients with lung cancer (n = 106) and with benign lung disease (n = 68) by qRT-PCR. The mRNA expression levels of E6, SP1, and hTERT were significantly increased in the malignant group compared with the benign group (P < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group (P < 0.01). Furthermore, the correlation between E6, Sp1, hTERT, and LKB1 was performed, our results indicated that E6, Sp1, and hTERT with positive, but LKB1 with negative correlation (P < 0.01). To investigate the potential relationship between these genes, using double directional genetic manipulation, we showed that overexpression of E6 in H1299 cells down-regulated LKB1 mRNA and protein expression but up-regulated SP1 and hTERT as well as the transcriptional activity of Sp1. In contrast, knockdown of E6 in A549 cells by short-interference RNAs (siRNAs) up-regulated LKB1 expression, but down-regulated SP1 and hTERT expression as well as Sp1 activity. LKB1 loss upregulated both SP1 and hTERT at the protein and mRNA level as well as SP1 activity. To verify that the role of E6 on hTERT was mediated by SP1, siRNA knockdown of SP1 was performed on both H1299 and A549 cell lines. Inhibition of SP1 downregulated hTERT expression. Our results indicate that HPV16 E6 indirectly upregulated the expression of hTERT by inhibition of LBK1 expression and upregulation of Sp1 expression, thus suggesting a HPV-LKB1-SP1-hTERT axis for the tumorigenesis of lung cancer. Our study also provides new evidence to support the critical role of SP1 and LKB1 in the pathogenesis of HPV-related lung cancer, and suggests novel therapeutic targets.
Asunto(s)
Neoplasias Pulmonares/metabolismo , Proteínas Oncogénicas Virales/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Represoras/metabolismo , Telomerasa/metabolismo , Factor de Transcripción AP-1/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Adulto , Anciano , Línea Celular Tumoral , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genes Reporteros , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/genética , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Proteínas Represoras/genética , Telomerasa/genética , Factor de Transcripción AP-1/genéticaRESUMEN
BACKGROUND: Foreign bodies within the sinuses, orbit, and skull base (FBSOS) are rare; hence, diagnosis and management guidelines are lacking. Endoscopic sinus surgery (ESS) removal is preferred because of the less invasiveness and minimal morbidity. This study was designed to summarize clinical experience with ESS management of FBSOS. METHODS: We retrospectively reviewed clinical manifestations, imaging findings, treatment, and outcomes in consecutive patients with ESS removal of FBSOS between 2004 and 2015 at a tertiary academic medical center. The Chi-square test was performed to compare the infection rate between wooden and nonwooden FBSOS. RESULTS: There were 23 male and five female patients, with median age of 11 years. FBSOS were located within the sinuses (86%), orbit (75%), and skull base/intracranial region (46%). Wooden FBSOS had a significantly higher risk of infection (78%) compared with nonwooden FBSOS (5%, P < 0.05). Contrast-enhanced computed tomography (CT) plus three-dimensional reconstruction was sensitive in all cases. Twenty-seven (96%) FBSOS were removed by ESS alone, while 1 (4%) FBSOS was removed using the combined ESS and lateral cervical approach. Four of the nine intracranial penetrating FBSOS patients had intraoperative cerebrospinal fluid (CSF) leak and received endoscopic CSF leak repair. Twelve (43%) patients suffered complications (meningitis, diplopia, and vision loss). CONCLUSIONS: ESS is a minimally invasive, safe, and promising surgical approach for FBSOS removal. Contrast-enhanced CT is effective in preoperative diagnosis and intraoperative guidance. Wooden FBSOS had higher risk of infection, thus antibiotics are recommended.
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Cuerpos Extraños/cirugía , Órbita/cirugía , Base del Cráneo/cirugía , Adolescente , Adulto , Preescolar , Endoscopios , Femenino , Humanos , Masculino , Estudios RetrospectivosAsunto(s)
Asma , Pólipos Nasales , Enfermedad Crónica , Endoscopía , Humanos , Pronóstico , Rinitis , SinusitisRESUMEN
BACKGROUND: Functional endoscopic sinus surgery (FESS) is considered to be the standard procedure for chronic rhinosinusitis with nasal polyps (CRSwNP). However, for CRSwNP that accompanies asthma, the results are not satisfying. Extensive endoscopic sinus surgery (EESS) aimed at reducing the inflammatory load has been indicated as a viable option for refractory chronic rhinosinusitis. OBJECTIVE: To evaluate the clinical outcomes and safety of EESS (middle turbinate and superior turbinate resection and total ethmoidectomy) for patients with CRSwNP and with asthma. METHODS: This was a prospective, single-institute cohort study conducted in a tertiary teaching hospital. Patients with CRSwNP and with asthma who were proceeding to surgery were enrolled. There were 23 patients in the EESS group and 24 patients in the FESS group. The preoperative disease severity was evaluated by the visual analog scale (VAS), Lund-Kennedy (L-K) endoscopy score, computed tomography Lund-Mackay score, asthma control test (ACT), and pulmonary function test. Clinical outcomes were comparatively evaluated between the two groups after a 1-year follow-up by using the VAS score, the postoperative endoscopic score (E score), L-K score, ACT score, and pulmonary function test. RESULTS: The disease severity (general VAS score, endoscopic L-K score, computed tomography score, ACT score) showed no significant differences between the two groups before surgery (p > 0.05). One year after surgery, both groups achieved significant improvement in the VAS score and endoscopic L-K score. The EESS group showed better improvement in the olfactory VAS score and E score compared with the FESS group (mean [standard deviation] change of olfactory VAS, 6.00 ± 3.67 versus 3.30 ± 3.44, p = 0.015; mean [standard deviation] E score, 0.31 ± 0.18 versus 0.66 ± 0.26, p < 0.001). No significant differences were found in the change of general nasal symptom VAS score, other individual VAS scores (nasal congestion, discharge, headache and/or facial pain), L-K score, ACT score, and pulmonary function between the two groups (p > 0.05). CONCLUSION: EESS for patients with CRSwNP and with asthma may help to improve the subjective olfaction and endoscopic appearance.
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Asma/cirugía , Pólipos Nasales/cirugía , Rinitis/cirugía , Rinoplastia , Sinusitis/cirugía , Cornetes Nasales/cirugía , Adulto , Anciano , Asma/complicaciones , Enfermedad Crónica , Estudios de Cohortes , Endoscopía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/complicaciones , Estudios Prospectivos , Pruebas de Función Respiratoria , Rinitis/complicaciones , Sinusitis/complicaciones , Olfato , Tomografía Computarizada por Rayos X , Cornetes Nasales/diagnóstico por imagenRESUMEN
Chronic inflammation and degradation of elastin are the main processes in the development of abdominal aortic aneurysm (AAA). Recent studies show that zinc has an anti-inflammatory effect. Based on these, zinc may render effective therapy for the treatment of the AAA. Currently, we want to investigate the effects of zinc on AAA progression and its related molecular mechanism. Rat AAA models were induced by periaortic application of CaCl2. AAA rats were treated by daily intraperitoneal injection of ZnSO4 or vehicle alone. The aorta segments were collected at 4 weeks after surgery. The primary rat aortic vascular smooth muscle cells (VSMCs) were stimulated with TNF-α alone or with ZnSO4 for 3 weeks. The results showed that zinc supplementation significantly suppressed the CaCl2-induced expansion of the abdominal aortic diameter, as well as a preservation of medial elastin fibers in the aortas. Zinc supplementation also obviously attenuated infiltration of the macrophages and lymphocytes in the aortas. In addition, zinc reduced MMP-2 and MMP-9 production in the aortas. Most importantly, zinc treatment significantly induced A20 expression, along with inhibition of the NF-κB canonical signaling pathway in vitro in VSMCs and in vivo in rat AAA. This study demonstrated, for the first time, that zinc supplementation could prevent the development of rat experimental AAA by induction of A20-mediated inhibition of the NF-κB canonical signaling pathway.
Asunto(s)
Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/prevención & control , Proteínas de Unión al ADN/metabolismo , FN-kappa B/metabolismo , Sulfato de Zinc/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Aorta Abdominal/efectos de los fármacos , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/etiología , Células Cultivadas , Modelos Animales de Enfermedad , Elastina/metabolismo , Quinasa I-kappa B/metabolismo , Proteínas I-kappa B/metabolismo , Inflamación/metabolismo , Inflamación/prevención & control , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Inhibidor NF-kappaB alfa , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfaRESUMEN
High-risk human papillomavirus (HPV) infection may play an important role in non-small cell lung carcinoma (NSCLC) development. However, some recent studies have proved that it was not directly associated with lung cancer. The aim of this study was to evaluate the underlying molecular mechanism that HPV16 regulate the expression of GLUT1 and may promote the development of lung cancer. HPV16, HIF-1α, and GLUT1 were detected in pleural effusions of patients with lung cancer (n = 95) and with benign lung disease (n = 55) by immunocytochemistry. Western blotting and qRT-PCR were used to detect the expression chances of HPV16 E6/E7, HIF-1α, and GLUT1 in lung cancer cells. HPV16, HIF-1α, and GLUT1 were significantly more likely to be expressed in the malignant group than in the benign group as detected by immunocytochemistry (ICC), and HIF-1α was significantly correlated with HPV16 or GLUT1 in the malignant group (P < 0.01). Expression changes of E6 and E7 significantly promoted the protein expression of HIF-1α, the expression of both protein and mRNA of GLUT1, but had no effect on the expression of HIF-1α mRNA in lung cancer cells. After inhibition of HIF-1α, it obviously downregulated the expression of both protein and mRNA of GLUT1 in lung cancer cells. E6 and E7 regulated the expression of GLUT1 may be due to the mediation of HIF-1α in lung cancer cells. These results suggest that both E6 and E7 play the important role in the regulation of Warburg effect and may be a valuable therapeutic target for HPV-related cancer.
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Adenocarcinoma/genética , Transportador de Glucosa de Tipo 1/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Neoplasias Pulmonares/genética , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/genética , Proteínas Represoras/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/virología , Adulto , Anciano , Estudios de Casos y Controles , Línea Celular Tumoral , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Regulación Viral de la Expresión Génica , Transportador de Glucosa de Tipo 1/metabolismo , Papillomavirus Humano 16/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/virología , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/virología , Proteínas Represoras/metabolismo , Activación Transcripcional , Regulación hacia ArribaRESUMEN
DJ-1, a novel mitogen-dependent oncogene, has an important role in the progression of human malignancies, whereas tumor suppressor phosphatase and tensin homolog (PTEN) is known to control a variety of processes associated with cell survival, proliferation and invasion. DJ-1 overexpression was reported to be negatively correlated with PTEN expression in tumor tissues of patients with laryngeal squamous cell carcinoma (LSCC). In the present study, the effect of DJ-1 on PTEN in laryngeal cancer cells was investigated by transfecting DJ-1-specific small interfering (si)RNA into Hep-2 and SNU-899 cells. Cell survival and cell proliferative and invasive capacity were then evaluated. The results showed that siRNA targeting of DJ-1 effectively upregulated PTEN expression, resulting in enhanced cell death as well as decreased proliferation and invasion of Hep-2 and SNU-899 cells. The results of the present study indicated, for the first time, to the best of our knowledge, that DJ-1-induced PTEN downregulation is associated with proliferative and invasive activity of laryngeal cancer cells. The DJ-1 gene may have an important role in the tumorigenesis of LSCC.
Asunto(s)
Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Laríngeas/genética , Invasividad Neoplásica/genética , Proteínas Oncogénicas/genética , Fosfohidrolasa PTEN/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular , Regulación hacia Abajo , Humanos , Neoplasias Laríngeas/patología , Laringe/metabolismo , Laringe/patología , Invasividad Neoplásica/patología , Proteína Desglicasa DJ-1 , Interferencia de ARN , ARN Interferente Pequeño/genéticaRESUMEN
BACKGROUND: Bleeding during functional endoscopic sinus surgery is a challenge for the quality of the surgical field for surgeons. This study aimed to evaluate the effect of desmopressin premedication on blood loss and the quality of the surgical field in endoscopic sinus surgery. METHODS: A total of 90 American Society of Anesthesiologists physical status I-II patients underwent endoscopic sinus surgery for chronic sinusitis. They were randomly allocated to receive either desmopressin 0.3 µg/kg or saline before the operation. Management of anesthesia was achieved with propofol and remifentanil infusions, with moderate, controlled hypotension. Blood loss and quality of the surgical field were assessed after surgery. Effects of desmopressin on anesthetic requirements and hemodynamic variables were analyzed. RESULTS: Blood loss was significantly less in the desmopressin group (mean ± SD, 42 ± 8.7 ml) than in the control group (70 ± 9.2 ml, P < 0.001). Surgeons were more satisfied with the surgical field in the desmopressin group than in the control group (median score, 4 [3-5] vs. 7 [6-9], P < 0.001). Requirements for remifentanil and esmolol were lower in the desmopressin group than in the control group. CONCLUSIONS: Premedication with desmopressin 0.3 µg/kg can effectively reduce bleeding during endoscopic sinus surgery.
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Pérdida de Sangre Quirúrgica/prevención & control , Desamino Arginina Vasopresina/farmacología , Endoscopía/métodos , Sinusitis/cirugía , Adulto , Desamino Arginina Vasopresina/administración & dosificación , Femenino , Hemostáticos/administración & dosificación , Hemostáticos/farmacología , Humanos , Masculino , Persona de Mediana Edad , Piperidinas/administración & dosificación , Propofol/administración & dosificación , Estudios Prospectivos , Remifentanilo , Método Simple Ciego , Adulto JovenRESUMEN
MicroRNA (miR)-9 has been demonstrated to regulate the radiosensitivity of tumor cells. In the present study, the mechanism by which miR-9 modulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to ultraviolet (UV) radiation was investigated. The results demonstrated that exposure of NPC cells to UV light resulted in a significant increase in the expression of miR-9, and that CNE2 cells overexpressing miR-9 exhibited reduced levels of DNA damage and increased levels of total glutathione upon UV exposure. Accordingly, the inhibition of the expression of miR-9 promoted UV-induced DNA damage and apoptosis. Although miR-9 inhibited the expression of E-cadherin in the CNE2 cells and increased their resistance to UV radiation, the use of small interfering RNA to inhibit the expression of E-cadherin was not sufficient to decrease the radiosensitivity of the NPC cells. These data demonstrated that miR-9 did not modulate the sensitivity of the CNE2 cells to UV radiation through E-cadherin, but suggested that miR-9 regulated radiosensitivity through its effects on glutathione. These findings suggest that miR-9 may be a potential target for modulating the radiosensitivity of NPC cells.
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Células Epiteliales/efectos de la radiación , Regulación Neoplásica de la Expresión Génica , Glutatión/metabolismo , MicroARNs/genética , Tolerancia a Radiación/genética , Apoptosis , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Daño del ADN , Células Epiteliales/metabolismo , Células Epiteliales/patología , Glutatión/agonistas , Glutatión/antagonistas & inhibidores , Humanos , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Nasofaringe/metabolismo , Nasofaringe/patología , Nasofaringe/efectos de la radiación , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Rayos UltravioletaRESUMEN
CD4+ regulatory T cells (Tregs) mediate immune tolerance in laryngeal squamous cell carcinoma (LSCC). However, Tregs are functionally heterogeneous. Recently, we reported that three distinct Treg subsets (resting Tregs, activated Tregs and cytokine-secreting CD45RA-Foxp3lowCD4+ T cells) vary in the peripheral circulation of patients with head and neck squamous cell carcinoma (HNSCC); however, the potential implication of these Treg subsets in LSCC immunity is unclear. Here, we report that activated Tregs and cytokinesecreting CD45RA-Foxp3lowCD4+ T cells were increased in LSCC patients compared with healthy donors (HD) (p<0.001, p<0.001), whereas resting Tregs were decreased (p<0.001). Activated Tregs inhibited the proliferation of CD4+CD25- T cells (p<0.001) and secreted lower levels of interleukin-2 (p<0.001), interferon-γ (p<0.001) and tumor necrosis factor-α (p<0.001) compared with the cytokine-secreting CD45RA-Foxp3lowCD4+ T cells. Importantly, activated Treg prevalence was correlated with tumor stage (p=0.001) and nodal status (p=0.007). The prevalence of naïve CD4+ (p<0.001), naïve CD8+ (p=0.002), and Th1 T-cell subsets (p<0.001, p<0.001) was decreased in the LSCC patients. In conclusion, our findings showed that activated Tregs with suppressive activity are a distinct subset of Tregs in LSCC, and correlate with disease progression. Several immune system abnormalities in LSCC patients are represented by expansion of functionally activated Tregs, both in the circulation and tumor microenvironment along with decreased frequencies of naïve T-cell populations and Th1-cell populations.
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Neoplasias Laríngeas/inmunología , Neoplasias de Células Escamosas/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Neoplasias Laríngeas/patología , Antígenos Comunes de Leucocito/metabolismo , Subgrupos Linfocitarios/inmunología , Masculino , Persona de Mediana Edad , Neoplasias de Células Escamosas/patología , Valores de Referencia , Linfocitos T Reguladores/metabolismo , Células TH1/inmunologíaRESUMEN
AIM: To explore the efficacy of PCI-24781, a broad-spectrum, hydroxamic acid-derived histone deacetylase inhibitor, in the treatment of gastric cancer (GC). METHODS: With or without treatment of PCI-24781 and/or cis-diamminedichloroplatinum (CDDP), GC cell lines were subjected to functional analysis, including cell growth, apoptosis and clonogenic assays. Chromatin immunoprecipitation and luciferase reporter assays were used to determine the interacting molecules and the activity of the enzyme. An in vivo study was carried out in GC xenograft mice. Cell culture-based assays were represented as mean ± SD. ANOVA tests were used to assess differences across groups. All pairwise comparisons between tumor weights among treatment groups were made using the Tukey-Kramer method for multiple comparison adjustment to control experimental-wise typeâ Iâ error rates. Significance was set at P < 0.05. RESULTS: PCI-24781 significantly reduced the growth of the GC cells, enhanced cell apoptosis and suppressed clonogenicity, and these effects synergized with the effects of CDDP. PCI-24781 modulated the cell cycle and significantly reduced the expression of RAD51, which is related to homologous recombination. Depletion of RAD51 augmented the biological functions of PCI-24781, CDDP and the combination treatment, whereas overexpressing RAD51 had the opposite effects. Increased binding of the transcription suppressor E2F4 on the RAD51 promoter appeared to play a major role in these processes. Furthermore, significant suppression of tumor growth and weight in vivo was obtained following PCI-24781 treatment, which synergized with the anticancer effect of CDDP. CONCLUSION: These data suggest that RAD51 potentiates the synergistic effects of chemotherapy with PCI-24781 and CDDP on GC.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Recombinasa Rad51/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Benzofuranos/administración & dosificación , Sitios de Unión , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Factor de Transcripción E2F4/metabolismo , Femenino , Inhibidores de Histona Desacetilasas/administración & dosificación , Humanos , Ácidos Hidroxámicos/administración & dosificación , Ratones SCID , Regiones Promotoras Genéticas , Recombinasa Rad51/genética , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Factores de Tiempo , Transfección , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. The present treatment including surgery, chemotherapy and radiation, which have only 40% long-term cure rates, and usually cause tumor recurrence. Thus, looking for new effective and less toxic therapies has important significance. XAV939 is a small molecule inhibitor of tankyrase 1(TNKS1). The objective of this study is to investigate the effect of XAV939 on the proliferation and apoptosis of NB cell lines, and the related mechanism. METHODS: In the present study, we used both XAV939 treatment and RNAi method to demonstrate that TNKS1 inhibition may be a potential mechanism to cure NB. MTT method was used for determining the cell viability and the appropriate concerntration for follow-up assays. The colony formation assay, Annexin V staining and cell cycle analysis were used for detecting colony forming ability, cell apoptosis and the percentage of different cell cycle. The Western blot was used for detecting the expression of key proteins of Wnt/ beta-catenin (Wnt/ß-catenin) signaling pathway. RESULTS: The results showed that TNKS1 inhibition decreased the viability of SH-SY5Y, SK-N-SH and IMR-32 cells, induced apoptosis in SH-SY5Y as well as SK-N-SH cells, and led to the accumulation of NB cells in the S and G2/M phase of the cell cycle. Moreover, we demonstrated TNKS1 inhibition may in part blocked Wnt/ß-catenin signaling and reduced the expression of anti-apoptosis protein. Finally, we also demonstrated that TNKS1 inhibition decreased colony formation in vitro. CONCLUSIONS: These findings suggested that TNKS1 may be a potential molecule target for the treatment of NB.
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Inhibidores Enzimáticos/farmacología , Compuestos Heterocíclicos con 3 Anillos/farmacología , Neuroblastoma/tratamiento farmacológico , Vía de Señalización Wnt/efectos de los fármacos , Apoptosis/efectos de los fármacos , División Celular/efectos de los fármacos , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Fase G2/efectos de los fármacos , Humanos , Neuroblastoma/enzimología , Neuroblastoma/patología , Tanquirasas/antagonistas & inhibidores , Tanquirasas/metabolismoRESUMEN
OBJECTIVE: To investigate the effects of down-regulated miR-9 expression on ultraviolet rays (UV)-induced reactive oxygen species (ROS) damage in nasopharyngeal carcinoma (NPC) cells. METHODS: The NPC cells were transfected with inhibitors of miR-9 by lipofectamine to decrease the expression of miR-9, and the cells transfected with inhibitor control as the control. ROS levels following UV exposure were examined with DCF-DA method and the concentration of glutathione was analyzed via the benzoic acid method; DNA damage and apoptosis also were evaluated. RESULTS: There was significant difference in ROS levels between miR-9 expression-inhibited cells and control cells (26 895 ± 218 vs 15 765 ± 927, t = 39.754, P < 0.001), and also there were significant differences in DNA damage rates (28.0% ± 10.0% vs 23.6% ± 9.2%) and in apoptosis rates (8.0% ± 0.9% vs 4.5% ± 0.8%) following UV exposure between two groups of cells. The miR-9 expression-inhibited cells showed lower level (1.87 ± 0.15) µmol/L of glutathione compared with the control cells (9.85 ± 0.15) µmol/L (t = -48.832, P < 0.001). CONCLUSION: Inhibition of miR-9 expression promoted UV-induced ROS damage in nasopharyngeal carcinoma cells.
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MicroARNs/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Carcinoma , Línea Celular Tumoral , Daño del ADN , Humanos , Carcinoma Nasofaríngeo , TransfecciónRESUMEN
AIM: To investigate the effects of the PPAR-γ agonist rosiglitazone on acute lung injury induced by the herbicide paraquat (PQ) and the underlying mechanisms of action. METHODS: Male Sprague-Dawley rats were injected with PQ (20 mg/kg, ip). Rosiglitazone (3 or 10 mg/kg, ip) was administered 1 h before PQ exposure. Peripheral blood was collected at 4, 8, 24 and 72 h after PQ exposure for measuring the levels of MDA, TNF-α and IL-1ß, and the SOD activity. Lung tissues were collected at 72 h after PQ exposure to determine the wet-to-dry (W/D) ratios and lung injury scores, as well as the protein levels of NF-κBp65, PPAR-γ, Nrf2, IκBα and pIκBα. RESULTS: At 72 h after PQ exposure, the untreated rats showed a 100% cumulative mortality, whereas no death was observed in rosiglitazone-pretreated rats. Moreover, rosiglitazone pretreatment dose-dependently attenuated PQ-induced lung edema and lung histopathological changes. The pretreatment significantly reduced the levels of TNF-α, IL-1ß and MDA, increased SOD activity in the peripheral blood of PQ-treated rats. The pretreatment also efficiently activated PPAR-γ, induced Nrf2 expression and inhibited NF-κB activation in the lung tissues of PQ-treated rats. Furthermore, the pretreatment dose-dependently inhibited IκB-α degradation and phosphorylation, thus inhibiting NF-κB activation. CONCLUSION: Pretreatment with rosiglitazone protects rats against PQ-induced acute lung injury by activating PPAR-γ, inducing Nrf2 expression and inhibiting NF-κB activation.
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Lesión Pulmonar Aguda/prevención & control , PPAR gamma/agonistas , Paraquat/toxicidad , Tiazolidinedionas/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/fisiopatología , Animales , Relación Dosis-Respuesta a Droga , Herbicidas/toxicidad , Interleucina-1beta/sangre , Masculino , Malondialdehído/sangre , Factor 2 Relacionado con NF-E2/genética , FN-kappa B/metabolismo , Edema Pulmonar/fisiopatología , Edema Pulmonar/prevención & control , Ratas , Ratas Sprague-Dawley , Rosiglitazona , Superóxido Dismutasa/metabolismo , Tiazolidinedionas/administración & dosificación , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Cancer stem cells are regarded as the cause of tumour formation and recurrence in nasopharyngeal carcinoma (NPC). However, ideal surface markers for stem cells in NPC remain unidentified. In the present study, we investigated the expression of CD133, Nanog and Sox2 in the nasopharyngeal carcinoma cell line CNE2 and primarily cultured NPC cells using immunofluorescence or flow cytometry. A cell population with a CD133(+) phenotype was enriched using magnetic-activated cell sorting technology. We demonstrated that CD133(+) cells exhibited a strong potential for self-renewal, proliferation and differentiation and a greater potential for in vivo tumour formation in nude mice compared to CD133(-) cells, although the percentage of CD133(+) cells was small. However, the specific marker antigens Nanog and Sox2 were simultaneously expressed in normal cancer stem cells. Our results showed that CD133 can serve as a specific surface marker for nasopharyngeal cancer stem cells.
Asunto(s)
Antígenos CD/metabolismo , Glicoproteínas/metabolismo , Proteínas de Homeodominio/biosíntesis , Neoplasias Nasofaríngeas/metabolismo , Péptidos/metabolismo , Factores de Transcripción SOXB1/biosíntesis , Antígeno AC133 , Animales , Antígenos CD/genética , Biomarcadores de Tumor/análisis , Carcinoma , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , Glicoproteínas/genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Proteína Homeótica Nanog , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Células Madre Neoplásicas/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/biosíntesis , Péptidos/genéticaRESUMEN
BACKGROUND: DJ-1 can induce the tumor cell proliferation and invasion via down-regulating PTEN in many malignant tumors, and correlated to prognostic significance. However, the tumorigenesis role and clinical significance of DJ-1 in supraglottic squamous cell carcinoma (SSCC) is unclear. We aimed to evaluate the DJ-1 the relationship between DJ-1 and clinicopathological data including patient survival. METHODS: The expression of DJ-1 and PTEN in SSCCs (52) and adjacent non-cancerous tissues (42) was assessed by immunohistochemistry (IHC), and the relationship between DJ-1 and clinicopathological data was analyzed. RESULTS: DJ-1 was detected mainly in SSCCs (88.5%) and less frequently in adjacent non-cancerous tissues (21.0%). PTEN expression was detected in 46.2% of SSCCs and in 90.5% of adjacent non-cancerous tissues. DJ-1 expression was linked to nodal status (P = 0.009), a highly significant association of DJ-1 expression with shortened patient overall survival (5-year survival rate 88.0% versus 53.9%; P = 0.007; log rank test) was demonstrated. CONCLUSIONS: Our data suggested that DJ-1 over-expression was linked to nodal status, and might be an independent prognostic marker for patients with SSCC.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Laríngeas , Proteínas Oncogénicas , Fosfohidrolasa PTEN , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Transformación Celular Neoplásica , Femenino , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Pronóstico , Proteína Desglicasa DJ-1 , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Recent studies have suggested that c-Jun N-terminal kinase (JNK) plays an important role in the formation of abdominal aortic aneurysms, and that direct blockade of JNK by specific inhibitors can effectively prevent the progression of aortic aneurysms. A study has demonstrated that curcumin can suppress the development of experimental abdominal aortic aneurysms by inhibiting inflammation. We sought to investigate whether curcumin could inhibit JNK pathways and apoptosis in thoracic aortic aneurysms. METHODS: We used a rat model of a CaCl2-induced thoracic aortic aneurysm followed by daily oral gavage with curcumin 100 mg/kg or vehicle alone. After treatment for 4 wk, tissue specimens were obtained for histologic assessments, and tissue composition was evaluated using immunohistochemistry, western blotting, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. RESULTS: Curcumin significantly suppressed the CaCl2-induced expansion of the thoracic aortic diameter and the structural preservation of medial elastin fibers. Most importantly, curcumin treatment significantly inhibited the phosphorylation of JNK and c-Jun, accompanied by less cell apoptosis in thoracic aortic aneurysm tissues. Furthermore, the expression levels of caspase-3 and the Bax/Bcl-2 ratio were significantly decreased in the aortic walls of curcumin-treated rats. CONCLUSION: The present study indicates that the beneficial effect of curcumin on degenerative aortic aneurysms is related to the inhibition of JNK and apoptosis in the walls of thoracic aortic aneurysms.
Asunto(s)
Aneurisma de la Aorta Torácica/prevención & control , Apoptosis/efectos de los fármacos , Curcuma/química , Curcumina/uso terapéutico , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Fitoterapia , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Aorta Torácica/patología , Aneurisma de la Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/patología , Cloruro de Calcio , Caspasa 3/metabolismo , Curcumina/farmacología , Modelos Animales de Enfermedad , Masculino , Fosforilación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Wistar , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE: To detect the expression of DJ-1 in laryngeal squamous cell carcinoma (LSCC) and to study the relationship between DJ-1 expression and clinical indexes of LSCC. METHODS: The expressions of DJ-1 protein in 71 LSCC samples and 9 cases control samples from laryngeal mucosa tissues of non-LSCC patients were detected using streptavidin peroxidase immunohistochemistry staining and the relationships between DJ-1 protein expression and clinicopathologic characteristics were analyzed. RESULTS: (1) The positive expression rate of DJ-1 protein in LSCC was 85.9%(61/71), which was significantly higher than the rate (55.5%, 5/9) in control laryngeal mucosa tissues (P < 0.05). (2) DJ-1 expression was related to tumor recurrence (P < 0.05), but not to sex, age, primary cancer position, T stage, clinical stage, lymph node metastasis and tumor differentiation. Tumor recurrence rate (53.3%) in the patients with higher expression of DJ-1 protein was higher than the rate (26.8%) in the patients with lower expression of DJ-1 protein (χ(2) = 5.164, P < 0.05). (3) With Kaplan-Meier curves and Cox regression analysis, the cumulative 5-year survival rates were correlated with DJ-1 expression levels in laryngeal cancer tissues or cervical lymph node metastasis (all P < 0.05), but not to sex, age, primary cancer position, T stage, clinical stage and tumor differentiation. CONCLUSIONS: The expression of DJ-1 protein in LSCC is higher than that in control laryngeal mucous tissues. Overexpression of DJ-1 is associated with poor overall survival in LSCC patients.
Asunto(s)
Carcinoma de Células Escamosas/patología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Laríngeas/patología , Recurrencia Local de Neoplasia , Proteínas Oncogénicas/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Laríngeas/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proteína Desglicasa DJ-1RESUMEN
OBJECTIVE: To explore the etiological factor, diagnostic localization and treatment of delayed cerebrospinal fluid (CSF) rhinorrhea. METHODS: The medical records of 79 patients who had undergone endoscopic repair of CSF rhinorrhea between 2000 and 2008 were reviewed. Thirteen patients with CSF leaks occurred 3 months after head trauma. All 13 patients with delayed CSF leak were retrospectively evaluated with CT or MRI and surgically treated. The operative findings were compared with the results of CT or MRI to estimate the diagnostic value of imaging technique. RESULTS: Bony defects had been found on CT scanning in all 13 patients. Neural tissue herniation into the nasal sinuses was found in 11 patients during the surgery. The sizes of the leak ranged from 0.1 cm x 0.2 cm to 1.2 cm x 1.5 cm. Reconstruction of the skull base was done through endoscopic approach. No complications were found. Thirteen patients were followed up from 12 - 36 months, and none was recurrence. CONCLUSIONS: Herniation of mucosal tissue into the nasal sinuses after skull base defects could result in delayed CSF leak. CT and MRI can clearly show the skull base defects and neural tissue herniation. Endoscopic closure of CSF leaks was both safe and effective.
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Rinorrea de Líquido Cefalorraquídeo/diagnóstico , Rinorrea de Líquido Cefalorraquídeo/cirugía , Adolescente , Adulto , Rinorrea de Líquido Cefalorraquídeo/etiología , Traumatismos Craneocerebrales/complicaciones , Endoscopía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To clarify the utility of a safe and effective endoscopic procedure for closing frontal sinus cerebrospinal fluid (CSF) leaks. METHODS: A retrospective review of all 15 patients seen at our hospital from 2002 to 2008 whose CSF leak originated within the frontal sinus or frontal recess. A transnasal endoscopic or combined transfrontal endoscopic approach was used to repair the CSF leak. RESULTS AND SURGICAL OUTCOMES: Four defects originated in the frontal recess and 11 involved the posterior wall of the frontal sinus. Nine patients were repaired by a direct endoscopic approach and 4 patients were repaired after widening the frontal recess endoscopically. Two patients were repaired using the combined transfrontal and transnasal approach. The leak was stopped in 14 cases (93%) after the first operation. One patient (7%) required a second repair 1 month after initial surgery and has remained well after 27 months. Complications included a frontal lobe abscess and a frontal sinus obstructive mucocele. These 2 patients were successfully treated without further complications. Patient follow-up ranged from 4 to 44 months (mean 30 months). CONCLUSIONS: Most frontal CSF leaks can be successfully closed by an endoscopic surgical approach.