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1.
Cancer Biomark ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31815689

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common type of cancer around the world. The aim of this study was to seek the long non-coding RNAs (lncRNAs) acting as diagnostic and prognostic biomarker of HNSCC. METHODS: Base on TCGA dataset, the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified between HNSCC and normal tissue. The machine learning and survival analysis were performed to estimate the potential diagnostic and prognostic value of lncRNAs for HNSCC. We also build the co-expression network and functional annotation. The expression of selected candidate mRNAs and lncRNAs were validated by Quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: A total of 3363 DEmRNAs (1822 down-regulated and 1541 up-regulated mRNAs) and 32 DElncRNAs (13 down-regulated and 19 up-regulated lncRNAs) between HNSCC and normal tissue were obtained. A total of 13 lncRNAs (IL12A.AS1, RP11.159F24.6, RP11.863P13.3, LINC00941, FOXCUT, RNF144A.AS1, RP11.218E20.3, HCG22, HAGLROS, LINC01615, RP11.351J23.1, AC024592.9 and MIR9.3HG) were defined as optimal diagnostic lncRNAs biomarkers for HNSCC. The area under curve (AUC) of the support vector machine (SVM) model, decision tree model and random forests model and were 0.983, 0.842 and 0.983, and the specificity and sensitivity of the three model were 95.5% and 96.2%, 77.3% and 97.6% and 93.2% and 97.8%, respectively. Among them, AC024592.9, LINC00941, LINC01615 and MIR9-3HG was not only an optimal diagnostic lncRNAs biomarkers, but also related to survival time. The focal adhesion, ECM-receptor interaction, pathways in cancer and cytokine-cytokine receptor interaction were four significantly enriched pathways in DEmRNAs co-expressed with the identified optimal diagnostic lncRNAs. But for most of the selected DEmRNAs and DElncRNAs, the expression was consistent with our integrated analysis results, including LINC00941, LINC01615, FOXCUT, TGA6 and MMP13. CONCLUSION: AC024592.9, LINC00941, LINC01615 and MIR9-3HG was not only an optimal diagnostic lncRNAs biomarkers, but also were a prognostic lncRNAs biomarkers.

2.
J Cancer ; 10(27): 6910-6914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839826

RESUMO

CCL18 is a cytokine secreted by M2 type tumor associated macrophages, which frequently over-expressed in diverse human cancers. However, the clinical significance of serum CCL18 in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. In this study, serum CCL18 was initially quantified by enzyme-linked immunosorbent assay (ELISA) in 146 patients with LSCC, 25 patients with precancerous lesions and 72 healthy volunteers. In addition, the correlations between serum CCL18 and clinicopathological parameters were analyzed. Our data revealed that serum CCL18 was obviously increased in patients with LSCC. Moreover, serum CCL18 level was significantly associated with primary tumor site (Glottic vs Others), T classification (T1+T2 vs T3+T4), clinical stage (I+II vs III+IV) and lymph node metastasis (N0 vs N+). Survival analysis demonstrated that patients with high serum CCL18 displayed a shorter survival time than those in patients with low serum CCL18. Importantly, serum CCL18 level and clinical stage were independent prognostic factors in patients with LSCC. Taken together, serum CCL18 could be used as a promising biomarker in patients with LSCC.

3.
Cancer Sci ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31778279

RESUMO

Metastasis is a critical determinant for the treatment strategy and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). However, the mechanisms underlying SCCHN metastasis are poorly understood. Our study sought to determine the key microRNA and their functional mechanisms involved in SCCHN metastasis. For The Cancer Genome Atlas (TCGA) data analysis, quantitative PCR was used to quantify the level of miR-30e-5p in SCCHN and its clinical significance was further analyzed. A series of in vitro and in vivo experiments were applied to determine the effects of miR-30e-5p and its target AEG-1 on SCCHN metastasis. A mechanism investigation further revealed that AEG-1 was implicated in the angiogenesis and metastasis mediated by miR-30e-5p. Overall, our study confirms that miR-30e-5p is a valuable predictive biomarker and potential therapeutic target in SCCHN metastasis.

4.
J Cancer ; 10(19): 4633-4638, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528227

RESUMO

As a classical ligand in the canonical Wnt/ß-catenin signaling pathway, the role of Wnt3a in laryngeal squamous cell carcinoma (LSCC) remains unclear. Therefore, the expression pattern of the Wnt3a protein in 222 primary LSCC, and 19 corresponding adjacent non-carcinoma specimens, was detected by immunohistochemistry and further correlated with clinicopathological parameters. The results showed that LSCC tissue expressed higher levels of the Wnt3a protein when compared to the corresponding adjacent non-cancerous tissues. High expression of Wnt3a was closely related to histological grade (P = 0.031), clinical stage (I+II / III+IV; P = 0.004), and lymph node metastasis (P = 0.03). Kaplan-Meier analysis evidenced that a worse overall survival (OS) was correlated to the group with high Wnt3a expression (P = 0.003). When stratified survival analyses were performed, patients with lymph node metastasis/advanced clinical stages and high Wnt3a expression had worse OS rates than patients with other features (P < 0.001). Finally, multivariate analysis showed that Wnt3a expression was an independent prognosis factor for LSCC patients. The current findings suggest that Wnt3a is tightly related to the LSCC progression and could serve as a valuable clinic biomarker for LSCC patients.

5.
J Cell Mol Med ; 23(7): 4711-4722, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31111621

RESUMO

The canonical Wnt/ß-catenin signalling pathway and autophagy play critical roles in cancer progression. However, the role of Wnt-mediated autophagy in cancer radioresistance remains unclear. In this study, we found that irradiation activated the Wnt/ß-catenin and autophagic signalling pathways in squamous cell carcinoma of the head and neck (SCCHN). Wnt3a is a classical ligand that activated the Wnt/ß-catenin signalling pathway, induced autophagy and decreased the sensitivity of SCCHN to irradiation both in vitro and in vivo. Further mechanistic analysis revealed that Wnt3a promoted SCCHN radioresistance via protective autophagy. Finally, expression of the Wnt3a protein was elevated in both SCCHN tissues and patients' serum. Patients showing high expression of Wnt3a displayed a worse prognosis. Taken together, our study indicates that both the canonical Wnt and autophagic signalling pathways are valuable targets for sensitizing SCCHN to irradiation.

6.
Mol Med Rep ; 17(3): 4767-4776, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29328423

RESUMO

Cisplatin and cetuximab, an anti­epidermal growth factor receptor (EGFR) monoclonal humanized antibody, have been used for treatment of laryngeal squamous cell carcinoma (LSCC). It has been demonstrated that cisplatin and inhibition of EGFR signaling may induce endoplasmic reticulum (ER) stress­associated apoptosis. However, ER protein thioredoxin domain­containing protein 5 (TXNDC5) reportedly protects cells from ER stress­associated apoptosis. The present study investigated the interaction between cisplatin, cetuximab and TXNDC5 on ER stress­associated apoptosis in LSCC cells. AMC­HN­8 human LSCC cells with or without TXNDC5 overexpression or knockdown were treated with cisplatin (5, 10, 20 and 40 µM) and/or cetuximab (10, 50, 100 and 150 µg/ml), for 12, 24, 36 and 48 h. Cisplatin and cetuximab concentration­ and time­dependently increased and decreased the expression of TXNDC5 in AMC­HN­8 cells, respectively. Knockdown of TXNDC5 markedly augmented cisplatin­induced levels of CCAAT/enhancer­binding protein homologous protein (CHOP), caspase­3 activity and apoptosis; while overexpression of TXNDC5 largely eliminated cetuximab­induced levels of CHOP, caspase­3 activity and apoptosis. Cisplatin and cetuximab demonstrated a combinatorial effect on increasing the levels of CHOP, caspase­3 activity and apoptosis, which was largely eliminated by overexpression of TXNDC5 or a reactive oxygen species (ROS) scavenger/antagonist. In addition, promoter/luciferase reporter assays revealed that cisplatin and cetuximab regulated the expression of TXNDC5 at the gene transcription/promoter level. In conclusion, the findings suggested that ER stress­associated apoptosis is a major mechanism underlying the apoptotic effect of cisplatin and cetuximab on LSCC cells; cetuximab enhanced cisplatin­induced ER stress­associated apoptosis in LSCC cells largely by inhibiting the expression of TXNDC5 and thereby increasing ROS production; cisplatin and cetuximab had stimulatory and inhibitory effects on the TXNDC5 gene promoter, respectively. The present study offered novel insights into the pharmacological effects of cisplatin and cetuximab on LSCC. It also suggested that TXNDC5 may be a potential therapeutic target for LSCC.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Apoptose/efeitos dos fármacos , Cetuximab/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Isomerases de Dissulfetos de Proteínas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Histonas/metabolismo , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Regiões Promotoras Genéticas , Isomerases de Dissulfetos de Proteínas/antagonistas & inibidores , Isomerases de Dissulfetos de Proteínas/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição CHOP/metabolismo
7.
Am J Cancer Res ; 7(12): 2554-2565, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29312808

RESUMO

PURPOSE: MicroRNAs function through regulating specific target mRNA expression and then participate in the development and progression of diverse human cancers. MiR-98 shows aberrant expression and dysfunction in tumors. However, its clinical significance and exact role in squamous cell carcinoma of the head and neck (SCCHN) remain elusive. METHODS: MiR-98 expression was examined by qRT-PCR and correlated with clinicopathological variables and prognosis in SCCHN patients. Effects of miR-98 on epithelial-mesenchymal transition (EMT) and the malignant phenotypes of SCCHN were studied. Finally, the role of target gene metadherin (MTDH) in miR-98 mediated effects were assayed. RESULTS: Our results demonstrated that miR-98, as an endogenous inhibitor of MTDH via directly binding to its 3'-untranslated region (UTR) region, decreased significantly in SCCHN tissues. Decreased miR-98 expression was negatively correlated with T classification, clinical stage, lymph node metastasis and a shorter survival status in SCCHN patients. Loss-of-function and gain-of-function analyses confirmed that miR-98 inhibited cell proliferation, migration and invasion of SCCHN cells in vitro. Moreover, miR-98 repression led to increased MTDH expression and induced EMT alteration. Importantly, ectopic expression of MTDH partially reversed the effects caused by miR-98 overexpression. CONCLUSIONS: Our study identifies that miR-98 serves as a suppressor in SCCHN progression via targeting oncogene MTDH.

8.
Artigo em Chinês | MEDLINE | ID: mdl-26685398

RESUMO

OBJECTIVE: This study aimd to evaluate the application and clinical effect of improved submental island flap in hypopharyngeal cancer reserved laryngeal function surgery. METHOD: A retrospective review of clinical data was performed on 38 patients of hypopharyngeal cancer reserved laryngeal function using sumental island flaps, by the way of improving in design of vascular pedicle, reconstructive mode of laryngeal and hypopharyngeal function and closing of wound of neck following hypopharyngeal cancer resection. Meanwhile, the effect and prognosis was comprehensively assessed on patients with hypopharyngeal cancer reserved laryngeal function using improved submental island flaps. RESULT: The submental flaps kept alive in all 38 cases. During the follow-up period, 18 cases were dead, and of them, 7 cases died of the second primary carcinoma, included 4 cases of esophagus cancer, 1 case of cancer of soft palate, 2 cases of nasopharyngeal carcinoma; and 5 cases died of cervical or parapharyngeal lymph nodes recurrence; 2 cases died of hepatic metastasis; and 4 cases died of pulmonary metastasis. The overall 5-years survival rate was 52.6%. CONCLUSION: Improved submental island flap repairing postoperative defect of hypopharyngeal cancer reserved laryngeal function has many advantages including higher success rate, more security, easy and simple to operate as well as good clinical effects, and is worth to widespread using.


Assuntos
Neoplasias Hipofaríngeas/cirurgia , Laringe , Procedimentos Cirúrgicos Reconstrutivos , Retalhos Cirúrgicos , Humanos , Hipofaringe/cirurgia , Pescoço/cirurgia , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
Oncol Rep ; 33(2): 942-50, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25501015

RESUMO

Tongue squamous cell carcinoma (TSCC) is one of the most common head and neck cancers. Cisplatin is effective as a single agent or in combination with other drugs for the treatment of TSCC. Treatment with cisplatin-based chemotherapy has been found to improve the prognosis of patients with TSCC. However, one of the most important clinical issues of cisplatin-based TSCC chemotherapy is the intrinsic/acquired chemoresistance to cisplatin. Increased expression of miR-23a reportedly promotes cisplatin chemoresistance in TSCC cells. High expression of Twist is also associated with cancer chemoresistance and poor prognosis of TSCC patients. In the present study, we explored the interaction between miR-23a and Twist in TSCC cells, and assessed its impact on TSCC chemoresistance to cisplatin. miR-23a and/or Twist were overexpressed or knocked down in SCC-4 and Tca8113 human TSCC cells. The expression levels of miR-23a and Twist were determined. The half maximal inhibitory concentration (IC50) of cisplatin and cell apoptosis rate under cisplatin treatment were used as measures of cisplatin chemoresistance. Overexpression of miR-23a in both SCC-4 and Tca8113 cells markedly increased Twist expression, c-Jun N-terminal kinase (JNK) activity and the half maximal inhibitory concentration (IC50) of cisplain, and decreased cisplatin-induced apoptosis, all of which was abolished by knockdown of Twist or selective JNK inhibitor SP600125. On the other hand, knockdown of miR-23a significantly decreased Twist expression, JNK activity and IC50 of cisplain, and increased cisplatin-induced apoptosis, all of which was completely reversed by overexpression of Twist. In conclusion, the present study for the first time demonstrates that miR-23a promotes cisplatin chemoresistance and protects cisplatin-induced apoptosis in TSCC cells through inducing Twist expression by a JNK-dependent mechanism. It adds new insights into the molecular mechanisms underlying TSCC chemoresistance.


Assuntos
Apoptose , Carcinoma de Células Escamosas/metabolismo , Cisplatino/química , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias da Língua/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Humanos , Concentração Inibidora 50 , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lentivirus/genética , MAP Quinase Quinase 4/metabolismo , MicroRNAs/genética , Proteínas Nucleares/genética , Fosforilação , Estrutura Terciária de Proteína , Neoplasias da Língua/genética , Proteína 1 Relacionada a Twist/genética
10.
Mol Med Rep ; 11(2): 924-30, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25351620

RESUMO

Ephrin type­A receptor 2 (EphA2) is a receptor tyrosine kinase that is associated with cancer cell metastasis. There has been little investigation into its impact on the regulation of sensitivity to paclitaxel in nasopharyngeal carcinoma (NPC). In the present study, upregulation of EphA2 expression enhanced the survival of NPC 5­8F cells, compared with control cells exposed to the same concentrations of paclitaxel. Flow cytometry and western blot analysis demonstrated that over­expression of EphA2 decreased NPC cancer cell sensitivity to paclitaxel by regulating paclitaxel­mediated cell cycle progression but not apoptosis in vitro. This was accompanied by alterations in the expression of cyclin­dependent kinase inhibitors, p21 and p27, and of inactive phosphorylated­retinoblastoma protein. Furthermore, paclitaxel stimulation and EphA2 over­expression resulted in activation of the phosphoinositide 3­kinase (PI3K)/Akt signalling pathway in NPC cells. Inhibition of the PI3K/Akt signalling pathway restored sensitivity to paclitaxel in 5­8F cells over­expressing EphA2, which indicated that the PI3K/Akt pathway is involved in EphA2­mediated paclitaxel sensitivity. The current study demonstrated that EphA2 mediates sensitivity to paclitaxel via the regulation of the PI3K/Akt signalling pathway in NPC.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Nasofaríngeas/patologia , Paclitaxel/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor EphA2/metabolismo , Animais , Apoptose/efeitos dos fármacos , Carcinoma , Linhagem Celular Tumoral/efeitos dos fármacos , Ciclina E/genética , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Coelhos , Receptor EphA2/genética , Transdução de Sinais
11.
Artigo em Chinês | MEDLINE | ID: mdl-22932142

RESUMO

OBJECTIVE: To investigate the mRNA and protein expressions of high mobility group box-1 (HMGB1) in the tumor tissues and sera of patients with laryngeal squamous cell carcinoma (LSCC) and their clinical significance. METHODS: Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were used to detected the expressions of HMGB1 mRNA and protein in the tumors and adjacent normal epithelial tissues in 30 patients with LSCC. Serum HMGB1 protein levels in the patients with LSCC and in 10 healthy volunteers were detected with enzyme-linked immunosorbent adsorption experiment (ELISA). RESULTS: RT-PCR demonstrated that the mean relative mRNA expression levels of HMGB1 (HMGB1/GAPDH) in LSCC tissues and in adjacent normal epithelial tissues were 1.25 ± 0.12 and 0.32 ± 0.04, respectively (t = 40.27, P < 0.05). Western blot revealed that the mean relative protein expression levels of HMGB1 (HMGB1/ß-actin) were 1.29 ± 0.10 and 0.34 ± 0.03 (t = 49.84, P < 0.05), respectively. Both mRNA and protein expression levels of HMGB1 were associated with T stage, clinical stage, lymph node metastasis status and smoking (all P < 0.05), but no significant correlation with age, alcohol consumption and primary tumor grade and location (all P > 0.05). Mean serum HMGB1 protein levels in patients with LSCC and healthy volunteers were (24.80 ± 14.08) ng/ml and (23.58 ± 14.69) ng/ml (t = 0.37, P > 0.05). CONCLUSIONS: Both mRNA and protein expressions of HMGB1 were obviously elevated in LSCC, which were associated closely with T stage, clinical stage and lymph node metastasis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteína HMGB1/metabolismo , Neoplasias Laríngeas/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Proteína HMGB1/sangue , Proteína HMGB1/genética , Humanos , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
Zhonghua Zhong Liu Za Zhi ; 34(2): 132-6, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22780932

RESUMO

OBJECTIVE: To evaluate the expression of HMGB1 protein in tissue specimens of laryngeal squamous cell carcinoma (LSCC) and adjacent normal mucosa, and explore the correlation of HMGB1 protein expression with clinicopathologic features and prognosis in LSCC. METHODS: Ninty-three cases of LSCC and 5 cases of adjcent mucosal tissue samples were included in this study. Immunohistochemical staining was performed on paraffin-embedded tissue specimens to examine the HMGB1 protein expression. The data were futher correlated with the clinicopathological features and prognosis of the LSCC patients. RESULTS: The positive rates of HMGB1 expression in LSCC specimens was 87.1%, significantly higher than that in the adjcent normal mucosa samples (46.7%, P = 0.001), and its overexpresion was closely correlated with T stage (Chi2 = 10.878, P = 0.004), clinical stage (Chi2 = 21.115, P < 0.01), metastasis (Chi2 = 28.298, P < 0.01) and recurrence (Chi2 = 14. 923, P = 0.001) in patients with LSCC. Patients with HMGB1 overexpression had both poorer disease-free survival and poorer overall survival compared with that in patients with low HMGB1 expression (Chi2 = 13.815, Chi2 = 11.912; Both P < 0.01). Univariate and multivariate Cox regression analyses revealed that HMGBI expression is an independent prognostic factor for patients with LSCC. CONCLUSIONS: The results of this study demonstrate that HMGB1 protein expression is significantly increased in LSCC tissues, and HMGB1 protein overexpression is associated with a poorer prognosis in patients with LSCC. These results suggest that HMGB1 may play a critical role in the initiation and progression of LSCC, implicating HMGB1 may become a valuable marker for the prediction of prognosis in patients with LSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proteína HMGB1/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Laríngeas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Taxa de Sobrevida
13.
Artigo em Chinês | MEDLINE | ID: mdl-22737875

RESUMO

OBJECTIVE: To investigate the synergistic cytotoxicity of TRAIL and paclitaxel on nasopharyngeal cell lines CNE-1 and CNE-2. METHOD: CCK-8 assays the growth inhibition rate of CNE-1 and CNE-2 which was treated with TRAIL or paclitaxel or combination of both. Flow cytometry tests the apoptosis rate of CNE-1 and CNE-2 which was treated with TRAIL or paclitaxel or combination of each other. RESULT: In certain range of time and concentration,TRAIL and paclitaxel inhibited the growth of the cell lines of CNE-1 and CNE-2 in a time-dose dependent manner (P < 0.05). The rate of growth inhibition and apoptosis in TRAIL and paclitaxel combinative group was more significant than that in the TRAIL and paclitaxel singular group (P < 0.05). CONCLUSION: TRAIL and paclitaxel had a synergistic killing effect on NPC cell lines and showed better affection than singular group, which provides a novel and prospective strategy for NPC chemotherapy.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Nasofaríngeas/patologia , Paclitaxel/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Carcinoma , Linhagem Celular Tumoral , Humanos , Carcinoma Nasofaríngeo
14.
Artigo em Chinês | MEDLINE | ID: mdl-22455776

RESUMO

OBJECTIVE: To investigate the effects of EphA2 on the angiogenesis and cervical lymph node metastasis of squamous cell carcinoma of the head and neck (SCCHN) in vivo. METHODS: EphA2 short hairpin (shRNA) lentiviral particles were used to knockdown the expression of EphA2 in SCCHN cell line M2 with high lymph nodes metastasis rate. Stable clones, obtained by puromycin screening, were assayed by RT-PCR and Western blot to validate the gene silencing efficiency and were used to establish SCCHN metastatic xenograft mouse model. Hematoxylin-eosin staining was applied to identify cervical lymph node metastasis of SCCHN in xenografted tumors. Immunohistochemistry was used to observe microvessel density. Western blot was used to investigate the protein expressions of EphA2 and vascular endothelial, growth factor (VEGF). RESULTS: EphA2 shRNA lentiviral particles efficiently decreased the mRNA and protein expressions of EphA2 in SCCHN cell line M2, which were further successfully utilized to establish SCCHN metastatic xenograft mouse model. Compared with xenografted tumors in control group, xenografted tumors in M2EphA2RNAi(+) group decreased significantly tumor volume [(430.7 ± 190.0) mm(3) (x(-) ± s) vs (1179.0 ± 289.4) mm(3)] and weight [(0.26 ± 0.10) g vs (0.54 ± 0.12) g] (both P < 0.05). More importantly, bilateral cervical lymph node metastasis rate in M2EphA2RNAi(+) was also greatly declined (Mann-Whitney U = 10.0, P < 0.05). Decreased protein expressions of EphA2 and VEGF and microvessel density were observed in M2EphA2RNAi(+) group (t = 26.751, P < 0.01). CONCLUSIONS: Knockdown of EphA2 expression led to the inhibition of tumor growth and metastasis in SCCHN nude mouse model. More importantly, SCCHN angiogenesis was also impeded, which might be associated with the decreased expression of VEGF.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neovascularização Patológica , Receptor EphA2/genética , Animais , Linhagem Celular Tumoral , Inativação Gênica , Humanos , Metástase Linfática , Camundongos , Camundongos Nus , Prognóstico , RNA Interferente Pequeno , Carcinoma de Células Escamosas de Cabeça e Pescoço
15.
Oncol Lett ; 4(3): 429-434, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23741245

RESUMO

EphA2 is frequently overexpressed and functionally altered in a variety of human cancers. However, its roles in human nasopharyngeal carcinoma (NPC) remain unclear. To investigate the roles of EphA2 in the development and progression of NPC, we initially evaluated the expression pattern of EphA2 protein in NPC tissues using western blotting and CCK-8 assay. Fluorescence-activated cell sorting analysis and invasion assay were conducted to observe the effects of EphA2 inhibition in vivo. Our results demonstrated that EphA2 was overexpressed in NPC specimens and the expression of EphA2 was significantly associated with T classification, advanced clinical stage and lymph node metastasis. Moreover, human NPC 5-8F cells were infected with lentiviral vector-mediated EphA2-specific shRNA, which resulted in the significant inhibition of cell growth, invasion of 5-8F cells and markedly enhanced the sensitivity of 5-8F cells to the chemotherapeutic agent paclitaxel in vitro. Collectively, our results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human NPC.

16.
Med Oncol ; 29(2): 721-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21479953

RESUMO

ERp29 is an endoplasmic reticulum (ER) stress-inducible protein. It was found that ERp29 was highly expressed in several cancers and associated with resistance to oxidative and radiation stress, which may serve as a novel target for nasopharyngeal carcinoma (NPC) anticancer approach. In this study, we used immunohistochemistry to detect ERp29 expression in radioresistant and radiosensitive NPC tissues. As a result, ERp29 was up-regulated in radioresistant NPC tissues compared to radiosensitive NPC tissues. We also found that ERp29 knockdown attenuated radioresistance of NPC CNE-1 cells and ERp29 overexpression enhanced radioresistance of NPC CNE-2 cells. When exposed to radiation, ERp29 knockdown CNE-1 cells increased radiation-induced cell apoptosis and ERp29 overexpression CNE-2 cells reduced radiation-induced cell apoptosis. Further, we demonstrated that ERp29 up-regulated the expression of Hsp27. In conclusion, our study supports ERp29 could potentiate resistance to radiation in NPC cells, targeting of ERp29 is a rational strategy in treating radioresistant NPC.


Assuntos
Apoptose/efeitos da radiação , Proteínas de Choque Térmico/antagonistas & inibidores , Proteínas de Choque Térmico/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Tolerância a Radiação/genética , Western Blotting , Carcinoma , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Técnicas Imunoenzimáticas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
17.
J Proteome Res ; 11(2): 1100-7, 2012 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-22070577

RESUMO

The present study was to identify and quantitate differentially expressed proteins in laryngeal squamous cell carcinoma (LSCC) tissues with or without lymph node metastasis and to explore transcriptional factors and regulation networks associated with the process. Tissue specimens were taken from 20 patients with LSCC, including 10 cases of LSCC without metastasis LSCC (N0) and 10 cases of LSCC with metastasis LSCC (Nx). Among the 643 unique proteins identified by using iTRAQ labeling and quantitative proteomic technology, 389 proteins showed an abundance change in LSCC (Nx) as compared to LSCC (N0). Cytoskeleton remodeling, cell adhesion, and immune response activation were found to be the main processes in LSCC metastasis. The construction of transcription regulation networks identified key transcription regulators for lymph node metastasis of LSCC, including Sp1, c-myc, and p53, which may affect LSCC metastasis through the epithelial-mesenchymal transition. Furthermore, our results suggest that ubiquitination may be a critical factor in the networks. The present study provides insights into transcriptional factors and regulation networks involved in LSCC metastasis, which may lead to new strategies for treatment of LSCC metastasis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Laríngeas/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Adesão Celular , Citoesqueleto/metabolismo , Regulação para Baixo , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Laríngeas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mapas de Interação de Proteínas , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fator de Transcrição Sp1/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
18.
Artigo em Chinês | MEDLINE | ID: mdl-21650061

RESUMO

OBJECTIVE: To investigate the expression and biological significance of HMGB1 and VEGF protein in tissue specimens of laryngeal squamous cell carcinoma (LSCC), and further study the correlation between HMGB1 and VEGF protein. METHOD: The expression of HMGB1 and VEGF protein was evaluated by immunohistochemical staining in 69 cases of LSCC specimens and 15 cases of adjacent epithelial tissue samples, and futher correlated with clinicopathologic parameters. RESULT: The positive rates of HMGB1 and VEGF in LSCC tissues were significantly higher than those in adjacent non-cancerous mucosa (P < 0.01), and the expression of these two marks was closely correlated with clinical stage (P < 0.05) and metastasis (P < 0.05) in LSCC. While the expression of HMGB1 and VEGF had no significant correlations with age, sex, histological differentiation and tumor site (P > 0. 05). There was a positive correlation between the expression of HMGB1 and VEGF (P < 0.05). The Kaplan-Meier survival analysis showed that patients with strong expression of HMGB1 or VEGF had poorer overall survival compared with that in patients with relative low HMGB1 or VEGF expression (P < 0.05). Multivariate COX regression analysis revealed that both lymph node metastasis and HMGB1 expression were independent prognostic factors for patients with LSCC. CONCLUSION: This study demonstrated that HMGB1 and VEGF protein overexpression were closely associated with clinical stage, metastasis and poorer prognosis in patients with LSCC. Increased expression of these two proteins in LSCC suggested that HMGB1 and VEGF might play a critical role in the initiation and progression of LSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteína HMGB1/metabolismo , Neoplasias Laríngeas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Laríngeas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
19.
Zhonghua Zhong Liu Za Zhi ; 33(3): 197-201, 2011 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-21575519

RESUMO

OBJECTIVE: To evaluate the expression of EphA2 protein in tissue specimens and cell lines of laryngeal squamous cell carcinoma (LSCC), and to further study the correlation of EphA2 protein expression with clinicopathological characteristics and prognosis in LSCC. METHODS: Western blot was applied to assess the EphA2 protein expression in LSCC cell line Hep-2 cells and the head and neck immortalized epithelial cell line NP-69 cells. Immunohistochemical staining was performed on paraffin sections of 88 cases of LSCC specimens and 16 cases of adjcent normal tissue samples to investigate the EphA2 protein expression, and to futher elucidate its correlation with clinicopathological characteristics. RESULTS: Compared with the NP-69 cells, EphA2 expression in LSCC cell line Hep-2 cells was upregulated. The positive rates of EphA2 expression in LSCC and adjcent normal tissues samples were 80.7% and 43.8%, respectively, with a significant difference between the two groups (P < 0.001). EphA2 overexpresion was closely correlated with clinical stage (I + II/III + IV, P = 0.005), metastasis (P = 0.025) and recurrence (P = 0.021) in LSCC. Furthermore, patients with EphA2 overexpression had poorer tumor-free survival and 5-year overall survival compared with that in patients with low EphA2 expression (33.3% vs. 63.2%, P = 0.003; 46.7% vs. 81.6%, P = 0.002). EphA2 expression combined with clinical stage provided a better predictive value in prognosis. Univariate and multivariate Cox regression analysis revealed that EphA2 expression is an independent prognostic factor for patients with LSCC (P = 0.019). CONCLUSIONS: The results of this study demonstrate that EphA2 protein expression is significantly increased in LSCC tissues and cell lines, and EphA2 protein overexpression is associated with tumor recurrence, metastasis and poorer prognosis in LSCC patients. These results suggest that EphA2 may play a critical role in the initiation and progression of LSCC, implicating EphA2 as a valuable marker for the prediction of recurrence, metastasis and prognosis in LSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Receptor EphA2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Linhagem Celular , Linhagem Celular Tumoral , Intervalo Livre de Doença , Células Epiteliais/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Laríngeas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pescoço , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Taxa de Sobrevida
20.
Eur J Cancer ; 46(16): 3007-15, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20724142

RESUMO

PURPOSE: HMGB1 overexpression has been reported in a variety of human cancers. However, the role of HMGB1 in squamous-cell carcinoma of the head and neck (SCCHN) remains unclear. The aim of the present investigation was to analyse HMGB1 protein expression in both SCCHN tissue and cell levels and to assess its prognostic significance in SCCHN. METHODS: HMGB1 protein expression in 103 primary SCCHN tissue specimens was analysed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, HMGB1 protein expression was evaluated in cell level by Western blotting. RESULTS: By Western blotting analysis, all the 5 SCCHN cell lines overexpressed HMGB1 protein, whereas the non-transformed immortalised cell line NP-69 had relatively weak HMGB1 protein expression. Immunohistochemical staining revealed that HMGB1 protein was detected in 91 (91/103, 88.3%) primary tumour samples, but only in 7 (7/16, 43.75%) adjacent non-carcinoma samples (p<0.001); moreover, HMGB1 overexpression was significantly associated with T classification (p=0.001), clinical stage (p<0.001), recurrence (p<0.001) and lymph node metastasis (p<0.001). Survival analysis demonstrated that high HMGB1 expression was significantly associated with shorter disease-free and overall survival (both p<0.001), especially in late patients with SCCHN. When HMGB1 expression and lymph node status were combined, patients with HMGB1 overexpression/lymph node (+) had both poorer disease-free and overall survival than others (both p<0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with SCCHN. CONCLUSIONS: HMGB1 protein may contribute to the malignant progression of SCCHN, and present as a novel prognostic marker and a potential therapeutic target for patients with SCCHN.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteína HMGB1/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem , Células Tumorais Cultivadas
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