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1.
Front Chem ; 9: 649287, 2021.
Article in English | MEDLINE | ID: mdl-33869144

ABSTRACT

Seven undescribed cembranoids, sacraoxides A-G (1, 3-8) were isolated from the gum resin of Boswellia sacra. Their structures were elucidated by extensive physicochemical and spectroscopic analysis, as well as ECD calculation, modified Mosher's method and X-ray diffraction crystallography. Compounds 6 and 7 exhibited inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells with IC50 values of 24.9 ± 1.7 and 36.4 ± 2.9 µM.

2.
Aging (Albany NY) ; 13(6): 8611-8619, 2021 03 10.
Article in English | MEDLINE | ID: mdl-33714208

ABSTRACT

Long noncoding RNA (lncRNA) plays a critical role in tumorigenesis. How lncRNA regulates laryngeal squamous cell carcinoma (LSCC) progression remains poorly understood. In the present study, we found that LINC01638 was highly expressed in LSCC tissues. And LINC01638 expression was positively correlated with clinical stage and lymph node metastasis. Patients with LINC01638 high expression displayed a low survival rate. Results from CCK8, colony formation, and transwell assays showed that LINC01638 knockdown suppressed the proliferation, migration and invasion of LSCC cells in vitro. Animal experiments indicated that LINC01638 silencing attenuated tumor growth in vivo. In terms of mechanism, LINC01638 was found to sponge miR-523-5p and promote BATF3 expression. In summary, our results demonstrated that LINC01638/miR-523-5p/BATF3 axis plays a crucial function in initiating LSCC development and may be a potential target for tumor therapy.


Subject(s)
Basic-Leucine Zipper Transcription Factors/genetics , Laryngeal Neoplasms/pathology , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Repressor Proteins/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Adult , Aged , Animals , Basic-Leucine Zipper Transcription Factors/metabolism , Disease Progression , Female , Gene Expression Regulation, Neoplastic/physiology , Heterografts , Humans , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/metabolism , Middle Aged , RNA, Long Noncoding/metabolism , Repressor Proteins/metabolism , Signal Transduction/physiology , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/metabolism
3.
Front Oncol ; 11: 683915, 2021.
Article in English | MEDLINE | ID: mdl-34976784

ABSTRACT

OBJECTIVE: Our purpose was to develop and verify an immune-related signature for predicting recurrence risk of patients with laryngeal cancer. METHODS: RNA-seq data of 51 recurrence and 81 non-recurrence laryngeal cancer samples were downloaded from TCGA database, as the training set. Microarray data of 34 recurrence and 75 non-recurrence cancer samples were obtained from GEO dataset, as the validation set. Single factor cox regression was utilized to screen prognosis-related immune genes. After LASSO regression analysis, an immune-related signature was constructed. Recurrence free survival (RFS) between high- and low- recurrence risk patients was presented, followed by ROC. We also evaluated the correlation between immune infiltration and the signature using the CIBERSORT algorithm. The genes in the signature were validated in laryngeal cancer tissues by western blot or RT-qPCR. After RCN1 knockdown, migration and invasion of laryngeal cancer cells were investigated. RESULTS: Totally, 43 prognosis-related immune genes were identified for laryngeal cancer. Among them, eight genes were used for constructing a prognostic signature. High risk group exhibited a higher recurrence risk than low risk group. The AUC for 1-year was separately 0.803 and 0.715 in the training and verification sets, suggesting its well efficacy for predicting the recurrence. Furthermore, this signature was closely related to distinct immune cell infiltration. RCN1, DNAJA2, LASP1 and IBSP were up-regulated in laryngeal cancer. RCN1 knockdown restrained migrated and invasive abilities of laryngeal cancer cells. CONCLUSION: Our findings identify a reliable immune-related signature that can predict the recurrence risk of patients with laryngeal cancer.

4.
Int J Med Sci ; 17(13): 1992-2001, 2020.
Article in English | MEDLINE | ID: mdl-32788878

ABSTRACT

Papillary thyroid carcinoma (PTC) accounts for the largest proportion of thyroid cancers; and its morbidity rate has dramatically increased in recent decades. However, the pathogenesis mechanisms of PTC are still not clear. This study aimed to reveal that miR-145 acts as an antitumor miRNA in the progression of PTC. In the present study, the expression of miR-145 was analyzed in 57 paired PTC patient samples. The relationship between clinicopathological features and miR-145 expression were also defined. The tumor suppressive function of miR-145 on PTC cell metastasis, proliferation and apoptosis were revealed in vitro. Also, we used dual luciferase reporter assay to define the relationship of miR-145 and RAB5C. RAB5C was reported to participate in cell invasion and cell motility. We found that miR-145 was downregulated in PTCs, which was negatively correlated with PTC progression and metastasis. MiR-145 inhibited PTC migration, proliferation and promoted apoptosis by directly suppresing RAB5C. In conclusion, miR-145 functions as a tumor suppressor in PTC by inhibiting RAB5C. MiR-145 and RAB5C are potential therapeutic targets in therapy of aggressive PTC cases.


Subject(s)
MicroRNAs/genetics , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/genetics , rab5 GTP-Binding Proteins/genetics , Adult , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Humans , Male , Middle Aged , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathology , rab5 GTP-Binding Proteins/metabolism
5.
BMC Cancer ; 19(1): 1093, 2019 Nov 12.
Article in English | MEDLINE | ID: mdl-31718618

ABSTRACT

BACKGROUND: Anaplastic thyroid cancer (ATC) is considered to be a rare type of thyroid cancer but takes up the most important proportion of thyroid cancer-related deaths. Therefore, the development of molecular targeted therapy is an exciting strategy in the management of ATC. METHODS: miR-155 and SOCS1 expression were measured by qRT-PCR as well as western blot analysis. 8305c and FRO cells were transfected and cultured for apoptosis assays, transwell, MTT on miR-155 or SOCS1 suppression and overexpression. Dual-luciferase reporter assays and SOCS1 restoration experimentswas implemented for define the relation between SOCS1 and miR-155. In addition, the correlation between miR-155 expression and patients' clinicopathological features were also explored. RESULTS: Aberrant miR-155 and SOCS1 expression and inverse correlation were found in ATC samples. In addition, it indicated that miR-155 expression correlated with cervical metastasis as well as extrathyroidal invasion. Moreover, we demonstrated that miR-155 inhibited 8305c and FRO cells apoptosis, promoted proliferation, invasion and migration. Furthermore, miR-155 inhibition was associated with a significant overexpression of SOCS1. Additionally, luciferase reporter assays presented that miR-155 could bind to SOCS1 3'-UTR, influencing its stability negatively and finally lowering SOCS1 levels. Moreover, it was illustrated that the impacts of miR-155 suppression were reversed by the inhibition of SOCS1 on cell proliferation, apoptosis as well as invasion. CONCLUSIONS: Aberrant miR-155/SOCS1 expression has been included in ATC progression: miR-155 overexpression leads to SOCS1 suppression and develops ATC progression. Thus, miR-155 has been considered to be an underlying therapeutic target for ATC.


Subject(s)
Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , RNA Interference , Suppressor of Cytokine Signaling 1 Protein/genetics , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Carcinoma, Anaplastic/pathology , 3' Untranslated Regions , Apoptosis/genetics , Caspase 3/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Disease Progression , Female , Gene Silencing , Humans , Male , Neoplasm Staging , Thyroid Carcinoma, Anaplastic/metabolism
6.
J Cell Biochem ; 120(12): 19832-19840, 2019 12.
Article in English | MEDLINE | ID: mdl-31310372

ABSTRACT

Larynx squamous cell carcinoma (LSCC) is the second most aggressive head and neck squamous cell carcinoma. Numerous genes have been identified to be aberrantly expressed during the development of LSCC. However, currently, researchers focus more on the individual molecule and downstream genes, leaving the coexpression among genes and key upstream disease driver genes unexploited. In this study, we applied weighted gene coexpression analysis (WGCNA) to decipher potential hub genes driving the development of LSCC. After downloading of LSCC microarray profile from gene expression omnibus, different expression analysis was performed, which was used to conduct functional enrichment analysis. Then, we applied WGCNA to highlight the hub genes which were relevant to the carcinogenesis and progression. A total of 2858 differentially expressed genes were identified in LSCC samples compared with adjacent non-neoplastic tissues. WGCNA revealed three LSCC set-specific modules having significant Kyoto Encyclopedia of Genes and Genomes enrichment effect, including pink, cyan, and black module. Nine hub genes were identified to be crucial in LSCC onset and progression, which may assist clinical decisions and serve as potential targets for LSCC treatment.


Subject(s)
Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Laryngeal Neoplasms/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Biomarkers, Tumor/genetics , Cluster Analysis , Gene Ontology , Humans
7.
Biomed Pharmacother ; 106: 665-671, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29990856

ABSTRACT

Genistein, a plant isoflavone, is reported to have therapeutic potentials in multiple cancers, However, the molecular mechanism underlying promoting cell apoptosis in laryngeal cancer remains unclear. In this study, we report that miR-1469 was induced by genistein in laryngeal cancer. Elevated miR-1469 promoted cell apoptosis and inhibited Mcl1 expression. In addition, we also observed that tumor suppressor p53 was increased under genistein treatment. Elevation of p53 promoted miR-1469 expression, leading to miR-1469 increase and Mcl1 decrease. Therefore, our findings suggest that genistein can suppress laryngeal cancer cell survival through p53 -miR-1469-Mcl1pathway.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Genistein/pharmacology , Laryngeal Neoplasms/drug therapy , MicroRNAs/physiology , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Tumor Suppressor Protein p53/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/metabolism , Laryngeal Neoplasms/pathology , MicroRNAs/genetics , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Signal Transduction/drug effects , Time Factors , Tumor Suppressor Protein p53/genetics
8.
Onco Targets Ther ; 11: 3619-3635, 2018.
Article in English | MEDLINE | ID: mdl-29950866

ABSTRACT

INTRODUCTION: Each year, ~50,000 patients worldwide die of laryngeal squamous cell carcinoma (LSCC) because of its highly metastatic properties. However, its pathogenic mechanisms are still unclear, and in particular, the prediction of metastasis remains elusive. This study aimed to define the role of microRNA-145 (miR-145) in LSCC progression. We also aimed to elucidate the clinical significance of the miR-145/MYO5A pathway, especially the predictive function of MYO5A in neck lymph node metastasis. MATERIALS AND METHODS: MYO5A and miR-145 expression was analyzed in 132 patients with LSCC, and associations between their expression and clinicopathological features were evaluated. We validated the regulatory relationship between miR-145b and MYO5A by dual luciferase reporter assay. The role of the miR-145/MYO5A pathway in proliferation, metastasis, and apoptosis was examined in vitro. The predictive functions of MYO5A in neck lymph node metastasis and prognosis were defined according to patient follow-up. RESULTS: Our results showed downregulation of miR-145 in LSCC, which was negatively correlated with MYO5A suppression of LSCC progression and metastasis. MiR-145 directly regulated MYO5A expression in vitro and suppressed LSCC proliferation and invasion while promoting apoptosis by inhibiting MYO5A. CONCLUSION: Notably, overexpression of serum MYO5A in LSCC predicted cervical nodal occult metastasis and poor prognosis, providing an effective indicator for predicting neck lymph node metastasis and assessing LSCC prognosis.

9.
Biochem Biophys Res Commun ; 501(2): 584-592, 2018 06 22.
Article in English | MEDLINE | ID: mdl-29753737

ABSTRACT

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) has the second highest incidence among the head and neck malignancies. Additionally, the incidence of LSCCs has been recently increasing. Therefore, understanding the mechanisms of LSCC tumorigenesis and identifying novel biomarkers to accurately predict and improve the prognosis of patients with LSCC is extremely important. METHODS: miR-196b and SOCS2 expression was measured by qRT-PCR and western blot. Their correlation was analyzed with the Pearson test. TU212 and TU177 cells were cultured and transfected for MTT, Transwell, and apoptosis assays upon miR-196b knockdown, SOSC2 overexpression or SOCS2 silencing. Dual-luciferase reporter assay were conducted to identify the relationship between miR-196b and SOCS2. Moreover, the correlation between clinicopathological parameters and miR-196b/SOCS2 expression in patients was analyzed. Univariate and multivariate analysis and log-rank tests were used to determine if miR-196 was an independent LSCC prognostic factors. RESULTS: We reported the aberrant expression and inverse correlation of miR-196b and SOCS2 in LSCC samples. miR-196b promoted LSCC cells proliferation and invasion, and suppressed apoptosis by directly inhibiting SOCS2 expression in vitro. Moreover, we also revealed that miR-196b/SOCS2 expression correlated with T stage and cervical metastasis. miR-196b was demonstrated to be an independent prognostic factor for overall survival of patients with LSCC. CONCLUSIONS: Overexpression of miR-196b suppresses SOCS2 in human LSCC resulting in tumor progression and poor prognosis. miR-196b is a potential marker for prognosis assessment and targeting miR-196b may be a novel valuable strategy for the treatment of LSCC.


Subject(s)
Carcinoma, Squamous Cell/genetics , Gene Expression Regulation, Neoplastic , Laryngeal Neoplasms/genetics , MicroRNAs/genetics , Suppressor of Cytokine Signaling Proteins/genetics , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Female , Humans , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/pathology , Male , Middle Aged , Prognosis , Up-Regulation
10.
Future Oncol ; 14(16): 1579-1589, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29517281

ABSTRACT

AIM: In this study, we investigated the role of Y-box binding protein-1 (YB-1), c-Myb and miR-155 in human laryngeal squamous cell carcinoma (LSCC) progression. MATERIALS & METHODS: Quantitative real-time PCR, western blot, MTT and Transwell were conducted to determine the expression and function of YB-1/miR-155 pathway. Univariate and multivariate analyses were used to determine the prognostic factors. RESULTS: Expression of YB-1, c-Myb and miR-155 was higher in LSCC tissues. YB-1 promoted proliferation, invasiveness and migration of Hep-2 cells in vitro. Patients with higher YB-1 correlated with advanced T stage, poor differentiation and cervical metastasis. LSCC patients with high YB-1 expression showed poor overall survival. CONCLUSION: YB-1 promotes LSCC progression by increasing miR-155 levels via c-Myb and acts as a prognostic factor.


Subject(s)
Carcinoma, Squamous Cell/pathology , Genes, myb/genetics , Laryngeal Neoplasms/pathology , MicroRNAs/genetics , Y-Box-Binding Protein 1/genetics , Aged , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/surgery , Male , Middle Aged , Prognosis , Y-Box-Binding Protein 1/metabolism
11.
Future Oncol ; 14(17): 1741-1753, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29517349

ABSTRACT

AIM: We sought to determine the function of miR-181a/GATA6 pathway in the progression of laryngeal squamous cell carcinoma (LSCC). MATERIALS & METHODS: The expression of miR-181a and GATA6 were detected using quantitative real-time-PCR and western blotting in 127 LSCC samples and 32 corresponding control mucosa tissues. Cell death, migration and apoptosis were measured in Hep-2 cells using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Transwell migration assay and apoptosis assay, respectively. The prognosis was determined by the follow-up, univariate analysis and multivariate analysis. RESULTS: We observed decreased miR-181a levels and increased GATA6 expression in LSCC samples compared with control mucosa tissues. Transfection of miR-181a decreased GATA6 expression, suppressed migration and promoted apoptosis in Hep-2 cells. Furthermore, silencing GATA6 suppressed cell migration and promoted apoptosis in Hep-2 cells. Notably, patients with high miR-181a levels had a longer life span. CONCLUSION: MiR-181a inhibits LSCC progression via suppressing GATA6 expression. MiR-181a is an independent prognostic factor in LSCC patients.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/genetics , GATA6 Transcription Factor/metabolism , Gene Expression Regulation, Neoplastic , Laryngeal Neoplasms/genetics , MicroRNAs/genetics , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Case-Control Studies , Cell Movement , Cell Proliferation , Disease Progression , Female , Follow-Up Studies , GATA6 Transcription Factor/genetics , Humans , Laryngeal Neoplasms/metabolism , Laryngeal Neoplasms/pathology , Male , Middle Aged , Prognosis , Survival Rate , Tumor Cells, Cultured
12.
Oncol Rep ; 35(6): 3313-20, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27035645

ABSTRACT

Nin one binding protein (NOB1) plays important roles in the synthesis and degradation of proteins, thus having effects on the cellular process. In the present study, the expression level of NOB1 in laryngeal cancer patients was detected by quantitative PCR and western blotting, and the effect of NOB1 on growth and metastasis of laryngeal cancer cells was explored. Silence of NOB1 was found to inhibit the proliferation of laryngeal cancer cells, arrest cell cycle and induce cell apoptosis. NOB1 silence was also found to inhibit the migration and invasion of laryngeal cancer cells and to downregulate the protein levels of matrix metalloproteinases (MMPs)-2 and MMP-9. Further mechanism study revealed that the JNK signaling pathway was involved in the function of NOB1. Our present results suggest that NOB1 plays an oncogenic role in laryngeal cancer cells through the regulation of JNK signaling pathway, and lays a theoretical foundation for further exploration of NOB1.


Subject(s)
JNK Mitogen-Activated Protein Kinases/physiology , Laryngeal Neoplasms/pathology , MAP Kinase Signaling System/physiology , Nuclear Proteins/physiology , RNA-Binding Proteins/physiology , Apoptosis , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation , Humans , Neoplasm Invasiveness , Neoplasm Metastasis , Nuclear Proteins/analysis , Nuclear Proteins/antagonists & inhibitors , RNA-Binding Proteins/analysis , RNA-Binding Proteins/antagonists & inhibitors
13.
Article in Chinese | MEDLINE | ID: mdl-26211163

ABSTRACT

OBJECTIVE: Study the clinical characteristics, treatment results and prognostic factors of hypopharyngeal carcinoma. MMETHOD: A retrospective analysis was performed of 97 hypopharyngeal cases that were treated in Department of Dtolaryngology of our hospital from January 2008 to December 2012. 93 cases of them are male patients, and 4 cases are female patients. The tumors are originated from pyriform sinus(75 cases), posterior pharyngeal wall (16 cases) and post-cricoid area (6 cases). Of the 97 patients,21 patients were treated with partial hypopharynx resection (21. 6%), 7 were treated with partial laryngectomy+ partial hypopharynx resection (7. 2%), 53 were treated with total laryngectomy+partial hypopharynx resection (54. 6%), 12 were treated with total laryngectomy and total hypopharynx resection, gastric-pharyngeal anastomosis (12. 4%) and 4 were treated with total laryngectomy and total hypopharynx resection, enteric-pharyngeal anastomosis (4. 1%). Sixty-one cases undergo postoperative radiotherapy in Oncology. Use Chi-square test to do enumeration data analysis, the survival rate is calculated with the life table method, survival analysis with Kaplan-Meier method, parallel Log-rank test. Cox regression multivariate analysis model is used to find the factors affecting prognosis. RESULT: The follow-up rate of this group was 90. 7%. All patients' 1-year survival rate is 76. 0% , 3-year survival rate is 56. 0%, pathological lymph node metastasis rate is 71. 1%, occult lymph node metastasis rate is 19. 6%. Local recurrence rate is 21. 6%. The main reasons of death in patients include : cervical lymph node metastasis in 7 patients (21. 9%), local recurrence in 12 cases (37. 5%), distant metastases in 10 patients (31. 3%) and so on. Univariate analysis showed that tumor size (P<0. 01) and tumor T stage (P<0. 05) have impact on survival prognosis, no risk factors was found with Cox regression multivariate analysis. CONCLUSION: Hypopharyngeal carcinoma is difficult to be found early, prone to recurrence and metastasis after operation, carefully chosen surgical excision and neck dissection, adjuvant postoperative radiation therapy is the main treatment strategy. Posterior pharyngeal wall carcinoma tend to have higer recurrence and metastasis rate than the other two types of hypopharyngeal caocinom, and treatment would cause much larger injury, so more attention should be paid to this type of hypopharyngeal caocinom.


Subject(s)
Hypopharyngeal Neoplasms/surgery , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/surgery , Female , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/surgery , Humans , Hypopharyngeal Neoplasms/diagnosis , Hypopharynx/surgery , Laryngectomy , Lymphatic Metastasis , Male , Neck Dissection , Neoplasm Recurrence, Local , Pharynx , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Survival Rate , Treatment Outcome
14.
Article in Chinese | MEDLINE | ID: mdl-26201180

ABSTRACT

OBJECTIVE: To discuss the function recovery and treatment effect of extended supraglottic orizontal-partial laryngectomy in the treatment of advanced laryngeal carcinoma and vallecula carcinoma. METHOD: Forty-four patients who received extended supraglottic orizontal partial laryngectomy were followed up on the survival, breath function, pronunciation and swallowing function. RESULT: The 2-year, 3-year survival rates of this group were 72.7% and 71.4%, respectively. There were no recurrence cases in this group. All cases of death were due to cervical lymph node metastasis or recurrent cervical lymph node metastasis after cervical lymph node dissection. The extractive rate of tracheostomy tube was 97.7%. Forty-two patients own good pronunciations. Two patients who received partial arytenoid cartilage resection own weaker pronunciations. After practising, all the patients can eat without the nasal feeding tube. CONCLUSION: Extended supraglottic orizontalpartial laryngectomy give complete resection of the primary lesion. Patients who received extended supraglottic orizontalpartial laryngectomy have good breath, swallowing and pronunciation function.


Subject(s)
Epiglottis/pathology , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Arytenoid Cartilage/surgery , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Neck Dissection , Neoplasm Recurrence, Local , Survival Rate , Tracheostomy
15.
Oncol Rep ; 33(3): 1221-6, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25586265

ABSTRACT

Laryngeal cancer is one of the most commonly occurring malignant cancers of the head and neck region. In the present study, we investigated the roles of miR-221 in laryngeal squamous cell carcinoma cell line, Hep-2. We examined the function and mechanism of miR-221 in Hep-2 cells using techniques of cell biology and molecular pathology, such as western blotting, quantitative PCR, immunohistochemical staining and flow cytometry. Using a luciferase assay, the apoptotic protease activating factor-1 (Apaf-1) mRNA 3'-UTR was shown to have complementary binding sites using bioinformatics prediction software including TargetScan, PicTar and miRanda. In conclusion, our results showed that miR-221 inhibition caused elevated expression levels of the Apaf-1 apoptotic pathway proteins caspase-3, -8 and -9. miR-221 may therefore be used as a novel therapeutic target for laryngeal cancer.


Subject(s)
Apoptosis/genetics , Apoptotic Protease-Activating Factor 1/biosynthesis , Laryngeal Neoplasms/genetics , MicroRNAs/genetics , Animals , Apoptotic Protease-Activating Factor 1/genetics , Binding Sites/genetics , Caspase 3/metabolism , Caspase 8/metabolism , Caspase 9/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Cyclin-Dependent Kinase Inhibitor p27/biosynthesis , Down-Regulation , Gene Expression Regulation, Neoplastic/genetics , Humans , Laryngeal Neoplasms/pathology , Male , Mice , Mice, Nude , Neoplasm Transplantation , Transplantation, Heterologous
16.
Article in Chinese | MEDLINE | ID: mdl-27093819

ABSTRACT

OBJECTIVE: To study the expression of human ether-α-go-go-related gene (herg) and hERG protein expressed by the gene in laryngeal carcinoma compared with the control group(mucosa adjacent to cancer of 2 cm). METHOD: Expression of herg and hERG protein was detected by immunohistochemistry (SP) and real-time PCR in resected tissue of laryngeal carcinoma and mucosa adjacent to cancer of 2 cm. RESULT: (1) By immunohistochemistry, the positive expression rate of hERG in laryngeal carcinoma was 76.7% (23/30), while it was 10.0% (2/20) in mucosa adjacent to cancer of 2 cm, the difference between which was statistically significant (P < 0.05). (2) By real-time PCR, the expression level of herg mRNA in laryngeal carcinoma is 2.25 times higher than that in mucosa adjacent to cancer of 2 cm. CONCLUSION: Herg is highly expressed in tissue of laryngeal carcinoma, and it may be have some relevance to the happening and development of laryngeal carcinoma.


Subject(s)
Ether-A-Go-Go Potassium Channels/metabolism , Laryngeal Neoplasms/metabolism , ERG1 Potassium Channel , Humans , RNA, Messenger
17.
Oncol Lett ; 9(1): 35-42, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25452816

ABSTRACT

The aim of the present study was to investigate the association between O6-methylguanine-DNA methyltransferase (MGMT) gene expression levels, and DNA methylation status and histone modifications in laryngeal squamous cell carcinoma (LSCC). Chromatin immunoprecipitation, methylation-specific polymerase chain reaction (PCR), and reverse transcription-quantitative PCR were performed to analyze histone modifications, DNA methylation status and mRNA expression levels in the promoter region of the MGMT gene in laryngeal carcinoma HEp-2 cells, as well as in 50 paired healthy and LSCC tissue samples. The present study demonstrated that treatment of HEp-2 cells with 5-aza-2'-deoxycytidine (Aza), a DNA methyltransferase inhibitor, significantly upregulated MGMT mRNA expression levels, reduced MGMT DNA methylation, reduced MGMT histone H3 lysine 9 (H3K9) di-methylation, and increased MGMT histone H3 lysine 4 di-methylation without a significant change in H3K9 acetylation. Trichostatin A (TSA), a histone deacetylase inhibitor, marginally upregulated MGMT mRNA expression levels without affecting the DNA methylation status, or H3K9 or H3K4 di-methylation, however, TSA treatment caused a significant increase in H3K9 acetylation. Furthermore, Aza and TSA combination treatment produced a synergistic effect. In the LSCC samples, the rate of DNA methylation in the MGMT gene was 54%, compared with 24% in the healthy control group (P<0.05). Therefore, data from the present study indicates that MGMT may serve as a novel therapeutic target in the treatment of LSCC.

18.
Article in Chinese | MEDLINE | ID: mdl-25017220

ABSTRACT

OBJECTIVE: Through clinical observation of granuloma after CO2 laser cordectomy under suspensive laryngoscope to discuss the effects of laryngopharyngeal reflux(LPR) to traumatic granuloma. METHODS: According to the classification of depth and range of CO2 laser cordectomy, 111 cases were divided into 5 groups, and the incidence of postoperative granuloma of each group was observed. The largest number of the 5 groups was 49 cases of type III CO2 laser cordectomy which was subdivided into 4 groups according to whether or not laryngopharyngeal reflux and whether or not proton pump inhibitor (PPI) treatment. RESULTS: In 111 cases, 56 cases (50.5%) developed granuloma after CO2 laser cordectomy. The incidence of traumatic granuloma after surgery was 10% (1/10), 26.1% (6/23), 53.1% (26/49), 78.6% (11/14), 80.0% (12/15) in I, II, III, IV, V type, respectively. It had statistical significance in chi-square test between 5 kinds of operative classification and the incidences of postoperative granuloma (χ² = 20.32, P < 0.01) and Spearman correlation analysis showed positive correlation between classification of operation and incidences of granuloma (r = 0.44, P < 0.01). According to LPR (-), LPR (+)and PPI (+), PPI (-), the incidence of granuloma had statistical significance in these 4 group patients of 49 type III cases (χ²= 5.83, P < 0.05). The incidence of granuloma after surgery was the lowest in LPR (-) PPI (+) group (30%) and the highest in LPR (+) PPI (-) group (80%), and it showed significant difference (χ² = 6.25, P < 0.05). CONCLUSIONS: With the increase of removal depth and the range after CO2 laser cordectomy, it appears rising trend in incidence of granuloma. Laryngopharyngeal reflux and PPI therapy on the incidence of traumatic granuloma has certain influence.


Subject(s)
Granuloma/epidemiology , Laryngopharyngeal Reflux , Laryngoscopy/adverse effects , Laser Therapy/adverse effects , Adult , Aged , Aged, 80 and over , Female , Granuloma/pathology , Humans , Laryngoscopy/methods , Lasers, Gas , Male , Middle Aged
19.
Article in Chinese | MEDLINE | ID: mdl-25007671

ABSTRACT

OBJECTIVE: To investigate the expression of CXCR4 in maxillary sinus carcinoma cells IMC3 under hypoxia. METHOD: IMC3 cells were cultured for 6 h, 12 h, 24 h and 48 h under normoxia and hypoxia. Real-Time PCR was applied to detect the expression of mRNA of CXCR4 and immunohistochemisrty was applied to investigate its protein level. RESULT: CXCR4 mRNA level was about 0.035 under normal conditions, which was obviously upregulated by hypoxia. The mRNA levels after culturing under hypoxia for 6 h, 12 h, 24 h and 48 h were 0.283, 0.313, 0.426, 0.510 respectively. There was statistically significant difference between the mRNA levels of each two groups (P < 0.05, Mann-Whiney Test) with a time dependent course, except for the difference between the groups of 6 h and 12 h. Immunohistochemistry showed that there was almost negative staining for CXCR4 in the cell cultured in nomoxia, while stong positive staining of CXCR4 was observed in cells cultured in hypoxia . The positive staining was located mainly in the cell membrane and cytoplasm and little in the nucleus. CONCLUSION: Hypoxia could induce expression of CXCR4 in IMC3 cells at both mRNA and ptrotein levels. The upregulation of CXCR4 by hypoxia showed an obvious time dependent course.


Subject(s)
Maxillary Sinus/metabolism , Receptors, CXCR4/metabolism , Cell Hypoxia , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Maxillary Sinus/pathology
20.
Int J Oncol ; 44(5): 1678-84, 2014 May.
Article in English | MEDLINE | ID: mdl-24603804

ABSTRACT

Plasma miRNAs have been reported as biomarkers for various diseases. In this study, we investigated whether plasma concentrations of miR-126 may be useful as biomarkers for laryngeal squamous cell carcinoma (LSCC). We examined the function and mechanism of miR-126 in LSCC by using cell biology and molecular pathology techniques such as western blotting, quantitative PCR, IHC and IF. The expression of Camsap1 mRNA and protein is higher in cancer tissues compared to that in normal tissues. Both miR-126 and Camsap1 were related with the prognosis of LSCC patients. We found that miR-126 was able to inhibit LSCC partly by suppressing Camsap1 expression. In addition, Camsap1 expression induced microtubule formation and aggregation. This mechanism possibly explains why loss of miR-126 is frequently associated with tumor metastasis.


Subject(s)
Carcinoma, Squamous Cell/pathology , Laryngeal Neoplasms/pathology , MicroRNAs/blood , MicroRNAs/genetics , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Animals , Carcinoma, Squamous Cell/blood , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Laryngeal Neoplasms/blood , Male , Mice , Mice, Nude , Microtubules/metabolism , Middle Aged , Neoplasm Metastasis/genetics , Neoplasm Metastasis/pathology , Neoplasms, Experimental , Phylogeny , Prognosis , Tumor Microenvironment
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