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Dong H.,Chinese National Human Genome Center at Shanghai | Zhang H.,General Hospital of Air Force P.L.A. | Liang J.,Hunan Province Tumor Hospital | Yan H.,Ningbo No.2 Hospital | And 8 more authors.
BMC Medical Genomics | Year: 2011

Background: Hepatocellular carcinoma (HCC) is a worldwide malignant liver tumor with high incidence in China. Subchromosomal amplifications and deletions accounted for major genomic alterations occurred in HCC. Digital karyotyping was an effective method for analyzing genome-wide chromosomal aberrations at high resolution. Methods. A digital karyotyping library of HCC was constructed and 454 Genome Sequencer FLX System (Roche) was applied in large scale sequencing of the library. Digital Karyotyping Data Viewer software was used to analyze genomic amplifications and deletions. Genomic amplifications of genes detected by digital karyotyping were examined by real-time quantitative PCR. The mRNA expression level of these genes in tumorous and paired nontumorous tissues was also detected by real-time quantitative RT-PCR. Results: A total of 821,252 genomic tags were obtained from the digital karyotyping library of HCC, with 529,162 tags (64%) mapped to unique loci of human genome. Multiple subchromosomal amplifications and deletions were detected through analyzing the digital karyotyping data, among which the amplification of 7q21.3 drew our special attention. Validation of genes harbored within amplicons at 7q21.3 locus revealed that genomic amplification of SGCE, PEG10, DYNC1I1 and SLC25A13 occurred in 11 (21%), 11 (21%), 11 (21%) and 23 (44%) of the 52 HCC samples respectively. Furthermore, the mRNA expression level of SGCE, PEG10 and DYNC1I1 were significantly up-regulated in tumorous liver tissues compared with corresponding nontumorous counterparts. Conclusions: Our results indicated that subchromosomal region of 7q21.3 was amplified in HCC, and SGCE, PEG10 and DYNC1I1 were probable protooncogenes located within the 7q21.3 locus. © 2011 Dong et al; licensee BioMed Central Ltd.

Liu W.,Central South University | Yin T.,Central South University | Ren J.,Central South University | Li L.,Nanchang University | And 3 more authors.
European Archives of Oto-Rhino-Laryngology | Year: 2014

Cholesteatoma is a benign keratinizing squamous epithelial lesion characterized by the hyper-proliferation of keratinocytes with abundant production of keratin debris in the middle ear. The epidermal growth factor receptor (EGFR)/Akt/nuclear factor-kappa B (NF-κB)/cyclinD1 signaling pathway is one of the most important pathways in regulating cell survival and proliferation. We hypothesized that the EGFR/Akt/NF-κB/cyclinD1 signaling pathway may be activated and involved in the cellular hyperplasia mechanism in acquired cholesteatoma epithelium. Immunohistochemical staining of phosphorylated EGFR (p-EGFR), phosphorylated Akt (p-Akt), activated NF-κB and cyclinD1 protein was performed in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium. Protein expression of p-EGFR, p-Akt, activated NF-κB and cyclinD1 in cholesteatoma epithelium was significantly increased when compared with normal EAC epithelium (p < 0.01). In cholesteatoma epithelium, a significant positive association was observed between p-EGFR and p-Akt expression and between the expressions of p-Akt and NF-κB, NF-κB and cyclinD1, respectively (p < 0.01). No significant relationships were observed between the levels of investigated proteins and the degree of bone destruction (p > 0.05). The increased protein expression of p-EGFR, p-Akt, NF-κB and cyclinD1 and their associations in cholesteatoma epithelium suggest that the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway is active and may be involved in the regulatory mechanisms of cellular hyperplasia in cholesteatoma epithelium. © Springer-Verlag 2013.

Liu L.-P.,Hunan Province Tumor Hospital | Cao X.-C.,Hunan Normal University | Liu F.,Hunan Normal University | Quan M.-F.,Hunan Normal University | And 2 more authors.
Oncology Letters | Year: 2014

Casticin is an active ingredient derived from Fructus Viticis, a traditional Chinese medicine. This study aimed to investigate the role of forkhead box O3 (FOXO3a) in breast cancer cells and examine the regulatory mechanisms of FOXO3a in response to casticin treatment of the cells by ELISA, flow cytometry, small interfering RNA (siRNA) transfection and western blot analysis. Casticin treatment induced apoptosis and reduced the expression of the transcription factor forkhead box protein M1 (FOXM1). In addition, FOXM1 repression induced by casticin treatment was associated with the activation of FOXO3a via increased dephosphorylation. Notably, silencing FOXO3a expression by siRNA-mediated gene knockdown attenuated casticin-mediated apoptosis. Collectively, these findings suggest that FOXO3a is a critical mediator of the inhibitory effects of casticin on apoptosis in breast cancer cells.

Zhou J.,Capital Medical University | Zhou J.,Hunan Normal University | Xiao X.,Hunan Normal University | Yi H.,Hunan Normal University | And 3 more authors.
ORL | Year: 2012

Gp96 (GRP94) is a chaperone that is responsible for molecular folding and assembly of proteins. To investigate correlations among Gp96 expression, sensitivity to radiotherapy and clinical features of nasopharyngeal carcinoma (NPC), the expression of Gp96 in 98 NPC samples was analyzed by immunohistochemistry and Western blotting at the protein level, and by real-time PCR at the mRNA level. Clinicopathological features, including stage, sex, grade and survival, were compared between the high and low Gp96 expression groups. As a result, Gp96 was expressed at a higher level in NPC tissues than in noncancerous nasopharyngeal mucosa (p = 0.001). Univariate analysis suggested that a higher Gp96 expression level was associated with significantly decreased disease-free and 5-year survival rates (p = 0.000, p = 0.000, respectively). Multivariate Cox proportional-hazard regression analysis, which adjusts for clinicopathological variables, indicated that it was only associated with the 5-year overall survival rate (p = 0.002). Furthermore, patients with high Gp96 expression levels were significantly more resistant to radiotherapy (p = 0.001). These data are the first indication of a positive correlation between Gp96 expression levels and radiosensitivity and 5-year survival rate. Gp96 might serve as a novel candidate marker for predicting the long-term prognostic outcome of NPC. Copyright © 2012 S. Karger AG.

Chen J.,Hunan Province Tumor Hospital
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2011

To investigate the diagnosis and treatments of thyroid goiters invading mediastinum and thoracic cavity. Seventy-eight cases of thyroid goiters invading mediastinum and thoracic cavity and undergoing surgery from 1995 to 2005 were reviewed. There were 22 males and 56 females and their age ranged from 45 years to 78 years with a median age of 59 years. According to the classification of intrathoracic thyroid goiters, there were 50 cases in Class I, 20 cases in Class II and 8 cases in Class III. In these patients, 38 cases suffered from dyspnea at degree I and 20 cases at degree II. Of the patients, 71 underwent thyroidectomy through neck approach and 7 underwent thyroidectomy by a combined approach of neck incision plus sternotomy or lateral thoracotomy. Tracheal defects in 4 cases and esophageal defects in 3 cases were repaired. Postoperative residual diseases were found in tracheoesophageal wall (5 cases) and mediastinum (6 cases). Eleven patients received postoperative radiotherapy and 18 underwent (131)I treatment. No case died of operation and no case with wound infection. The time of follow-up was 60 - 180 months with a median of 110 months. Three patients lost follow-up. Dyspnea in 58 cases were improved after operation. Three of 49 patients with nodular goiters died from cardiocerebrovascular diseases. Of 29 patients with thyroid papillary carcinoma, 2 died from lung metastasis and 3 died from neck relapse. Five-year survival rate was 75.0% in the patients with thyroid cancer. Most of thyroid goiters invading mediastinum and thoracic cavity can be completely resected via neck approach, but a combined approach of neck incision plus sternotomy or lateral thoracotomy may be used in some cases with malignant goiters to dissect the diseases completely. Postoperative external beam radiotherapy are required for the residual diseases. (131)I may be considered in high-risk differentiated thyroid carcinoma cases.

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