Song W.,Central South University |
Xin W.,Hunan Cancer Hospital
Chinese Journal of Tissue Engineering Research | Year: 2014
BACKGROUND: The increase of serum cholesterol levels is positively correlated with the increasing incidence of osteoarthritis. Little is known about the role of high-fat diet in the degeneration of articular cartilage and induced arthritis. OBJECTIVE: To observe the morphology change of the articular cartilage of New Zealand rabbits after high-fat diet, and explore the role of food in the articular cartilage degeneration. METHODS: Forty New Zealand white rabbits were randomly divided into two groups. In control group, rabbits were fed with basal diet. In high-fat diet group, rabbits were fed with high-fat diet (20% lard and 80% basal diet). Fasting blood samples was taken every 4 weeks, to detect the triglyceride and total cholesterol levels. After rabbit were fed for 28 weeks, the knee joint was grossly observed and the femoral condyle cartilage was scanned by scanning electron microscope. RESULTS AND CONCLUSION: Compared with the control group, the triglyceride and total cholesterol levels were significantly increased in the high fat group (P < 0.05). Under scanning electron microscope, the high-fat group showed rough surface of condylar cartilage, shallow pouch, messy arrangement, irregular shape and uneven size. The surface of cartilage exhibited focal denudation, irregular arrangement, uneven porosity and fractured cavity. Under higher magnification, small mountain-like structure of cartilage surface became shallow and flattened, the pores disappeared. Long-term high-fat diet may induce and aggravate cartilage damage, suggesting it may be involved in the pathogenesis of osteoarthritis. © 2014 Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.
Pei L.,Central South University |
Xie P.,Central South University |
Zhou E.,Central South University |
Yang Q.,Central South University |
And 2 more authors.
Molecular Medicine Reports | Year: 2011
DEP domain containing mammalian target of rapamycin (mTOR)-interacting protein (DEPTOR), a recently identified mTOR-interacting protein, is a novel candidate oncogene. Previous studies reveal that high DEPTOR expression is required to maintain PI3K and Akt activation and to inhibit apoptosis. However, its significance in differentiated thyroid carcinoma (DTC) is not yet known. The present study verifies the mRNA and protein expression of DEPTOR in five cell lines, DTC tissues and normal adjacent tissues. Tissue microarrays of 114 DTC patients were used to detect DEPTOR protein expression. The assessment of DEPTOR levels demonstrated that DEPTOR in DTC cells and tissues was significantly increased compared with normal cells and adjacent normal tissues. DEPTOR protein expression was significantly associated with lymph node status, extrathyroid extension and distant metastasis. Patients exhibiting high DEPTOR expression were statistically susceptible to earlier recurrence and poorer survival than those with low expression. Univariate and multivariate analyses showed that DEPTOR expression was an independent prognostic factor for DTC recurrence. In conclusion, our data indicate DEPTOR as a novel prognostic marker for DTC.
Jiang W.,Central South University |
Wei R.,Central South University |
Su J.,Central South University |
He L.,Hunan Cancer Hospital |
Yang Z.,Central South University
Journal of Central South University (Medical Sciences) | Year: 2012
Objective: To observe the clinical results and the toxicities of normal tissues in untreated nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT). Methods: A total of 90 patients with untreated NPC received IMRT. According to the 1992 Fuzhou staging system, 3 patients were in stage I, 29 in stage II, 26 in stage III, and 32 in stage IVa. For IMRT, the prescription dose was 71.94-77.88 Gy/33f for the planning target volume of the gross tumor volume in the nasopharynx (PGTVnx); 69.96 Gy/33f for the positive neck lymph nodes (GTVnd); 60-66 Gy/33f for the planning target volume of the high risk regions (PTV1); and 50.4-56 Gy/28f for the planning target volume of the low risk regions (PTV2). Chemotherapy included concurrent and adjuvant protocols. The overall survival rate, local control rate, and distant metastasis-free survival rate were estimated by Kaplan-Meier method. Cox regression was used for multivariate analysis. Acute and late toxicities were graded according to RTOG radiation morbidity scoring criteria. Results: The median follow-up time was 33 months (12-56 months). The 1-, 2-, 3-and 4-year survival rate was 97.8%, 90.6%, 86% and 80%; the local control tate was 98.8%, 97.5%, 92.1% and 77.4%; and the distant metastasis-free survival rate was 95.3%, 90.7%, 88.4% and 85.8%, respectively. The most serious acute toxicity was irradiated inflammation of mocosa with Grade 1 to 4 of 16.7%, 60%, 23.3% and 0, respectively. In the multivariate analysis, clinical stages were the prognostic factors for the survival rate. The most serious toxicity was salivary gland. The rate of grade xerostomia 1-year after the radiotherapy with Grade 1 to 4 was 18.1%, 9.6%, 0 and 0, respectively. Conclusion: IMRT combined chemotherapy can improve the survival rate, and late adverse reaction is obviously decreased. Local recurrence and distant metastasis are the main reasons for low survival rate.
Huang W.,Central South University |
Liu J.,Central South University |
Feng X.,Central South University |
Chen H.,Central South University |
And 7 more authors.
Medical Oncology | Year: 2015
Loss of deleted in liver cancer-1 (DLC-1) can induce apoptosis and inhibit the mobility, migration and metastasis in several cancers. Previously, we revealed that ectopic expression of DLC-1 can suppress proliferation, mobility, migration and tumorigenesis in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms accounting for the roles of DLC-1 in NPC are still obscure. In the present work, we attempted to study and uncover the mechanisms underlying the functions of DLC-1 in NPC. The apoptosis of 5-8F-DLC-1 cells, established previously, was analyzed by mitochondrial membrane potentials assay and flow cytometer analysis. And the antibodies involving pathways such as mitochondrial-associated apoptosis, epithelial mesenchymal transition and metastasis were applied to detect and compare the expression level of targeted proteins. The obvious apoptosis of 5-8F-DLC-1 cells was observed reflected by mitochondrial depolarization and lower ratio in cell viability. Subsequently, the activation of mitochondrial apoptosis was verified by the increased expressions of Bax, Apaf1, cleave-caspases and cleave-PARP, etc, and the decreased expressions of Bcl-2, Bcl-xL, Mcl-1, Survivin, etc, in 5-8F-DLC-1 cells. Then, the inhibited epithelial mesenchymal transition of 5-8F-DLC-1 cells was validated by upregulated expression of E-cadherin and downregulated expression of N-cadherin, Snail, Vimentin. Subsequently, downregulated expressions of proteins such as FAK, RhoA, ROCK1 and cdc25 related to cell adhesion and cytoskeleton organization were also observed. And expressions of MMPs were inhibited in 5-8F-DLC-1 cells. At last, the inhibited activity of EGFR/Akt/NF-κB axis was revealed by the decreased expressions of phosho-EGFR, phosho-Akt, phosho-p38MAPK, phosho-IKKα and phosho-p65. Here, we systematically explored the mechanisms underlying the negative roles of DLC-1 in NPC cells. For the first time, we confirmed that the ectopic expression DLC-1 can induce mitochondrial apoptosis, inhibit EMT and related processes by targeting the EGFR/Akt/NF-κB pathway, which, beyond all doubt, offered beneficial guidelines for other studies and laid a good foundation for its clinical applications ultimately. © 2015, Springer Science+Business Media New York.
Shi Y.,Peking Union Medical College |
Shi Y.,Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs |
Zhang L.,Sun Yat Sen University |
Liu X.,307 Hospital of the Academy of Military Medical science |
And 29 more authors.
The Lancet Oncology | Year: 2013
Background: Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods: In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings: 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033). Interpretation: Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding: Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program. © 2013 Elsevier Ltd.