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1.  Challenges in the modification of the M1 stage of the TNM staging system for nasopharyngeal carcinoma: A study of 1027 cases and review of the literature 
A series of modifications have been introduced to the TNM staging system over time for nasopharyngeal carcinoma (NPC), mainly focused on the T (primary tumor) and N (local node) components of the system. The M1 stage is a ‘catch all’ classification, covering a group of patients whose outlook ranges from potentially curable to incurable. Since the current M1 stage does not allow clinicians to stratify patients according to prognosis or guide therapeutic decision-making and allow comparison of results of radical and non-radical treatments, we aimed to subdivide the M1 stage according to a retrospective study of 1027 metastatic NPC patients and to review the relevant literature. Between 1995 and 2007, 1027 inpatients with distant metastasis from NPC were retrospectively analyzed. Various possible subdivisions of the M1 stage were considered, looking at different metastatic sites, the number of metastatic organs and the number of metastases. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. The most frequently involved metastatic sites were the bone, lung and liver. The incidence rates of solitary metastatic lesions and pulmonary metastasis were 16.2 and 41.3%. Despite the poor survival of these patients with a median survival of 30.8 months, patients in the metachronous metastatic group with metastases to the lung and/or solitary lesions, were defined as M1a, and were significantly associated with favorable median survival of 41.5 and 49.1 months in the univariate and multivariate analysis, respectively. Patients in the metachronous metastatic group with metastasis to the lung and/or solitary lesions (M1a) have a more favorable prognosis compared with those patients with multiple metastases located in other anatomic sites (M1b). These data, in one of the largest reported metastatic NPC cohorts, are the first to show the prognostic impact of metastatic status in NPC. As a powerful predictor, the potential clinical value of a modified M1 of the TNM system for NPC will facilitate patient counseling and individualize management.
PMCID: PMC3460246  PMID: 23139721
distant metastasis; M1 stage; nasopharyngeal carcinoma; metastatic survival; prognostic factors
2.  Correlation of obesity and osteoporosis: Effect of free fatty acids on bone marrow-derived mesenchymal stem cell differentiation 
Studies on the relationship between obesity and bone have recently become widespread. The aim of this study was to investigate the effect of obesity on bone, utilizing a diet-induced obese mouse model, and to explore the role of free fatty acids (FFAs) in the osteogenesis/adipogenesis of mouse bone marrow-derived mesenchymal stem cells (BMSCs). An obese mouse model was established by a high-fat diet (HFD). Proximal femurs were collected at sacrifice, and bone mineral density (BMD) in the proximal femurs was measured by dual-energy X-ray absorptiometry. Bone histomorphometry was performed using undecalcified sections of the proximal femurs. The effect of obesity on the differentiation of mouse BMSCs was assessed by colony formation assays and gene expression analysis. In vitro, various osteogenic and adipogenic genes were determined by real-time quantitative PCR in mouse BMSCs after exposure to conditioned medium (CM) from FFA-treated 3T3-L1 adipocytes. Western blotting was further performed to analyze the representative protein expression of PPARγ and Runx2. BMD and trabecular thickness were significantly greater in the HFD mice than in the control mice. CFU-osteo assay showed significantly increased osteogenesis of BMSCs. The mRNA level of Runx2 was significantly higher, while PPARγ and Pref-1 were significantly lower in BMSCs from the HFD mice compared to the control mice. In mouse BMSCs, the Sox9 and Runx2 genes were significantly up-regulated after exposure to CM from FFA-treated adipocytes, while PPARγ and CEBP-α were significantly down-regulated. Osteogenesis was significantly increased, while adipogenesis was significantly decreased. In conclusion, HFD-induced obesity may play a protective role in bone formation by concomitantly promoting osteogenic and suppressing adipogenic differentiation of BMSCs through factors secreted by FFA-treated adipocytes.
PMCID: PMC3445940  PMID: 22993583
mesenchymal stem cells; free fatty acids; obesity; osteogenesis; adipogenesis
3.  Gene expression patterns in the histopathological classification of epithelial ovarian cancer 
The purpose of this study was to screen cancer-related genes and to identify histopathological gene expression patterns as potential biomarkers in human epithelial ovarian cancer (EOC). Fifty genes were screened by reverse-transcription polymerase chain reaction assay with cDNA from 83 EOC tissues and 48 normal ovarian specimens of ovarian cancer patients and evaluated by gel electrophoresis analysis. Twenty expressed genes were assessed by real-time relative-quantity (RQ)-PCR in 30 EOC specimens for gene signature study. Four genes, TAL2, EGF, ILF3 and UBE2I, were investigated for gene expression patterns in histopathological classification of EOC. RQ-value (Ct, ΔCt, ΔΔCt, RQ and gene expression plots) was generated by ABI 7500 Fast System SDS Software (version 1.4). SPSS 15.0 software was used for statistical analysis. Using real-time RQ-PCR, we found that TAL2, EGF, ILF3 and UBE2I demonstrated distinct expression patterns in histological types of epithelial ovarian cancer. The expression of ILF3 and UBE2I in tumors was significantly higher than in normal tissue, with extremely high expression in serous carcinomas compared to mucinous, endometrium and clear cell carcinomas. In addition, ILF3 and UBE2I were overexpressed in advanced stage and advanced grade ovarian cancer, compared to early stage or well-differentiated ovarian cancer. This is the first report of TAL2 and ILF3 expression in the normal human ovary and epithelial ovarian cancer. Our results indicate that overexpression of ILF3 and UBE2I in advanced stage and advanced grade suggest that these two genes may play an important role in tumorigenesis/tumor progression and pathological differentiation of the disease. Notably, ILF3 plays a role in DNA binding activity and transcriptional and post-transcriptional regulation; UBE2I is required in ubiquitination and sumoylation and is involved in DNA repair and apoptosis of cells. Further investigations to reveal the molecular mechanisms related to the activation of ILF3 and UBE2I in the development of EOC are warranted.
PMCID: PMC3490392  PMID: 23136613
gene signature; histopathological types; epithelial ovarian cancer; real-time quantitative PCR

Results 1-3 (3)