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Hong-Bo Wang,
Gui-Hong Liu,
Hua Zhang,
Shan Xing,
Li-Juan Hu,
Wei-Feng Zhao,
Bo Xie,
Man-Zhi Li,
Bo-Hang Zeng,
Yingqiu Li, Mu-Sheng Zeng
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ABSTRACT: Bmi1, a member of the polycomb group, is elevated and involved in the pathogenesis of various aggressive cancers, including nasopharyngeal carcinoma (NPC). To date, the mechanisms underlying the high expression of Bmi1 in NPC remain obscure. To gain new insights into the transcriptional regulation of BMI1, we cloned and characterized the promoter region of BMI1. Luciferase reporter assays demonstrated that the region from -783 to +375 exhibited significant promoter activity. Using a series of 5' and 3' deletion promoter constructs in luciferase reporter assays, the regions +167/+232 and -536/-134 were found to be sufficient for full promoter activity. Transcriptional activity of the BMI1 promoter was dependent on the Sp1 binding sites cluster (+181/+214) as well as the E-box elements (-181) and was abolished after mutation of the two cis-elements. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated that Sp1 bound to the region from +181 to +214 within the BMI1 promoter. In addition, gain- and loss-of-function analyses revealed that Sp1 augmented Bmi1 expression. Further investigations using immunohistochemistry and qRT-PCR disclosed a significant positive correlation between the expression of Sp1 and Bmi1 in NPEC/NPC cells and NPC tissue specimens. In addition, Myc, the known transcription factor for BMI1 in neuroblastomas, also activated the transcription of BMI1 through binding to the E-box element (-181) within its promoter, and showed a positive correlation with the mRNA level of BMI1 in NPC. In conclusion, these findings provide valuable mechanistic insights into the role of Sp1 and c-Myc on BMI1 transcription in NPC, suggesting that targeting Sp1 or c-Myc may be a potential therapeutic strategy for NPC. This article is protected by copyright. All rights reserved.
FEBS Journal 04/2013; · 3.79 Impact Factor
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ABSTRACT: Background: This study was to investigate the relationship between pretreatment nutritional status and prognosis of nasopharyngeal carcinoma (NPC). Methods: Pretreatment nutritional status was evaluated by ideal body weight percentile (IBW %) and serum albumin for 512 NPC patients received radical radiotherapy. Kaplan-Meier methods, log-rank test, and a Cox model were applied for survival analysis. Results: Before radiotherapy, IBW% < 90% was related to poorer overall survival (OS) and distant metastasis free survival (DMFS) (P=0.031, P = 0.012); albumin ≤ 43.0 g/ L was related to poorer OS and DMFS (P < 0.001, P = 0.042); both IBW% and albumin were independent prognostic factors for OS; those patients with IBW% < 90% and albumin ≤ 43.0 g/ L simultaneously had the worst OS and DMFS. Conclusions: Decrease of pretreatment IBW% and albumin was related to poorer survival of NPC. Head Neck, 2013.
Head & Neck 04/2013; · 2.40 Impact Factor
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ABSTRACT: Tandutinib is a novel inhibitor of tyrosine kinases FLT3, PDGFR and KIT. Our study was to explore the capability of tandutinib to reverse ABC transporter-mediated multidrug resistance. Tandutinib reversed ABCG2-mediated drug resistance in ABCG2-482-R2, ABCG2-482-G2, ABCG2-482-T7 and S1-M1-80 cells and increased the accumulation of doxorubicin, rhodamine 123 and [H(3)] mitoxantrone in ABCG2-overexpressing cells. Importantly, tandutinib selectively sensitized side population cells to mitoxantrone. Taken together, our results advocate the potency of tandutinib as an ABCG2 modulator and stem-like cells targeted agent to increase efficiency of anticancer drugs.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 04/2013; · 2.61 Impact Factor
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Si Wei Li,
Hua Wang,
Mei Lian Liu,
Hai Bo Zhang,
Yan Qun Xiang,
Xing Lv,
Wei Xiong Xia, Mu Sheng Zeng,
Hai Qiang Mai,
Ming Huang Hong,
Xiang Guo
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ABSTRACT: The purpose of this prospective study is to investigate the predictive and prognostic significance of the Raf kinase inhibitory protein (RKIP) in locoregionally advanced nasopharyngeal carcinoma (NPC). Immunohistochemical assays were performed to detect the RKIP protein expression of samples from 212 patients with locoregionally advanced NPC. All patients were assigned randomly into the inductive chemotherapy plus radiation therapy (IC + RT) group, the concurrent chemoradiotherapy (CCRT) group, the inductive chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) group, and the radiation therapy alone (RT) group. The patients in the IC + RT group were treated with IC using 2-3 cycles of cisplatin (80 mg/m(2)) and fluorouracil (500 mg/m(2)), repeated every 3 weeks, followed by radiotherapy. Those in the CCRT group were treated with weekly cisplatin (40 mg/m(2)) for 6-7 cycles during radiotherapy. In the IC + CCRT group, the chemotherapy prior to radiation was similar to the cisplatin-fluorouracil regimen in the IC + RT group, whereas it cisplatin regimen was identical to that in the CCRT group. The results show that RKIP is an independent prognostic factor for 5-year distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). Patients with high RKIP expression benefited more from reduced metastasis in the IC + RT and the IC + CCRT group, with improved OS and PFS in each treatment group compared with that among patients with low RKIP expression. In the high RKIP expression subgroup, chemotherapy combined with radiotherapy improved the DMFS when compared with the RT group, but this effect was not observed in the low RKIP expression subgroup. RKIP was predictive of distant metastasis with good sensitivity and specificity. Clinically, high RKIP expression inhibited distant metastasis in advanced NPC, and its detection might be used to predict distant metastasis with good sensitivity and specificity. The effect of chemotherapy on distant metastasis in combined chemoradiotherapy might be related to the RKIP expression level. Patients with high RKIP expression showed more improved OS and PFS than their low RKIP expression counterparts. Higher RKIP expression improves the DMFS of patients who receive inductive high-dose cisplatin-based chemoradiotherapy, with or without concurrent cisplatin. Low RKIP expression is also a predictive marker for cancer progression and metastasis, which could be used to stratify patients with high risk of metastasis and death.
Medical Oncology 03/2013; 30(1):322. · 2.14 Impact Factor
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ABSTRACT: SIAH is widely expressed in lot of kinds of tumors. It plays a significant role in human cancer, but its clinicopathologic and prognostic significance in laryngeal squamous cell carcinoma (LSCC) has not yet been elucidated. The SIAH expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry in LSCC tissues and adjacent normal larynx tissues. Statistical analyses were applied to test the associations between SIAH expression, clinicopathologic factors, and prognosis. Western blots and RT-PCR showed that the expression level of SIAH was lower in LSCC tissues than in adjacent normal larynx tissues. By immunohistochemical analysis, reduced expression of SIAH was found in 71.67 % LSCCs. After multivariate analysis, along with pathologic differentiation, the protein expression level of SIAH was an independent and significant predictive factor (P = 0.04). Furthermore, patients with SIAH-low tumors had a shorter disease-free survival and overall survival (P = 0.002 and P = 0.045, respectively). Our study suggests that SIAH protein expression is a valuable biomarker for LSCC. Low expression of SIAH is associated with poor disease-free survival and overall survival in LSCC patients.
Medical Oncology 03/2013; 30(1):485. · 2.14 Impact Factor
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ABSTRACT: Protein tyrosine kinase 6 (PTK6), also known as breast tumor kinase (Brk), was a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. The deregulated expression of PTK6 was observed in various human cancers. However, little was known about PTK6 expression and its clinicopathological significance in human laryngeal squamous cell carcinoma (LSCC).
PTK6 expression was evaluated in 7 pairs of surgically resectable laryngeal tissues by Western blotting and in 13 pairs of surgically resectable laryngeal tissues by reverse transcription-PCR (RT-PCR). Using immunohistochemistry, we performed a retrospective study of the PTK6 expression levels on 134 archival LSCC paraffin-embedded samples. Prognostic outcomes correlated with PTK6 were examined using Kaplan-Meier analysis and Cox proportional hazards model.
The PTK6 expression level was lower in LSCC tissues than in the adjacent noncancerous epithelial laryngeal tissues by Western blots and RT-PCR. By immunohistochemical analysis, we observed high expression of PTK6 in 25 of 76 (32.9%) adjacent noncancerous epithelial laryngeal tissues and in 39 of 134 (29.1%) of LSCC, respectively. Multivariate analysis demonstrated that pN status and the expression level of PTK6 (P < 0.05) were independent and significant prognostic factors. In the primary LSCC category, median DFS (disease free survival) of high, medium and low PTK6 expression patients were 88.5 months ,74.5 months and 49.0 months (log-rank test, P = 0.002); median OS (overall survival) of high, medium and low PTK6 expression patients were 88.5 months ,76.3 months and 65.7 months (log-rank test, P = 0.002). Reduced cytoplasmic PTK6 expression in LSCC was significantly associated with late pN status (P =0.005, r = 0.27), advanced pTNM stages (III and IV) (P =0.027, r = 0.147), and poor differentiated LSCC (P <0.0001, r = 0.486). In adjacent paracancerous laryngeal epithelial samples, median DFS of high, medium and low PTK6 expression patients were 92.6 months ,75.6 months and 48.5 months (log-rank test, P = 0.020); median OS of high, medium and low PTK6 expression patients were 92.9 months ,78.9 months and 74.6 months (log-rank test, P = 0.042).
The present findings indicated that cytoplasmic PTK6 expression is a potential prognostic factor for survival in LSCC patients. High expression of PTK6 was associated with favorable OS and DFS in LSCC patients.
Journal of Translational Medicine 01/2013; 11:59. · 3.41 Impact Factor
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ABSTRACT: Background: The aim of this study is to explore the expression of beclin 1, an autophagy gene, in bladder cancer and to evaluate its clinical and prognostic significance in patients with bladder cancer.
Methods: Beclin 1 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry in bladder cancer tissues and adjacent normal bladder tissues. The relationship between the expression of beclin 1 and clinicopathological characteristics and prognosis was statistically analyzed.
Results: mRNA level, protein expression and immunoreactivity of beclin 1 were decreased in bladder cancer tissues compared with adjacent normal tissues. Downregulation of beclin 1 was more frequent in tumors with higher histological grades (the expression of beclin 1 was reduced by 49.0% in G1 and G2, and by 71.8% in G3, p=0.010), and was also reduced by 69.5% in the muscle invasive type and by 51.1% in the non-muscle invasive type (p=0.04). Reduced beclin 1 expression was positively associated with higher histological grade and more advanced clinical stage (p<0.05). Kaplan-Meier survival analysis revealed that patients exhibiting lower beclin 1 expression experienced a shorter survival than those with higher expression (p=0.006). Cox proportional hazards regression analysis showed that beclin 1 protein is an independent predictor of survival (p=0.005).
Conclusion: Beclin 1 has an influence on the progression of bladder cancer and might serve as a potential prognostic factor for patients with bladder cancer.
The International journal of biological markers 11/2012; · 1.48 Impact Factor
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Feng-Hua Xu,
Dan Xiong,
Ya-Fei Xu,
Su-Mei Cao,
Wen-Qiong Xue,
Hai-De Qin,
Wen-Sheng Liu,
Jing-Yan Cao,
Ying Zhang,
Qi-Sheng Feng,
Li-Zhen Chen,
Man-Zhi Li,
Zhi-Wei Liu,
Qing Liu,
Ming-Huang Hong,
Yin Yao Shugart,
Yi-Xin Zeng, Mu-Sheng Zeng,
Wei-Hua Jia
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ABSTRACT: Background Elevated levels of antibodies against antigens in the Epstein-Barr virus (EBV) lytic phase are important predictive markers for nasopharyngeal carcinoma (NPC) risk. Several lifestyle factors, including smoking, have also been associated with NPC risk. We hypothesized that some specific lifestyle factors induce transformation of EBV from the latent to the lytic stage and contribute to NPC occurrence. Methods We conducted a case-control study using data from male case patients (n = 1316) and control subjects (n = 1571) living in Guangdong Province, an area in China at high risk for NPC, to study potential NPC risk factors and EBV inducers. Two independent healthy male populations from a second high-risk area (n = 1657) and a low-risk area (n = 1961) were also included in the analysis of potential EBV inducers using logistic regression models. In vitro assays were performed to investigate the effect of cigarette smoke extract on EBV activation in two EBV-positive cell lines. All statistical tests were two-sided. Results Smoking was associated with an increased risk of NPC among the Guangdong participants with 20-40 and 40 or more pack-years vs never smokers (OR = 1.52, 95% CI = 1.22 to 1.88 and OR = 1.76, 95% CI = 1.34 to 2.32, respectively; P (trend) < .001). Smoking was the only factor linked to EBV seropositivity among the expanded control group and the independent low-risk population. In vitro experiments showed that cigarette smoke extract promoted EBV replication, induced the expression of the immediate-early transcriptional activators Zta and Rta, and increased transcriptional expression levels of BFRF3 and gp350 in the lytic phase. Conclusion Smoking is not only associated with NPC risk in individuals from China but is also associated with EBV seropositivity in healthy males and is involved in EBV activation.
CancerSpectrum Knowledge Environment 09/2012; 104(18):1396-410. · 14.07 Impact Factor
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ABSTRACT: Non-muscle myosin heavy chain IIA (NMHC IIA) plays a significant role in tumor progression and metastasis. The aim of this study was to explore the relationship between the expression levels of NMHC IIA and the characteristics, prognosis of patients who were cystectomy candidates with early-stage bladder cancer. Real-time PCR was used to examine the expression of NMHC IIA mRNA in 16 paired bladder cancer and the adjacent normal tissues. The expression of NMHC IIA protein in 167 specimens of bladder cancer was determined by immunohistochemistry assay. Statistical analyses were performed to evaluate the association between the expression of NMHC IIA, and clinicopathological features and prognosis. Compared with adjacent normal bladder tissues, upregulated expression of NMHC IIA mRNA was observed in 81.3% of bladder cancer tissues (P=0.011). Moreover, the higher levels of NMHC IIA expression were positively correlated with the histopathological classification (P=0.021), lymph node metastasis (P=0.047) and cancer-related mortality (P=0.030). The 5-year survival rate of patients with higher NMHC IIA expression was significantly lower than that of patients with lower NMHC IIA expression (P=0.004). Furthermore, in multivariate analysis by Cox regression model, high NMHC IIA expression was confirmed to be an independent molecular marker (P=0.047), while grade (P=0.020) and clinical T stage (P=0.049) were also significant prognostic factors. Expression of NMHC IIA mRNA was higher in bladder cancer compared to the adjacent normal tissues. The detection of NMHC IIA protein expression is potentially useful in prognostic evaluation of cystectomy candidates with early-stage bladder cancer.
Oncology Reports 08/2012; 28(5):1625-32. · 1.84 Impact Factor
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ABSTRACT: Aurora-A kinase (Aur-A), a member of a family of mitotic serine/threonine kinases, is known to be amplified in epithelial malignancies. In this study, we focused our investigation on Aur-A expression and its prognostic significance in nasopharyngeal carcinoma (NPC). Immunohistochemical staining for Aur-A was performed on the paraffin sections of 208 patients with NPC. Data were subjected to statistical analysis with respect to clinicopathological variables, overall survival and disease-free survival. An immunohistochemical analysis showed that Aur-A was highly expressed in 132 (63.5%) of the 208 NPC tissues examined. Aur-A expression was significantly correlated with T classification (P=0.012), clinical stage (P=0.003) and skull base invasion (P=0.003). Statistical analysis showed that Aur-A expression was inversely correlated with the 10-year overall and disease-free survival rates of NPC patients. Results of the multivariate analysis revealed that Aur-A expression was an independent prognostic indicator for patient survival. More significantly, Aur-A was found to be a marker for poor survival, which was mainly attributed to its high expression in the subgroup of T(4) tumor classification with aggressive local invasion. These results indicated that Aur-A expression is inversely correlated with survival and directly correlated with the malignant status of NPC. Therefore, Aur-A may serve as a potential biological marker for poor prognosis in the T(4) subgroup of patients.
Oncology letters 06/2012; 3(6):1237-1244. · 0.11 Impact Factor
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ABSTRACT: BACKGROUND: The purpose of this prospective study was to investigate the predictive significance of Raf kinase inhibitory protein (RKIP) in locoregionally advanced nasopharyngeal carcinoma (NPC) and its effect on distant metastasis. METHODS: The usual immunohistochemical stainings were performed to detect RKIP expression of cancer tissues from 210 patients with advanced NPC. After DNA samples from pretreatment plasma from these patients were extracted, real-time polymerase chain reaction (PCR) was performed to quantitatively analyze plasma Epstein-Barr virus (EBV) DNA. RESULTS: RKIP expression was significantly different for different N classifications and WHO pathologic grades, respectively (p < .05). Cox regression confirmed RKIP and EBV DNA were independent prognostic markers for 5-year distant metastasis-free survival (DMFS). In the high RKIP expression group, chemotherapy had a positive effect on improved DMFS, but not in the low RKIP expression group. CONCLUSIONS: RKIP could be identified as an independent prognostic factor on DMFS. For each combined treatment modality, the different impact of chemotherapy on distant metastasis might be related to the RKIP expression level. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
Head & Neck 05/2012; · 2.40 Impact Factor
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Xin-Jian Li,
Li-Xia Peng,
Jian-Yong Shao,
Wen-Hua Lu,
Jia-Xing Zhang,
Shi Chen,
Zhi-Yuan Chen,
Yan-Qun Xiang,
Ying-Na Bao,
Fang-Jing Zheng, Mu-Sheng Zeng,
Tie-Bang Kang,
Yi-Xin Zeng,
Bin Tean Teh,
Chao-Nan Qian
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ABSTRACT: Nasopharyngeal carcinoma (NPC) has the highest metastatic potential among head and neck cancers. Distant metastasis is the major cause of treatment failure. The role of interleukin-8 (IL-8) in NPC progression remains unknown. Our multivariate survival analyses of 255 patients with NPC revealed that higher IL-8 expression in primary NPC tissue was an independent prognostic factor for overall survival, disease-free survival, and distant metastasis-free survival of the patients. In vitro study revealed that IL-8 was highly expressed in the established high-metastasis NPC clone S18 relative to the low-metastasis cells. Suppression of IL-8 by short-hairpin RNA reduced the expression of IL-8 in S18 cells and subsequently inhibited migration, invasion, and hepatic metastasis of the cells without influencing cellular growth. Overexpression of IL-8 in S26 cells resulted in increased migration, invasion, and metastasis capabilities of the cells without affecting cellular growth. Exogenous IL-8 enhanced the migration and invasion of low-metastasis CNE-2 cells in a dose-dependent manner. An epithelial-mesenchymal transition (EMT) could be induced by IL-8 in various NPC cell lines. The high level of phosphorylated AKT in S18 cells could be suppressed by knocking down IL-8 expression. Further, IL-8-promoted migration and invasion could be abolished by either the application of the phosphoinositide-3-kinase inhibitor LY294002 or the knock down of AKT expression by using small-interfering RNA. In summary, IL-8 serves as an independent prognostic indicator of overall survival, disease-free survival, and metastasis-free survival for patients with NPC. IL-8 promotes NPC metastasis via autocrine and paracrine means, involving activation of AKT signaling and inducing EMT in NPC cells.
Carcinogenesis 05/2012; 33(7):1302-9. · 5.70 Impact Factor
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ABSTRACT: Tyrosine-protein phosphatase nonreceptor type 12 (PTPN12) is considered to be a tumor suppressor. It plays a significant role in human cancer, but its clinicopathologic and prognostic significance in esophageal squamous cell carcinoma (ESCC) has not yet been elucidated.
Using Western blot, we evaluated the PTPN12 expression in 20 pairs of surgically resected esophageal tissues. The PTPN12 was detected by immunochemistry in a tissue microarray from 260 surgically resected ESCCs, of which 260 were from primary cancer sites and 60 were from matched paracancerous normal tissues. Statistical analyses were applied to test the associations between PTPN12 expression, clinicopathologic factors, and prognosis.
Western blots showed that the expression level of PTPN12 was higher in normal paracancerous esophageal tissues than in ESCC tissues. By immunohistochemical analysis, high and low expression of PTPN12 was found in 62.1% and 37.9% of ESCCs, respectively. After multivariate analysis, along with pN status and tumor grade, the protein expression level of PTPN12 was an independent and significant predictive factor (p<0.001). Patients with PTPN12-high tumors had a longer disease-free survival and overall survival (p=0.002 and p=0.001, respectively), especially for those with stage II disease (both p<0.001).
Our study suggests that PTPN12 protein expression is a valuable biomarker for ESCC patients. High expression of PTPN12 is associated with favorable disease-free survival and overall survival in ESCC patients.
The Annals of thoracic surgery 03/2012; 93(5):1674-80. · 3.74 Impact Factor
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Feng Wang,
Shuqiang Yuan,
Kai-yuan Teng,
Celia Garcia-Prieto,
Hui-yan Luo, Mu-sheng Zeng,
Hui-lan Rao,
Yi Xia,
Wen-qi Jiang,
Hui-qiang Huang,
Zhong-jun Xia,
Xiao-fei Sun,
Rui-hua Xu
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ABSTRACT: Our previous studies found that patients with B-cell non-Hodgkin lymphoma (NHL) had a higher incidence of hepatitis B virus (HBV) infection in serum than patients with T-cell NHL or other cancers. We sought to identify a possible role of HBV infection in B-cell NHL tumorigenesis and to understand its underlying clinical relevance. Fresh and paraffin-embedded primary tumor tissue from patients with NHL as well as from those with other lymphatic system diseases were investigated by PCR and immunohistochemistry. Many more patients with B-cell lymphoma whose serum was positive for hepatitis B surface antigen (HBsAg) were also positive for HBV-DNA than were those with T-cell NHL or other lymphatic system diseases whose serum was positive for HBsAg, in both fresh (55 vs. 15.4%) and paraffin-embedded (38.3 vs. 11.8%) tissue. Positive expression of the HBV-associated proteins HBsAg and hepatitis B core antigen was found in B-cell NHL lymphocytes and endothelial cells. Only 8.3% of patients with B-cell NHL who were negative for HBsAg but positive for other HBV markers were positive for HBV-DNA in tumor tissue. These results suggest that chronic HBV infection in lymph nodes could be associated with B-cell lymphoma.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 03/2012; 21(3):261-7. · 2.21 Impact Factor
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Ya-Lan Tao,
Yan Li,
Jin Gao,
Zhi-Gang Liu,
Zi-Wei Tu,
Guo Li,
Bing-Qing Xu,
Dao-Li Niu,
Chang-Bin Jiang,
Wei Yi,
Zhi-Qiang Li,
Jing Li,
Yi-Ming Wang,
Zhi-Bin Cheng,
Qiao-Dan Liu,
Li Bai,
Chun Zhang,
Jing-Yu Zhang, Mu-Sheng Zeng,
Yun-Fei Xia
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ABSTRACT: Early diagnosis and treatment is known to improve prognosis for nasopharyngeal carcinoma (NPC). The study determined the specific peptide profiles by comparing the serum differences between NPC patients and healthy controls, and provided the basis for the diagnostic model and identification of specific biomarkers of NPC. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can be used to detect the molecular mass of peptides. Mass spectra of peptides were generated after extracting and purification of 40 NPC samples in the training set, 21 in the single center validation set and 99 in the multicenter validation set using weak cationic-exchanger magnetic beads. The spectra were analyzed statistically using FlexAnalysis™ and ClinProt™ bioinformatics software. The four most significant peaks were selected out to train a genetic algorithm model to diagnose NPC. The diagnostic sensitivity and specificity were 100% and 100% in the training set, 90.5% and 88.9% in the single center validation set, 91.9% and 83.3% in the multicenter validation set, and the false positive rate (FPR) and false negative rate (FNR) were obviously lower in the NPC group (FPR, 16.7%; FNR, 8.1%) than in the other cancer group (FPR, 39%; FNR, 61%), respectively. So, the diagnostic model including four peptides can be suitable for NPC but not for other cancers. FGA peptide fragments identified may serve as tumor-associated biomarkers for NPC.
Journal of Cellular Biochemistry 02/2012; 113(7):2268-78. · 2.87 Impact Factor
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ABSTRACT: Serum enzymes that play potential roles in tumor growth have recently been reported to have prognostic relevance in a diverse array of tumors. However, prognosis-related serum enzymes are rarely reported for nasopharyngeal carcinoma(NPC). To clarify whether the level of serum enzymes is linked to the prognosis of NPC, we reviewed the pretreatment data of lactate dehydrogenase(LDH), alkaline phosphatase (ALP), and glutamyl transferase (GGT) in 533 newly diagnosed NPC patients who underwent radical radiotherapy between May 2002 and October 2003 at Sun Yat-sen University Cancer Center. Patients were grouped according to the upper limit of normal values of LDH, ALP, and GGT. The Kaplan-Meier method and log-rank test were used for selecting prognostic factors from clinical characteristics and serum enzymes, and the chi-square test was applied to analyze the relationships of clinical characteristics and serum enzymes. Finally, a Cox proportional hazards model was used to identify the independent prognostic factors. We found that increased levels of LDH had poor effects on both overall survival and distant metastasis-free survival (P = 0.009 and 0.035, respectively), and increased pretreatment level of serum ALP had poor effects on both overall survival and local recurrence-free survival (P = 0.037 and 0.039, respectively). In multivariate analysis, increased LDH level was identified as an independent prognostic factor for overall survival. Therefore, we conclude that increased pretreatment serum LDH and ALP levels are poor prognostic factors for NPC.
Chinese journal of cancer 01/2012; 31(4):197-206.
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ABSTRACT: Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), but it remains obscure whether EBV is a viral cause of, or only an accompaniment of, NPC. We will discuss the accumulated evidence pointing to the relationship between EBV infection and NPC initiation from epidemiologic, pathogenic, molecular oncogenic, and experimental animal studies. We believe that convincing evidence from these perspectives must be provided before we can ascertain the causal role of EBV infection in NPC. Specifically, (1) epidemiological studies should reveal EBV infection as a risk factor; (2) the introduction of EBV into an animal model should produce NPC; (3) in the animal model NPC, the main molecular event(s) or the involved signaling pathway(s) should be identical to that in human NPC; and (4) finally and most importantly, prevention of EBV infection or clearance of EBV from infected individuals must be able to reduce the incidence rate of NPC.
International Journal of Molecular Sciences 01/2012; 13(10):13737-47. · 2.60 Impact Factor
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Tian-Run Liu,
Li-Hua Xu,
An-Kui Yang,
Qian Zhong,
Ming Song,
Man-Zhi Li,
Li-Juan Hu,
Fu-Jin Chen,
Ze-Dong Hu,
Ping Han, Mu-Sheng Zeng
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ABSTRACT: To investigate the expression and role of special AT-rich sequence-binding protein-2 (SATB2) in laryngeal squamous cell carcinoma (LSCC) tissue and cell line (HEp2), and to evaluate the clinical and prognostic significance of SATB2 protein in patients with LSCC.
The expression of SATB2 was examined in LSCC tissue and HEp2 cells by Western-blotting, Real-time PCR and immunohistochemical staining. Cell growth curve assay and colony formation assay were used to verify the effect of SATB2 on the proliferation and tumor progression ability of HEp2 cells. Tumor formation assay in nude mice was used to analyze the effect of SATB2 on the tumorigenicity of HEp2 cells.
The status of SATB2 protein in carcinoma tissues is much lower than that in paracarcinoma tissues. The overall survival of the patients with high SATB2 expression was significantly higher than the low SATB2 expression group. Lower or negative SATB2 expression was significantly correlated with advanced clinical staging, histological grade and tumor recurrence. In vitro experiments demonstrated that over-expression of SATB2 in HEp2 cells inhibited cell proliferation and tumor progression ability, and down-regulation of SATB2 showed the opposite effects. Over-expression of SATB2 repressed the tumorigenicity of HEp2 cells by in vivo experiments. Moreover, multivariate analysis suggested that SATB2 expression might be an independent prognostic indicator for the survival of LSCC patients after curative surgery.
SATB2 might involve in the development and progression of LSCC as a tumor suppressor, and thereby may be a valuable prognostic marker for LSCC patients.
PLoS ONE 01/2012; 7(7):e40704. · 4.09 Impact Factor
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ABSTRACT: Bmi-1, a member of the polycomb family, it is involved in self renewal of stem cells and functions as an oncogene in many malignant human cancer types. Recent studies have demonstrated that Bmi-1 is a predictive factor for poor patient prognosis. However, the underlying mechanisms of radioresistance mediated by Bmi-1 are poorly understood. In this study, the dose-survival relationship was analyzed using a clonogenic survival assay and combined radiation treatment with Bmi-1 overexpression or silencing. DNA double-strand break (DSB) and repair was assessed by immunofluorescence staining of γH2AX foci. In addition, mitochondrial membrane potential was detected between Bmi-1 knockdown and control MCF-7 cells after irradiation. Apoptosis and cell cycle were evaluated by flow cytometry. We found that exposure of MCF-7 cells overexpressing Bmi-1 to ionizing radiation resulted in dramatically enhanced survival relative to control cells, whereas cells with silenced Bmi-1 showed markedly reduced survival. Bmi-1 inhibition significantly increased DSBs and decreased DSB repair. Furthermore, Bmi-1 knockdown induced loss of mitochondrial membrane potential and enhanced apoptosis by up-regulating p53, p21, Bax expression and down-regulating p-AKT and Bcl-2 expression. These results indicate that Bmi-1 may play an important role in radiosensitivity, and the suppression of its expression might be a potential therapeutic target for breast cancer.
Oncology Reports 12/2011; 27(4):1116-22. · 1.84 Impact Factor
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ABSTRACT: Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for maintenance of the episome and establishment of latency. In this study, we observed that heat treatment effectively induced EBNA1 transcription in EBV-transformed B95-8 and human LCL cell lines. Although Cp is considered as the sole promoter used for the expression of EBNA1 transcripts in the lymphoblastoid cell lines, the RT-PCR results showed that the EBNA1 transcripts induced by heat treatment arise from Qp-initiated transcripts. Using bioinformatics, a high affinity and functional heat shock factor 1 (HSF1)-binding element within the -17/+4 oligonucleotide of the Qp was found, and was determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Moreover, heat shock and exogenous HSF1 expression induced Qp activity in reporter assays. Further, RNA interference-mediated HSF1 gene silencing attenuated heat-induced EBNA1 expression in B95-8 cells. These results provide evidence that EBNA1 is a new target for the transcription factor HSF1.
Virology 12/2011; 421(2):184-91. · 3.35 Impact Factor
