[show abstract][hide abstract] ABSTRACT: BACKGROUND: The secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC) in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients. METHODS: The mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC) assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT). Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA), 30 ductual carcinoma in situ (DCIS) and 40 metastatic lymph nodes (LNs). The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to Rab27B expression. RESULTS: We observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P < 0.001). The elevated expression of Rab27B was closely correlated with lymph node metastasis, advanced clinical stage, ascending pathology classification, and positive ER status. Furthermore, patients with high expression of Rab27B had inferior survival outcomes. Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients' survival (P < 0.001). Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers. CONCLUSION: Our findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.
Journal of Translational Medicine 12/2012; 10(1):242. · 3.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study was aimed to investigate the potential role of microRNA-29c (miR-29c) in regulating the sensitivities of nasopharyngeal carcinoma (NPC) to ionizing radiation (IR) and cisplatin. Low expression of miR-29c was positively associated with therapeutic resistance in 159 NPC cases. Our further in vitro and in vivo studies illustrated ectopic restoration of miR-29c substantially enhanced the sensitivity of NPC cells to IR and cisplatin treatment by promoting apoptosis. Furthermore, we detected miR-29c repressed expression of anti-apoptotic factors, Mcl-1 and Bcl-2 in NPC tissues and cell lines. These data indicate miR-29c might serve as a potential therapeutic sensitizer in NPC treatment.
[show abstract][hide abstract] ABSTRACT: It was suggested that the enhancer of zeste homolog 2 (EZH2) gene is a putative candidate oncogene in several types of human cancer. The potential oncogenic role of EZH2 and its clinical/prognostic significance, however, in ovarian carcinoma are unclear. In this study, EZH2 expression was examined by immunohistochemistry (IHC) in cohorts of normal and tumorous ovarian tissues. High expression of EZH2 was examined in none of the normal ovaries, in 3% of the cystadenomas, in 23% of the borderline tumors and in 50% of the ovarian carcinomas, respectively. In the ovarian carcinomas, high expression of EZH2 was positively correlated with an ascending histological grade and/or advanced stage of the disease (P < 0.05). Moreover, high expression of EZH2 in ovarian carcinoma was determined to be a strong and an independent predictor of short overall survival (P < 0.05). In ovarian carcinoma HO-8910 and UACC-326 cell lines, EZH2 knockdown by RNA interference led to a G(1) phase cell cycle arrest, reduced cell growth/proliferation and inhibited cell migration and/or invasion in vitro. In addition, EZH2 knockdown was found to reduce transforming growth factor-beta1 (TGF-beta1) expression and increase E-cadherin expression either in the transcript or in the protein levels. Furthermore, a significant positive correlation between overexpression of EZH2 and TGF-beta1 in ovarian carcinoma tissues was observed (P < 0.001). These findings suggest a potential important role of EZH2 in the control of cell migration and/or invasion via the regulation of TGF-beta1 expression, and the high expression of EZH2, as detected by IHC, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma.
[show abstract][hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is a common human cancer worldwide. The levels of serum clusterin in HCC patients and its potential diagnostic significance is not clear. We aimed to evaluate the clinical use of serum clusterin levels as a surveillance tool for HCC with hepatitis B virus (HBV) related cirrhosis.
Twenty-two cases of healthy subjects, 31 cases of HBV carriers, 26 patients with chronic hepatitis B, 29 patients with cirrhosis, and 76 patients with HCC were enrolled in this study. Serum levels of clusterin were measured by a sandwich enzyme-linked immunosorbent assay.
The serum clusterin levels in HCC patients were significantly lower than that in healthy, HBV carriers and chronic hepatitis B, but statistically higher than in cirrhosis patients. Receiver operator characteristic (ROC) curve indicated that a serum clusterin value of 50 microg/mL yielded the best sensitivity (91%) and specificity (83%) for differentiating HCC patients with HBV-related cirrhosis from those with HBV-related cirrhosis. The optimal alpha fetoprotein (AFP) cutoff value was 15 ng/mL and was inferior to the clusterin value of 50 microg/mL, the area under the ROC curves being 0.937 versus 0.781, respectively (P < 0.05).
Serum clusterin was more sensitive and specific than serum AFP for differentiating HCC patients with HBV-related cirrhosis from those with HBV-related liver cirrhosis, and may be a useful surveillance tool of HCC based on HBV-related cirrhosis.
Journal of Gastroenterology and Hepatology 06/2010; 25(6):1123-8. · 3.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Epstein-Barr virus encoded nuclear antigen 1 (EBNA1) is required for the replication and maintenance of the episomal EBV genome and for the transactivation of viral gene expression. EBNA1 has been classified into five subtypes, among which the V-val subtype was reported to be associated with nasopharyngeal carcinoma (NPC). Here we report a higher transcriptional activity of the V-val subtype of EBNA1 than for the prototype derived from B95.8 cells to transactivate FR-containing luciferase plasmid, which was mainly a consequence of the mutations in the carboxy-terminus of EBNA1. This interpretation was further supported by the finding that the variant form of EBNA1 has a higher binding affinity for the FR sequence than the prototype by electrophoretic mobility shift assays. The functional advantage of the V-val EBNA1 investigated in this study may contribute to the oncogenesis of NPC.
[show abstract][hide abstract] ABSTRACT: It has been suggested that the B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays an oncogenic role in several types of human cancer, but the status of Bmi-1 amplification and expression in ovarian cancer and its clinical/prognostic significance are unclear.
The methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of Bmi-1 in 30 normal ovaries, 30 ovarian cystadenomas, 40 borderline ovarian tumors and 179 ovarian carcinomas.
Intensive expression of Bmi-1 was detected in none of the normal ovaries, 3% cystadenomas, 10% borderline tumors, and 37% ovarian carcinomas, respectively. Amplification of Bmi-1 was detected in 8% of ovarian carcinomas. In ovarian carcinomas, significant positive associations were found between intensive expression of Bmi-1 and the tumors ascending histological grade, later pT/pN/pM and FIGO stages (P < 0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of Bmi-1 with shortened patient survival (mean 49.3 months versus 100.3 months, p < 0.001) was demonstrated. Importantly, Bmi-1 expression provided significant independent prognostic parameters in multivariate analysis (p = 0.005).
These findings provide evidence that intensive expression of Bmi-1 might be important in the acquisition of an invasive and/or aggressive phenotype of ovarian carcinoma, and serve as a independent biomarker for shortened survival time of patients.
[show abstract][hide abstract] ABSTRACT: Our previous study has suggested that the cell cycle-related kinase (CCRK) is a putative candidate oncogene in glioblastoma tumorigenesis. The potential oncogenic role of CCRK and its clinical/prognostic significance, however, in ovarian carcinoma are unclear. In this study, CCRK expression was examined by immunohistochemistry in a series of ovarian carcinoma tissues. Overexpression of CCRK was detected in 53% of the ovarian carcinomas, and it was positively correlated with an ascending histological grade and/or advanced clinical stage of the disease (p < 0.05). In addition, overexpression of CCRK in ovarian carcinoma was determined to be a strong and an independent predictor of short overall survival (p < 0.05). In ovarian carcinoma cells, CCRK knockdown by RNAi led to a G1 phase cell cycle arrest, while CCRK overexpression by stable transfection of CCRK-containing plasmid pcDNA-CCRK promoted cell proliferation in vitro and tumor growth in vivo. In addition, CCRK knockdown was found to reduce cyclin D1 expression. Consistently, CCRK overexpression increased cyclin D1 expression, and furthermore, a significant correlation between expression of CCRK and cyclin D1 in ovarian carcinomas was observed (p < 0.001). These findings suggest a potential important role of CCRK in the control of cell proliferation via regulation of cyclin D1 expression, and the overexpression of CCRK, as detected by immunohistochemistry, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma.
International Journal of Cancer 07/2009; 125(11):2631-42. · 6.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: AIB1 (amplified in breast cancer 1) is frequently overexpressed in esophageal squamous cell carcinoma (ESCC), but the significance of AIB1 expression in chemoradiotherapy (CRT) sensitivity and its effect on prognosis are still unclear. In this study, the expression of AIB1 was examined by immunohistochemistry in 98 biopsy specimens of primary ESCC patients treated with definitive CRT. AIB1 overexpression was found in 63/98 (64.3%) of the ESCCs. There was a significant association between AIB1 overexpression and distant lymph node metastases (P = 0.011), but not regional lymph node metastases. In the M0 subgroup, overexpression of AIB1 was observed more frequently in stage T4 than in stage T2-3 (66.7%vs 38.5%, P = 0.031). In addition, AIB1 expression was the only factor that showed a significant correlation with CRT response, in which overexpression of AIB1 was observed more frequently in the CRT resistant group than in the CRT effective group (86.5%vs 50.8%, P < 0.001). Univariate analysis revealed that AIB1 overexpression was associated with poor progression-free survival (PFS) (P < 0.001) and poor disease-specific survival (DSS) (P <0.001). Furthermore, AIB1 expression could stratify patient survival in stages T2-3, T4, N1, and M0 (P < 0.05), as well as in the CRT effective group (P < 0.05), and AIB1 overexpression and CRT resistance were evaluated as significant independent prognostic factors for both PFS and DSS in multivariate analysis. These findings suggest that overexpression of AIB1 is a useful predictor of CRT resistance and an independent molecular marker of poor prognosis for ESCC patients.
Cancer Science 05/2009; 100(9):1591-6. · 3.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to investigate the clinical significance of THY1 protein expression in epithelial ovarian cancer.
Immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining were used to detect the protein expression of THY1, Ki67 and cell apoptosis in 76 epithelial ovarian cancers by tissue microarray. The correlation between THY1 expression and patients' clinical features was analyzed.
Of the 76 epithelial ovarian cancer samples, 64 were informative for IHC and TUNEL assays and 42 (65.6%) among them showed down-regulated/loss expression of THY1 protein. A significant positive correlation of THY1 protein expression with clinical stage and distant metastasis was observed in this ovarian cancer cohort (P < 0.05). The more advanced the tumor stage, the more frequency of loss expression of THY1 protein. In addition, the mean positive rate of Ki67 staining in tumors with down-regulated/loss expression of THY1 was 33.7% +/- 3.5%, significantly higher than that in the tumors with normal expression of THY1 (17.3% +/- 6.1%, P = 0.0027). However, no significant correlation was observed between THY1 protein expression and tumor cell apoptosis as well as patients' survival in this series (P > 0.05).
Down-regulated/loss expression of THY1 protein in epithelial ovarian cancer is significantly correlated with cancer cell proliferation and metastasis in the epithelial ovarian cancer, and it may be used as one of the new molecular biomarkers to predict the disease progression in patients.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 04/2009; 31(3):203-7.
[show abstract][hide abstract] ABSTRACT: Overexpression of YKL-40 has been detected in the sera from patients with various kinds of malignant tumors, including epithelial ovarian cancer. Moreover, YKL-40 expression is closely related to clinical phenotypes of some malignant tumors. This study was to investigate the expression and clinical significance of YKL-40 protein in epithelial ovarian cancer tissues.
Protein expression of YKL-40 was detected by immunohistochemistry (IHC) using tissue microarray (TMA) consisting of 86 specimens of epithelial ovarian cancer and 20 specimens of normal ovarian tissues. The correlations of YKL-40 expression to clinical features and prognosis, as well as to the expression of clusterin protein in epithelial ovarian cancer were evaluated.
The expression of YKL-40 in all normal ovarian tissues was negative or at low levels. In 74 evaluable specimens of epithelial ovarian cancer, overexpression of YKL-40 was detected in 42 cases (56.8%). YKL-40 expression was closely associated with the clinical stage of epithelial ovarian cancer (p < 0.0001). The overall survival time in patients with overexpression of YKL-40 was significantly shorter than that in patients with normal expression of YKL-40 (p = 0.0389). Moreover, expression of YKL-40 protein was positively correlated with that of clusterin protein in epithelial ovarian cancer (p < 0.0001).
YKL-40 may be used as a new molecular marker to predict the prognosis of epithelial ovarian cancer.
Ai zheng = Aizheng = Chinese journal of cancer 02/2009; 28(2):142-5.
[show abstract][hide abstract] ABSTRACT: To understand the role of Epstein-Barr virus (EBV) and viral products in associated with immunophenotype and clinical outcome of primary nasopharyngeal carcinoma (NPC), the expression levels of chemokines IFN-g-induced protein 10 (IP-10, CXCL10), stromal-derived factor-1 (SDF-1, CXCL12) and its receptor CXCR4 was investigated in 56 primary NPC biopsy specimens from Chinese NPC patients in parallels with LMP1 antigen and EBER1 by immunohistochemisty (IHC) and in situ hybridization (ISH). Moreover, the expression levels of HLA class I (b-microglobulin) and II antigen (HLA-DR), and co-stimulatory molecule CD54 were also evaluated in 31 out of these 56 patients using immunohistochemisty (IHC). Our results showed that (a) the elevated expression levels of IP10, SDF-1, CXCR4, b-microglobulin, HLA-DR and CD54 in NPC lesions was 66%, 36%, 30%, 42%, 55% and 69%, respectively. (b) High expression of SDF-1 was observed in advanced NPC (N stage, p < 0.05). (c) LMP1 expression correlated with upregulation of CXCR4 and translocation of CXCR4 to the nucleus of the tumor cells. This role of LMP1 in regulating the expression of CXCR4 was confirmed in the EBV positive NPC cell line C666 by inhibition of LMP1 expression with small interfering RNA (siRNA). Our findings provide new insights on the immune status of the malignant cells which may affect the outcome of immunotherapy in NPC. The differentiated nonkeratinizing and undifferentiated types of nasopharyngeal carcinoma (NPC) are associated with Epstein-Barr virus (EBV) in South China, which has the highest incidence rate in the world. The EBV latent type II antigens include nuclear antigen 1 (EBNA1), and latent membrane protein 1 (LMP1, in approximately 50%, seen in ref. 2) and protein 2 (LMP2), in addition small non-polyadenylated viral RNAs non-coding nuclear RNAs (EBERs) and BamHI-A rightward transcripts (BARTs) expressed in NPC tumor cells. The expressions of EBV antigens in NPC tumor cells provide the targets for adoptive immunotherapy. However, the poorly differentiated NPC is always characterized by the presence of a highly cellular lymphoid stroma admixed with tumor cells. However, the role of local immunity surrounding NPC cells and the role EBV and viral products expressed in tumor cell remain unclear, which is associated with the expression of immune-related molecules including chemokines and receptors, HLA class I and II antigens, and co-stimulatory molecules and the role of EBV and viral products to alter the expression of immune-related molecules on tumor cells. It has been reported that the expression pattern of immune related-molecules on tumor cells will affect the outcome of T-cell-based adoptive immunotherapy for NPC.
Cancer biology & therapy 12/2007; 6(12):1997-2004. · 3.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the therapeutic mechanism of Jiawei Mojie Tablet (JMT) in treating primary dysmenorrhea (PD) by observing its effect on plasma oxytocin (OT) level in patients in menstrual period.
Sixty-three patients with PD enrolled in the study were randomly divided into the JMT group (n = 33) and the control Group (n = 30, treated with Yueyueshu Granule) to observe the change of OT level in the menstrual period before and after treatment.
OT level in patients with PD was obviously higher than that in healthy subjects (P < 0.01), and was positively correlated with the degree of pain (r = 0.738, P < 0.01). OT level reduced significantly after treatment (P < 0.01), the reduction was more significant in the JMT group than that in the control group (P < 0.01).
JMT could reduce the OT level in menstrual period.
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 05/2003; 23(5):354-6.