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Nanjing, China

Sun Y.,Chinese Academy of Sciences | Wu Y.-L.,Guangdong Academy of Medical science | Zhou C.-C.,Tongji University | Zhang L.,Sun Yat Sen University | And 11 more authors.
Lung Cancer | Year: 2013

Introduction: This randomized, open-label study compared pemetrexed versus docetaxel as second-line therapy for Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint tested non-inferiority of overall survival (OS) on the combined data from these patients and those in the global registration trial. Data from patients in the current study only (Chinese patients) were the basis for the study's secondary objectives. Methods: Patients with stage IIIB/IV disease were randomized (1:1) to receive pemetrexed (500mg/m2; 107 randomized; 106 treated) or docetaxel (75mg/m2; 104 randomized; 102 treated) on Day 1 of each 21-day cycle. Treatment continued until progressive disease, unacceptable toxicity or patient/investigator decision. All efficacy and safety data were analyzed at the pre-specified study completion; supplementary OS analyses were performed later, after additional events had been recorded. Results: The primary endpoint of OS noninferiority of pemetrexed to docetaxel was not met, the lower CL was <50% and P> 0.025 (efficacy retained = 97.9% [95% CLs: 47.1, 141.9]; P= 0.0276), in the combined population (pemetrexed: n= 390, docetaxel: n= 392). Supplementary values were 101.3% (95% CLs: 57.9, 148.8), P= 0.0186. For the secondary objectives, assessed in the population from the current study (pemetrexed: n= 107, docetaxel: n= 104), median OS was 11.7 and 12.2 months for the pemetrexed and docetaxel arms, respectively (HR [95% CLs]: 1.14 [0.78, 1.68], P= 0.492). Supplementary values were 11.4 and 11.5 months, respectively (HR [95% CLs]: 1.02 [0.74, 1.40], P= 0.926). Median PFS values were 2.8 and 3.1 months (HR [95% CLs]: 1.05 [0.75, 1.46], P= 0.770) and ORR values were 9.6% and 4.1% (odds ratio [95% CLs]: 2.50 [0.76, 8.25], P= 0.133) for pemetrexed and docetaxel, respectively. Pemetrexed-treated patients had significantly fewer drug-related grade 3-4 adverse events (pemetrexed: 20.8%, docetaxel: 40.2%; P= 0.003). Few drug-related serious adverse events were reported (pemetrexed: 5 patients, docetaxel: 8 patients). Conclusion: The comparable efficacy and superior tolerability of pemetrexed compared with docetaxel in this study supports the use of single-agent, second-line pemetrexed for advanced non-squamous NSCLC in Chinese patients. ClinicalTrials.gov: NCT00391274. © 2012.

Wang J.,Zhengzhou Orthopedics Hospital | Ma L.,Guangdong Pharmaceutical University | Yang S.,The 81st Hospital of PLA | Wang S.,Zhengzhou Orthopedics Hospital | And 2 more authors.
Inflammation | Year: 2016

Rheumatoid arthritis (RA) is a common autoimmune disease associated with progressive disability, systemic complications, and early death. Multiple lines of evidence have placed adaptive immune responses in the center of RA pathogenesis. However, the functional roles of T helper cells are insufficiently described. Here, we examined the Th2 cell subsets and their functions in RA patients. A downregulation of IL-4+ cells in CD4+ T cells were observed in RA patients, indicating a downregulation of Th2 cells, and these results were confirmed by using and CXCR3 and CCR6 surface markers. We then found that CXCR3-CCR6− Th2 cells can be separated into IL-4+ (single positive), IL-10+ (single positive), and IL-4+IL-10+ (double positive) subsets. Further results showed that CXCR5 only expressed on IL-10+ Th2 cells. The CXCR5+ and CXCR5− Th2 cells each exhibited distinctive features in helping B cell antibody secretion. CXCR5+ Th2 cells were more potent at stimulating total Ig and IgM secretion, while CXCR5− Th2 cells were more potent at stimulating IgE. IL-10 was required for helping B cell total Ig, IgM, and IgE production, while IL-4 was required for total Ig and IgE. The frequencies of IL-10+ and IL-4+IL-10+ Th2 cells were positively correlated with rheumatoid factor titer in vivo. Together, our study demonstrated distinctive subsets within Th2 cells, each with different impacts on antibody production and RA disease. © 2016, Springer Science+Business Media New York.

Yan B.,Shanghai University of Traditional Chinese Medicine | Yan B.,Chinese PLA General Hospital | Gu W.,Shanghai University of Traditional Chinese Medicine | Yang Z.,The 81st Hospital of PLA | And 4 more authors.
Tumor Biology | Year: 2014

In recent years, the role of long noncoding RNAs (lncRNAs) in cancer is increasingly focused. ncRuPAR is a newly detected lncRNA; in previous study, we found out that ncRuPAR could inhibit tumor progression by downregulating protease-activated receptor-1 (PAR-1), but its role in colorectal cancer (CRC) is never elucidated. Here, we conducted a self-control study which includes 105 CRC samples. By quantitative real time PCR (qRT-PCR) and immunohistochemical staining, we detected the expression of ncRuPAR and PAR-1 as well as their correlation; we further associated these data with the clinicopathologic parameters. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of ncRuPAR and PAR-1, respectively. Our results indicated that the expression of ncRuPAR was significantly downregulated in CRC compared with paired adjacent nontumor tissues, but the level of PAR-1 mRNA in cancerous tissues was significantly higher than in adjacent normal areas. The expression of ncRuPAR was significantly correlated with lymph node metastasis, distant metastasis, Duck’s stage, differentiation, and TNM stage and was potentially negatively associated with the mRNA levels and EI scores of PAR-1. The area under the ROC curve of ncRuPAR was 0.81 (95 % confidence interval (CI): 0.75–0.87); at a cutoff value of 8.34, the ncRuPAR measurement had a sensitivity of 97.14 %, a specificity of 65.87 %, and an accuracy of 82.86 % to predict CRC. © 2014, International Society of Oncology and BioMarkers (ISOBM).

Liu L.,Shanghai University of Traditional Chinese Medicine | Yan B.,Shanghai University of Traditional Chinese Medicine | Yang Z.,The 81st Hospital of PLA | Zhang X.,Shanghai University of Traditional Chinese Medicine | And 2 more authors.
Tumor Biology | Year: 2014

ncRuPAR is a newly discovered long noncoding RNA molecule that can upregulate protease-activated receptor-1 (PAR-1) during embryonic growth; however, its role in cancer has not been elucidated. Here, we conducted a study to investigate the role of ncRuPAR in gastric cancer. Significant downregulation of ncRuPAR was detected in gastric cancer tissues compared with paired adjacent nontumor tissues; however, both PAR-1 and vascular endothelial growth factor (VEGF) messenger RNA (mRNA) levels were significantly higher in cancerous tissues compared with adjacent normal tissues. Additionally, the expression level of ncRuPAR was found to be significantly correlated with tumor invasion depth, lymph node metastasis, distant metastasis, tumor size, and tumor-nodes-metastasis (TNM) stage and inversely associated with the mRNA levels and extent (E) × intensity (I) scores of PAR-1 and VEGF. The protein level of PAR-1 was significantly correlated with tumor size only, while the VEGF protein level was significantly correlated with invasion depth and tumor size. The area under the receiver operating characteristic (ROC) curve of ncRuPAR was 0.84 (95 % CI 0.79–0.88) at a cutoff value of 4.97; ncRuPAR had a sensitivity of 88.41 %, a specificity of 73.91 %, and an accuracy of 81.16 % for the prediction of gastric cancer. These results suggest that ncRuPAR inhibits gastric cancer development, and its underlying mechanism involves the inhibition of PAR-1. In addition, ncRuPAR could be regarded as a marker for gastric cancer in the future. © 2014, International Society of Oncology and BioMarkers (ISOBM).

Qu F.,Anhui Medical University | Zhang B.,The 81st Hospital of PLA | Xu M.,The 105th Hospital of PLA
Chinese Journal of Cancer Biotherapy | Year: 2016

Objective:To explore the clinical efficacy of dendritic cell vaccine combined with radiofrequency ablation (RFA) for treatment of colorectal liver metastasis (CRLM) patients. Methods: Forty-six patients with comfirmed CRLM underwent RFA in 81st Hospital of PLA from Aug. 2012 to Aug. 2014 were retrospectively analyzed, the patients were randomly divided into 2 groups: DC treatment combined with RFA group (n=26) and treatment group RFA control (n=20). After treatment, the two groups were compared for the recent curative effect, the long-term curative effect, immune function, safety and improvement in quality of life.Results:(1) The significant differences was found in the overall response rate between DC-RFA group and RFA group (92.31% vs 70.00%, P<0.05); the six month survival rate of DC-RFA group and RFA group was 96.15% and 90.00% respectively. The 1- and 2- year survival rate of DC-RFA groups was slightly less better than that of RFA group (P > 0.05); (2) in DC-RFA group, percentage of CD3 + and CD4 + the ratio of CD4 +CD8 + in peripheral blood increased significantly (P<0.05), but CD8 + reduced (P > 0.05) after the treatment; In the RFA group, percentage of CD3 +and CD4 +, the ratio of CD4 + CD8 + increased remarkably after treatment(P<0.05), while CD8 + slightly increased(P > 0.05). (3) In DC-RFA group, there were 2 cases of fever, 1 case of allergic reaction, and the patients recovered after treatment. (4) The life quality of the patients was improved in the DC-RFA group, especially in the aspects of mental state and pain control. Conclusion:In the treatment of patients with CRLM, DC vaccine combined with RFA can improve the therapeutic effect of RFA treatment, prolong the survival time, improve the immune function, and can effectively improve the quality of life and possess good treatment safety. © 2016, Editorial office of Chinese Journal of Cancer Biotherapy. All rights reserved.

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