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Lin G.,Sun Yat Sen University | Wang J.,Sun Yat Sen University | Lao X.,Sun Yat Sen University | Li L.,Dongguan ShiLong Peoples Hospital | And 5 more authors.
Journal of Immunotherapy | Year: 2012

The presence of regulatory T cells in patients who received therapeutic cytokine-induced killer (CIK) cells may inhibit host immunity, leading to failed immunotherapy. In this study, we investigated the impact of using interleukin-6 (IL-6) on the phenotype alteration, proliferation, and cytotoxic activity of CIK cells generated from the peripheral blood mononuclear cells of patients with hepatocellular carcinoma. We found that addition of IL-6 to CIK-cell culture medium decreased the percentage of Treg/CD4 +, Treg/CD3 +T cells in the resultant CIK cells and simultaneously increased the proliferation ability, the expression of CD45RO +CD62L lowCCR7 low effector memory phenotype, and cytotoxicity of the CIK cells against hepatocellular carcinoma in vitro. Our results also showed that the percentage of Th17/CD4 +cells was increased in CIK cells, but the proportion of Th17/CD4 +cells was not affected by the addition of IL-6 to CIK-cell culture medium. Collectively, these data suggest that IL-6 may have the potential to improve antitumor activity of CIK cells in cancer immunotherapy. Copyright © 2012 by Lippincott Williams & Wilkins.

Cheng F.,Sun Yat Sen University | Cheng F.,Dongguan Shilong Peoples Hospital | Wang Y.,Sun Yat Sen University | Li J.,Sun Yat Sen University | And 7 more authors.
International Journal of Cardiology | Year: 2013

Background: Circulating endothelial microparticles (EMPs) lead to endothelial dysfunction by increasing oxidative stress. Berberine has a beneficial effect on endothelial function, but no data are available on the EMP-mediated oxidative stress. The present study tests the hypothesis that berberine contributes to the improvement of endothelial function in humans via inhibiting EMP-mediated oxidative stress in vascular endothelium. Methods: Twelve healthy subjects received a 1-month berberine therapy and eleven healthy subjects served as control. Endothelium-dependent and -independent function in the brachial artery was assessed by flow-mediated vasodilation (FMD) and sublingual nitroglyceride-mediated vasodilation (NMD). Circulating EMPs and serum malondialdehyde (MDA) were measured before and after therapy. Furthermore, in vitro human umbilical vein endothelial cells (HUVECs) were stimulated by EMPs with or without presence of anti-oxidant compound apocynin or berberine. Intracellular reactive oxygen species (ROS), nitric oxide (NO) production and NADPH oxidase 4 (Nox4) protein expressions were examined, respectively. Results: The levels of serum MDA and circulating CD31 +/CD42 - MPs were significantly reduced in the berberine group compared with the control group, which were associated with improvement of FMD. The EMPs in vitro facilitated ROS production and Nox4 protein expression and reduced NO synthesis in HUVECs. These alterations can be reversed by the presence of apocynin or berberine, respectively. Conclusion: The present study demonstrated for the first time that EMP-induced upregulation of Nox4 expression may enhance ROS production in HUVECs. Berberine treatment contributes to the amelioration of endothelial function through a partially reducing oxidative stress of vascular endothelium induced by circulating CD31 +/CD42 - microparticles in humans. © 2012 Elsevier Ireland Ltd.

Yang Y.-F.,Dongguan Shilong Peoples Hospital | Zhang X.-Y.,Dongguan Shilong Peoples Hospital | Yang M.,Dongguan Shilong Peoples Hospital | He Z.-H.,Guangxi Medical University | And 3 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014

Aim: Recent research suggests that nucleophosmin (NPM) may be a prognostic marker in colorectal carcinomas (CRC). We here tested its use to predict the survival of CRC patients. Methods: We investigated NPM expression by immunohistochemistry in histologically normal to malignant colorectal tissues and evaluated its association with clinicopathological variables. Overall and disease-free survival after tumor removal were calculated by the Kaplan-Meier method, and differences in survival curves were analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis of prognostic factors. Results: NPM expression was found significantly upregulated in CRC compared to adjacent colorectal tissue, villous adenoma, tubular adenoma and normal colorectal mucosa (p≤0.05 for all). NPM expression was statistically linked to cancer embolus, lymph node metastasis, differentiation grade, and recurrence of CRC. Overall and disease-free survival of NPM-negative CRC patients tended to be better than those for patients with NPM-positive lesions (log-rank statistic, p≤0.05 for all). Multivariate analysis indicated NPM expression as an independent prognostic indicator for CRC patients (p≤0.05 ). Conclusion: Our results suggest that NPM expression can predict the survival of CRC patients. Prognosis of CRC is determined by not only many known prognostic factors but also by NPM expression.

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