Limei Wang

Publications (2)8.24 Total impact

• Article: Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia.

  Min Cui, Limei Wang, Xiaohong Liang, Xuelian Ma, Yugang Liu, Mingfeng Yang, Kejing Liu, Xinbing Wei, Zhiqiang Zhou, Youhai H Chen, Wensheng Sun
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  ABSTRACT: Mechanisms underlying delayed selective neuronal death after global cerebral ischemia remain to be clarified. Here, we report a critical role for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of cerebral ischemia. C57BL/6j mice were subjected to transient global brain ischemia. RT-PCR and immunohistochemistry showed that the expression of TRAIL and DR5 was upregulated following transient ischemia-reperfusion. Dual immunofluorescence analysis indicated that TRAIL expression was significantly more pronounced in astrocytes and activated microglia/macrophages, whereas DR5 expression was more pronounced in neurons, which had a good correlation with the distribution of apoptotic cells. Treatment with soluble DR5 reduced ischemic cell death after transient global ischemia through blocking the interaction of endogenous TRAIL with DR5. These results indicate that TRAIL plays a deleterious role in the pathogenesis of delayed neuronal damage after global cerebral ischemia and inhibition of TRAIL function in the brain may represent a novel neuroprotective strategy to treat ischemic stroke.
  Neurobiology of Disease 03/2010; 39(2):138-47. · 5.40 Impact Factor
• Source

  Available from: PubMed Central

  Article: N(3)-o-toluyl-fluorouracil inhibits human hepatocellular carcinoma cell growth via sustained release of 5-FU.

  Xiaofan Zhang, Julia Li Zhong, Wei Liu, Zuhua Gao, Xia Xue, Pan Yue, Limei Wang, Cuirong Zhao, Wenfang Xu, Xianjun Qu
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  ABSTRACT: N(3)-o-toluyl-fluorouracil (TFU), the prodrug of 5-fluorouracil (5-FU), is the metabolite of N(1)-acetyl-N(3)-o-toluyl-fluorouracil (atofluding). In the present study, we aimed to evaluate the efficacy of TFU on the inhibition of human hepatocellular carcinoma cells via sustained release of 5-FU. The metabolism of TFU underlying the inhibitory effect was also analyzed. In vitro assays, inhibition of cell growth by TFU was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method. The levels of TFU and 5-FU in the cell culture supernatant fluid were measured by high-performance liquid chromatography (HPLC). In vivo assays, the efficacy of TFU was evaluated in a human hepatocellular carcinoma xenograft mice model after 3 weeks of oral administration. The distributions of TFU and 5-FU in plasma and homogenate tissues including liver, lung and tumor were determined by HPLC. N(3)-o-toluyl-fluorouracil weakly inhibited the proliferation of SMMC-7721 and PLC/PRF/5 cells in the absence of liver microsomal enzymes. In contrast, the inhibition rates were significantly increased in the presence of these enzymes. HPLC results revealed that TFU was metabolized slowly by liver microsomal enzymes and therefore the concentration of 5-FU was gradually increased with a longer retention time in cell culture supernatant fluid. The efficacy of TFU was confirmed in SMMC-7721 xenografts in Balb/c athymic (nu+/nu+) mice model. TFU treatment induced inhibition of SMMC-7721 growth with few side effects. HPLC results showed that high levels of TFU were still in liver 48 h after the end of oral administration, implying that TFU preferentially accumulated in liver with slow conversion to 5-FU by enzymes. This led to a long-lasting concentration of 5-FU in plasma. Further, a high level of 5-FU was found in tumors with a relatively low level in lungs. These results suggest that the metabolite of TFU was preferentially converted or taken up by tumor cells. The distributions of 5-FU may contribute to its high anti-tumor activity and low adverse reactions in vivo. These results demonstrate that TFU is a promising prodrug of 5-FU for cancer treatment via sustained release of 5-FU in liver.
  Cancer Chemotherapy and Pharmacology 09/2009; 66(1):11-9. · 2.83 Impact Factor