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Liu Z.,Shanghai University | Zhu Z.,Shanghai University | Zhang H.,Eastern Hepatobiliary Surgery Hospital | Tan G.,Shanghai University | And 2 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011

The first successful combination of ultrasound assisted microwave extraction (UAME) with liquid chromatography analysis is described for the quality evaluation of Fructus Corni, a commonly used traditional Chinese medicine (TCM). Due to their multifarious biological activities, seven representative bioactive constituents (two phenolics and five iridoids) were chosen as targets for the quality assessment. The chromatographic separation was performed on a C18 Aq column with gradient elution using methanol and aqueous solution containing 0.2% acetic acid. The quantitative method developed was validated and successfully applied to determine the seven markers in 12 batches of Fructus Corni extract from various habitats. Significant variations were demonstrated in the contents of seven compounds. Further 13 components were tentatively identified by online TOF mass analysis. © 2011 Elsevier B.V.

Zheng L.-Y.,Changhai Hospital | Zhou D.-X.,Eastern Hepatobiliary Surgery Hospital | Lu J.,Changhai Hospital | Zhang W.-J.,Changhai Hospital | Zou D.-J.,Changhai Hospital
Biochemical and Biophysical Research Communications | Year: 2012

The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n=16) and hepatocellular carcinoma (n=169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6 + tumor-initiating cells (T-ICs) and high frequency of nuclear β-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/β-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC. © 2012 Elsevier Inc.

Hou J.,Second Military Medical University | Hou J.,Tsinghua University | Lin L.,Zhejiang University | Zhou W.,Eastern Hepatobiliary Surgery Hospital | And 16 more authors.
Cancer Cell | Year: 2011

The full scale of human miRNome in specific cell or tissue, especially in cancers, remains to be determined. An in-depth analysis of miRNomes in human normal liver, hepatitis liver, and hepatocellular carcinoma (HCC) was carried out in this study. We found nine miRNAs accounted for ∼88.2% of the miRNome in human liver. The third most highly expressed miR-199a/b-3p is consistently decreased in HCC, and its decrement significantly correlates with poor survival of HCC patients. Moreover, miR-199a/b-3p can target tumor-promoting PAK4 to suppress HCC growth through inhibiting PAK4/Raf/MEK/ERK pathway both in vitro and in vivo. Our study provides miRNomes of human liver and HCC and contributes to better understanding of the important deregulated miRNAs in HCC and liver diseases. © 2011 Elsevier Inc.

Yin C.,Shanghai University | Wang P.-Q.,Shanghai University | Xu W.-P.,Shanghai University | Yang Y.,Eastern Hepatobiliary Surgery Hospital | And 7 more authors.
Hepatology | Year: 2013

Hepatocyte nuclear factor-4α (HNF4α) is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis. There is striking suppression of hepatocellular carcinoma (HCC) by HNF4α, although the mechanisms by which HNF4α reverses HCC malignancy are largely unknown. Herein, we demonstrate that HNF4α administration to HCC cells resulted in elevated levels of 28 mature microRNAs (miRNAs) from the miR-379-656 cluster, which is located in the delta-like 1 homolog (DLK1) -iodothyronine deiodinase 3 (DIO3) locus on human chromosome 14q32. Consistent with the reduction of HNF4α, these miRNAs were down-regulated in human HCC tissue. HNF4α regulated the transcription of the miR-379-656 cluster by directly binding to its response element in the DLK1-DIO3 region. Interestingly, several miRNAs in this cluster inhibited proliferation and metastasis of HCC cells in vitro. As a representative miRNA in this cluster, miR-134 exerted a dramatically suppressive effect on HCC malignancy by down-regulating the oncoprotein, KRAS. Moreover, miR-134 markedly diminished HCC tumorigenicity and displayed a significant antitumor effect in vivo. In addition, inhibition of endogenous miR-134 partially reversed the suppressive effects of HNF4α on KRAS expression and HCC malignancy. Furthermore, a positive correlation between HNF4α and miR-134 levels was observed during hepatocarcinogenesis in rats, and decreases in miR-134 levels were significantly associated with the aggressive behavior of human HCCs. Conclusion: Our data highlight the importance of the miR-379-656 cluster in the inhibitory effect of HNF4α on HCC, and suggest that regulation of the HNF4α-miRNA cascade may have beneficial effects in the treatment of HCC. © 2013 by the American Association for the Study of Liver Diseases.

Wang B.,Eastern Hepatobiliary Surgery Hospital | Wang B.,Shanghai University | Huang G.,Eastern Hepatobiliary Surgery Hospital | Wang D.,Hebei Medical University | And 5 more authors.
Journal of Hepatology | Year: 2010

Background & Aims: Studies investigating the associations between glutathione S-transferase (GST) genetic polymorphisms and hepatocellular carcinoma (HCC) risk have reported controversial results. Thus, a meta-analysis was performed to clarify the effects of GSTM1 and GSTT1 polymorphisms on HCC risk. Methods: We identified 132 relevant records through a literature search up to November 22, 2009, and 24 individual case-control studies from 23 publications were finally included, involving a total of 3349 HCC cases and 5609 controls. Subgroup analyses were performed by ethnicity, or by area according to the incidence rate and hepatitis virus status. Results: Analyses of total relevant studies showed an increased HCC risk was significantly associated with null genotypes of GSTM1 (OR = 1.26, 95% CI 1.03-1.54, pOR = 0.027) and GSTT1 (OR = 1.28, 95% CI 1.09-1.51, pOR = 0.002). In addition, the GSTM1-GSTT1 interaction analysis showed that the dual null genotype of GSTM1/GSTT1 was significantly associated with increased HCC risk (OR = 1.89, 95% CI 1.38-2.60, pOR < 0.001). Subgroup analyses showed that the associations above were still statistically significant in Asians (p GSTM1 = 0.017, pGSTT1 = 0.001, p Dual null genotype < 0.001), high-rate areas (pGSTM1 = 0.012, pGSTT1 = 0.006, pDual null genotype < 0.001), and HBV-dominant areas (pGSTM1 = 0.003, pGSTT 1 = 0.003, pDual null genotype < 0.001). Conclusions: This meta-analysis suggests null genotypes of GSTM1 and GSTT1 are both associated with increased HCC risk in Asians, and individuals with the dual null genotype of GSTM1/GSTT1 are particularly susceptible to developing HCC. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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