Jia Fan

Fudan University, Shanghai, Shanghai Shi, China

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Publications (314)1343.04 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose The role of minimally invasive colorectal resection for patients undergoing a simultaneous resection for synchronous liver metastases had not been established. This study compared the short- and long-term outcomes between minimally invasive and open colorectal resection for patients undergoing simultaneous resection for liver metastases. Methods This study reviewed 101 consecutive patients undergoing simultaneous colorectal resection and R0 resection of synchronous liver metastases between January 2008 and December 2012. In the study, 36 consecutive patients who underwent minimally invasive colorectal resection were matched with 36 patients who had an open approach by propensity scoring. The analyzed variables included patient and tumor characteristics and short-term and long-term outcomes. Results After propensity score matching, the two groups had similar clinicopathologic variables. No patient undergoing the minimally invasive procedure experienced conversion to the open technique. No postoperative mortality occurred in either group. In the minimally invasive group, the estimated blood loss (P P P P P = 0.794) and disease-free survival rate (38 vs. 27 %; P = 0.860). Conclusion Minimally invasive colorectal resection with simultaneous resection of liver metastases has an outcome similar to open approach but some short-term advantages.
    International Journal of Colorectal Disease 12/2014; · 2.24 Impact Factor
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    ABSTRACT: The loss of 5-hydroxymethylcytosine (5-hmC) has been identified as an epigenetic hallmark in several malignancies. However, its role in intrahepatic cholangiocarcinoma (ICC) is still unknown. Our study aims to investigate the level of 5-hmC in diagnosis and prognosis prediction of ICC. The 5-hmC levels were detected using dot blot, tissue microarray technique and immunohistochemical method, and the correlation between 5-hmC level and ICC clinicopathological parameters was analysed. Compared with matched liver tissues, most of ICC tissues presented with the loss of 5-hmC. Furthermore, the subgroups of cirrhotic and poor differentiation tissues showed the lowest level of 5-hmC. We found that 5-hmC level in non-elevated ICC patients was significantly related to lymph node metastasis and TNM stage and not related to vessel invasion, sex, age, HBV, cirrhosis or degree of differentiation. ICC patients with high TNM stage (stages III and IV) and lymph node metastases had significantly lower 5-hmC level than those with low TNM stage (stages I and II) and no lymph node metastases. Further analysis showed that low 5-hmC level is significantly correlated with worse overall survival (OS) and disease-free survival (DFS). Importantly, multivariate analysis indicated that 5-hmC level, tumour diameter, lymphatic metastasis and tumour differentiation could be used as independent prognostic factors for ICC. The loss of 5-hmC is implicated in the progression of ICC. Our results can contribute to the diagnostic ability and postoperative surveillance of ICC patients.
    Tumor Biology 12/2014; · 2.52 Impact Factor
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    ABSTRACT: Background Triggering receptors expressed on myeloid cells 1 (TREM-1) is a novel molecule that modulates inflammatory responses. Hepatocellular carcinoma (HCC) is a well-known type of inflammation-related cancer. However, TREM-1 expression and its direct effects on HCC cells have not been previously determined. Methods Western blotting, quantitative reverse transcription-PCR (qRT-PCR), and immunofluorescence were used to detect TREM-1 expression. TREM-1 upregulation by pcDNA (mammalian expression vector with the CMV promoter) and its downregulation by shRNA (short hairpin RNA) were used to determine the function of this molecule. Transwell, CCK-8, cell cycle, and apoptosis assays were used to detect the effects of TREM-1 on HCC cells. Immunohistochemical staining of samples from a cohort of 322 HCC patients was used to determine the prognostic value of TREM-1. Results TREM-1 investigation through Western blot, qRT-PCR, and immunofluorescence analyses revealed that TREM-1 was expressed in HCC cells and tumor tissues. Functional experiments suggested that TREM-1 significantly promoted proliferation, invasion, and inhibited apoptosis of HCC cells. Inflammatory cytokine profiles under TREM-1 up- or downregulation indicated the majority of proinflammation cytokines significantly and positively correlated with TREM-1 expression, including IL-1β, TNF-α, and MCP-1. Western blot analyses revealed that p65, STAT3, ERK, and AKT might be the downstream effectors of TREM-1 signal transduction. High TREM-1 expression correlated significantly with increased recurrence and poorer survival in HCC patients, and it was an independent prognostic factor for recurrence (P = 0.009). Conclusions TREM-1 was found to be expressed in HCC cells and to be a prognostic factor for the clinical outcome of HCC.
    Annals of Surgical Oncology 12/2014; · 4.12 Impact Factor
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    ABSTRACT: Pyruvate kinase M2 (PKM2) is a member of the pyruvate kinase family. Recent work has defined the "non-metabolic" functions of PKM2. However, the role of PKM2 in HCC remains unclear. To investigate the role of PKM2 in tumor growth, invasion and the prognosis of hepatocellular carcinoma (HCC), PKM2 expression was measured in HCC cell lines and tissues using qRT-PCR, western blot, and immunofluorescence assays. In in vitro experiments, PKM2 was knocked down using a short hairpin RNA lentivirus vector, and tumor cell behavior and the downstream signaling pathways and chemokine were analyzed. For the analysis of in vivo tumor growth, intratumoral and peritumoral lymphocyte infiltration were examined in nude mice. The prognostic value of PKM2 was analyzed by immunohistochemistry in two cohorts including 721 HCC patients. Together, our data obtained from cell lines, tumorigenicity studies, and primary HCC samples illustrate an oncogenic role for PKM2 in tumors. Moreover, PKM2 may serve as a novel prognostic indicator for HCC patients after curative resection, targeted therapy aimed at PKM2 may represent an effective treatment approach for HCC.
    Oncotarget 12/2014; · 6.64 Impact Factor
  • Nature Reviews Gastroenterology &#38 Hepatology 11/2014; · 10.43 Impact Factor
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    ABSTRACT: The optimal treatment for adrenal metastases from hepatocellular carcinoma (HCC) has not been established. This study analyzed the effects of radiation therapy (RT) for such metastases and identified clinical features and predictors of survival in these patients. We retrospectively investigated 55 patients with adrenal metastasis from HCC who had been treated with RT. Radiation doses to the adrenal lesions ranged from 26 to 60 Gy, while the intrahepatic lesions were treated by surgical resection, transarterial chemoembolization (TACE), liver transplantation, and/or RT. RT was conducted to adrenal lesions after their intrahepatic lesions were controlled more than 2 months. The parameters studied included survival rates and tumor responses to RT. The Kaplan-Meier method was used to evaluate survival rate and the Cox regression model was used to identify potential predictors of outcome. The patients treated by RT had adrenal metastasis on the right side (41), the left (6), or on both sides (8). In all 55 patients, the median survival duration was 13.6 months and there was 100% pain relief after completion of RT. Adverse effects were mild to moderate. Unfavorable pretreatment predictors determined by univariate analysis were associated with multiple intrahepatic foci, metastases to additional organs, high gamma-glutamyltransferase and alpha-fetoprotein levels, liver function of Child-Pugh classification B and uncontrolled primary HCC. By multivariate analysis, unfavorable predictors were multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC. Radiotherapy as treatment for adrenal metastases in HCC is a good palliative therapy that is associated with reasonable safety. It appears reasonable that such patients should be considered to be treated with radiotherapy. Multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC were unfavorable predictors.
    BMC Cancer 11/2014; 14(1):878. · 3.33 Impact Factor
  • Nature Reviews Clinical Oncology 11/2014; · 15.03 Impact Factor
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    ABSTRACT: Upregulation of CXCR2 in tumor cells has been documented in several types of cancer. As one of its ligands, CXCL5 is associated with neutrophil infiltration and poor prognosis in hepatocellular carcinoma (HCC). However, little is known about the role of CXCR2/CXCL5 axis in the invasion and metastasis of HCC cells. In this study, we examined CXCR2 expression in human HCC cell lines and in three independent cohorts of HCC patients. The molecular effects of high expression levels of CXCR2 and CXCL5 in HCC cells were determined using qRT-PCR, western blot analysis, immunofluorescence, matrigel invasion assay, and xenograft mouse models. We found that high levels of CXCR2 correlated with progression and poor prognosis in human HCC. CXCR2/CXCL5 together promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through activation of the PI3K/Akt/GSK-3β/Snail signaling pathway. In clinical HCC samples, high expression of both CXCR2 and CXCL5 showed a significant correlation with the activation of PI3K/Akt/GSK-3β/Snail signaling and EMT phenotype. In conclusion, our data showed that CXCR2/CXCL5 axis contributes to EMT of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling, and it may serve as a potential therapeutic target. Copyright © 2014. Published by Elsevier Ireland Ltd.
    Cancer letters. 11/2014;
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    ABSTRACT: Macrophages are a major component of the leukocyte infiltrate of tumors and play a pivotal role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which macrophages promote HCC invasion are poorly understood. The present study was undertaken to investigate the relationship between macrophages and epithelial-mesenchymal transition (EMT) of HCC. Double-staining immunohistochemistry was used to observe the association between macrophages and EMT markers in clinical HCC samples and it showed that EMT primarily occurred at the edge of the tumor nest, in which infiltrating macrophages were always observed. This indicated that CD68 which is a marker of macrophages, was correlated with EMT marker levels. In addition, after being cultured with macrophages for 24 h, the ability of HCC cells to migrate and invade increased, Snail and N-Cadherin expression was upregulated, and E-Cadherin was downregulated. An antibody array assay was applied to analyze the supernatant of these cultures and it demonstrated IL-8 increased significantly in the macrophage co-culture system. Finally, the role of macrophage-derived IL-8 in the invasion of HCC cells was assayed, and downstream signaling pathways were also investigated. We found that IL-8: i) may induce EMT and promote HCC cell migration and invasion and ii) is associated with the JAK2/STAT3/Snail signaling pathway. Taking together, these findings revealed that macrophages that have infiltrated tumors may induce epithelial-mesenchymal transition of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway. Thus, this may offer a potential target for developing new HCC therapies.
    International journal of oncology. 11/2014;
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    ABSTRACT: The 14-3-3 proteins are highly conserved molecules that are involved in many vital biologic processes and are associated with the progression of cancer. The role of 14-3-3ζ, a dimeric isoform of 14-3-3, in intrahepatic cholangiocarcinoma (ICC) was investigated in this study. The expression of 14-3-3ζ in tumour samples from patients with ICC was examined by Western blot and immunohistochemistry, and the correlation between its expression and various clinicopathological features was determined. Then, the capacity for invasion, migration and proliferation as well as the expression of epithelial-mesenchymal transition (EMT)-related markers in ICC cells were assessed after 14-3-3ζ depletion. Finally, the prognostic significance of 14-3-3ζ in patients with ICC was further evaluated by Kaplan-Meier and Cox regression analyses. The expression of 14-3-3ζ was significantly higher in ICC tissues compared to peritumoural tissues. High expression of 14-3-3ζ positively correlated with lymphatic metastasis and tumour-node-metastasis (TNM) stage. The inhibition of 14-3-3ζ expression was able to impair the invasion, migration and proliferation of ICC cells in vitro. The expression of 14-3-3ζ was significantly correlated with the expression of the EMT-related markers snail and E-cadherin in ICC samples. Moreover, the down-regulation of 14-3-3ζ also decreased the phosphorylation of extracellular signal-regulated kinase (ERK) in ICC cells. Clinically, patients with ICC with high 14-3-3ζ expression demonstrated a poor prognosis in terms of a short overall survival and a high recurrence rate of the disease. A multivariate analysis revealed that 14-3-3ζ overexpression was an independent prognostic indicator for patients with ICC. 14-3-3ζ may enhance the invasive and proliferative capacity of tumour cells and thus prompt the progression of ICC via the activation of ERK signalling and the induction of EMT. The overexpression of 14-3-3ζ may be used as a prognostic biomarker and therapeutic target in patients with ICC.
    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 11/2014;
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    ABSTRACT: Extracellular pH of solid tumor is generally acidic due to excessive glycolysis and poor perfusion. But whether acidic tumor microenvironment influenced the stromal cells infiltrating in tumor remains unknown. As the predominant progenitor of stromal cells in liver, the number of activated hepatic stellate cells (HSCs) was found positively correlated to the acidification level in the tumor tissues of HCC patients in our study. Whereas, in vitro acidic culture condition and in vivo co-implanting xenograft model were adopted to study the response of HSCs and its influence on HCC progression. HSCs were activated under acidic culture condition depending on the phosphorylation of cellular signal-regulated kinase (ERK). Acidity-activated HSCs promoted HCC metastasis in vitro and in vivo. Osteopontin (OPN) excretion from HSCs was increased under acidic condition and proved to promote the migration of HCC cells. Furthermore, the expression level of OPN was significantly associated with myofibroblasts and the combination of α-SMA with OPN was a powerful predictor for poor prognosis of HCC patients. Activation of HSCs in acidic tumor microenvironment represents a novel mechanism for HCC metastasis and provides a potential therapeutic strategy for HCC. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Cancer letters. 10/2014;
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    ABSTRACT: RYBP is a member of the polycomb group (PcG) proteins that typically act as transcriptional repressors via epigenetic modification of chromatin. The present study was designed to investigate the role of RYBP in HCC progression, chemosensitivity, and patient survival, and to explore the underlying molecular mechanism(s). In this study we investigated the expression of RYBP in 400 pairs of human HCC tissues and matched noncancerous samples. The effects of RYBP on HCC tumor growth and metastasis and chemosensitivity were determined both in vitro and in vivo. We herein demonstrate that the RYBP expression in HCC tissue samples was significantly lower than that in matched noncancerous liver tissues. Clinically, the low expression of RYBP was an independent predictor of a poor prognosis in patients with HCC. In in vitro HCC models, enforced RYBP expression inhibited cell growth and invasion, induced apoptosis, and increased the chemosensitivity of the cells, while RYBP knockdown led to the opposite effects. Furthermore, RYBP expression was induced by cisplatin, and adenovirus-mediated RYBP expression inhibited HCC tumor growth and sensitized HCC to conventional chemotherapy in vivo. Our results demonstrate that reactivating RYBP in cancer cells may provide an effective and safe therapeutic approach to HCC therapy.
    Oncotarget 10/2014; · 6.64 Impact Factor
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    ABSTRACT: Purpose Recurrence is a disastrous outcome in patients with hepatitis-related hepatocellular carcinoma (HCC) who have undergone curative resection, and little is known about whether high levels of hepatitis B surface antigen (HBsAg) increase the risk of HCC recurrence. Patients and Methods This retrospective study included 1,360 HBsAg-positive postoperative HCC patients with hepatitis B viral (HBV) DNA levels Results We demonstrated that 1,000 IU/mL, but not 10 or 100 IU/mL, was a meaningful cutoff level for significantly discriminating these patients into an HBsAgLow group and an HBsAgHigh group based on correlations between the HBsAg level and liver cirrhosis (p = 0.028), tumor size (p = 0.039), and hepatitis B e antigen level (p Low group were significantly higher than those of HCC patients in the HBsAgHigh group. Accordingly, the 5-year recurrence-free survival (RFS) rates of patients in the HBsAgLow group were markedly higher than those of HCC patients in the HBsAgHigh group. The HBsAg level was a prognostic indicator for OS (p = 0.014) and RFS (p = 0.01). Conclusion HBsAg level is correlated with more aggressive tumor behavior and serves as a prognostic indicator in patients with surgically resected HCC with low HBV load.
    Annals of Surgical Oncology 10/2014; · 4.12 Impact Factor
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    ABSTRACT: Purpose: We developed a novel systemic immune-inflammation index (SII) based on lymphocyte, neutrophil, and platelet counts and explored its prognostic value in hepatocellular carcinoma (HCC). Experimental Design: The SII was developed based on a retrospective study of 133 HCC patients undergoing resection between 2005 and 2006, and validated in a prospective study of 123 patients enrolled from 2010 to 2011. The circulating tumor cell (CTC) level in the validation cohort was measured using the CellSearch system. Prediction accuracy was evaluated with area under the receiver operating characteristic curve (AUC). Results: An optimal cutoff point for the SII of 330×109 stratified the HCC patients into high (≥330) and low SII (<330) groups in the training cohort. Univariate and multivariate analyses revealed the SII was an independent predictor for overall survival and relapse-free survival, and prognostic for patients with negative alpha-fetoprotein and Barcelona Clinic Liver Cancer stage 0+A. The AUCs of the SII for survival and recurrence were higher than other conventional clinical indices. An SII≥330 was significantly associated with vascular invasion, large tumors, and early recurrence. CTC levels were significantly higher in the SII≥330 group (1.71±0.34 versus 4.37±1.04, P=0.029). In patients with detectable CTCs, those with SII≥330 had higher recurrence rates and shorter survival time than patients with SII<330. Conclusion: The SII was a powerful prognostic indicator of poor outcome in patients with HCC and is a promising tool for HCC treatment strategy decisions. The dismal outcome in patients with high SII scores might be related to higher CTC levels.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 09/2014;
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    ABSTRACT: Atypical chemokine receptors (ACRs) have been discovered to participate in the regulation of tumor behavior. Here, we reported a tumor suppressive role of a novel ACR member, CC chemokine receptor like 1 (CCRL1), in human hepatocellular carcinoma (HCC). Both mRNA and protein expressions of CCRL1 correlated with malignant phenotype of HCC cells and were significantly down-regulated in tumor tissue compared with paired normal liver tissue. In both the initial and validation cohorts (n = 240 and 384, respectively), CCRL1 deficiency was associated with advanced tumor stage and was an independent index for worse survival and increased recurrence. Furthermore, knockdown or forced expression of CCRL1 revealed that CCRL1 suppressed the proliferation and invasion of HCC cells in vitro and reduced tumor growth and lung metastasis in vivo, with depressed levels of CCL19 and CCL21. By sequestrating CCL19 and CCL21, CCRL1 reduced their binding to CCR7 and consequently mitigated the detrimental impact of CCR7, including Akt/GSK-3β pathway activation and nuclear accumulation of β-catenin in tumor cells. Clinically, the prognostic value of the CCR7 expression in HCC depended on the expression level of CCRL1, suggesting that CCRL1 may serve as an upstream switch for the CCR7 signaling cascade. Together, our findings suggest that CCRL1 impairs chemotactic events that associated with CCR7 in progression and metastasis of HCC. Our results also show a potential interplay between typical and atypical chemokine receptors in human cancer.
    The Journal of Pathology 09/2014; · 7.59 Impact Factor
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    ABSTRACT: Therapeutic intervention in neddylation pathway is an emerging area for cancer treatment. Herein, we evaluated the clinical relevance and therapeutic potential of targeting this pathway in intrahepatic cholangiocarcinoma (ICC). Immunohistochemistry of neddylation pathway components in a cohort of 322 cases showed that E1 (NAE1 and UBA3) and E2 (UBC12) enzymes, as well as global NEDD8 conjugation, were upregulated in over 2/3 of human ICC. Notably, NAE1 was identified as an independent prognosticator for postoperative recurrence (P=0.009) and a combination of NEDD8 and NAE1 provided a better power for predicting patient clinical outcomes. In vitro treatment with MLN4924, a small-molecule NEDD8-activating enzyme inhibitor, led to a dose-dependent decrease of viability in both established and primary cholangiocarcinoma cell lines. Additionally, MLN4924 exhibited at least additive effect when combined with cisplatin. By blocking cullins neddylation, MLN4924 inactivated Cullin-Ring ligase (CRL) and caused the accumulation of CRL substrates that triggered cell cycle arrest, senescence or apoptosis. Meanwhile, MLN4924 was well-tolerated and significantly inhibited tumor growth in xenograft model of cholangiocarcinoma. Taken together, our findings indicated that upregulated neddylation pathway was involved in ICC progression and interference in this pathway could be a promising target for ICC therapy.
    Oncotarget 08/2014; · 6.64 Impact Factor
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    ABSTRACT: Purpose: This study aimed to construct a novel platform for the detection of circulating tumor cells (CTCs) in patients with hepatocellular carcinoma (HCC) and investigate the clinical significance of epithelial cell adhesion molecule mRNA-positive (EpCAMmRNA+) CTCs using this platform. Experimental Design: An optimized platform for CTC detection was constructed by evaluating different negative enrichment, mRNA isolation, and cDNA synthesis procedures and compared with CellSearch system. A total of 299 HCC patients were recruited into this prospective study; of these, 157 who received curative resection, 76 who received transcatheter arterial chemoembolization (TACE), and 66 who received radiotherapy were tested using our platform. The diagnostic value of EpCAMmRNA+ CTCs was investigated in 122 HCC patients who underwent resection and 120 control subjects. Results: The optimized negative enrichment and qRT-PCR-based CTC detection platform had high sensitivity, specificity, and reproducibility and a low sample volume requirement. This platform showed a potential diagnostic value in HCC patients and exhibited 76.7% consistency with the CellSearch system (r=0.54, P<0.050). Pretreatment CTC level showed prognostic significance in HCC patients treated with resection, TACE, and radiotherapy (all P<0.050). Most of the patients showed a decrease in CTC levels after treatment that reflected tumor response. In contrast, patients with an increased CTC level showed disease progression after treatment. Conclusions: We established an optimized platform based on negative enrichment and qRT-PCR for highly sensitive, specific, and reproducible CTC detection. This platform might be clinically useful in auxiliary diagnosis, treatment response assessment, and early decision-making to tailor the most effective antitumor strategies.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 07/2014;
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    ABSTRACT: There have been progressive increases in both the incidence and death rates of female patients with hepatocellular carcinoma (HCC). Our objective was to investigate the clinicopathologic characteristics and prognostic factors influencing the recurrence and survival of female patients with HCC.
    Surgery 07/2014; · 3.37 Impact Factor
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    ABSTRACT: Our previous data had shown that Dickkopf-1 (DKK1) combined with β-catenin was a novel prognostic predictor for hepatocellular carcinoma (HCC) patients. However, the role and mechanism of DKK1 in HCC recurrence or metastasis remain poorly understand. This study was to assess the role of DKK1 in tumor metastasis for patients with hepatocellular carcinoma after orthotopic liver transplantation (OLT). The expression of DKK1 protein was detected in hepatic cell lines, HCC cell lines, and HCC patients after OLT with different potential of metastasis. After DKK1 expression in the HCCLM3 cells was downregulated by siRNA-mediated approach, the role of DKK1 in cell invasion and metastasis was investigated. cDNA genechip was used to analyze the differential expressed genes related with DKK1 in two pairs of HCC cells. The prognostic significance of DKK1 was further assessed by Kaplan-Meier and Cox regression analyses in 148 HCC patients after OLT. The expression of DKK1 protein was higher in the high-invasive HCC cells and HCC patients of the disease recurrence group. With the downregulation of DKK1, HCCLM3 cells showed decreased aggressiveness in vitro and lower metastatic ability in vivo. DKK1 could regulate many genes involved in biological processes and pathways related with tumor progression. Furthermore, DKK1 overexpression correlated with tumor microvessel density in clinical HCC samples. Multivariate analysis revealed that DKK1 was an independent prognostic indicator for overall survival and cumulative recurrence in this cohort of HCC patients post-OLT. Collectively, overexpression of DKK1 was implicated in invasion/metastasis of HCC after OLT and DKK1 overexpression may be potential molecular therapeutic targets for liver cancer.
    Medical oncology (Northwood, London, England). 07/2014; 31(7):966.
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    ABSTRACT: The aim of our study was to elucidate the effect of tacrolimus (FK506) and of C-X-C chemokine receptor type 4 (CXCR4), which is a receptor specific to the stromal cell-derived factor-1α (SDF‑1α), on growth and metastasis of hepatocellular carcinoma (HCC). Following treatment with different concentrations of FK506, AMD3100 or normal saline (NS), the proliferation of Morris rat hepatoma 3924A (MH3924A) cells was measured by the MTT assay, the expression of CXCR4 was analyzed with immunohistochemistry, and the morphological changes and the invasiveness of cells were studied with a transwell assay and under a scanning electron microscope, respectively. In addition, August Copenhagen Irish rat models implanted with tumor were used to examine the pathological changes and invasiveness of tumor in vivo, the expression of CXCR4 in tumor tissues and the expression of SDF‑1α in the adjacent tissues to the HCC ones, using immunohistochemistry. In vitro, FK506 (100‑1,000 µg/l) significantly promoted the proliferation of MH3924A cells (P<0.01), and increased the expression of CXCR4 in MH3924A cells, albeit with no significance (P>0.05). By contrast, AMD3100 had no effect on the proliferation of MH3924A cells, but significantly reduced the expression of CXCR4 (P<0.05). The invasiveness of MH3924A cells was significantly (P<0.01) enhanced following treatment with FK506, SDF‑1α, FK506 + AMD3100, FK506 + SDF‑1α or FK506 + AMD3100 + SDF‑1α. In vivo, tumor weight (P=0.041), lymph node metastasis (P=0.002), the number of pulmonary nodules (P=0.012), the expression of CXCR4 in tumor tissues (P=0.048) and that of SDF‑1α in adjacent tissues (P=0.026) were significantly different between the FK506-treated and the NS group. Our results suggest that FK506 promotes the proliferation of MH3924A cells and the expression of CXCR4 and SDF‑1α in vivo. Therefore, inhibiting the formation of the CXCR4/SDF‑1α complex may partly reduce the promoting effect of FK506 on HCC.
    Molecular Medicine Reports 06/2014; · 1.17 Impact Factor

Publication Stats

4k Citations
1,343.04 Total Impact Points


  • 2001–2014
    • Fudan University
      • Institutes of Biomedical Sciences
      Shanghai, Shanghai Shi, China
  • 2013
    • National Cancer Institute (USA)
      • Laboratory of Human Carcinogenesis
      Maryland, United States
  • 2008–2013
    • Shandong University
      • School of Public Health
      Chi-nan-shih, Shandong Sheng, China
  • 2012
    • Renji Hospital
      Shanghai, Shanghai Shi, China
    • University of Michigan
      • Life Sciences Institute
      Ann Arbor, MI, United States
  • 2011
    • Shanghai Punan Hospital
      Shanghai, Shanghai Shi, China
  • 2004–2011
    • Shanghai Cancer Institute
      Shanghai, Shanghai Shi, China
  • 2007–2010
    • University of Pittsburgh
      • • Pittsburgh Cancer Institute
      • • Department of Pathology
      Pittsburgh, Pennsylvania, United States
    • Moffitt Cancer Center
      Tampa, Florida, United States
  • 2009
    • Hangzhou First People's Hospital
      Hang-hsien, Zhejiang Sheng, China
    • National Institutes of Health
      • Center for Cancer Research
      Bethesda, MD, United States
  • 1998–2002
    • Shanghai Medical University
      • • Department of Radiology
      • • Liver Cancer Institute
      Shanghai, Shanghai Shi, China