Feng Shen

Second Military Medical University, Shanghai, Shanghai, Shanghai Shi, China

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Publications (98)350.28 Total impact

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    ABSTRACT: The selection criteria of hepatectomy for patients with multiple hepatocellular carcinomas (HCCs) remain controversial.
    Annals of Surgical Oncology 09/2014; · 4.12 Impact Factor
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    ABSTRACT: Although many studies have shown glycogen synthase kinase-3β(GSK-3β) was associated with type 2 diabetes mellitus(T2DM) and implicated with a wide range of cancers, the role of GSK-3β in hepatocellular carcinoma(HCC) and the correlation among GSK-3β, T2DM and HCC remains unclear. Our objectives were to identify the effect of p-Ser9-GSK-3β on the prognosis of patients with HCC and to learn more about the interaction among T2DM, GSK-3β and the prognosis of HCC.
    PLoS ONE 08/2014; 9(8):e105624. · 3.53 Impact Factor
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    ABSTRACT: A randomized controlled trial was conducted to find out whether antiviral therapy in patients with hepatitis B-related hepatocellular carcinoma (HCC) improves long-term survival after hepatic resection.
    Annals of surgery. 07/2014;
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    ABSTRACT: Background & AimsThis study aimed to establish a prognostic artificial neural network model (ANN) for early hepatocellular carcinoma (HCC) following partial hepatectomy.Methods Consecutive patients who were operated between February 2005 to March 2012 were prospectively studied. 75% and 25% of these patients were randomly selected as a training cohort and an internal validation cohort. Similar patients from another hospital formed an external validation cohort. The predictive accuracy of the ANN for postoperative survival was measured by the area under the curve (AUC) on receiver operating characteristic (ROC) curve analysis. The results were compared with those obtained using the conventional Cox proportional hazard model, and the IHPBA, TNM 6th and BCLC staging systems.ResultsThe number of patients in the training, internal validation and external validation cohorts were 543, 182 and 104, respectively. On linear regression analysis, tumor size, number, alpha¬fetoprotein, microvascular invasion, and tumor capsule were independent factors affecting survival (P < 0.05). The ANN model was established based on these factors. In the training cohort, the AUC of the ANN was larger than that of the Cox model (0.855 vs. 0.826, P = 0.0115), and the staging systems(0.784 vs. TNM 6th: 0.639, BCLC: 0.612, IHPBA: 0.711, P < 0.0001 for all). These findings were confirmed with the internal and external validation cohorts.Conclusion The ANN was significantly better than the other commonly used model and systems in predicting survival of patients with early HCC who underwent partial hepatectomy.
    Journal of Gastroenterology and Hepatology 07/2014; · 3.33 Impact Factor
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    ABSTRACT: After pancreaticoduodenectomy (PD), the postoperative gastroduodenal artery stump (GDAS) hemorrhage is one of the most serious complications. The purpose of this study is to determine whether wrapping the GDAS during PD could decrease the postoperative GDAS hemorrhage incidence.
    06/2014; 26(3):299-308.
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    ABSTRACT: Background Health-related quality of life (HRQL) is an important outcome measure in studies of cancer therapy. This study aimed to investigate HRQL and survival in patients with small hepatocellular carcinoma (HCC) treated with either surgical resection or percutaneous radiofrequency ablation (RFA).Methods Between January 2006 and June 2009, patients with newly diagnosed solitary, small (3 cm or less) HCC were invited to participate in this non-randomized prospective parallel cohort study. The Functional Assessment of Cancer Therapy – Hepatobiliary (FACT-Hep) instrument was used for assessing HRQL. HRQL and survival were compared between the two treatment groups.ResultsA total of 389 patients were enrolled. Questionnaires were completed fully by 99·7 per cent of invited participants (388 of 389) at baseline, 98·7 per cent (383 of 388) at 3 months, 99·0 per cent (379 of 383) at 6 months, 98·4 per cent (365 of 371) at 1 year, 96·6 per cent (336 of 348) at 2 years and 95·1 per cent (289 of 304) at 3 years. There were no significant differences in disease-free and overall survival between the two groups. Patients treated with percutaneous RFA had significantly better HRQL total scores after 3, 6, 12, 24 and 36 months than those who had surgical resection (P < 0·001, P < 0·001, P = 0·001, P = 0·003 and P = 0·025 respectively). On multivariable analysis, the presence of concomitant disease, cirrhosis and surgical resection were significant risk factors associated with a worse HRQL score after treatment.Conclusion Percutaneous RFA produced better post-treatment HRQL than surgical resection for patients with solitary small (no more than 3 cm) HCC.
    British Journal of Surgery 05/2014; · 4.84 Impact Factor
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    ABSTRACT: Our objective was to explore the short-term effects of preoperative serum hepatitis B virus DNA level (HBV DNA) on postoperative hepatic function in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma (HCC). The clinical data of 1,602 patients with hepatitis B-related HCC who underwent partial hepatectomy in our department were retrospectively studied. The patients were divided into three groups according to their preoperative HBV DNA levels: group A <200 IU/mL, group B 200-20,000 IU/mL, and group C >20,000 IU/mL. The rates of postoperative complications, especially the rate of postoperative liver failure, were compared. There were significant differences among the three groups in the rates of postoperative liver failure. On multivariate logistic regression analysis, a high preoperative HBV DNA level was an independent risk factor for postoperative liver failure. Preoperative HBV DNA level was a significant risk factor for postoperative hepatic dysfunction.
    World Journal of Surgery 04/2014; · 2.23 Impact Factor
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    ABSTRACT: IMPORTANCE In patients with low viral loads, high levels of hepatitis B surface antigen (HBsAg) have been shown to predict development of hepatocellular carcinoma (HCC). Whether high levels of HBsAg increase the risk for HCC recurrence after hepatic resection remains unknown. OBJECTIVE To investigate the association between levels of HBsAg and the risk for tumor recurrence after curative resection in HCC patients with low levels of hepatitis B virus (HBV) DNA. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective analysis of the clinical data of 1062 patients with low HBV DNA levels (<200 IU/mL) who underwent partial hepatectomy for HCC. In particular, we investigated the association between levels of HBsAg and recurrence of HCC. EXPOSURE Partial hepatectomy for HCC. MAIN OUTCOMES AND MEASURES The risk for first tumor recurrence between patients with high and low HBsAg levels. We calculated cumulative incidences and hazard ratios after adjusting for competing mortality. RESULTS The risk for tumor recurrence increased with HBsAg levels of 1000 IU/mL or greater. When we compared the groups with low (<1000 IU/mL) and high (≥1000 IU/mL) HBsAg levels, the 5-year disease-free survival rate (46.1% vs 34.1% [P = .002]) and the overall survival rate (57.5% vs 48.8% [P = .004]) were better in the group with low HBsAg levels. On multivariate analysis, hepatitis B e antigen seropositivity, HBsAg level of 1000 IU/mL or greater, tumor size of greater than 5 cm, blood transfusion, surgical margin of less than 1.0 cm, the presence of satellite nodules, and the presence of portal vein tumor thrombus were independent risk factors for HCC recurrence. When compared with hepatitis B e antigen status, HBsAg level better predicted recurrence of HCC. CONCLUSIONS AND RELEVANCE A preoperative HBsAg level of 1000 IU/mL or greater is an independent risk factor for HCC recurrence in patients with low HBV DNA levels.
    JAMA surgery. 04/2014;
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    ABSTRACT: A study of 7,388 consecutive patients after hepatic resection between 2011 and 2012 identified hepatolithiasis, cirrhosis, and intraoperative blood transfusion as the only independent risk factors of both incisional and organ/space surgical site infection (SSI). Patients with these conditions should be cared for with caution to lower SSI rates.
    Infection Control and Hospital Epidemiology 03/2014; 35(3):317-20. · 4.02 Impact Factor
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    ABSTRACT: Background:Pulmonary metastasis (PM) following curative hepatectomy for hepatocellular carcinoma (HCC) is indicative of a poor prognosis. This study aimed to develop a nomogram to identify patients at high risks of PM.Methods:A primary cohort of patients who underwent curative hepatectomy for HCC at the Eastern Hepatobiliary Surgery Hospital from 2002 to 2010 was prospectively studied. A nomogram predicting PM was constructed based on independent risk factors of PM. The predictive performance was evaluated by the concordance index (c-index), calibration curve and decision curve analysis (DCA). During the study period, a validation cohort was included at the First Affiliated Hospital of Fujian Medical University.Results:Postoperative PMs were detected in 106 out of 620 and 45 out of 218 patients, respectively, in two cohorts. Factors included in the nomogram were microvascular invasion, serum alpha-fetoprotein, tumour size, tumour number, encapsulation and intratumoral CD34 staining. The nomogram had a c-index of 0.75 and 0.82 for the two cohorts for predicting PM, respectively. The calibration curves fitted well. In the two cohorts, the DCA demonstrated positive net benefits by the nomogram, within the threshold probabilities of PM >10%.Conclusion:The nomogram was accurate in predicting PM following curative hepatectomy for HCC.British Journal of Cancer advance online publication, 30 January 2014; doi:10.1038/bjc.2014.19 www.bjcancer.com.
    British Journal of Cancer 01/2014; · 5.08 Impact Factor
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    ABSTRACT: Background Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad outcome. Although largely use in medical literature, there are no studies measuring the benefit of liver transplantation (LT) over hepatic resection (HR) for hepatocellular carcinoma (HCC) in terms of “Number of patients needed To Transplant (NTT).” Methods Exclusion criteria: Child-Turcotte-Pugh (CTP) Classes B–C, very large (>10 cm) and multi-nodular (>2 nodules) tumours, macroscopic vascular invasion and extra-hepatic metastases. Study population: 1028 HCC cirrhotic patients from one Eastern (n=441) and two Western (n=587) surgical units. Patient survival observed after HR by proportional hazard regression model was compared to that predicted after LT by the Metroticket calculator. The benefit obtainable from LT compared to resection was analysed in relationship with number of nodules (modelled as ordinal variable: single vs. oligonodular), size of largest nodule (modelled as a continuous variable), presence of microscopic vascular invasion (MVI), and time horizon from surgery (5-year vs. 10-year). Results 330 patients were beyond the Milan criteria (32%) and 597 (58%) had MVI. The prevalence of MVI was 52% in patients within Milan criteria and 71% in those beyond (p0.0001). In the 5-year transplant benefit analysis, nodule size and HCC number were positive predictors of transplant benefit, while MVI had a strong negative impact on NTT. Transplantation performed as an effective therapy (NTT<5) only in oligonodular HCC with largest diameter > 3 cm (beyond conventional LT criteria) when MVI was absent. The 10-year scenario increased drastically the transplant benefit in all subgroups of resectable patients, and LT became an effective therapy (NTT <5) for all patients without MVI whenever tumor extension and for oligonodular HCC with MVI within conventional LT criteria. Conclusion Based on NTT analysis, the adopted time horizon (5-year vs. 10-year scenario) is the main factor influencing the benefit of LT in patients with resectable HCC and Child A cirrhosis.
    Journal of Hepatology 01/2014; 45:S6. · 9.86 Impact Factor
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    ABSTRACT: Let-7 family microRNAs have been reported to be downregulated in human hepatocellular carcinoma in comparison with normal hepatic tissues. Among them, let-7g was identified as the lowest expression using real-time RT-PCR. However, the mechanism by which let-7g works in hepatocellular carcinoma remains unknown. Here, in our present study, we have had let-7g reexpressed in vitro in hepatocellular carcinoma cell lines MHCC97-H and HCCLM3 via transfection. The proliferation after reexpression of let-7g was assayed using MTT method; the migration and invasion after restoration were detected by wound-healing and Transwell assay, respectively. We found using Western-blotting that let-7g can regulate epithelial-mesenchymal transition (EMT) by downregulating K-Ras and HMGA2A after reexpresssion. Xenografted nude mice were used to observe whether or not reexpression of let-7g could have potential therapeutic ability. In vivo, to observe the association with let-7g expression and overall prognosis, 40 paired cases of hepatocellular carcinoma were analyzed using in situ hybridization (ISH). It was found that reexpression of let-7g can inhibit the proliferation, migration, and invasion significantly, and that low expression of let-7g was significantly associated with poorer overall survival. Taken together, let-7g could be used as a promising therapeutic agent in vivo in the treatment of hepatocellular carcinoma at the earlier stage.
    BioMed research international. 01/2014; 2014:742417.
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    ABSTRACT: Mucin-producing bile duct tumors (MPBTs) are unusual, and we present our experience with nine surgically proven cases. Between November 2002 and November 2012, 9 patients with surgically proven MPBTs (including history of relevant hepatobiliary surgery in 6 patients) were encountered. Their clinical, imaging, and surgical findings were reviewed. The most common symptom is intermittent jaundice, which occurs in seven patients. The diagnostic specificity was 77.8% by preoperative Magnetic Resonance Cholangiopancreatography (MRCP). All the patients underwent ipsilateral hemihepatectomy or remnant hemihepatectomy, accompanied caudate lobectomy in one case and concomitant Roux-en-Y choledochojejunostomy in four cases. Postoperative course was uneventful. One patient, who had intra-abdominal recurrence 59 months after surgery, was received reoperation without recurrence at the last follow-up. The remaining eight patients were alive without disease recurrence. Based on our follow up of 9 cases that were surgically treated for MPBTs, we conclude that ipsilateral hemihepatectomy is a safe surgical procedure with an observed recurrence risk of 11.1% and all long-term survival.
    PLoS ONE 01/2014; 9(4):e92010. · 3.53 Impact Factor
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    ABSTRACT: This study aimed to investigate the virological status in liver (both tumor and adjacent non-tumor tissue), the clinical features and the contribution of occult HBV infection (OBI) to postoperative prognosis in HBeAg-negative(-) hepatocellular carcinoma (HCC) patients in China. Using quantitative TaqMan fluorescent real-time PCR assays, HBV covalently closed circular DNA (cccDNA) and total DNA (tDNA) were both quantified in 11 (HBsAg(-)) and 57 (HBsAg-positive(+)) pairs of tumor tissue (TT) and adjacent non-tumor tissue (ANTT) obtained from HBeAg(-) HCC patients who received no antiviral treatment and were negative for anti-HCV before surgical treatment. Of 11 HBsAg(-) patients, 36% were with HBsAb(+) HBeAb(+) HBcAb(+). However, only 9% of the HBsAg(-) patients were HBsAb(-) HBeAb(+) HBcAb(+), which accounted for the majority (93%) in the HBsAg(+) group. TT and ANTT HBV tDNAs in 11 HCC patients with HBsAg (-) and HBeAg (-) were all detectable. HBV cccDNA and tDNA were all lower in the HBsAg(-) group than those in the HBsAg(+) group. By Kaplan-Meier analysis, patients with OBI were associated with a lower risk of cirrhosis and better overall survival (OS). The intracellular HBV DNAs, such as HBV cccDNA and tDNA are valuable biological markers for the diagnosis of occult HBV infection in HCC patients. This would assist the clinical implementation of a more personalized therapy for viral re-activation control and improve the survival rate of OBI patients.
    PLoS ONE 01/2014; 9(9):e107162. · 3.53 Impact Factor
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    ABSTRACT: Reflux cholangitis has been the most common complication after Roux-en-Y choledochojejunostomy. In this study we intended to evaluate the perioperative and long-term efficacy of a new anastomosis method for choledochojejunostomy. Clinical data of 143 eligible patients who underwent choledochojejunostomy in the Eastern Hepatobiliary Surgery Hospital affiliated to the Second Military Medical University, China between January 2007 and December 2010 were retrospectively analyzed. Among the patients, 38 consecutive cases underwent this new anastomosis method for choledochojejunostomy (improved group, IG) and 105 underwent standard Roux-en-Y choledochojejunostomy (control group, CG). Changes in the incidence of cholangitis, the time of beginning to eat liquid meals, post-operative delayed gastric emptying and liver function between the two groups were compared. There was no statistical difference in the levels of alanine transaminase, alkaline phosphomonoesterase and gamma-glutamy transferase between the two groups. The time of beginning to eat liquid meals was significantly shorter in IG than CG (P < 0.05). The incidence of delayed gastric emptying was lower in IG than CG, with statistical tendency between the two groups (P = 0.052). Among nine patients with different degrees of acute cholangitis in the two groups, one patient (2.6%) in IG and eight (7.6%) in CG suffered from acute cholangitis within six months of follow-up after discharge, but with no statistical difference between the two groups (P > 0.05). Of the nine patients with acute cholangitis, none in IG and four in CG were hospitalized for further treatment (P > 0.05). Patients in IG had satisfactory perioperative and long-term prognosis with shorter time of beginning to eat liquid meals and lower incidence of delayed gastric emptying. This new procedure of choledochojejunostomy by the way behind antrue pyloricum was easy and safe to perform with no mortality and low complication rates.
    Chinese medical journal 12/2013; 126(24):4633-7. · 0.90 Impact Factor
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    The Lancet 11/2013; 382(9906):1703-1704. · 39.21 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the prognostic value of tumor size alone on long-term survival and recurrence after curative resection for solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion. A single-center cohort of 615 patients with solitary HCC (a single tumor, without macroscopic vascular invasion or distant metastasis) undergoing curative hepatic resection from 2002 to 2010 was retrospectively studied. Using 2.0, 3.0, 4.0, 5.0, 8.0, and 10.0 cm as cut-off values of tumor size, the overall survival (OS) and recurrence-free survival (RFS) rates were compared between the groups of patients with tumor size up to a certain cut-off value and the groups of patients with tumor size above that cut-off value. Thus, multiple comparisons were done. The prognostic factors of OS and RFS were evaluated using univariate and multivariate analyses. The median tumor size of all HCCs was 4.0 cm (range 0.9-22.0 cm). The in-hospital mortality rate was 1.0 %, and the overall morbidity rate was 22.3 %. The 1-, 3-, and 5-year OS rates were 96.0, 79.8, and 69.9 %, and the corresponding RFS rates were 83.6, 72.7, and 57.2 %, respectively. On univariate analyses, the 1-, 3-, and 5-year OS and RFS rates were significantly different between the individual two groups of patients as divided by the aforementioned different cut-off values of tumor sizes (all p < 0.05). However, when tumor size was put as a continuous variable into multivariate analysis, it was no longer an independent prognostic factor of OS or RFS after curative resection. Tumor size did not independently affect long-term survival and recurrence after curative resection of solitary HCC without macroscopic vascular invasion. Therefore, there is no size limit that precludes hepatic resection for solitary HCC, provided the tumor is resectable.
    World Journal of Surgery 11/2013; · 2.23 Impact Factor
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    ABSTRACT: Whether anatomic resection (AR) for hepatocellular carcinoma (HCC) can really confer a survival advantage over non-AR (NAR), especially for cirrhotic patients, remains unclear. Prospectively collected data of 543 cirrhotic patients in Child-Pugh class A submitted to AR (n = 228) versus NAR (n = 315) for early HCC in an Eastern (n = 269) and a Western (n = 274) surgical unit, were reviewed. To control for confounding variable distributions, a 1-to-1 propensity score match was applied to compare AR and NAR outcomes (n = 298). The 5-year recurrence-free and overall survivals of the 543 patients were 32.3% and 60.0%, respectively, without differences between the 2 centers (P = .635 and .479, respectively). AR conferred better overall and recurrence-free survival than NAR (P = .009 and .041, respectively), but NAR patients suffered from significantly worse hepatic dysfunction. After 1-to-1 match, AR (n = 149) and NAR (n = 149) patients had similar covariate distributions. In this matched sample, AR still conferred better recurrence-free survival over NAR (P = .044) but the beneficial effect of AR was limited to the reduction of early recurrence (<2 years) of poorly differentiated tumors and of tumors with microvascular invasion (P < .05), resulting in better overall survival (P = .018). In cirrhotic patients, AR for early HCC can lead to a lower early recurrence rate in tumors with unfavorable tumor features, whereas NAR will not worsen the recurrence rate in well/moderately differentiated tumors or in the absence of microvascular invasion.
    Surgery 10/2013; · 3.37 Impact Factor
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    ABSTRACT: Interaction between tumor and stromal cells plays an important role in cancer progression. The aim of this study was to explore the effects of tumor-associated fibroblasts on regulation of hepatocellular carcinoma (HCC) progression. Sixty-five cases of HCC and the corresponding normal liver tissues were recruited for immunohistochemical assessment of α-smooth muscle actin (α-SMA) expression, a biomarker for activated fibroblasts. Clinicopathological data were also collected from HCC patients for association with α-SMA expression. Primary cell culture of fibroblasts from HCC tissues was used to generate conditioned medium for testing the effect on regulation of HCC cell migration capacity in the transwell cell migration assay. α-SMA protein was expressed in 84.0 % (21 out 25 cases) of the fibroblasts from the metastatic HCCs, 45 % (18/40) from HCCs without metastasis, and 19.2 % (5/26) from normal liver tissues, difference of which was statistically significant (P < 0.01). The expression of α-SMA protein in HCC tissues was associated with tumor thrombosis, poor pathology grade, advanced clinical stages, and lymph node metastasis. The conditioned medium from the primary cultured fibroblasts with α-SMA expression significantly promoted the migration capacity of HCC Hep3B cells compared to the heat-inactivated conditioned medium. The data from the current study demonstrated that expression of α-SMA protein in HCC fibroblasts associated with tumor metastasis and advanced clinical stages and that the conditioned medium from α-SMA-positive fibroblasts enhanced HCC cell migration. This study indicates that α-SMA protein might serve as a biomarker to predict HCC progression.
    Medical Oncology 09/2013; 30(3):593. · 2.14 Impact Factor
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    ABSTRACT: & Aims: Aberrant expression of MUC15 correlates with development of colorectal adenocarcinoma, and MUC15 has been reported to prevent trophoblast invasion of human placenta. However, little is known about the role of MUC15 in pathogenesis of hepatocellular carcinoma (HCC). We analyzed HCC samples and matched, non-tumor liver tissues (controls) collected from 313 patients who underwent hepatectomy in Shanghai, China, from January 2006 through September 2009. Levels of mRNAs and proteins were determined by immunohistochemical, quantitative reverse transcription PCR, and immunoblot analyses. Statistical analyses were used to associate levels of MUC15 with tumor features and patient outcomes. Levels of MUC15 mRNA and protein were reduced in a greater percentage HCC samples than control tissues. Tumors with reduced levels of MUC15 were more likely to have aggressive characteristics (high levels of 003F-fetoprotein, vascular invasion, lack of encapsulation, poor differentiation) than those with low levels. Patients whose tumors had reduced levels of MUC15 had shorter overall survival times (24 months, vs 46 months for patients with tumors with high levels of MUC15) and time to disease recurrence. Stable expression of MUC15 in HCC cell lines (SMMC-7721 and HCC-LM3) reduced their proliferation and invasive features in vitro, and ability to form metastatic tumors in mice. MUC15 reduced transcription of the matrix metalloproteinases (MMPs) 2 and 7 increased expression of tissue inhibitor of metalloproteinase-2 (TIMP2), which required phosphoinositide 3-kinase (PI3K)-AKT signaling. Physical interaction between MUC15 and epidermal growth factor receptor (EGFR) led to its relocation and degradation within early endosomes and was required for inactivation of PI3K-AKT signaling. Reduced levels of MUC15 in HCCs are associated with shorter survival times of patients and reduced time to disease recurrence. Expression of MUC15 in HCC cells reduces their aggressive behavior in vitro and in mice, by inducing dimerization of EGFR and decreasing PI3K signaling via AKT.
    Gastroenterology 08/2013; · 12.82 Impact Factor

Publication Stats

555 Citations
350.28 Total Impact Points

Institutions

  • 1997–2014
    • Second Military Medical University, Shanghai
      • International Cooperation Laboratory on Signal Transduction
      Shanghai, Shanghai Shi, China
  • 2012
    • Southeast University (China)
      Nan-ching-hsü, Jiangxi Sheng, China
    • The Chinese University of Hong Kong
      Hong Kong, Hong Kong
    • Wenzhou Medical College
      Yung-chia, Zhejiang Sheng, China
  • 2007–2011
    • Shanghai Institutes for Biological Sciences
      Shanghai, Shanghai Shi, China
  • 2010
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
  • 2009
    • Government of the People's Republic of China
      Peping, Beijing, China
  • 2008
    • Chinese Academy of Sciences
      • Institute of Mechanics
      Beijing, Beijing Shi, China
    • Northeast Institute of Geography and Agroecology
      • Institute of Neuroscience
      Beijing, Beijing Shi, China