Qiang Xia

Shanghai Cancer Institute, Shanghai, Shanghai Shi, China

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Publications (230)324.29 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Elsholtzia splendens (ES) is, rich in flavonoids, used to repair copper contaminated soil in China, which has been reported to benefit cardiovascular systems as folk medicine. However, few direct evidences have been found to clarify the vasorelaxation effect of total flavonoids of ES (TFES). The vasoactive effect of TFES and its underlying mechanisms in rat thoracic aortas were investigated using the organ bath system. TFES (5-200mg/L) caused a concentration-dependent vasorelaxation in endothelium-intact rings, which was not abolished but significantly reduced by the removal of endothelium. The nitric oxide synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (100μM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,2-α]quinoxalin-1-one (30μM) significantly blocked the endothelium-dependent vasorelaxation of TFES. Meanwhile, NOS activity in endothelium-intact aortas was concentration-dependently elevated by TFES. However, indomethacin (10μM) did not affect TFES-induced vasorelaxation. Endothelium-independent vasorelaxation of TFES was significantly attenuated by KATP channel blocker glibenclamide. The accumulative Ca(2+)-induced contraction in endothelium-denuded aortic rings primed with KCl or phenylephrine was markedly weakened by TFES. These results revealed that the NOS/NO/cGMP pathway is likely involved in the endothelium-dependent vasorelaxation induced by TFES, while activating KATP channel, inhibiting intracellular Ca(2+) release, blocking Ca(2+) channels and decreasing Ca(2+) influx into vascular smooth muscle cells might contribute to the endothelium-independent vasorelaxation conferred by TFES.
    Environmental toxicology and pharmacology. 08/2014; 38(2):453-459.
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    ABSTRACT: Dermatopontin (DPT), a tyrosine-rich, acidic matricellular protein, has been implicated in several human cancers. However, its biological functions and molecular mechanisms in cancer progression, particular hepatocellular carcinoma (HCC), remain unknown. We demonstrated that DPT was significantly down-regulated in 202 HCC clinical samples and that its expression level was closely correlated with cancer metastasis and patient prognosis. The overexpression of DPT dramatically suppressed HCC cell migration in vitro and intrahepatic metastasis in vivo. We further revealed that the down-regulation of DPT in HCC was due to epigenetic silencing by promoter DNA methylation. And the inhibitory effects of DPT on HCC cell motility were associated with dysregulated focal adhesion assembly, decreased RhoA activity and reduced focal adhesion kinase (FAK) and c-Src tyrosine kinase (Src) phosphorylation, and all of these alterations required the involvement of integrin signaling. Furthermore, we determined that the inhibitory effects of DPT on HCC cell motility were primarily mediated through α3β1 integrin. Our study provides new evidence for epigenetic control of tumor microenvironment, and suggests matricellular protein DPT may serve as a novel prognostic marker and act as a HCC metastasis suppressor.
    Oncotarget 07/2014; · 6.64 Impact Factor
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    ABSTRACT: Hepatoblastoma (HB) is the most common primary liver tumor in children. Mutations in the β-catenin gene that leads to constitutive activation of Wnt pathway have been detected in a large proportion of HB tumors. To identify novel mutations in HB, we performed whole-exome sequencing of 6 paired HB tumors and their corresponding lymphocytes. This identified 24 somatic non-synonymous mutations in 21 genes, many of which were novel, including three novel mutations targeting the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) genes in the Wnt pathway, and genes previously shown to be involved in the ubiquitin ligase complex (SPOP, KLHL22, TRPC4AP and RNF169). Functionally, both the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) were observed to be gain-of-functional mutations, and the CAPRIN2 (R968H/S969C) was also shown to activate the Wnt pathway in HB cells. These findings suggested the activation of the Wnt pathway in HB, which was confirmed by immunohistochemical staining of the β-catenin in 42 HB tumors. We further used shRNA-mediated interference to assess the effect of 21 mutated genes on HB cell survival. The results suggested that 1 novel oncogene (CAPRIN2) and 3 tumor suppressors (SPOP, OR5I1 and CDC20B) influence HB cell growth. Moreover, we found that SPOP S119N is a loss-of-function mutation in HB cells. We finally demonstrated that one of the mechanisms by which SPOP inhibits HB cell proliferation is through regulating CDKN2B expression. Conclusion: these results extend the landscape of genetic alterations in HB and highlight the dysregulation of Wnt and ubiquitin pathways in HB tumorigenesis. (Hepatology 2014;).
    Hepatology 06/2014; · 12.00 Impact Factor
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    ABSTRACT: To compare the surgical outcomes between living-donor and deceased-donor liver transplantation in patients with hepatic carcinoma. From January 2007 to December 2010, 257 patients with pathologically confirmed hepatic carcinoma met the eligibility criteria of the study. Forty patients who underwent living-donor liver transplantation (LDLT) constituted the LDLT group, and deceased-donor liver transplantation (DDLT) was performed in 217 patients. Patients in the LDLT group were randomly matched (1:2) to patients who underwent DDLT using a multivariate case-matched method, so 40 patients in the LDLT group and 80 patients in the DDLT group were enrolled into the study. We compared the two groups in terms of clinicopathological characteristics, postoperative complications, long-term cumulative survival and relapse-free survival outcomes. The modified Clavien-Dindo classification system of surgical complications was used to evaluate the severity of perioperative complications. Furthermore, we determined the difference in the overall biliary complication rates in the perioperative and follow-up periods between the LDLT and DDLT groups. The clinicopathological characteristics of the enrolled patients were comparable between the two groups. The duration of operation was significantly longer (553 min vs 445 min, P < 0.001) in the LDLT group than in the DDLT group. Estimated blood loss (1188 mL vs 1035 mL, P = 0.055) and the proportion of patients with intraoperative transfusion (60.0% vs 43.8%, P = 0.093) were slightly but not significantly greater in the LDLT group. In contrast to DDLT, LDLT was associated with a lower rate of perioperative grade II complications (45.0% vs 65.0%, P = 0.036) but a higher risk of overall biliary complications (27.5% vs 7.5%, P = 0.003). Nonetheless, 21 patients (52.5%) in the LDLT group and 46 patients (57.5%) in the DDLT group experienced perioperative complications, and overall perioperative complication rates were similar between the two groups (P = 0.603). No significant difference was observed in 5-year overall survival (74.1% vs 66.6%, P = 0.372) or relapse-free survival (72.9% vs 70.9%, P = 0.749) between the LDLT and DDLT groups. Although biliary complications were more common in the LDLT group, this group did not show any inferiority in long-term overall survival or relapse-free survival compared with DDLT.
    World Journal of Gastroenterology 04/2014; 20(15):4393-400. · 2.55 Impact Factor
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    ABSTRACT: Monoamine oxidase A (MAOA), a catecholamine neurotransmitter degrading enzyme, is closely associated with neurological and psychiatric disorders. However, its role in cancer progression remains unknown. Hepatocellular carcinoma (HCC) tissue arrays (n=254) were used to investigate the correlation between MAOA expression and clinicopathological findings. In vitro invasion and anoikis assays, and in vivo intrahepatic and lung metastasis models were used to determine the role of MAOA in HCC metastasis. Quantitative real-time PCR, western blotting, immunohistochemical staining and HPLC analysis were performed to uncover the mechanism of MAOA in HCC. We found that MAOA expression was significantly downregulated in 254 clinical HCC samples and was closely correlated with cancer vasoinvasion, metastasis and poor prognoses. We then demonstrated that MAOA suppressed norepinephrine/epinephrine (NE/E)-induced HCC invasion and anoikis inhibition, and uncovered that the effects of NE/E on HCC behaviors were primarily mediated through alpha 1A (ADRA1A) and beta 2 adrenergic receptors (ADRB2). In addition to the canonical signaling pathway, which is mediated via adrenergic receptors (ADRs), we found that ADR-mediated EGFR transactivation was also involved in NE-induced HCC invasion and anoikis inhibition. Notably, we found that MAOA could synergize with EGFR inhibitors or ADR antagonists to abrogate NE-induced HCC behaviors. Taken together, the results of our study may provide insights into the application of MAOA as a novel predictor of clinical outcomes and indicate that increasing MAOA expression or enzyme activity may be a new approach that can be used for HCC treatment.
    Journal of Hepatology 03/2014; · 9.86 Impact Factor
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    ABSTRACT: The aim of this study was to assess serum levels of presurgical α-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9) as prognostic markers in patients with hepatic carcinoma after liver transplantation (LT). A total of 226 patients were recruited for the analysis of serum AFP and CA19-9 levels, on the basis of which the tumor marker type (TMT) was defined and evaluated for prognostic prediction. Overall survival (OS) and relapse-free survival (RFS) were analyzed using Kaplan-Meier curves, and univariate and multivariate Cox models. One-year and 5-year OS were 79.0 and 58.0%, respectively, whereas RFS were 70.3 and 62.2%, respectively, in this cohort of patients. There were six variables predicting both OS and RFS, including TMT, tumor size, number of tumor lesions, extrahepatic or vascular invasion, and histopathological grade. Among these, TMT, tumor size, and extrahepatic invasion were all independent predictors of OS and RFS among these patients. Further, on the basis of TMT, novel LT selection criteria for patients with hepatic carcinoma, which supplemented the Milan criteria, were adopted, because the patients within the Milan criteria (n=107) and those exceeding Milan but fulfilling the proposed criteria (n=30) had similar 5-year OS (77.8 vs. 79.3%, P=0.862) and RFS (85.5 vs. 75.1%, P=0.210) rates. The data from this study showed that serum levels of preoperative AFP and CA19-9 were able to predict survival of patients with hepatic carcinoma after LT. This study included novel criteria, adding serum AFP and CA19-9 levels to the selection criteria for LT eligibility of patients, in addition to the Milan criteria.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
    European journal of gastroenterology & hepatology 03/2014; · 1.66 Impact Factor
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    ABSTRACT: To investigate the influence of total flavonoids of Elsholtzia splendens (TFES) on isolated ischemia/reperfusion rat hearts and its underlying mechanisms.
    03/2014; 30(2):161-5.
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    ABSTRACT: Orthotopic liver transplantation is currently the best treatment option for selected patients with hepatocellular carcinoma (HCC). From 1980 to 2011, 8874 patients with HCC in China underwent liver transplantation. The organ donation classification criteria of China (China criteria), which are established by the Government of China, are divided into three parts: China criteria I, donation after brain death; China criteria II, donation after cardiac death and China criteria III, donation after dual brain-cardiac death. Data from the China Liver Transplant Registry(CLTR) System shows that patients within the Milan criteria have higher survival rates than those who are beyond these criteria. Based on CLTR data, altogether 416 patients received living-donor liver transplantation(LDLT) in China. Their 1-year and 3-year survival rates were significantly higher than those of the non-LDLT recipients. The most common early stage(<30 days after liver transplantation) complications include pleural effusion, diabetes, peritoneal effusion or abscess, postoperative infection, hypertension and intraperitoneal hemorrhage; while the most common late stage (≥ 30 days after liver transplantation) complications were diabetes, hypertension, biliary complications,postoperative infection, tacrolimus toxicity and chronic graft rejection. The incidence of vascular complication, which is the main reason for acute graft failure and re-transplantation, was 2.4%. Liver transplantation is an effective treatment for patients with HCC in China.
    Journal of Digestive Diseases 02/2014; 15(2):51-3. · 1.85 Impact Factor
  • Ping Wan, Xin Yu, Qiang Xia
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    ABSTRACT: Living donor liver transplantation (LDLT) has emerged as an alternative to deceased donor liver transplantation (DDLT) with the increasing number of patients waiting for a liver transplant. However, whether it can achieve similar operative outcomes compared with DDLT in adult patients remains controversial. We conducted this meta-analysis to compare the operative outcomes between LDLT and DDLT recipients. A literature search was performed to identify clinical controlled studies comparing LDLT with DDLT published before October 2013. Four perioperative outcomes (duration of recipient operation, red blood cell transfusion requirement, length of hospital stay and cold ischemia time) and five postoperative complication outcomes (biliary complications, vascular complications, intraabdominal bleeding, perioperative death and retransplantation) were the main outcomes assessed. Nineteen studies with a total of 5450 patients were included in the meta-analysis. Compared with DDLT, LDLT was associated with significantly longer duration of recipient operation, and shorter cold ischemia time. We found biliary complications (Weighted mean difference [WMD]: 3.08, 95% confidence interval [CI]: 1.97 to 4.81, P<0.001), vascular complications (WMD: 2.16, 95% CI: 1.32 to 3.54, P=0.002) and retransplantation (WMD: 1.76, 95% CI: 1.09 to 2.83, P= 0.02) occurred more frequently in LDLT recipients, and the subgroup analysis indicated biliary complication rate decreased dramatically with greater LDLT experience. No significant difference was observed in red blood cell transfusion requirement, length of hospital stay, intraabdominal bleeding rate and perioperative mortality between LDLT and DDLT recipients. In conclusion, LDLT was associated with a higher rate of surgical complications post-transplantation. Reduction of postoperative complication rate could be achieved as centers gained greater experience with LDLT. However, LDLT still offered an excellent alternative to DDLT because it facilitated access to a liver transplant. Liver Transpl , 2014. © 2014 AASLD.
    Liver Transplantation 01/2014; · 3.94 Impact Factor
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    ABSTRACT: Little information is available regarding the impact of cytochrome P450 (CYP) 3A5 on the metabolism of TAC in infant LTx. Therefore, the CYP3A5 genotype of Chinese pediatric recipients (intestine) as well as donors (graft liver) was performed for the purpose of establishing an optimal dosage regimen in children. Sixty-four patients were divided according to CYP3A5 genotype (expression of *1 allele: EX and NEX) for each recipient (R) and donor (D), EX-R/EX-D (n = 21), EX-R/NEX-D (n = 8), NEX-R/EX-D (n = 8) and NEX-R/NEX-D (n = 27). Results indicated that initial TAC daily dose requirement was higher among EX-R/EX-D children compared with those who did not express CYP3A5 (0.28 ± 0.10 vs. 0.19 ± 0.08 mg/kg/day, p < 0.01). CYP3A5 expression contributed an overall of 38.35% to its C/D ratios, and graft liver was a key determinant. Additionally, the EX-R/EX-D group showed significantly higher incidence of infectious complications, lower immune response and was an independent risk factor for the development of infections (odds ratio 3.86, p = 0.025). Donor CYP3A5 expression partially explains TAC dose requirement, the effect of CYP3A5 variation may influence clinical outcomes; therefore, monitoring immune response may be important for preventing risks associated with under- and over-immunosuppression.
    Pediatric Transplantation 01/2014; · 1.50 Impact Factor
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    ABSTRACT: Cbx4 is a polycomb group protein that is also a SUMO E3 ligase, but its potential roles in tumorigenesis remain to be explored. Here, we report that Cbx4, but not other members of the Cbx family, enhances hypoxia-induced vascular endothelial growth factor (VEGF) expression and angiogenesis in hepatocellular carcinoma (HCC) cells through enhancing HIF-1α sumoylations at K391 and K477 in its two SUMO-interacting motifs-dependent mechanisms and increasing transcriptional activity of HIF-1. The Cbx4 expression is significantly correlated with VEGF expression, angiogenesis, and the overall survival of HCC patients and also in subcutaneously and orthotopically transplanted mice HCC models. Collectively, our findings demonstrate that Cbx4 plays a critical role in tumor angiogenesis by governing HIF-1α protein.
    Cancer cell 01/2014; 25(1):118-31. · 25.29 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality, and is characterized by high potential for metastasis and recurrence. The outcome of it is still poor due to lacking of targeted therapeutic strategies. There is an urgent need to find new therapeutic targets for interventions against HCC metastasis and recurrence. In the present study, we found cytohesin-3, a member of the cytohesin family, was upregulated in HCC tissues, and its expression was negatively correlated with the overall survival and relapse-free survival of HCC patients. Further clinicopathological correlation analysis revealed that cytohesin-3 expression was related with tumor size and vascular invasion. And in vitro studies revealed that knock-down of cytohesin-3 suppressed HCC cells proliferation and migration. These results suggest that cytohesin-3 may act as a novel prognostic factor of HCC, and it might also be useful to exploit targeted therapeutic drugs against HCC growth and metastasis.
    International journal of clinical and experimental pathology. 01/2014; 7(5):2123-32.
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    ABSTRACT: Objective The purpose of this meta-analysis was to compare outcomes of different techniques used for biliary reconstruction in adult donor liver transplantation. Methods We searched the literature via Pubmed, Embase, Ovid, the Cochrane Hepato-Biliary Group Controlled Trials Regsistry, the Cochrane Central Registry of Controlled Trials, the Cochrane Library database, and Web of Science. Then with the data extracted from the literature, the effects that biliary reconstruction techniques in living-donor liver transplantation (LDLT) had on the occurrence of biliary complications were compared. With the use of random-effects and fixed-effect models, the results were obtained and expressed as odds ratio. Results We found 16 eligible studies from various medical centers around the world. Duct-to-duct (DD) reconstruction was performed in the majority of patients (922/1,564). Multiple biliary ducts were encountered in 16.7%–60.4%, and ductoplasty was performed in 7.9%–74% of the patients. Both graft and posterior layer of bile duct anastomosis in DD reconstruction were studied, and no statistically differences in incidence of biliary complications were found between the Roux-en-Y hepaticojejunostomy (RYHJ) and DD groups. Nonsurgical management of biliary complications was the first choice of treatment. Conclusions Our study found that there is no clear evidence in favor of using DD or RYHJ during adult LDLT.
    Transplantation Proceedings 01/2014; 46(1):208–215. · 0.95 Impact Factor
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    ABSTRACT: MicroRNA-24 (miR-24) may be involved in neoplastic process; however, the role of this microRNA in the hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) has not been well elaborated. Here, we tested miR-24 expression in 207 pathology-diagnosed HCC cases from high AFB1 exposure areas and HCC cells. We found that miR-24 was upregulated in HCC tumor tissues relative to adjacent noncancerous tissue samples, and that the high expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation. Additionally, this microRNA overexpression modified the recurrence-free survival (relative hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.66-8.47) and overall survival (HR = 3.58, 95% CI = 2.34-5.46) of HCC patients. Furthermore, we observed some evidence of joint effects between miR-24 and AFB1 exposure on HCC prognosis. Functionally, miR-24 overexpression progressed tumor cells proliferation, inhibited cell apoptosis, and developed the formation of AFB1-DNA adducts. These results indicate for the first time that miR-24 may modify AFB1-related HCC prognosis and tumorigenesis.
    BioMed research international. 01/2014; 2014:482926.
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    ABSTRACT: To establish a prognostic prediction system for patients with hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation (LT). A total of 130 patients undergoing LT for HCC exceeding Milan criteria were enrolled into the study. Independent predictors for relapse-free survival (RFS) were adopted to establish a grading system to predict the risk of post-LT tumor recurrence. Multivariate Cox analysis revealed that tumor size >10 cm [vs. ≤5 cm: relative risk (RR) = 4.214, P < 0.001], preoperative alpha fetoprotein > 400 ng/ml (vs. ≤400 ng/ml: RR = 1.657, P < 0.001), extrahepatic invasion (RR = 2.407, P = 0.005) and vascular invasion (RR = 1.917, P = 0.013) were independent predictors for RFS. The risk index of each patient was defined as the sum of the RR obtained in the Cox analysis for RFS. The risk of tumor recurrence was classified into four grades: grade I-risk index equal to 0, grade II-risk index from 0 to 2, grade III-risk index from 2 to 6 and grade IV-risk index >6. RFS rates of patients with grade I-IV (n = 35, 46, 30 and 19) were 87.5, 57.8, 34.7 and 0 % in 1 year; and 74.4, 41.7, 14.4 and 0 % in 5 years. Both of overall survival (OS) and RFS correlated well with the risk index grade. Patients with grade I achieved comparable prognostic outcomes with the Milan group patients (n = 119) (5-year OS = 73.7 vs. 74.7 %, P = 0.748; 5-year RFS = 74.4 vs. 85.7 %, P = 0.148). The new grading system was proved to be a promising system in predicting the patient prognosis after LT for HCC exceeding Milan criteria.
    Journal of Cancer Research and Clinical Oncology 12/2013; · 2.91 Impact Factor
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    ABSTRACT: Although the protective effect of lipopolysaccharide (LPS) pretreatment on renal ischemia/reperfusion injury is known, a link to hypoxia-inducible factors (HIFs) has not been established. Here we show that LPS treatment led to HIF-2α accumulation in mouse kidneys and endothelial cells, a result of nuclear factor-κB activation. Inactivation of HIF-2α, rather than HIF-1α, completely negated LPS-mediated protection against renal ischemia/reperfusion injury. LPS-stimulated renoprotection was related to inducible/endothelial nitric oxide synthase (iNOS/eNOS) expression, increased production of nitric oxide, and enhanced postischemic microcirculatory recovery. All these effects were lost in HIF-2α knockout mice. Preischemic administration of a nitric oxide donor, rather than erythropoietin, restored the lost preconditioning effect of LPS in HIF-2α knockout mice. In vitro and in vivo studies demonstrated that HIF-2α in endothelial cells, rather than myeloid cells or hepatocytes, was responsible for the LPS-mediated effects. Thus, our results demonstrated that LPS preconditioning protected against renal ischemia/reperfusion injury by HIF-2α activation in endothelial cells that subsequently improved renal microvascular perfusion and reduced ischemic tubular damage.Kidney International advance online publication, 11 September 2013; doi:10.1038/ki.2013.342.
    Kidney International 09/2013; · 8.52 Impact Factor
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    ABSTRACT: A multilocular cystic hepatic lesion detected at computed tomography (CT) and magnetic resonance (MR) imaging is a common but nonspecific radiologic finding that can cause potential challenges for differential diagnosis. This imaging pattern may be observed in a wide spectrum of common and uncommon neoplastic or nonneoplastic entities. Neoplastic lesions include cystadenoma, cystadenocarcinoma, hepatocellular carcinoma (HCC), metastases, mesenchymal hamartoma, and inflammatory myofibroblastic tumor. Nonneoplastic lesions include hepatic abscess, echinococcal cyst, intrahepatic hematoma, and biloma. The multiple coalescent cysts seen in polycystic liver disease may exhibit an imaging pattern similar to that of a multilocular cystic lesion. Mural nodularity, irregular thickness of the septa, ragged inner surface, and typical enhancement pattern in the solid portion of the lesion are often indicative of malignancy, although multilocular primary or secondary malignant tumors are uncommon. Recognition of the more common necrosis or cystic change of HCC and metastases induced by locoregional or systemic treatment also is important. The nonenhanced cystic component may be composed of different types of fluids (eg, serous, mucinous, proteinaceous, hemorrhagic, bilious, or mixed) or spontaneous or treatment-related necrosis, whereas the septa may be formed by a wide range of tissues depending on the lesion type. An understanding of the CT and MR imaging findings of these lesions and their respective pathologic correlation aids in accurate diagnosis.
    Radiographics 09/2013; 33(5):1419-33. · 2.79 Impact Factor
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    ABSTRACT: OBJECTIVES: To assess the performance of the Milan, Shanghai Fudan and Hangzhou Criteria based on preoperative evaluation in patients undergoing liver transplantation (LT) for hepatitis B-related hepatocellular carcinoma (HCC). METHODS: Using a prospectively collected database, data of consecutive patients with hepatitis B-related HCC undergoing LT from January 2005 to December 2009 were reviewed. Overall survival and tumor recurrence rates of patients fulfilled Milan, Shanghai Fudan and Hangzhou Criteria were compared using the log-rank test. RESULTS: Altogether 148 patients were enrolled in the study, in which 88 fulfilled the Milan criteria, 24 and 39 were beyond Milan but within Shanghai Fudan or Hangzhou criteria, respectively. After followed up for a median period of 44 months, survival rates did not differ among the three groups (P = 0.8780). Recurrence rates was significantly lower for newly eligible patients by Shanghai Fudan or Hangzhou Criteria compared with those within the Milan Criteria. CONCLUSIONS: The Milan criteria should be applied as the preferred criteria of hepatitis B-related HCC. Moderate expansion of Milan criteria must be performed cautiously considering high tumor recurrence rates and donor scarcity until high quality clinical trials are conducted.
    Journal of Digestive Diseases 06/2013; · 1.85 Impact Factor
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    ABSTRACT: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity and may play an important role in carcinogenesis. We investigated the role of genetic polymorphisms at XRCC4 codon 247 (rs3734091, XRCC4P) and XRCC5 codon 180 (rs80309960, XRCC5P) in liver cancer (hepatocellular carcinoma) caused by aflatoxin B1 (AFB1). A hospital-based case-control study, including 1499 liver cancer cases and 2045 controls without any liver disease, was conducted in a high aflatoxin exposure area in the Guangxi region of China to assess the relationship between these two polymorphisms and aflatoxin-related liver cancer risk and prognosis. Genotypes, mRNA levels, and the hot-spot mutation of TP53 gene (TP53M) related to AFB1 exposure was tested using TaqMan-PCR technique. XRCC4 protein level was analyzed by immunohistochemistry. For XRCC4P and XRCC5P, only XRCC4P modified liver cancer risk. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased liver cancer risk (odds ratio [OR] = 1.35 and 2.02, respectively). Significant interactive effects between risk genotypes (OR > 1) and aflatoxin exposure status were also observed in the joint effects analysis. Moreover, this polymorphism was associated not only with lower XRCC4 expression levels but also with higher AFB1-DNA adduct levels and increasing TP53M and portal vein tumor risk. Additionally, XRCC4P modified the recurrence-free survival and overall survival of cases, especially under conditions of high aflatoxin exposure. XRCC4P may be a genetic modifier for the risk and outcome of hepatocellular carcinoma induced by AFB1 exposure.
    Epidemiology (Cambridge, Mass.) 06/2013; · 5.51 Impact Factor
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    ABSTRACT: WSB-1 is involved in DNA damage response by targeting homeodomain-interacting protein kinase 2 (HIPK2) for ubiquitination and degradation. Here, we report that hypoxia significantly up-regulates the expression of WSB-1 in human hepatocellular carcinoma (HCC) cells. We also provide evidence that WSB-1 is a target of hypoxia-inducible factor 1 (HIF-1). Silencing the expression of HIF-1α in HCC cells by RNA interference abolishes hypoxia-induced WSB-1 expression. Using chromatin immunoprecipitation and luciferase reporter assays, we identified a HRE of the WSB-1 gene. Moreover, silencing the expression of WSB-1 by RNA interference rescues HIPK2 expression in hypoxic HCC cells and promotes etoposide-induced cell death in hypoxic HCC cells. Taken together, these data shed light on the mechanisms underlying hypoxia-induced chemoresistance in HCC cells.
    FEBS letters 06/2013; · 3.54 Impact Factor

Publication Stats

1k Citations
324.29 Total Impact Points

Institutions

  • 2014
    • Shanghai Cancer Institute
      Shanghai, Shanghai Shi, China
  • 2009–2014
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
    • Shanghai Jiao Tong University
      • • Shanghai Chest Hospital
      • • School of Medicine
      Shanghai, Shanghai Shi, China
    • China Three Gorges University
      Tung-hu, Hubei, China
  • 2013
    • Xuzhou Medical College
      Hang-hsien, Zhejiang Sheng, China
    • Youjiang Medical College For Nationalities
      T’ien-yüan-shih, Zhejiang Sheng, China
  • 2008–2011
    • Renji Hospital
      Shanghai, Shanghai Shi, China
  • 2001–2011
    • Zhejiang University
      • • Department of Physiology
      • • School of Medicine
      • • Department of Physics
      Hangzhou, Zhejiang Sheng, China
  • 2010
    • Jiaxing University
      Kashing, Zhejiang Sheng, China
    • Sir Run Run Shaw Hospital
      Hang-hsien, Zhejiang Sheng, China
  • 2009–2010
    • Hangzhou Normal University
      Hang-hsien, Zhejiang Sheng, China
  • 2005–2010
    • Shaoxing University
      Shao-hsing, Zhejiang Sheng, China
  • 1992–2005
    • The University of Hong Kong
      • • Department of Physiology
      • • Department of Medicine
      Hong Kong, Hong Kong
  • 2004
    • Lands Department of The Government of the Hong Kong Special Administrative Region
      Hong Kong, Hong Kong
  • 1998
    • Zhejiang Medical University
      Hang-hsien, Zhejiang Sheng, China