Qiang Xia

Shanghai Cancer Institute, Shanghai, Shanghai Shi, China

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Publications (237)333.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A remolded microenvironment in hepatocellular carcinoma (HCC) caused by abnormally expressed matricellular proteins could promote HCC progression. The cell-matrix interactions mediated by integrins play an important role in tumor microenvironment. Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3), an extracellular matrix (ECM) protein with angiogenic and anti-inflammatory effects, is abnormally highly expressed in HCC. Here we aim to analyze its expression in liver and HCC tissues, investigate the underlined mechanisms accounted for HCC progression.
    Molecular cancer. 10/2014; 13(1):226.
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    ABSTRACT: Biliary atresia is the major kind of liver disease that mainly affects the new born infants. The pathological and biological mechanism of biliary atresia is still unclear to date. In this work, we attempt to identify biliary atresia relevant genes and to get the knowledge of the underlying genetic basis. We collected liver samples from new born infants with biliary atresia and congenital choledochocyst, and the RNA-seq technology was used to performed a transcriptome profiling in order to comprehensively study their expression signatures. We identified 877 differentially expressed genes between samples from biliary atresia and congenital choledochocyst patients in total. Several biological pathways related to the immunity and inflammation response were found to involve in the development of biliary atresia. Our results may helps to better investigate the molecular mechanisms of this disease.
    Molecular Biology Reports 09/2014; · 2.51 Impact Factor
  • Dong Zhao, Xi-Dai Long, Qiang Xia
    Clinical pediatrics. 09/2014;
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    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: To summarize the clinical characteristics, early diagnosis, comprehensive treatment and prognosis of 6 cases of children with post-transplantation lymphoproliferative disorder (PTLD) after liver transplantation.
    Zhonghua er ke za zhi. Chinese journal of pediatrics 08/2014; 52(8):579-82.
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    ABSTRACT: To evaluate the growth of children in weight and height before and after liver transplantation and the relation between malnutrition and postoperative time.
    Zhonghua er ke za zhi. Chinese journal of pediatrics 08/2014; 52(8):575-8.
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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: To investigate the differentiation potential of human umbilical mesenchymal stem cells (HuMSCs) and the key factors that facilitate hepatic differentiation.
    PLoS ONE 01/2014; 9(8):e104133. · 3.53 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.

Publication Stats

1k Citations
333.96 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