Xu-An Wang

Shanghai Jiao Tong University, Shanghai, Shanghai Shi, China

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Publications (12)12.75 Total impact

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    ABSTRACT: Coagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection.
    BMC Cancer 08/2014; 14(1):566. · 3.33 Impact Factor
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    ABSTRACT: Individuals with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here we report the identification of somatic mutations for GBC in 57 tumor-normal pairs through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate (FDR) < 0.05) of non-silent mutations include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multivariate analyses further show that cases with ErbB pathway mutations have a worse outcome (P = 0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.
    Nature genetics. 07/2014;
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    ABSTRACT: Gallbladder carcinoma is the most common malignancy of the biliary tract and is associated with a very poor outcome. The aim of the present study was to investigate the effects of oxymatrine (OM) on gallbladder cancer cells and the possible mechanism of its effects. The effects of OM on the proliferation of gallbladder cancer cells (GBC-SD and SGC-996) were investigated using cell counting kit-8 and colony formation assays. Annexin V/propidium iodide double staining was performed to investigate whether OM could induce apoptosis in gallbladder cancer cells. The mitochondrial membrane potential (ΔΨm) and expression of apoptosis-associated proteins were evaluated to identify a mechanism for the effects of OM. In addition, the RNA expression of relevant genes was measured by qRT-PCR using the SYBR Green method. Finally, a subcutaneous implantation model was used to verify the effects of OM on tumor growth in vivo. We found that OM inhibited the proliferation of gallbladder cancer cells. In addition, Annexin V/propidium iodide double staining showed that OM induced apoptosis after 48 h and the ΔΨm decreased in a dose-dependent manner after OM treatment. Moreover, the activation of caspase-3 and Bax and downregulation of Bcl-2 and nuclear factor κB were observed in OM-treated cells. Finally, OM potently inhibited in-vivo tumor growth following subcutaneous inoculation of SGC-996 cells in nude mice. In conclusion, OM treatment reduced proliferation and induced apoptosis in gallbladder cancer cells, which suggests that this drug may serve as a novel candidate for adjuvant treatment in patients with gallbladder cancer.
    Anti-Cancer Drugs 05/2014; · 2.23 Impact Factor
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    ABSTRACT: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies have demonstrated that MALAT1 plays an important role in other malignancies. However, little is known about the role of MALAT1 in gallbladder carcinoma (GBC), which is the most common cancer of the biliary tract and has an extremely poor prognosis. In this study, we focused on the expression, biological functions and mechanism of MALAT1 in GBC and found that MALAT1 was significantly upregulated in GBC tissues compared with corresponding non-cancerous tissues. Knockdown of MALAT1 in GBC cell lines using lentivirus-mediated RNA interference significantly inhibited the proliferation and metastasis of the GBC cells both in vitro and in vivo. Furthermore, ERK/MAPK pathway was found to be inactivated in the GBC cell lines after MALAT1 knockdown. These results indicated that MALAT1 might serve as an oncogenic lncRNA that promotes proliferation and metastasis of GBC and activates the ERK/MAPK pathway.
    Cancer biology & therapy 03/2014; 15(6). · 3.29 Impact Factor
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    ABSTRACT: Ursolic acid (UA), a plant extract used in traditional Chinese medicine, exhibits potential anticancer effects in various human cancer cell lines in vitro. In the present study, we evaluated the anti-tumoral properties of UA against gallbladder carcinoma and investigated the potential mechanisms responsible for its effects on proliferation, cell cycle arrest and apoptosis in vitro.
    Cancer Cell International 01/2014; 14(1):96. · 2.09 Impact Factor
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    ABSTRACT: Gallbladder cancer, with high aggressivity and extremely poor prognosis, is the most common malignancy of the bile duct. The main objective of the paper was to investigate the effects of schisandrin B (Sch B) on gallbladder cancer cells and identify the mechanisms underlying its potential anticancer effects. We showed that Sch B inhibited the viability and proliferation of human gallbladder cancer cells in a dose-, time -dependent manner through MTT and colony formation assays, and decrease mitochondrial membrane potential (ΔΨm) at a dose-dependent manner through flow cytometry. Flow cytometry assays also revealed G0/G1 phase arrest and apoptosis in GBC-SD and NOZ cells. Western blot analysis of Sch B-treated cells revealed the upregulation of Bax, cleaved caspase-9, cleaved caspase-3, cleaved PARP and downregulation of Bcl-2, NF-κB, cyclin D1 and CDK-4. Moreover, this drug also inhibited the tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data demonstrated that Sch B induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that Sch B may be a promising drug for the treatment of gallbladder cancer.
    Molecules (Basel, Switzerland). 01/2014; 19(9):13235-13250.
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    ABSTRACT: Gallbladder cancer is the most common malignant tumor of the biliary tract, and this condition has a rather dismal prognosis, with an extremely low five-year survival rate. To improve the outcome of unresectable and recurrent gallbladder cancer, it is necessary to develop new effective treatments and drugs. The purpose of the present study was to evaluate the effects of cordycepin on human gallbladder cells and uncover the molecular mechanisms responsible for these effects. The Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that cordycepin affected the viability and proliferation of human gallbladder cancer cells in a dose- and time-dependent manner. Flow cytometric analysis showed that cordycepin induced S phase arrest in human gallbladder cancer cell lines(NOZ and GBC-SD cells). Cordycepin-induced apoptosis was observed using an Annexin V/propidium iodide (PI) double-staining assay, and the mitochondrial membrane potential (ΔΨm) decreased in a dose-dependent manner. Additionally, western blot analysis revealed the upregulation of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP and Bax and the downregulation of Bcl-2, cyclin A and Cdk-2 in cordycepin-treated cells. Moreover, cordycepin inhibited tumor growth in nude mice bearing NOZ tumors. Our results indicate that this drug may represent an effective treatment for gallbladder carcinoma.
    Molecules (Basel, Switzerland). 01/2014; 19(8):11350-11365.
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    ABSTRACT: It is well known that conventional splenectomy, which requires careful handling and ligation of tissue of the splenic hilum, can easily cause complications such as splenic fever and pancreatic fistula. Here, we use the technique of dissection of the secondary branches of the splenic pedicle to handle the hilum in the portal hypertension patients who are subjected to splenectomy. We retrospectively compared and analyzed the complications, postoperative hospital stay, operative time, and occurrence of hemorrhage in 121 patients with portal hypertension undergoing splenectomy and devascularization of the gastric cardia from January 1999 to December 2007. The selected cases consisted of 51 patients undergoing conventional splenectomy and 70 patients undergoing dissection of secondary branches of the splenic pedicle. In addition, we analyzed the relationship between size of the spleen and occurrence of complications. The incidence of pancreatic fistula and splenic fever (0/70 and 9/70) was lower in patients undergoing dissection of secondary branches of the splenic pedicle as compared with that of the conventional group (5/51 and 18/51 respectively). In addition, there was no significant difference in operative time and volume of blood loss between two groups. The spleen thickness of those patients who had pancreatic fistula and splenic fever was significantly greater than those without complications. These results indicate that dissection of secondary branches of the splenic pedicle in portal hypertension patients undergoing splenectomy can decrease the incidence of splenic fever and pancreatic fistula, and shorten the postoperative hospital stay, especially in the patients with a large spleen. So dissection of secondary branches of the splenic pedicle is a valuable technique for splenectomy.
    Chinese medical journal 12/2008; 121(22):2250-3. · 0.90 Impact Factor
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    ABSTRACT: To investigate the effects of vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotide (ASODN) on the mRNA and protein expression of VEGF, Flt-1, and kinase insert domain containing receptor (KDR) and VEGF excretion in human gallbladder carcinoma cells. Human gallbladder carcinoma cells of the line GBC-SD were cultured and transfected with VEGF ASODN and sense oligodeoxynucleotide (SODN) mediated by Oligofectamine. The toxicity of SODN and Oligofectamine to the GBC-SD cells was examined by MTT method. RT-PCR was used to detect the mRNA and expression of VEGF, Flt-1, and KDR, and ELISA was used to detect the protein expression of VEGF. MTT method showed that SODN and Oligofectamine were not toxic to the GBC-SD cells. The mRNA expression levels of VEGF, Flt-1, and KDR of the ASODN and ASODN + Oligofectamine groups were all significantly lower than those of the control group (all P < 0.05), and were the lowest 72 hours after transfection, and then gradually increased. ELISA showed that there were not significant differences in the VEGF protein concentration in the supernatant of the GBC-SD cells among the SODN, SODN + Oligofectamine, and control groups (all P < 0.05), however, the VEGF protein concentration in the supernatant of the GBC-SD cells of the ASDN and ASDN + Oligofectamine groups were significantly lower than that of the control group (both P < 0.05). VEGF ASODN inhibits the mRNA and protein expression of VEGF, Flt-1, and KDR and VEGF excretion in human gallbladder carcinoma cells. Oligofectamine strengthens the effect of ASODN.
    Zhonghua yi xue za zhi 12/2007; 87(47):3329-34.
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    ABSTRACT: Choledochal cyst is rare in western countries. The relatively high incidence of coexistent hepatobiliary disease increases the difficulty of the surgical management of choledochal cyst. Here we analyze the diagnosis and treatment of congenital bile duct cyst in 122 Chinese adults. The clinical data of 122 patients with congenital choledochal cysts admitted from 1981 to 2006 were analyzed. Clinical symptoms in most cases were nonspecific, resulting in delayed diagnosis. Sixty-one patients (50%) had coexistent pancreatobiliary disease. Among the 122 patients, 119 patients underwent ultrasonic examination; ERCP/MRCP was performed in 63 cases and CT in 102 cases. Abnormal pancreatobiliary duct junction was found in 48 patients. Sixteen patients had malignant lesions in the bile duct, arising in 11 of them from incomplete choledochal cyst that underwent various operations including cystenterostomy or cystojejunostomy. There was significant difference between the patients who underwent incomplete cyst resection and complete cyst resection in malignancy rate of bile duct (Chi square test, P = 0.000; odds ratio, 7.800; 95% confidence interval, 2.450 to 24.836). ERCP, CT and MRCP had proved their great values in the classification of the disease. Cyst excision with Roux-en-Y hepaticojejunostomy is recommended as the treatment of choice for patients with type I or type IV cysts. For type V cyst (Caroli's disease) with recurrent cholangitis, liver transplantation should be considered.
    Chinese medical journal 09/2007; 120(16):1404-7. · 0.90 Impact Factor
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    ABSTRACT: To investigate the regulatory effects of rat mesenchymal stem cell (MSC) on T lymphocyte proliferation by examining the early activated markers such as CD25 and CD69. MSC had been isolated and expanded in vitro. Then it was identified by cell morphology, membrane phenotype, and differentiation potential. Nylon wool column was applied to purify T-lymphocytes. MSCs and T-lymphocytes were cultured together and were stimulated by phytohaemagglutinin (PHA), and then the expressions of CD25 and CD69 were assessed. The levels of TGF-beta1 and IL-10 in the supernatants of MSC cultures were detected by using ELISA. (1) The expression of CD25 is suppressed in a dose-dependent manner when the T-lymphocytes are co-cultured with 10,000 MSCs or more, while 100 MSCs have no detectable effect; (2) The suppression of CD25 can be lasted more than 96 hrs; (3) The down regulation of CD25 is mediated by some soluble factors; (4) The reduced expression of CD25 caused by MSC inhibition is not mediated by TGF-beta1 and IL-10. MSCs have significant immune regulatory effects on PHA-stimulated T-lymphocyte culture. It might provide a remarkable immune suppression in organ-transplantation to achieve better outcome in the near future.
    Zhonghua yi xue za zhi 09/2007; 87(30):2136-9.
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    ABSTRACT: To evaluate wound healing after pancreaticojejunostomy of three anastomotic methods. Fifty-four domestic piglets were divided into three groups according to the types of anastomoses: group of end-to-end pancreaticojejunal invagination (EE group), group of binding pancreaticojejunostomy (BP group) and group of inkwell pancreaticojejunostomy (IP group). Bursting pressure, breaking strength and histopathological findings of anastomosis were assessed on operative day and on the 5th and 10th day after operation. Bursting pressure was (67+/-8) mm Hg, (96+/-11) mm Hg and (131+/-9) mm Hg in EE group on day 0, 5 and 10; and (140+/-8) mm Hg, (179+/-10) mm Hg and (269+/-13) mm Hg in BP group; and (102+/-10) mm Hg, (171+/-18) mm Hg and (254+/-24) mm Hg in IP group. Compare to EE group, bursting pressure of BP group and IP group were all increased with significant differences (P<0.05). Another significant difference was observed between BP group and IP group after anastomoses on operative day. Breaking strength was (4.6+/-0.6) N, (5.8+/-0.5) N and (7.1+/-0.6) N in EE group on 0 d, 5 d and 10 d; and (4.5+/-0.4) N, (6.6+/-0.4) N and (10.0+/-0.6) N in BP group; and (4.6+/-0.3) N, (6.5+/-0.4) N and (9.1+/-0.9) N in IP group. A similar value of anastomoses was shown in BP group and IP group on day 0, day 5 and day 10, but significant increase was demonstrated compared to EE group on day 5 and 10. Anastomotic site was well repaired by connective tissue and the cut surface of pancreatic stump was covered by mucosal epithelium in BP group and IP group on day 10, but the cut surface was incompletely repaired by granulation tissue and no regeneration of the epithelium was found in EE group. Wound healing of binding pancreaticojejunostomy and inkwell pancreaticojejunostomy is more rapid and better than end-to-end pancreaticojejunal invagination, but breaking strength of inkwell pancreaticojejunostomy is weaker than binding pancreaticojejunostomy.
    Zhonghua wai ke za zhi [Chinese journal of surgery] 03/2006; 44(5):339-43.

Publication Stats

13 Citations
12.75 Total Impact Points

Institutions

  • 2014
    • Shanghai Jiao Tong University
      • School of Medicine
      Shanghai, Shanghai Shi, China
  • 2006–2008
    • Zhejiang University
      • Department of Surgery
      Hangzhou, Zhejiang Sheng, China