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1.
Oncotarget ; 6(29): 28151-63, 2015 Sep 29.
Article in English | MEDLINE | ID: mdl-26305675

ABSTRACT

LincRNA-p21 is a downstream long non-coding RNA (lncRNA) transcript of p53. LincRNA-p21 serves as a repressor in p53-dependent transcriptional responses and participates in diverse biological processes, including apoptosis, cell cycle, metabolism and pluripotency. However, the role of lincRNA-p21 in human hepatocellular carcinoma remains to be defined. Here in this work, we demonstrated that lincRNA-p21 acted as a tumor suppressive lncRNA in human hepatocellular carcinoma. We firstly found the downregulation of lincRNA-p21 level in human hepatocellular carcinoma tissues, and showed that low expression of lincRNA-p21 was associated with high disease stage and predicted poor survival. Further we showed that lincRNA-p21 knockdown promoted proliferation and colony formation of HepG2, Huh7 and Bel-7042 cells in vitro, while lincRNA-p21 overexpression obtained oppose results. Using tumor xenograft experiments, we also demonstrated that lincRNA-p21 inhibited HepG2 cell growth in vivo and lincRNA-p21 contributed to sorafenib-induced growth regression of HepG2 cell in vivo. Further mechanism analysis revealed that lincRNA-p21 promoted ER stress both in vitro and in vivo, which facilitated apoptosis of hepatocellular carcinoma cells. Finally, we demonstrated that ER stress accounted for lincRNA-p21 effects on apoptosis, proliferation and in vivo growth of hepatocellular carcinoma. These findings implicate that lincRNA-p21 is a potential prognostic factor and therapeutic target for human hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular/genetics , Endoplasmic Reticulum Stress/genetics , Liver Neoplasms/genetics , RNA, Long Noncoding/genetics , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Blotting, Western , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockdown Techniques , Hep G2 Cells , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Male , Mice, Inbred BALB C , Mice, Nude , Niacinamide/analogs & derivatives , Niacinamide/pharmacology , Phenylurea Compounds/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Sorafenib , Transplantation, Heterologous , Tumor Burden/drug effects , Tumor Burden/genetics
2.
Mol Biol Rep ; 41(7): 4313-20, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24577752

ABSTRACT

The study investigates the expression and clinical role of GLP-1R in intrahepatic cholangiocarcinoma (ICC) tissues. ICC tissue, tissue around tumour and normal liver tissue samples from 176 ICC patients were investigated for GLP-1R expression by immunohistochemistry and western blots. Expression levels were correlated to clinical variables and to the postoperative outcome. High GLP-1R expression levels were detected in tumor tissue samples. Kaplan-Meier method was used for survival analysis of patients follow-up data. Results showed that median survival time of patients with high GLP-1R positive expression in ICC tissue were 22 months. Median survival time of patients with low GLP-1R positive expression in ICC tissue were 19.8 months. There wasn't statistical difference (p = 0.332) between two groups. Immunohistochemistry semi-quantitative analysis showed that tissue differentiation is not prognostic risk factors. In patients with GLP-1R positive expression in ICC tissue, lymph node metastasis was important prognostic factors (p = 0.001). Although statistical analysis showed that GLP-1R can not be judged as a risk prognostic factors, GLP-1 might become a new target for therapy of ICC.


Subject(s)
Bile Duct Neoplasms/genetics , Bile Ducts, Intrahepatic/metabolism , Cholangiocarcinoma/genetics , Receptors, Glucagon/genetics , Adult , Aged , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Female , Gene Expression , Glucagon-Like Peptide-1 Receptor , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Middle Aged , Receptors, Glucagon/metabolism , Survival Analysis , Tumor Microenvironment/genetics
3.
World J Gastroenterol ; 17(2): 249-53, 2011 Jan 14.
Article in English | MEDLINE | ID: mdl-21246000

ABSTRACT

AIM: To study the association between hilar cholangiocarcinoma (HC) and pre-existing medical conditions. METHODS: Three hundred and thirteen HC patients admitted to the Eastern Hepatobiliary Surgery Hospital (Shanghai, China) in 2000-2005 and 608 healthy controls were enrolled in this study. Association between HC and pre-existing medical conditions was studied with their adjusted odds ratio (OR) calculated by logistic regression analysis. RESULTS: The prevalence of choledocholithiasis (adjusted OR = 2.704, P = 0.039), hepatolithiasis (adjusted OR = 3.278, P = 0.018), cholecystolithiasis (adjusted OR = 4.499, P < 0.0001), cholecystectomy (adjusted OR = 7.012, P = 0.004), biliary ascariasis (adjusted OR = 7.188, P = 0.001), liver fluke (adjusted OR = 10.088, P = 0.042) and liver schistosomiasis (adjusted OR = 9.913, P = 0.001) was higher in HC patients than in healthy controls. CONCLUSION: Biliary tract stone disease (choledocholithiasis, hepatolithiasis, cholecystolithiasis) and parasitic liver disease (biliary ascariasis, liver fluke, liver schistosomiasis) are the risk factors for HC in Chinese population.


Subject(s)
Bile Duct Neoplasms/diagnosis , Cholangiocarcinoma/diagnosis , Adult , Aged , Aged, 80 and over , Animals , Ascariasis/epidemiology , Case-Control Studies , China , Cholecystectomy/methods , Cholecystolithiasis/epidemiology , Choledocholithiasis/epidemiology , Fasciola hepatica , Female , Humans , Lithiasis/epidemiology , Liver Diseases/epidemiology , Male , Middle Aged , Odds Ratio , Regression Analysis , Risk Factors , Schistosomiasis/epidemiology
4.
Zhonghua Gan Zang Bing Za Zhi ; 18(1): 41-4, 2010 Jan.
Article in Chinese | MEDLINE | ID: mdl-20128968

ABSTRACT

OBJECTIVE: To evaluate therapeutical effect of combined hepatic resection and fenestration on patients with severe adult polycystic liver disease (APLD). METHODS: Preoperative clinical symptoms, postoperative complications and prognoses from 33 patients with severe adult polycystic liver disease (APLD) treated with combined hepatic resection and fenestration were recorded. According to the number and location of cysts before surgery and the remnant liver parenchyma after operation, all patients were classified into two types: class A and B. And patients in each type were further classified into three grades: Grade I, II and III. The frequency of postoperative complications of two types patients was compared. RESULTS: The mean follow-up time was 57 months. There were three patients with recurrence of symptoms at 81, 68 and 43 mouths after operation. Two patients died of renal failure due to polycystic kidney disease at 137 and 85 mouths after operation. And one patient with postoperative hepatic inadequacy received an orthotopic liver transplantation. The total number of patients with postoperative complications was 26 cases, including one patient with bleeding, two patients with bile leakage, fourteen patients with mild ascites, twelve patients with severe ascites and eighteen patients with pleural effusion, and the overall incidence was 78.8%. There were 22 patients with imaging data, including 6 patients within A type and sixteen patients within B type. The frequencies of postoperative complications were 4 and 31, respectively, and the difference was statistically significant (Chi-square test = 4.99, P less than 0.05). CONCLUSION: Combined hepatic resection and fenestration is a safe and acceptable procedure for the treatment of severe APLD.


Subject(s)
Cysts/surgery , Hepatectomy/methods , Liver Diseases/surgery , Adult , Aged , Ascites/epidemiology , Ascites/etiology , Cysts/diagnostic imaging , Cysts/pathology , Female , Follow-Up Studies , Humans , Liver/diagnostic imaging , Liver/pathology , Liver/surgery , Liver Diseases/diagnostic imaging , Liver Diseases/pathology , Male , Middle Aged , Pleural Effusion/epidemiology , Pleural Effusion/etiology , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Prognosis , Recurrence , Retrospective Studies , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
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