Jiang R.,Nanjing Medical University |
Jiang R.,The key Laboratory of living donor liver transplantation |
Wang H.,The key Laboratory of living donor liver transplantation |
Wang H.,Nanjing Medical University |
And 16 more authors.
BMC Cancer | Year: 2013
Background: It has been previously reported that IL-22, one of the cytokines secreted by Th17 cells, demonstrates both a protective and inflammatory promotion effect in inflammatory bowel disease (IBD) through STAT3 signaling activation. We sought to investigate the role of IL-22 expression in colon cancer (CC).Methods: The expression of IL-22 and related molecules were detected in human CC, the detail function and mechanism of IL-22 were investigated by in vivo and in vitro model.Results: Our results demonstrated significant upregulation of IL-22 in human CC tumor infiltrated leukocytes (TILs) compared to peripheral lymphocytes. Moreover, our findings demonstrated that IL-22 expression was significantly higher in ulcerative colitis (UC) tissues versus normal colon tissues. Both IL-22 receptor α1 (IL-22RA1) and IL-23 were highly expressed in CC and UC tissues compared to normal controls. TILs exhibiting various IL-22 expression levels isolated from CC patients were demonstrated to enhance tumor growth and metastasis co-transplanted with Hct-116 cells underwent subcutaneous transplantation in mice model. Tumor growth and metastasis was promoted by STAT3 phosphorylation and upregulation of its downstream genes such as Bcl-xl, CyclinD1, and VEGF. In vitro studies confirmed the anti-apoptotic and pro-proliferation effect of IL-22 according to the BrdU cooperation assay and peroxide induced apoptosis analysis with or without the presence of IL-22.Conclusion: In this study we demonstrated that excessive IL-22 in the CC and UC microenvironment leads to tumor growth, inhibition of apoptosis, and promotion of metastasis depend on STAT3 activation. © 2013 Jiang et al.; licensee BioMed Central Ltd.
Tan Z.-M.,Nanjing Medical University |
Tan Z.-M.,The Key Laboratory of Living Donor Liver Transplantation |
Sun B.-C.,Nanjing Medical University |
Sun B.-C.,The Key Laboratory of Living Donor Liver Transplantation
World Journal of Gastroenterology | Year: 2013
Chronic hepatitis B virus (HBV) infection is the key driving force of liver disease progression, resulting in the development of hepatic dysfunction, cirrhosis and hepatocellular carcinoma (HCC). The primary aim of therapy is to suppress or eliminate HBV replication to reduce the activity of hepatitis, thus reducing the risk of, or slowing the progression of, liver disease. Nucleos(t)ide analogues (Nucs) may result in rapid suppression of HBV replication with normalization of serum transaminases and restore liver function, thus increasing survival in patients with hepatic decompensation. Long-term Nuc therapy may result in histologi-cal improvement or reversal of advanced fibrosis and reduction in disease progression, including the development of HCC. The long-term benefits of a finite course of interferon (IFN)-α therapy also include a sustained and cumulative response, as well as hepatitis B surface antigen seroclearance and reduction in the development of cirrhosis and/or HCC. Pegylated IFN and newer Nucs may achieve better long-term outcomes because of improved efficacy and a low risk of drug resistance. However, treatment outcomes are still far from satisfactory. Understanding the effects of anti-HBV treatment against HCC incidence and recurrence after hepatec-tomy or liver transplantation is required for further improvement of outcome. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.
Hou J.,Nanjing Medical University |
Hou J.,The Key Laboratory of Living Donor Liver Transplantation |
Xu J.,Nanjing University |
Jiang R.,Nanjing Medical University |
And 12 more authors.
Hepatology | Year: 2013
Protein tyrosine phosphatase receptor type O (PTPRO), one of the receptor types of phosphotyrosine phosphatases (PTP), was recently described as a tumor suppressor in various kinds of cancers. We aimed to clarify the role of PTPRO in hepatocellular carcinoma (HCC). It was demonstrated in 180 pairs (120 male and 60 female) of clinical HCC specimens that the PTPRO level was significantly reduced, as compared with adjacent tissue, and the PTPRO level in male adjacent tissue was lower than in female. We further found that estrogen receptor alpha (ERα) could up-regulate PTPRO expression as a transcription factor. Moreover, an in vitro study showed that cell proliferation was inhibited and apoptosis was promoted in PTPRO-transduced HCC cell lines, whereas an in vivo study represented that tumor number and size was increased in ptpro-/- mice. As a result of its tumor-suppressive position, PTPRO was proved to down-regulate signal transducers and activators of transcription (STAT3) activity dependent on Janus kinase 2 (JAK2) and phosphoinositide 3-kinase (PI3K) dephosphorylation. Conclusions: PTPRO expression results in pathological deficiency and gender bias in HCC, which could be attributed to ERα regulation. The suppressive role of PTPRO in HCC could be ascribed to STAT3 inactivation. © 2012 American Association for the Study of Liver Diseases.