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1.
Annals of the Academy of Medicine, Singapore ; : 548-547, 2010.
Article in English | WPRIM | ID: wpr-234098

ABSTRACT

<p><b>INTRODUCTION</b>Akt, a serine/threonine protein kinase, mediates growth factor-associated cell survival. In several human cancers, including pancreatic cancer, constitutive activation of Akt (phosphorylated Akt, p-Akt) has been observed and may be associated with chemotherapy and radiotherapy resistance. However, there are contradictory viewpoints in p-Akt in pancreatic cancer on prognosis, and the clinical relevance of p-Akt in pancreatic cancer is not well understood. This study aims to investigate the expressions and relevance of Akt and p-Akt1 in pancreatic cancer tissues and their clinical significance.</p><p><b>MATERIALS AND METHODS</b>The expressions of Akt and p-Akt in 74 surgically resected paraffin-embedded pancreatic ductal adenocarcinoma samples and 10 normal pancreatic tissue samples were examined by immunohistochemistry. The associations of their expression with clinicopathological and survival data were analysed.</p><p><b>RESULTS</b>The positive expression rate of Akt and p-Akt1 were 87.8% and 83.8%, respectively, which were remarkably higher then those in normal pancreatic tissue (P <0.05). There was a positive correlation between the expression of Akt and p-Akt1. High p-Akt1 expression correlated with lower T stage (P = 0.004), while Akt was not associated with any clinicopathologic variables. Kaplan-Meier survival analysis revealed that higher expression of Akt, p-Akt1 were respectively correlated with favourable prognosis (16.0[4.7-27.3] vs 9.3[9.0-9.6] months, P = 0.007, and 23.0[12.2-33.8] vs 11.1[7.5-14.7] months, P = 0.004, respectively). Multivariate analysis identified p-Akt1 as a significant independent favourable prognostic factor (HR=0.421, P = 0.010).</p><p><b>CONCLUSIONS</b>These results suggest that high p-Akt1 expression may be a favourable prognostic factor in pancreatic cancer.</p>


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Pancreatic Ductal , Metabolism , Immunohistochemistry , Kaplan-Meier Estimate , Pancreatic Neoplasms , Metabolism , Prognosis , Proto-Oncogene Proteins c-akt , Metabolism
2.
Chinese Journal of Surgery ; (12): 1010-1013, 2008.
Article in Chinese | WPRIM | ID: wpr-245486

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of RNAi-mediated STAT3 gene inhibition on metastasis of human pancreatic cancer cells and its underlying mechanism.</p><p><b>METHODS</b>STAT3 shRNA expression vector was constructed and transfected into SW1990 cells. STAT3 mRNA and STAT3 DNA-binding activity were examined using reverse transcription polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. The metastasis ability of SW1990 cells in vivo was determined in acute hematogenous metastasis model using nude mice. RT-PCR was performed to detect the mRNA expression of the MMP-2 and VEGF.</p><p><b>RESULTS</b>The mRNA expression of STAT3 and STAT3 DNA-binding activity were inhibited significantly by stable transfection of STAT3 shRNA expressing vectors. RNAi inhibition of STAT3 significantly suppressed the metastasis ability of SW1990 cells in vivo, and also markedly reduced the mRNA expression of MMP-2 and VEGF in SW1990 cells.</p><p><b>CONCLUSIONS</b>Inhibition of STAT3 by RNAi significantly inhibits the metastasis ability of pancreatic cancer cells through down-regulation of MMP-2 and VEGF, and may provide a novel strategy for preventing the metastasis of pancreatic cancer.</p>


Subject(s)
Animals , Humans , Mice , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Genetic Vectors , Matrix Metalloproteinase 2 , Genetics , Metabolism , Mice, Nude , Pancreatic Neoplasms , Genetics , Metabolism , Pathology , RNA Interference , RNA, Messenger , Genetics , STAT3 Transcription Factor , Genetics , Metabolism , Signal Transduction , Genetics , Transfection , Vascular Endothelial Growth Factor A , Genetics , Metabolism , Xenograft Model Antitumor Assays
3.
Chinese Journal of Oncology ; (12): 890-893, 2006.
Article in Chinese | WPRIM | ID: wpr-316273

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of blockade of STAT3 signaling pathway by JAK specific inhibitor-AG490 on invasion and metastasis of human highly metastatic pancreatic cancer line SW1990 in vitro.</p><p><b>METHODS</b>AG490 was added into the culture media for SW1990 cells. The invasion ability of SW1990 cells was determined by cell invasion assay kit. Western blot was performed to detect the protein expression of the STAT3, phosphorylated STAT3 (p-STAT3), MMP-2 and VEGF. RT-PCR was performed to detect the mRNA expression of the MMP-2 and VEGF.</p><p><b>RESULTS</b>20 micromol/L AG490 significantly inhibited the invasion ability of SW1990 cells and the inhibitory rate of invasion ability was (77.67 +/- 7.79) %. The use of AG490 not only markedly reduced the protein expression of p-STAT3, MMP-2 and VEGF, but also greatly reduced the mRNA expression of MMP-2 and VEGF.</p><p><b>CONCLUSION</b>Blocking STAT3 activation with AG490 can inhibit the invasion and metastasis ability of pancreatic cancer cells in vitro through down-regulation of MMP-2 and VEGF expression. Blocking STAT3 signaling pathway may provide a novel strategy in prevention of invasion and metastasis of pancreatic cancer.</p>


Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Blotting, Western , Cell Line, Tumor , Dose-Response Relationship, Drug , Gene Expression Regulation, Neoplastic , Janus Kinases , Matrix Metalloproteinase 2 , Genetics , Metabolism , Neoplasm Invasiveness , Neoplasm Metastasis , Pancreatic Neoplasms , Genetics , Metabolism , Pathology , Phosphorylation , RNA, Messenger , Genetics , Reverse Transcriptase Polymerase Chain Reaction , STAT3 Transcription Factor , Metabolism , Signal Transduction , Tyrphostins , Pharmacology , Vascular Endothelial Growth Factor A , Genetics , Metabolism
4.
Chinese Journal of Surgery ; (12): 940-943, 2004.
Article in Chinese | WPRIM | ID: wpr-360952

ABSTRACT

<p><b>OBJECTIVE</b>To summarize the initial experience of simultaneous pancreas kidney transplantation (SPK) with portal venous and enteric drainage.</p><p><b>METHODS</b>Between Jane 2001 and Jane 2003, SPK were performed in 5 patients. Systemic venous-enteric drainage (SED) was used in the first 2 patients and portal venous-enteric drainage (PED) in the last 3 cases. All patient were immunosuppressed with quadruple therapy, which included anti-CD25 mAb (Zenapax/Simulect) induction therapy, FK506, mycophenolate mofetil (MMF), and prednisone baseline therapy. The complications were analyzed.</p><p><b>RESULTS</b>Serum glucose and renal function of the 5 cases were normal and no further insulin was needed within 7 days post-operation. No technique complications such as duodenal fistula and thrombosis were observed, One episode of acute rejection of kidney allograft occurred in one patient with SED, and resolved with a bolus corticosteroids. One case with SED and one with PED were died of sepsis and FK506 toxicity 4 weeks after transplantation. The death occurred with functioning pancreas graft. No latter complications were observed in the 3 survived patients with excellent graft functions.</p><p><b>CONCLUSIONS</b>Both methods of SED and PED can be performed successfully and with no latter complications. But with its potential physiologic and immunologic advantages, PED might be a standard procedure for SPK.</p>


Subject(s)
Adult , Female , Humans , Male , Diabetes Mellitus, Type 1 , General Surgery , Diabetic Nephropathies , General Surgery , Drainage , Methods , Follow-Up Studies , Intestines , General Surgery , Kidney Transplantation , Methods , Pancreas Transplantation , Methods , Portal Vein , General Surgery , Transplantation, Homologous , Treatment Outcome , Uremia , General Surgery
5.
Chinese Journal of General Surgery ; (12)2000.
Article in Chinese | WPRIM | ID: wpr-674304

ABSTRACT

Objective To investigate the correlation between the expression of STAT3 and MMP-2 in human pancreatic cancer,and to probe the mechanism by which STAT3 signal pathway regulates the expression of MMP-2 in pancreatic cancer cells.Methods Immunohistochemistry was used to detect the expression of STAT3,phosphorylated STAT3(p-STAT3)and MMP-2 in pancreatic cancer tissues of 34 cases and normal pancreatic tissues of 10 cases.Correlation between the expression of STAT3、p-STAT3 and MMP- 2 were statistically analyzed.Human pancreatic cancer cell lines SW1990 was cultured.AG490,an inhibitor of the upstream Janus kinase(JAK)of STAT3 was added into the culture medium.Electrophoretic mobility shift assay(EMSA)was used to detect STAT3 DNA-binding activity in SW1990 cells.Western blot was used to detect the expression of STAT3,p-STAT3 in SW1990 cells.In addition,the protein and mRNA expression of MMP-2 in SW1990 cells were determined by Western blot and RT-PCR,respectively. Results Immunohistochemistry revealed that the expression rate of STAT3,p-STAT3 were both higher in pancreatic cancer tissues than in normal pancreas tissues(P

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