Publications (8)21.05 Total impact
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Article: Continuous and low-energy 125I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth.
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ABSTRACT: Iodine 125 (125I) seed irradiation is an effective treatment for unresectable pancreatic cancers. However, the radiobiological mechanisms underlying brachytherapy remain unclear. Therefore, we investigated the influence of continuous and low-energy 125I irradiation on apoptosis, expression of DNA methyltransferases (DNMTs) and cell growth in pancreatic cancers. For in vitro 125I seed irradiation, SW-1990 cells were divided into three groups: control (0 Gy), 2 Gy, and 4 Gy. To create an animal model of pancreatic cancer, the SW 1990 cells were surgically implanted into the mouse pancreas. At 10 d post-implantation, the 30 mice with pancreatic cancer underwent 125I seed implantation and were separated into three groups: 0 Gy, 2 Gy, and 4 Gy group. At 48 or 72 h after irradiation, apoptosis was detected by flow cytometry; changes in DNMTs mRNA and protein expression were assessed by real-time PCR and western blotting analysis, respectively. At 28 d after 125I seed implantation, in vivo apoptosis was evaluated with TUNEL staining, while DNMTs protein expression was detected with immunohistochemical staining. The tumor volume was measured 0 and 28 d after 125I seed implantation. 125I seed irradiation induced significant apoptosis, especially at 4 Gy. DNMT1 and DNMT3b mRNA and protein expression were substantially higher in the 2 Gy group than in the control group. Conversely, the 4 Gy cell group exhibited significantly decreased DNMT3b mRNA and protein expression relative to the control group. There were substantially more TUNEL positive in the 125I seed implantation treatment group than in the control group, especially at 4 Gy. The 4 Gy seed implantation group showed weaker staining for DNMT1 and DNMT3b protein relative to the control group. Consequently, 125I seed implantation inhibited cancer growth and reduced cancer volume. 125I seed implantation kills pancreatic cancer cells, especially at 4 Gy. 125I-induced apoptosis and changes in DNMT1 and DNMT3b expression suggest potential mechanisms underlying effective brachytherapy.Journal of Experimental & Clinical Cancer Research 04/2011; 30:35. · 2.15 Impact Factor -
Article: Upregulated histone deacetylase 1 expression in pancreatic ductal adenocarcinoma and specific siRNA inhibits the growth of cancer cells.
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ABSTRACT: So far, there are no investigations about the role of histone deacetylase 1 (HDAC1) in tumorigenesis of pancreatic ductal adenocarcinoma. This study was designed to elucidate the roles and mechanisms of HDAC1 in tumorigenesis of pancreatic ductal adenocarcinoma. Real-time reverse transcription-polymerase chain reaction and immunohistochemistry techniques were adopted to detect the expression of HDAC1 in human pancreatic ductal adenocarcinoma tissues and paired paracancerous tissues. The roles of HDAC1 in human pancreatic cell line PaTu8988 were investigated using siRNA. Histone deacetylase 1 mRNA in pancreatic cancer tissues were significantly higher than in paracancerous tissues (P < 0.05). Immunohistochemistry showed that the indices of HDAC1 in pancreatic cancer tissues and paracancerous tissues were 56.4% (SD, 23.1%) and 6.7% (SD, 5.0%), respectively (P < 0.001). Knockdown of HDAC1 can generate a remarkable defect in proliferation and also can significantly induce apoptosis and S-phase arrest in PaTu8988 cells (P < 0.05). The Bcl-2 mRNA expression was significantly downregulated, whereas the p21 and Bax mRNA expression were significantly upregulated. The HDAC1 overexpression might play an important role in tumorigenesis of pancreatic cancer. Our data support the development of selective inhibitors targeting HDAC1 for the treatment of pancreatic ductal adenocarcinoma. Histone deacetylase 1 could be a new gene therapy target in pancreatic ductal adenocarcinoma.Pancreas 05/2010; 39(7):994-1001. · 2.39 Impact Factor -
Article: E1B-55kD-deleted oncolytic adenovirus armed with canstatin gene yields an enhanced anti-tumor efficacy on pancreatic cancer.
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ABSTRACT: Conditionally-replicating adenovirus (CRAd) therapy is currently being tested against pancreatic cancer and has shown some promise. To improve the efficacy, a novel virus CRAd-Cans was designed by deletion of E1B-55kDa gene for selective replication in tumor cells, as well as carrying a new angiogenesis inhibitor gene, canstatin. CRAd-Cans mediated higher expression of canstatin in BxPC-3 pancreatic cancer cell line compared to the replication-deficient adenovirus Ad5-Cans. The modified CRAd-Cans manifested the same selective replication and cytocidal effects in pancreatic cancer cells as ONYX-015 in vitro, yet showed greater reduction of tumor growth in nude mice with markedly prolonged survival rate in vivo (P<0.05), compared to that of either ONYX-015 or Ad5-Cans. Pathological examination revealed viral replication, decreased microvessel density and increased cancer cell apoptosis in CRAd-Cans-treated xenografts. The results suggest that the novel oncolytic virus CRAd-Cans, showing synergistic effects of oncolytic therapy and anti-angiogenesis therapy, is a new promising therapeutics for pancreatic cancer.Cancer letters 05/2009; 285(1):89-98. · 4.86 Impact Factor -
Article: A novel approach for treatment of unresectable extrahepatic bile duct carcinoma: design of radioactive stents and an experimental trial in healthy pigs.
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ABSTRACT: Patients diagnosed with extrahepatic bile duct carcinoma (EBDC) have a poor prognosis. The purpose of these studies was to design radioactive stents for EBDC and to evaluate the feasibility and safety of the stents in healthy pigs. Plastic stents with inserted iodine-125 seeds were designed and tested in 11 healthy pigs. The pigs were divided into 4 groups on the basis of radiation doses. The stents with estimated radiation dose at a 5-mm radial distance from the axis of the seeds of 30 Gy, 60 Gy, and 90 Gy were implanted in the common bile duct (CBD) in groups A, B, and C (n = 3 in each group), with the control group (n = 2) being implanted with the stents containing nonradioactive seeds. Histologic evaluation was performed under a light microscope. The procedures were successfully performed on all pigs. Severe hyperplasia of the mucosa was seen in the control group. In the experimental groups, obvious mucosal necrosis near the radioactive seeds was observed but without perforation of the CBD wall. In lower-dose groups (30 Gy), mild hyperplasia of mucosal glands with fibrosis under the necrosis layer was seen. However, after the increase of the dose, mucosal glands were disappearing without a visible mucosal layer. The radioactive stents are safe at each dose in healthy pigs. Moreover, our observations indicate the feasibility to design specific radioactive stents according to the size, shape, and position of EBDC in future clinical applications.Gastrointestinal endoscopy 04/2009; 69(3 Pt 1):517-24. · 6.71 Impact Factor -
Article: [An experiment of 125I radioactive pancreatic duct stents implanted in the pancreatic ducts of pigs].
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ABSTRACT: To evaluate the feasibility and safety of radioactive pancreatic duct stents implanted in the pancreatic ducts of pigs by endoscopy. Different doses of 125I radioactive pancreatic duct stents were implanted in the pancreatic ducts of pigs by endoscopy. Blood tests were conducted before and after implantation. 14, 30 and 60 days after implantation of the radioactive stents, the pigs were euthanized in batch. All animals underwent post mortem examination to exclude intra-abdominal hemorrhage, pancreatic fistula or peritonitis. During autopsy, the liver, bile ducts, head of the pancreas, stomach and duodenum were examined for perforation, stricture or dilation and damage of the surrounding structures. Fourteen pigs were implanted with pancreatic duct stents by endoscopic procedures. There was no effusion, hemorrhage or necrosis in the adjacent duodenum, stomach, liver or right kidney. The normal morphological structures of the duct of Wirsung disappeared in all the treated pigs. Histopathological examination revealed that the stents were surrounded by necrotic tissue and outside fibrous tissue. During the follow-up period, the width of outside fibrous tissue gradually increased. There were no serious abnormalities noted in the blood tests after implantation. It is indicated that the radioactive stents are safe in all the different dose groups. For future clinical application, it is feasible to design a special radioactive stent for each patient according to the size, shape and position of the pancreatic tumor.Zhonghua nei ke za zhi [Chinese journal of internal medicine] 05/2008; 47(4):300-3. -
Article: [Detection of recombinant lysostaphin using antibody sandwish enzyme-linked immunoadsorbent assay].
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ABSTRACT: The double-antibody-sandwich enzyme-linked immunoadsorbent assay (ELISA) for detection of rLysostaphin in humans had been developed and established through this study. rLysostaphin of high purity ( > 95 % ) produced in Shanghai Hi-Tech United Bio-Technological Research & Development Co., Ltd (SHUBRD) was used to produce a rabbit anti-rLysostaphin polyclonal antibody. The standard curve of rLysostaphin polyclonal antibody that was constructed showed that the lowest range of detection was found at 0. 98 ng of rLysostaphin/mL, and the curve exhibited linearity preferably from 0. 98 to 500 ng of rLysostaphin/mL. When three serum samples of the same batch were assayed for 6 replicates, and more 3 samples from different batches for 6 replicates, the average intra-assay and inter-assay coefficient variances ( CV) were 6. 4% and 6. 5%, respectively. The relative recovery rate was 98.6% when quantitative standard antigens were added to the serum. The present method for detection of rLysostaphin in serum is specific, highly sensitive, highly precise, and exhibited a low CV and will be helpful in the further study of rLysostaphin pharmacokinetics and holds promise in clinical applications.Sheng wu gong cheng xue bao = Chinese journal of biotechnology 02/2007; 23(1):117-21. -
Article: Effects of recombinant human canstatin protein in the treatment of pancreatic cancer.
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ABSTRACT: To examine the effect of canstatin, a newly discovered endogenous inhibitor of angiogenesis, in the treatment of pancreatic cancer in vivo. The canstatin cDNA fragment was synthesized and amplified from the total RNA extracted from human placenta tissues by RT-PCR. The resulting product was firstly cloned into pUCm-T vector, then into plasmid pET-22b (+) and transformed into E. coli BL21. Isopropyl-1-thio-b-Dgalactopyran-oside (IPTG) was used to induce the expression of canstatin protein and affinity chromatography was used to purify the protein. To determine the activity of purified recombinant human canstatin (rhCanstatin), orthotopic xenograft human pancreatic cancer models were established. Human pancreatic cancer cells (SW1990) were injected into the pancreas of BALB/c nude mice. Twenty-four nude mice with orthotopic xenograft tumor were randomly divided into 3 groups 10 d after the inoculation, and were treated with PBS 0.3 mL, or canstatin 5 mg/kg, or 10 mg/kg per day for 3 wk intraperitoneally. When the experiment was over, all tumors were resected and the effects of rhCanstatin on tumor growth, microvessel density (MVD) were analyzed. After IPTG induction, SDS-PAGE showed a new monomeric 24 kDa protein band. This protein was purified through affinity chromatography and refolded through dialysis with a final concentration of 60 mg/L. In orthotopic pancreatic cancer models, the final tumor volume in groups treated with PBS, canstatin 5 mg/kg, 10 mg/kg were 355.21+/-39.54 mm3, 112.73+/-10.47 mm3, and 61.75+/-6.99 mm3 respectively. The immunohistochemical examination showed that the MVD in tumors treated with canstatin was significantly less than that in other group. These findings demonstrate that the rhCanstatin effectively retards the growth of pancreatic cancer in a dose-dependent manner through inhibiting angiogenesis and may be a promising therapeutic agent for pancreatic cancer treatment in the clinic.World Journal of Gastroenterology 12/2006; 12(41):6652-7. · 2.47 Impact Factor -
Article: Construction of a recombinant attenuated Salmonella typhimurium DNA vaccine carrying Helicobacter pylori hpaA.
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ABSTRACT: To construct a recombinant attenuated Salmonella typhimurium DNA vaccine carrying Helicobacter pylori hpaA gene and to detect its immunogenicity. Genomic DNA of the standard H pylori strain 17 874 was isolated as the template, hpaA gene fragment was amplified by polymerase chain reaction (PCR) and cloned into pUCmT vector. DNA sequence of the amplified hpaA gene was assayed, then cloned into the eukaryotic expression vector pIRES through enzyme digestion and ligation reactions. The recombinant plasmid was used to transform competent Escherichia coli DH5alpha, and the positive clones were screened by PCR and restriction enzyme digestion. Then, the recombinant pIRES-hpaA was used to transform LB5000 and the recombinant plasmid isolated from LB5000 was finally used to transform SL7207. After that, the recombinant strain was grown in vitro repeatedly. In order to identify the immunogenicity of the vaccine in vitro, the recombinant pIRES-hpaA was transfected to COS-7 cells using Lipofectamine2000, the immunogenicity of expressed HpaA protein was detected with SDS-PAGE and Western blot. The 750-base pair hpaA gene fragment was amplified from the genomic DNA and was consistent with the sequence of H pylori hpaA by sequence analysis. It was confirmed by PCR and restriction enzyme digestion that H pylori hpaA gene was inserted into the eukaryotic expression vector pIRES and a stable recombinant live attenuated Salmonella typhimurium DNA vaccine carrying H pylori hpaA gene was successfully constructed and the specific strip of HpaA expressed by pIRES-hpaA was detected through Western blot. The recombinant attenuated Salmonella typhimurium DNA vaccine strain expressing HpaA protein with immunogenicity can be constructed and it may be helpful for further investigating the immune action of DNA vaccine in vivo.World Journal of Gastroenterology 02/2005; 11(1):114-7. · 2.47 Impact Factor
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Institutions
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2008–2010
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The Second Military Medical University
Shanghai, Shanghai Shi, China
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