Shenyang General Hospital of PLA

Shenyang, China

Shenyang General Hospital of PLA

Shenyang, China
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Chen J.,Shenyang General Hospital of PLA | Guo X.-Z.,Shenyang General Hospital of PLA | Li H.-Y.,Shenyang General Hospital of PLA | Zhao J.-J.,Shenyang General Hospital of PLA | Xu W.-D.,Shenyang General Hospital of PLA
World Journal of Gastroenterology | Year: 2017

AIM To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) in vitro induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb). METHODS DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA were determined by western blotting and enzyme-linked immunosorbent assay. After co-culturing of autologous isolated PC cells with target DCs, the effects of secreting anti-DcR3 mAb on RNA-DCs' viability and apoptosis were assessed by MTT assay and flow cytometry. Analysis of enhanced antigen-specific immune response against PC induced by anti-DcR3 mAb secreting DCs was performed using a 51Cr releasing test. T cell responses induced by RNAloaded DCs were analyzed by measuring cytokine levels, including IFN-γ, IL-10, IL4, TNF-α and IL-12. RESULTS The anti-DcR3 mAb secreted by DCs reacted with recombinant human DcR3 protein and generated a band with 35 kDa molecular weight. The secreting mAb was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DCtumor- anti-DcR3 RNA for designated times, the DcR3 level in the supernatant of autologous PC cells was significantly down-regulated (P < 0.05). DCs secreting anti-DcR3 mAb could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA (P < 0.01). The anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA could enhance the induction of cytotoxic T lymphocytes (CTLs) activity toward RNA-transfected DCs, primary tumor cells, and PC cell lines, compared with CTLs stimulated by DC-total tumor RNA or control group (P < 0.05). Meanwhile, the antigen-specific CTL responses were MHC class I-restricted. The CD4+ T cells and CD8+ T cells incubated with anti-DcR3 mAb secreting DCs could produce extremely higher level IFN-γ and lower level IL4 than those incubated with DC-total tumor RNA or controls (P < 0.01). CONCLUSION DCs engineered to secrete anti-DcR3 antibody can augment CTL responses against PC in vitro, and the immune-enhancing effects may be partly due to their capability of down-regulating DC apoptosis and adjusting the Th1/Th2 cytokine network. © The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.

PubMed | PLA Fourth Military Medical University, The 251st Hospital of PLA and Shenyang General Hospital of PLA
Type: | Journal: Gastroenterology research and practice | Year: 2015

Splanchnic vein thrombosis (SVT) may be negatively associated with the prognosis of pancreatitis. We performed a systematic review and meta-analysis of literatures to explore the prevalence of SVT in pancreatitis. All observational studies regarding the prevalence of SVT in pancreatitis were identified via PubMed and EMBASE databases. The prevalence of SVT was pooled in the total of patients with pancreatitis. And it was also pooled in the subgroup analyses according to the stage and causes of pancreatitis, location of SVT, and regions where the studies were performed. After the review of 714 studies, 44 studies fulfilled the inclusion criteria. Meta-analyses showed a pooled prevalence of SVT of 13.6% in pancreatitis. According to the stage of pancreatitis, the pooled prevalence of SVT was 16.6% and 11.6% in patients with acute and chronic pancreatitis, respectively. According to the causes of pancreatitis, the pooled prevalence of SVT was 12.2% and 14.6% in patients with hereditary and autoimmune pancreatitis. According to the location of SVT, the pooled prevalence of portal vein, splenic vein, and mesenteric vein thrombosis was 6.2%, 11.2%, and 2.7% in pancreatitis. The prevalence of SVT in pancreatitis was 16.9%, 11.5%, and 8.5% in Europe, America, and Asia, respectively.

Li X.,Shenyang General Hospital of PLA | Li X.,The Fourth Peoples Hospital of Shenyang | Yan J.,General Hospital of PLA | Wang L.,Beijing Institute of Radiation Medicine | And 4 more authors.
Cancer Cell International | Year: 2013

Background: Beclin1 is a well-known key regulator of autophagy, which is also a haploinsufficient tumor suppressor. Current studies revealed that down-regulation or monoallelic deletions of Beclin1 were frequently found in various cancers. The purpose of this study was to investigate the effects of Beclin1 inhibition on autophagy and Gemcitabine-induced apoptosis of pancreatic cancer cells.Methods: Beclin1 expression was inhibited by siRNA transduction and gene expression was determined by Real-time PCR and Western blot. The effects of Beclin1 inhibition on autophagy and Gemcitabine-induced apoptosis of Miapaca2 cells were analyed through LC3 expression, cell viability, cell cycle and apoptosis by using Western blot.Results: We observed that Beclin1 silence promoted microtubule-associated protein 1 light chain 3-II (LC3-II) protein formation and increased punctate fluorescent signals in Miapaca2 cells transfected with green fluorescent protein (GFP)-tagged LC3. Beclin1 inhibition showed a greater suppressive effect on Gemcitabine-induced apoptosis of Miapaca2 cells.Conclusion: Our data suggested that Beclin1 silence not only up-adjusted autophagy process, but also played an important role in the regulation of apoptosis. Beclin1 inhibition could inhibit apoptosis signaling induced by Gemcitabine in Miapaca2 cells. © 2013 Li et al.; licensee BioMed Central Ltd.

Wu H.,Chinese PLA General Hospital | Jing Q.,Shenyang General Hospital of PLA | Wang J.,Chinese PLA General Hospital | Guo X.,Chinese PLA General Hospital
Journal of Critical Care | Year: 2011

Purpose: The aim of this study is to evaluate the preventive effect of proton pump inhibitors on gastrointestinal (GI) bleeding in patients with acute coronary syndromes (ACS) who are at high risk for GI bleeding. Materials and Methods: We enrolled 665 patients with ACS who had one or more of the following risk factors for GI bleeding: 75 years of age or older, history of peptic ulcer disease, history of GI bleeding, cardiogenic shock, and chronic renal dysfunction (serum creatinine, >2 mg/dL). Patients were randomly assigned to receive 40 mg of pantoprazole or placebo twice daily for 7 days, in addition to standard treatment of ACS. The primary end point was the occurrence of GI bleeding during hospitalization. Results: During a median time of hospitalization of 12 days, 12 (3.6%) of 332 patients in the placebo group had an occurrence of GI bleeding, as compared with 4 (1.2%) of the 333 patients in the pantoprazole group (P =.046, Fisher exact test). The log-rank test showed a significant difference between the 2 groups in the time to the occurrence of GI bleeding (P =.015). Major GI bleeding occurred in 5 (1.5%) patients in the placebo group but only in 1 (0.3%) in the pantoprazole group (P =.12). Pneumonia developed in 22 (6.6%) patients in the placebo group and 24 (7.2%) in the pantoprazole group (- 2 = 0.077, P =.88). The 30-day mortality was 10.2% (34/332) in the placebo group and 10.5% (35/333) in the pantoprazole group. Conclusions: In patients with ACS who are at high risk for GI hemorrhage, prophylactic treatment with pantoprazole could reduce the risk of GI bleeding with no significant effects on the incidence of hospital-acquired pneumonia and 30-day mortality. © 2011 Elsevier Inc.

Zhang Y.,PLA Fourth Military Medical University | Zhang Y.,Shenyang General Hospital of PLA | Gu Y.,PLA Fourth Military Medical University | Sha S.,PLA Fourth Military Medical University | And 5 more authors.
International Journal of Clinical Oncology | Year: 2014

Background: Deleted in breast cancer 1 (DBC1) was initially cloned from a region homozygously deleted in breast cancers, but its role in colorectal cancer remains unknown. The present study aims to examine the expression level of DBC1 and assess its prognostic value in human colorectal cancer. Methods: Immunohistochemical staining was performed to detect the expression level of DBC1 in a series of 186 colorectal cancer patients. Immunohistochemical staining results were analyzed and compared statistically with various clinicopathological characters and overall survival. Results: Compared with the corresponding non-tumor tissues, a higher expression level of DBC1 was detected in colorectal cancer (P < 0.01). Tissue microarray analysis revealed that DBC1 expression is significantly associated with tumor histological grade, TNM stage and metastatic status (P < 0.01). Importantly, Kaplan-Meier analysis showed that DBC1 expression is associated with shorter overall survival (P < 0.01). Univariate Cox regression suggested that DBC1 expression, poorly differentiation status and the presence of lymph node metastasis predict shorter overall survival in colorectal cancer (P < 0.05). Multivariate Cox regression analysis indicated that DBC1 acts as an independent prognostic factor in colorectal cancer (P < 0.01). Conclusions: These results suggest that DBC1 is over-expressed in colorectal cancer and that it might serve as a predictor for selecting patients at high risk of poor prognosis. © 2012 Japan Society of Clinical Oncology.

Ren L.,Shenyang General Hospital of PLA | Guo X.,Shenyang General Hospital of PLA | Shao X.,Shenyang General Hospital of PLA | Li H.,Shenyang General Hospital of PLA | Yao H.,Shenyang General Hospital of PLA
Molecular Medicine Reports | Year: 2015

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is a newly cloned factor that selectively acts on the endothelium of endocrine gland cells. EG-VEGF was previously identified as an important cytokine, involved in the modulation of apoptosis in pancreatic cancer cell lines. The present study examined the effects of EG-VEGF proliferation and migration, in pancreatic cancer cells. To determine the potential for EG-VEGF as a therapeutic target for pancreatic cancer, the expression of EG-VEGF were measured in pancreatic cancer tissue, and the association between its expression and the clinicopathological characteristics of the pancreatic cancer patients was determined. The results of the present study suggest that EG-VEGF may act as a novel tumor gene in pancreatic cancer. EG-VEGF was rarely expressed in the normal pancreatic tissue, but was highly expressed in the pancreatic cancer tissue. These data suggest that EG-VEGF may be a cancer-specific, and possibly tissue-specific, survival factor in the pancreas. In the Mia PaCa-2 pancreatic cancer cell line, EG-VEGF was shown to promote proliferation and cellular invasion, and modulate the phosphorylation of mitogen-activated protein kinase, a modulator for the malignant phenotype.

Wu C.Y.,Shenyang General Hospital of PLA | Guo X.Z.,Shenyang General Hospital of PLA | Li H.Y.,Shenyang General Hospital of PLA
Clinical and Translational Oncology | Year: 2015

Purpose: KAI1 closely correlates with pancreatic cancer metastasis. There might be some factors that protect the cells from a proliferation inhibition by KAI1 in the solid tumors’ microenvironment. Hypoxia and ischemia are the main characteristics of the microenvironment within solid tumors. Whether they affect the KAI1 inhibitory effects on cell proliferation is still unclear.Methods: MiaPaCa-2 human pancreatic cancer cells do not express KAI1 protein. However, after being infected with Ad5-KAI1, they expressed KAI1 protein. We cultured them under hypoxic and serum-free conditions to simulate the solid tumor hypoxic-ischemic microenvironment. The cells were divided into the control, hypoxic, serum-free, and hypoxic with serum-free groups. The proliferation and apoptosis were observed by CCK8 and Annexin V-FITC/PI, respectively. The green fluorescent protein-labeled light chain 3 association with autophagosome membranes was detected by confocal microscopy. The ratio of LC3-II–LC3-I expression level was detected by western blot. Pretreatment of 3-MA was used to inhibit the autophagy. We, then observed whether the hypoxic and serum-free conditions could change the effect of KAI1 on cell survival and whether the pretreatment of 3-MA could inhibit the effect of hypoxic and serum-free conditions on KAI1 function.Results: Hypoxia and serum-free media effectively reduced the apoptosis and proliferation inhibition caused by KAI1 and was beneficial to the cell survival. 3-MA pretreatment effectively blocked the protective effect of hypoxia and serum-free media on the cells by autophagy block.Conclusions: Serum-free media and hypoxia protected the MiaPaCa-2 cells from a KAI1-induced apoptosis and proliferation inhibition via autophagy induction. © 2014, Federación de Sociedades Españolas de Oncología (FESEO).

Chen J.,Shenyang General Hospital of PLA | Guo X.-Z.,Shenyang General Hospital of PLA | Li H.-Y.,Shenyang General Hospital of PLA | Liu X.,Shenyang General Hospital of PLA | And 3 more authors.
Vaccine | Year: 2013

Pancreatic cancer (PC) is one of the most devastating human malignancies without effective therapies. Tumor vaccine based on RNA-transfected dendritic cells (DCs) has emerged as an alternative therapeutic approach for a variety of human cancers including advanced PC. In the present study we compared the cytotoxic T lymphocyte (CTL) responses against PC cells in vitro, which were induced by DCs co-transfected with two mRNAs of tumor associated-antigens (TAA) MUC4 and survivin, versus DCs transfected with a single mRNA encoding either MUC4 or survivin. DCs co-transfected with two TAA mRNAs were found to induce stronger CTL responses against PC target cells in vitro, compared with the DCs transfected with a single mRNA. Moreover, the antigen-specific CTL responses were MHC class I-restricted. These results provide an experimental foundation for further clinical investigations of DC vaccines encoding multiple TAA epitopes for metastatic PC. © 2013 Elsevier Ltd.

PubMed | Liaoning Medical University and Shenyang General Hospital of PLA
Type: Journal Article | Journal: Journal of molecular neuroscience : MN | Year: 2016

Accumulation of amyloid -peptide (A) in the brain of Alzheimer disease (AD) patients is believed to be the main pathological feature of the disease. Meanwhile, miR-98-5p dysregulation was found in AD. However, whether miR-98-5p is involved in the accumulation of A in AD, the underlying molecule mechanism remains unclear. In the present study, we confirmed that miR-98-5p negatively regulated sorting nexin 6 (SNX6) expression by targeting the 3-UTR of SNX6 mRNA. Downregulation of miR-98-5p alleviated A-induced viability inhibition and decreased apoptosis in SK-N-SH and SH-SY5Y cells by upregulating SNX6 expression. Furthermore, downregulation of miR-98-5p decreased SNX6-dependent levels of A40, A42, -site APP-cleaving enzyme 1 (BACE1), soluble amyloid precursor protein (sAPP), and membrane-associated APP -carboxyl terminal fragment (CTF) in SK-N-SH and HEK293 cells. Our findings demonstrate that miR-98-5p modulates SNX6 expression and thus plays a critical role in accumulation of A. Therefore, miR-98-5p may be a novel therapeutic target for AD.

PubMed | Beijing Institute of Radiation Medicine, Qinghai Provincial Peoples Hospital and Shenyang General Hospital of PLA
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

The deregulation of HGF/c-Met signaling is implicated in epithelial-mesenchymal transition (EMT) and progress of hepatocellular carcinoma (HCC). However, the epigenetic mechanisms that HGF/c-Met regulates EMT and metastasis of HCC cells are less explored. In this study, we demonstrated that HCC cells express a high level of SUMO/sentrin-specific protease 1 (Senp1) which is induced by HGF/c-Met signals. Lentivirus-mediated small hairpin RNA (shRNA) transduction results in Senp1 silence in HCC cells. Senp1 silence reduces the HGF-induced proliferation and migration of HCC cells. Senp1 inhibition also induces HCC cell apoptosis and growth arrest. Furthermore, Senp1 knockdown inhibits epithelial-to-mesenchymal transition, with increase of E-cadherin and ZO-1 expression, decrease of fibronectin and N-cadherin expression. The EMT-related transcription factor Zeb1 was SUMO-modified and decreased in Senp1-silenced HCC cells. These results delineate that senp1 might play an important role in the regulation of HGF-induced invasion and migration of HCC cells.

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