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KAI1/CD82 gene and autotaxin-lysophosphatidic acid axis in gastrointestinal cancers

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World Journal of Gastrointestinal Oncology 2022年第8期14卷 1388-1405页

作者： Shuo Wang Jiang Chen xiao-zhong guo Department of Gastroenterology General Hospital of Northern Theater CommandShenyang 110840Liaoning ProvinceChina

The KAI1/CD82 gene inhibits the metastasis of most tumors and is remarkably correlated with tumor invasion and *** metabolism dysregulation is an important cause of tumor occurrence,development,and *** one of the important characteristics of tumors,cell metabolism dysregulation is attracting increasing research *** are an indispensable substance in the metabolism in various tumor *** metabolites have become important cell signaling *** pathological role of lysophosphatidic acid(LPA)in tumors was identified in the early ***,LPA inhibitors have entered clinical trials but are not yet used in clinical ***(ATX)has lysophospholipase D(lysoPLD)activity and can regulate LPA levels in *** LPA receptor family and ATX/lysoPLD are abnormally expressed in various gastrointestinal *** to our recent pre-experimental results,KAI1/CD82 might inhibit the migration and metastasis of cancer cells by regulating the ATX-LPA ***,no relevant research has been *** the mechanism of ATX-LPA in the inhibition of cancer metastasis by KAI1/CD82 will provide an important theoretical basis for targeted cancer *** this paper,the molecular compositions of the KAI1/CD82 gene and the ATX-LPA axis,their physiological functions in tumors,and their roles in gastrointestinal cancers and target therapy are reviewed.

关键词： KAI1/CD82 Autotaxin Lysophosphatidic acid Pancreatic cancer Liver cancer

KAI1 reverses the epithelial-mesenchymal transition in human pancreatic cancer cells

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Hepatobiliary & Pancreatic Diseases International 2019年第5期18卷 471-477页

作者： Xu Liu xiao-zhong guo Hong-Yu Li Jiang Chen Department of Gastroenterology General Hospital of Shenyang Military Area

Background: Epithelial-mesenchymal transition (EMT) plays an important role in pancreatic cancer (PC). In the present study, we investigated the effects of KAI1 gene overexpression on the EMT of human PC cell lines, MIA PaCa-2 and PACN-1. Methods: Plasmids overexpressing KAI1 and pCMV were transfected into MIA PaCa-2 and PACN-1 cells, respectively. After selection of differently transfected cells by G418, KAI1 protein levels were examined by Western blotting, and transfected cells were renamed as MIA PaCa-2-K, MIA PaCa-2-p, PACN-1-K and PACN-1-p. Wound healing and Transwell migration assays were then performed comparing the two groups of cells. EMT-related markers were analyzed by Western blotting. Results: The percentage of wound closure significantly decreased in MIA PaCa-2-K cells compared with MIA PaCa-2-p and MIA PaCa-2 cells after 24, 48 and 72 h ( P < 0.05). In PACN-1-K cells, the percentage of wound closure significantly decreased as well ( P < 0.05). Numbers of invading MIA PaCa-2, MIA PaCa-2-p and MIA PaCa-2-K cells were determined as 48.0 ±15.4, 50.0 ±12.4, and 12.0 ±3.8, respectively. The corresponding numbers of invading PACN-1, PACN-1-p and PACN-1-K cells were 29.0 ±10.6, 31.0 ±11.4, and 8.0 ±4.2, respectively. KAI1 overexpression induced a significant upregulation of E-cadherin and also significant downregulation of Snail, vimentin, matrix metalloproteinase 2 (MMP2) and MMP9 (all P < 0.05) in PC cells. Conclusions: KAI1 reversed EMT-related marker expression and inhibited migration and invasion of PC cells. Thus, KAI1 might represent a novel potential therapeutic target for PC.

关键词： KAI1 Epithelial-mesenchymal transition Pancreatic cancer

Portal hypertension in a patient with biliary hamartomas: A case report

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World Journal of Clinical Cases 2020年第9期8卷 1745-1751页

作者： Qian-Qian Li xiao-zhong guo Hong-Yu Li Xing-Shun Qi Department of Gastroenterology General Hospital of Northern Theater CommandShenyang 110840Liaoning ProvinceChina Postgraduate College Dalian Medical UniversityDalian 116044Liaoning ProvinceChina

BACKGROUND Biliary hamartomas(BH)are a rare benign disease caused by malformation of the intrahepatic bile *** are occasionally diagnosed,but often lack obvious clinical *** are usually diagnosed by biopsy and imaging tests in clinical *** studies have reported the association of BH with portal *** SUMMARY A 40-year-old man was repeatedly admitted to our hospital due to *** source of bleeding was considered to be gastroesophageal varices and portal hypertensive gastropathy by *** had no history of hepatitis virus infection,alcohol abuse,drug-induced liver injury,or autoimmune liver *** underwent magnetic resonance imaging,which showed rounded,irregular,low-signal-T1 and high-signal-T2 lesions diffusely distributed on the liver,that were not communicated with the biliary system on magnetic resonance *** to the imaging examination,the patient was considered to have a diagnosis of BH with portal *** Based on the present case report,BH may be a potential etiology of portal hypertension.

关键词： Biliary hamartomas Portal hypertension Variceal bleeding Computed tomography Magnetic resonance imaging Case report

KAI1 is a potential target for anti-metastasis in pancreatic cancer cells

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World Journal of Gastroenterology 2008年第7期14卷 1126-1132页

作者： Jian-Hua Xu xiao-zhong guo Li-Nan Ren Li-Chun Shao Min-Pei Liu Department of Gastroenterology The General Hospital of Shenyang Military Command Shenyang 110016 Liaoning Province China

AIM: To investigate whether KAI1, as a metastasis suppressor gene, is associated with invasive and metastatic ability of pancreatic cancer ***: KAI1 gene was transfected into pancreatic cancer cell line MiaPaCa Ⅱ by liposomes selected with G418. Expression of transfected cells was measured by Western blotting, immunofluorescence and immunocytochemistry. Tumor cell invasion and metastatic ability were detected through gelatinase activity and reconstituted basement membrane (Matrigel) assay. pCMV-KAI1 was directly injected into the heterotopic human pancreatic adenocarcinoma successfully established in the groin of BALB/C nude mice, by subcutaneous injection of MiaPaCa Ⅱ pancreatic cancer cells. The statistical analysis between groups was determined by Student's two tailed t ***: By Western blotting, MiaPaCa Ⅱ cells transfected by KAI1 gene indicated KAI1 expression at approximately 29.1 kDa. Cytoplasm staining was positive and uniformly spread in transfected cancer cells, using immunohistochemistry and immunofluorescence. The most obvious difference was present after 30 h (MiaPaca Ⅱ 43.6 ± 9.42, pCMV-MiaPaca Ⅱ 44.8 ± 8.56, pCMV-KAI1-MiaPaca Ⅱ 22.0 ± 4.69, P < 0.05). Gelatinolysis revealed a wider and clearer band of gelatinolytic activity in non-transfected than in transfected cells (MiaPaCa Ⅱ cells 30.8 ± 0.57, transfected cells 28.1 ± 0.65, P < 0.05). In vivo tumor growth rates of KAI1 transfectants with KAI1-Lipofectamine 1.22 ± 0.31 in A group were lower than control 4.61 ± 1.98 and pCMV-KAI 11.67 ± 0.81. Analyses of metastases with and without KAI1 transfection in mice were different in liver and lung between controls 1.62 ± 0.39, 0.45 ± 0.09, pCMV-KAI 1.01 ± 0.27, 0.33 ± 0.09 and KAI1-Lipofectamine 0.99 ± 0.21, 0.30 ± 0.09 respectively (P < 0.05).CONCLUSION: High expression of KAI1 gene was found in transfected MiaPaCa Ⅱ human pancreatic cancer cells with lower metastatic ability. KAI1 gene plays an important role in inhibiting metastasis of

关键词： KAI1 Pancreatic cancer cell line Transfection Immunocytochemistry Western blotting Immunofluorescence Gelatinolysis

Dendritic cells engineered to secrete anti-Dc R3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer in vitro

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World Journal of Gastroenterology 2017年第5期23卷 817-829页

作者： Jiang Chen xiao-zhong guo Hong-Yu Li Jia-Jun Zhao Wen-Da Xu Department of Gastroenterology Shenyang General Hospital of PLAShenyang 110016Liaoning ProvinceChina

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 Cr-51 releasing test. T cell responses induced by RNAloaded DCs were analyzed by measuring cytokine levels, including IFN-gamma, IL-10, IL4, TNF-alpha 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 respon

关键词： Dendritic cell Antibody-encoding RNA DcR3 Cytotoxic T lymphocyte response Pancreatic Cancer

Successful treatment of acute symptomatic extensive portal venous system thrombosis by 7-day systemic thrombolysis

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World Journal of Gastrointestinal Surgery 2022年第9期14卷 1082-1088页

作者： Fang-Bo Gao Le Wang Wen-Xiu Zhang xiao-Dong Shao xiao-zhong guo Xing-Shun Qi Department of Gastroenterology General Hospital of Northern Theater CommandShenyang 110840Liaoning ProvinceChina Postgraduate College Shenyang Pharmaceutical UniversityShenyang 110016Liaoning ProvinceChina

Acute portal venous system thrombosis(PVST)can cause acute mesenteric ischemia and even intestinal infarction,which are potentially fatal,and requires recanalization in a timely ***,we report a 56-year-old man with acute non-cirrhotic symptomatic extensive PVST who achieved portal vein recanalization after systemic thrombolysis combined with ***,anticoagulation with enoxaparin sodium for 4 d was ineffective,and then systemic thrombolysis for 7 d was *** that,his abdominal pain completely disappeared,and portal vein system vessels became gradually ***-term anticoagulation therapy was *** conclusion,7-d systemic thrombolysis may be an effective and safe choice of treatment for acute symptomatic extensive PVST which does not respond to anticoagulation therapy.

关键词： Portal vein Mesenteric vein Thrombosis Thrombolysis Anticoagulation Deep vein thrombosis

New tumor-associated antigen SC6 in pancreatic cancer

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World Journal of Gastroenterology 2005年第48期11卷 7671-7675页

作者： Min-Pei Liu xiao-zhong guo Jian-Hua Xu Di Wang Hong-Yu Li zhong-Min Cui Jia-Jun Zhao Li-Nan Ren Department of Experimental Medicine Northern Hospital Shenyang Liaoning Province China

AIM: To examine the concentration of a new antigen SC6 (SC6-Ag) recognized by monoclonal antibody (MAb)in patients with pancreatic cancer and other malignant or benign diseases and to understand whether SC6-Ag has any clinical significance in distinguishing pancreatic cancer from other gastrointestinal ***: Six hundred and ninety-five serum specimens obtained from 115 patients with pancreatic cancer, 154 patients with digestive cancer and 95patients with non-digestive cancer were used and classified in this study. Serum specimens obtained from 140 patients with benign digestive disease and 89 patients with non-benign digestive disease served as controls. Ascites was tapped from 16 pancreatic cancer patients, 19 hepatic cancer patients, 16 colonic cancer patients, 10 gastric cancer and 6 severe necrotic pancreatitis patients. The samples were quantitated by solid-phase radioimmunoassay. The cut-off values (CV)of 41, 80, and 118 U/mL were ***: The average intra- and interassay CV detected by immunoradiometric assay of SC6-Ag was 5.4% and 8.7%, respectively. The sensitivity and specificity were 73.0% and 90.9% respectively. The levels in most malignant and benign cases were within the normal upper limit. Among the 16 pancreatic cancer cases, the concentration of SC6-Ag in ascites was over the normal range in 93.8% patients. There was no significant difference in the concentration of *** expression of SC6-Ag in sera was significantly related to tumor differentiation. The concentration of SC6-Ag was higher in patients before surgery than after surgery. The specificity of SC6-Ag and CA19-9 was significantly higher than that of ultrasound and computer tomography (CT) in pancreatic cancer patients. Higher positive predictive values were indicated in 92.3% SC6-Ag and 88.5% CA19-9, but lower in 73.8% ultrasound and 76.2% ***: The combined test of SC6-Ag and CA19-9 may improve the diagnostic rate of primary cancer. The detection of

关键词： Tumor antigen SC6 Pancreatic neoplasm Immunoradiometric assay

KAI1 inhibits lymphangiogenesis and lymphatic metastasis of pancreatic cancer in vivo

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Hepatobiliary & Pancreatic Diseases International 2014年第1期13卷 87-92页

作者： Xu Liu xiao-zhong guo Hong-Yu Li Jiang Chen Li-Nan Ren Chun-Yan Wu Department of Gastroenterology General Hospital of Shenyang Military Area

BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study aimed to determine the role of KAI1 in lymphatic metastasis, specifically in pancreatic cancer. METHODS: The KAI1 gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1 by using liposomes and selected by G418, and the protein was measured by Western blotting. After successful infection, the cell growth curve was studied by MTT, vascular endothelial growth factor C(VEGF-C) secretion by pancreatic cancer cell were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected into the subcuticular layer of nude mice; both tumor growth and metastasis through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was measured by immunohistochemistry. RESULTS: The VEGF-C secretion was significantly reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa-2 and MIA PaCa-2-p tumors. CONCLUSION: The overexpression of KAI1 inhibits the lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.

关键词： KAI1 pancreatic cancer lymphatic metastasis lymphangiogenesis

Esophageal collateral veins in predicting esophageal variceal recurrence and rebleeding after endoscopic treatment:a systematic review and meta-analysis

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Gastroenterology Report 2020年第5期8卷 355-361,I0001,I0002页

作者： Qian-Qian Li Hong-Yu Li Zhao-Hui Bai Cyriac Abby Philips xiao-zhong guo Xing-Shun Qi Department of Gastroenterology General Hospital of Northern Theater CommandShenyangLiaoningP.R.China Postgraduate College Dalian Medical UniversityDalianLiaoningP.R.China Postgraduate College Shenyang Pharmaceutical UniversityShenyangLiaoningChina The Liver Unit and Monarch Liver Lab Cochin Gastroenterology GroupErnakulam Medical CenterKochiIndia

Background:Endoscopic treatment is recommended for the management of esophageal ***,variceal recurrence or rebleeding is common after endoscopic variceal *** study aimed to systematically evaluate the prevalence of esophageal collateral veins(ECVs)and the association of ECVs with recurrence of esophageal varices or rebleeding from esophageal varices after endoscopic ***:We searched the relevant literature through the PubMed,EMBASE,and Cochrane Library *** of paraesophageal veins(para-EVs),periesophageal veins(peri-EVs),and perforating veins(PVs)were *** ratio(RR)and odds ratio(OR)with 95%confidence intervals(CIs)were calculated for cohort studies and case-control studies,respectively.A random-effects model was *** among studies was ***:Among the 532 retrieved papers,28 were *** pooled prevalence of para-EVs,peri-EVs,and PVs in patients with esophageal varices was 73%,88%,and 54%,*** pooled prevalence of para-EVs and PVs in patients with recurrence of esophageal varices was 87%and 62%,*** risk for recurrence of esophageal varices was significantly increased in patients with PVs(OR=9.79,95%CI:1.95-49.22,P=0.006 for eight case-control studies),but not in those with para-EVs(OR=4.26,95%CI:0.38-38.35,P=0.24 for four case-control studies;RR=1.81,95%CI:0.83-3.97,P=0.14 for three cohort studies).Patients with para-EVs had a significantly higher incidence of rebleeding from esophageal varices(RR=13.00,95%CI:2.43-69.56,P=0.003 for two cohort studies).Statistically significant heterogeneity was notable across the ***:ECVs are common in patients with esophageal *** of ECVs could be helpful for predicting the recurrence of esophageal varices or rebleeding from esophageal varices after endoscopic treatment.

关键词： esophageal collateral veins esophageal varices prevalence rebleeding