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Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells

World Journal of Gastroenterology 2013年第28期19卷 4486-4494页

作者： Guo-Gang Li Lan Li Chao Li Long-Yun Ye Xiao-Wen Li Da-Ren Liu Qi Bao Yi-Xiong Zheng Da-Peng Xiang Li Chen Jian Chen Department of Surgery Second Affiliated Hospital College of Medicine Zhejiang University Department of Gastroenterology FirstAffiliated Hospital College of Medicine Zhejiang University

AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms. METHODS: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique. RESULTS: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm 3 vs 1115.1 ± 223.8 mm 3 , P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed. CONCLUSION: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.

关键词： Gastric cancer Delta-like ligand 4/Notch Matrix metalloproteinase Migration Invasion

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Bevacizumab as adjuvant therapy in the management of pterygium: a systematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2017年第7期10卷 1126-1133页

作者： Jian Liu Jie-Hui Xu Wen Xu Guan-Lu Liang Ji-Xian Lou Yi Wang Ji-Quan Wen Yong-Bao Cao Department of Ophthalmology Zhejiang Hospital Eye Center the Second Affiliated Hospital of Zhejiang UniversityCollege of Medicine

AIM： To evaluate the clinical effect of bevacizumab in pterygium ***： A systematic review and quantitative Metaanalysis was performed. Pub Med, EMBASE, Web of Science and Cochrane database were searched for eligible literatures published in English until June 2016. The endpoint was recurrence rate and pooled risk ratio（RR） was ***： Nine eligible studies were included and Metaanalysis results showed no significantly difference in patients treated with bevacizumab in short term followup [3mo： RR=0.70（0.34, 1.45）; 6mo： RR=0.55（0.23, 1.32）] compared with control groups. No significant effects were observed in favor of bevacizumab in subgroup analyses： patients with subconjunctival injection of bevacizumab [3mo： RR=0.95（0.70, 1.29）; 6mo： RR=0.83（0.55, 1.28）], primary pterygium [3mo： RR=0.59（0.23, 1.54; 6mo： RR=0.59（0.23, 1.53）], simple pterygium excision [3mo： 0.32（0.05, 2.04）, P=0.23; 6mo： 0.27（0.05, 1.53）] and excision with conjunctival autograft [3mo： 1.51（0.25, 9.15）; 6mo： 1.11（0.06, 21.69）].CONCLUSION： In this Meta-analysis, we did not found the significant effect of bevacizumab in pterygium treatment, at least in short term follow-up（3mo and 6mo）.

关键词： pterygium bevacizumab therapy recurrence Meta-analysis

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CCR3 monoclonal antibody inhibits airway eosinophilic inflammation and mucus overproduction in a mouse model of asthma

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Acta Pharmacologica Sinica 2006年第12期27卷 1594-1599页

作者： Hua-hao SHEN~2 Feng XU~2 Gen-sheng ZHANG Shao-bin WANG Wei-hua XU Department of Respiratory Diseases,the second affiliated hospital,zhejiang university college of medicine,Hangzhou 310009,China Department of Respiratory Diseases the Second Affiliated Hospital Zhejiang University College of Medicine Hangzhou China

Aim:To explore the effect of a rat anti-mouse CC-chemokine receptor-3(CCR3)monoclonal antibody(CCR3 mAb)on airway eosinophilia and mucus overpro-duction in asthmatic ***:An asthma model was sensitized and chal-lenged by ovalbumin(OVA)in male C57BL/6 *** mice were givendual administration(intraperitoneal injection and aerosol inhalation)of CCR3 mAbor nonspecific rat IgG(ns-IgG).The number of total and differential inflammatorycells in the bronchial alveolar lavage fluid(BALF)was *** number,the goblet cell percentage(GCP)and airway mucus index(AMI)were measured inthe lung ***(IL)-5 levels in the BALF were *** expres-sion of MUC5AC and the epidermal growth factor receptor(EGFR)mRNA in thelung tissues was detected by semi-quantitative *** results were com-pared among the ***:CCR3 mAb significantly suppressed theincreased eosinophils in the BALF and lung tissues in OVA-challenged mice com-pared with ns-IgG-treated ***-5 levels in the BALF in CCR3 mAb and ns-IgGadministration mice exhibited no obvious changes relative to OVA-challengedasthmatic ***3 mAb reduced the increased GCP and AMI after OVA chal-lenge and decreased the enhanced expression of MUC5AC and EGFR mRNA inlung tissues in asthmatic ***:CCR3 mAb can significantlyinhibit airway eosinophilia and mucus overproduction in asthmatic ***-age of CCR3 may represent a new strategy to asthma therapy.

关键词： asthma CCR3 monoclonal antibody eosinophilic inflammation mucus overproduction MUC5AC epidermal growth factor receptor

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Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts

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Journal of zhejiang university-Science B(Biomedicine & Biotechnology) 2013年第6期14卷 511-517页

作者： Yuan-yuan YAO Man-hua ZHU Feng-jiang ZHANG Chuan-yun WEN Lei-lei MA Wen-na WANG Can-can WANG Xian-bao LIU Li-na YU Ling-bo QIAN Jian-an WANG Min YAN Department of Anesthesiology the Second Affiliated HospitalSchool of MedicineZhejiang University Jiangsu Province Key Laboratory of Anesthesiology Xuzhou Medical College Department of Cardiology the Second Affiliated HospitalSchool of MedicineZhejiang University Department of Physiology Zhejiang Medical College

It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in *** aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion(I/R) *** male Sprague-Dawley rats were randomly divided into six groups(n=12):a sham-operation group,an I/R group,and four sevoflurane postconditioning groups(S2,S5,S10,and S15).In the S2,S5,S10,and S15 groups,the duration times of sevoflurane administration were 2,5,10,and 15 min after the onset of reperfusion,*** isolated rat hearts were mounted on the Langendorff system,and after a period of equilibrium were subjected to 40 min global ischemia and 120 min *** ventricular(LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30,60,90,and 120 min of reperfusion were *** infarct size at the end of reperfusion(n=7 in each group) and the expression of myocardial phosphorylated Akt(p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts(n=5 in each group).Compared with the I/R group,the S5,S10,and S15 groups had significantly improved left ventricular end-diastolic pressure(LVEDP),left ventricular developed pressure(LVDP),and the maximal rate of rise or fall of the LV pressure(±dP/dtmax),and decreased myocardial infarct size(P<0.05),but not the S2 *** 15 min of reperfusion,the expression of p-Akt was markedly up-regulated in the S5,S10,and S15 groups compared with that in the I/R group(P<0.05),but not in the S2 *** postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts.

关键词： Sevoflurane postconditioning Ischemia/reperfusion(I/R) injury Cardioprotection Duration of administration Akt

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Evodiamine induces extrinsic and intrinsic apoptosis of ovarian cancer cells via the mitogen-activated protein kinase/phosphatidylinositol-3-kinase/protein kinase B signaling pathways

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Journal of Traditional Chinese medicine 2016年第3期36卷 353-359页

作者： Wei Lijuan Jin Xiaoying Cao Zipei Li Wenlu Department of Traditional Chinese medicine the Second Affiliated Hospital of Zhejiang University School of Medicine Department of Urological Surgery the Second Hospital of Yinzhou District Department of Pharmacy the Second Affiliated Hospital of Zhejiang University School of Medicine

OBJECTIVE: To explore the effects of evodiamine on ovarian cancer cells and the mechanisms underlying such ***: Human ovarian cancer cells HO-8910 PM were treated with evodiamine at 0, 1.25,2.5, and 5 μM for 1-4 d. 3-(4,5-Dimethiylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was used to detect the growth inhibition rate of evodiamine-treated HO-8910 PM cells. The cell cycle was observed via propidium iodide(PI) staining. Apoptosis induction was assessed via Annexin V-fluorescein isothiocyanate/propidium iodide(Annexin V-FITC/PI) double staining assay. To verify the mechanism of apoptosis, caspase-dependent apoptotic pathway-related protein was detected by Western blot analysis. The expression levels of mitogen-activated protein kinase(MAPK)and/or phosphatidylinositol-3-kinase(PI3K)/pro-tein kinase B(Akt) pathway-related proteins were also ***: Evodiamine significantly inhibited the proliferation of HO-8910 PM cells in a dose- and time-dependent manner. Evodiamine induced G2/M arrest with an increase of cyclin B1 level, and promoted cell apoptosis with a decrease of B cell lymphoma/lewkmia-2(Bcl-2) and an increase of Bcl-2-associated X protein(Bax) level. In addition,evodiamine treatment led to the activation of caspase-8, caspase-9, and caspase-3 and the cleavage of poly(ADP-ribose)-polymerase(PARP). Evodiamine targeted the MAPK and/or PI3K/Akt pathways by reducing the expression and activity of PI3 K, Akt, and extracellular signal-regulated kinase mitogen-activated protein kinase(ERK1/2 MAPK)and the activity of p38 ***: Evodiamine can inhibit the growth of ovarian cancer cells by G2/M arrest and intrinsic and extrinsic apoptosis. In addition, evodiamine-induced PI3K/Akt, ERK1/2 MAPK, and p38 MAPK signaling may be involved in cell death.

关键词： Evodiamine Ovarian neoplasms Apoptosis Caspases Mitogen-activated protein kinase phosphatases MAP kinase signaling system

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Laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension

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World Journal of Gastroenterology 2014年第19期20卷 5794-5800页

作者： Xiao-Li Zhan Yun Ji Yue-Dong Wang Department of General Surgery Second Affiliated Hospital Zhejiang University College of Medicine

Since the first laparoscopic splenectomy(LS)was reported in 1991,LS has become the gold standard for the removal of normal to moderately enlarged spleens in benign *** with open splenectomy,fewer postsurgical complications and better postoperative recovery have been observed,but LS is contraindicated for hypersplenism secondary to liver cirrhosis in many institutions owing to technical difficulties associated with splenomegaly,well-developed collateral circulation,and increased risk of *** the improvements of laparoscopic technique,the concept is *** article aims to give an overview of the latest development in laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal *** a lack of randomized controlled trial,the publications obtained have shown that with meticulous surgical techniques and advanced instruments,LS is a technically feasible,safe,and effective procedure for hypersplenism secondary to cirrhosis and portal hypertension and contributes to decreased blood loss,shorter hospital stay,and less impairment of liver *** is recommended that the dilated short gastric vessels and other enlarged collateral circulation surrounding the spleen be divided with the LigaSure vessel sealing equipment,and the splenic artery and vein be transected en bloc with the application of the endovascular *** support the clinical evidence,further randomized controlled trials about this topic are necessary.

关键词： Laparoscopy Splenectomy Liver cirrhosis Portal hypertension Hypersplenism

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Overt gastrointestinal bleeding because of hookworm infection

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Asian Pacific Journal of Tropical medicine 2012年第4期5卷 331-332页

作者： Jia-Min Chen Xin-Mei Zhang Liang-Jing Wang Yan Chen Qin Du Jian-Ting Cai Department of Gastroenterology second affiliated hospital Zhejiang University College of Medicine

Hookworm infection is a relatively common cause of anemia in endemic *** most common hookworm species are Ancylostoma duodenale and Necator *** this report we present a case of overt gastrointestinal bleeding Wause of hookworm *** endoscopy revealed many hookworms in the lumen of proximal jejunum where active bleeding was seen. The patient was successfully treated with Albendazole.

关键词： Capsule endoscopy Hookworm infection Overt gastrointestinal bleeding

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Eosinophilic gastroenteritis associated with eosinophilic cystitis:Computed tomography and magnetic resonance imaging findings

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World Journal of Gastroenterology 2015年第10期21卷 3139-3145页

作者： Shu-Gao Han Ying Chen Zi-Hua Qian Li Yang Ri-Sheng Yu Xiu-Liang Zhu Qing-Hai Li Qian Chen Department of Radiology Second Affiliated Hospital Zhejiang University School of Medicine Department of Pathology Second Affiliated Hospital Zhejiang University School of Medicine

Eosinophilic gastroenteritis(EG) is a rare,distinct clinical entity,and EG associated with eosinophilic cystitis(EC) is extremely rare and has not been well ***,we report two cases of EG and coexistent EC along with findings from computed tomography(CT) and magnetic resonance imaging(MRI).An 18-year-old male with a history of hematuria,urgency and occasional urodynia for two weeks and a 34-year-old male with a history of abdominal distention for one week were admitted to our *** contrast-enhanced CT in both patients revealed wall thickening in different parts of the gastrointestinal tract with inhomogeneous reinforcement,coexistent with local or diffuse bladder wall thickening with progressive enhancement,and also showed that the bladder mucosal lining was *** MRI showed that the local or diffuse thickened bladder wall was iso-intense on T1-weighted images,hypointense on T2-weighted images,and slightly restricted on diffusion weighted imaging(DWI) in one *** therapy,the thickened wall of the gastrointestinal tract and urinary bladder had improved markedly in the two *** the best of our knowledge,this is the first report on the radiological imaging of EG and coexistent EC by both CT and MRI and the first with DWI findings.

关键词： Eosinophilic gastroenteritis Eosinophilic cystitis

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Biochemical metabolic changes assessed by ^(31)P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

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World Journal of Gastroenterology 2009年第22期15卷 2723-2730页

作者： Ri-Sheng Yu Liang Hao Fei Dong Jian-Shan Mao Jian-Zhong Sun Ying Chen Min Lin Zhi-Kang Wang Wen-Hong Ding Department of Radiology Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009 Zhejiang Province China Department of Internal medicine Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009 Zhejiang Province China Department of Pathology Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009 Zhejiang Province China

AIM： To compare the features of biochemical metabolic changes detected by hepatic phosphorus-31 magnetic resonance spectroscopy （^31p MRS） with the liver damage score （LDS） and pathologic changes in rabbits and to investigate the diagnostic value of ^31p MRS in acute hepatic radiation injury. METHODS： A total of 30 rabbits received different radiation doses （ranging 5-20 Gy） to establish acute hepatic injury models. Blood biochemical tests, ^31p MRS and pathological examinations were carried out 24 h after irradiation. The degree of injury was evaluated according to LD5 and pathology. Ten healthy rabbits served as controls. The MR examination was performed on a 1.5 T imager using a 1H/^31P surface coil by the 2D chemical shift imaging technique. The relative quantities of phosphomonoesters （PME）, phosphodiesters （PDE）, inorganic phosphate （Pi） and adenosine triphosphate （ATP） were measured. The data were statistically analyzed. RESULTS：（1） Relative quantification of phosphorus metabolites：（a） ATP： there were significant differences （P 〈 0.05）（LDS-groups：control group vs mild group vs moderate group vs severe group, 1.83±0.33 vs 1.55±0.24 vs 1.27±0.09 vs 0.98±0.18; pathological groups： control group vs mild group vs moderate group vs severe group, 1.83±0.33 vs 1.58±0.25 vs 1.32±0.07 vs 1.02±0.18） of ATP relative quantification among control group, mild injured group, moderate injured group, and severe injured group according to both LDS grading and pathological grading, respectively, and it decreased progressively with the increased degree of injury （r = -0.723, P = 0.000）. （b） PME and Pi; the relative quantification of PME and Pi decreased significantly in the severe injured group, and the difference between the control group and severe injured group was significant （P 〈 0.05）（PME： 1DS- control group vs LDS-severe group, 0.86±0.23 vs 0.58±0.22, P = 0.031; pathological control group vs pathological severe group, 0.86±0.23 vs 0.60±0.21, P = 0.037; Pi： LDS-control

关键词： Liver Magnetic resonance spectroscopy Animal models Pathology Adenosine triphosphate

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Metabolic syndrome risk factors and dry eye syndrome:a Meta-analysis

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International Journal of Ophthalmology(English edition) 2016年第7期9卷 1038-1045页

作者： Ye-Lei Tang Ya-Lan Cheng Yu-Ping Ren Xiao-Ning Yu Xing-Chao Shentu Department of Neurology the Second Affiliated HospitalSchool of Medicine Zhejiang University Eye Center the Second Affiliated Hospital School of Medicine Zhejiang University

AIM：To explore the relationship between metabolic risk factors and dry eye syndrome（DES）.METHODS：Retrieved studies on the association of metabolic syndrome risk factors（hypertension,hyperglycemia,obesity,and hyperlipidemia） and DES were collected from PubMed,Web of Science,and the Cochrane Library in December *** ratio（OR） with 95% confidence interval（Cl） were pooled to evaluate the final *** analyses were conducted according to diagnostic criteria of ***：Nine cross-sectional studies and three case-control studies were included in this *** pooled results showed that people with hypertension,hyperglycemia,and hyperlipidemia had a higher risk of suffering from DES（P〈0.05）,especially the typical DES *** the other hand,obesity did not increase the risk of ***：The present Meta-analysis suggests that all metabolic risk factors except obesity were risk factors for DES.

关键词： dry eye syndrome hypertension hyperglycemia obesity hyperlipidemia Meta-analysis

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