Adequate blood supply is essential for tumor survival, growth and metastasis. The tumor microenvironment (TME) is dynamic and complex, comprising cancer cells, cancer-associated stromal cells and their extracellular products. The TME serves an important role in tumor progression. Cancer-associated fibroblasts (CAFs) are the principal component of stromal cells within the TME, and contribute to tumor neo-angiogenesis by altering the proteome and degradome. The present paper reviews previous studies of the molecular signaling pathways by which CAFs promote tumor neo-angiogenesis and highlights therapeutic response targets. Also discussed are potential strategies for antitumor neo-angiogenesis to improve tumor treatment efficacy.

Objective To investigate the expression of ubiquitin-conjugating enzyme E2s (UBE2S) in gallbladder cancer (GBC) tissues and its clinical significance.Methods The expression of UBE2S was examined in 85 GBC,28 pre-malignant lesion and 15 benign lesion tissues of the gallbladder by immunohistochemistry,and was verified by western blotting.The relationship between UBE2S expression and clinicopathological characteristics and prognostic factors of GBC patients was analyzed.Results Immunohistochemistry showed that UBE2S was highly expressed in GBC tissues compared to pre-malignant lesion tissues [stain index (SI):4.082 ± 3.413 vs.2.607 ± 2.025,P =0.021)] and benign lesion tissues (SI:4.082 ± 3.413 vs.2.067 ± 1.335,P =0.001),and western blotting showed that UBE2S protein was highly expressed in GBC tissues compared to benign lesion tissues (grey-scale value:0.734 ±0.181 vs.0.197 ± 0.099,P =0.002).UBE2S was positively correlated with tumor differentiation degree (x2 =6.978,P =0.031) and liver metastasis (x2 =8.155,P =0.004).Cox model showed that UBE2S expression (P =0.024) as well as tumor differentiation degree (P =0.000),Nevin stage (P =0.040) and R0 resection (P =0.011) were prognostic factors of GBC patients.High UBE2S expression patients with GBC have a shorter survival time (P =0.011).Conclusion High UBE2S expression is an independent factor of unfavorable prognosis in GBC patients.

Objective To investigate the changes in the diagnostic and therapeutic methods for Lemmel′s syndrome over the past 20 years in China,and to provide experience for standardized diagnosis and treatment of this disease. Methods A retrospective analysis was performed for the clinical data of 23 patients with Lemmel′s syndrome who were diagnosed and treated in Tongji Hospital of Tongji University from Janu-ary 1998 to June 2017 and 384 patients with Lemmel′s syndrome reported in China during the same period of time(407 patients in total). According to the admission time,the patients were divided into groups A(139 patients admitted from 1998 to 2007)and B(268 patients admitted from 2008 to 2017). The patients′clinical features,diagnostic and therapeutic methods,and prognosis were recorded. The t-test was used for comparison of normally distributed continuous data between groups,and the Wilcoxon rank sum test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups. Results Compared with group A,group B had significantly higher age of onset(67.8 ± 17.8 vs 62.3 ± 12.3,t= -13.238,P= 0.019) and incidence rate of cholangitis(45.9% vs 32.4%,χ2=6.903,P=0.009). As for diagnostic methods,compared with group A,group B had a significantly higher proportion of patients who used multi-slice spiral CT(MSCT)(26.9% vs 8.6%,χ2=18.576,P<0.001), endoscopic ultrasonography(EUS)(15.7% vs 5.8%,χ2=8.352,P=0.004),magnetic resonance cholangiopancreatography(MRCP) (75.0% vs 33.1%,χ2=67.303,P<0.001),or endoscopic retrograde cholangiopancreatography(ERCP)(63.4% vs 36.7%,χ2=26.377,P<0.001),while the two groups had a similar false positive rate(22.8% vs 28.1%,χ2=1.385,P=0.239). As for therapeu-tic methods,compared with group A,group B had a significantly higher proportion of patients who underwent ERCP combined with conserva-tive pharmacotherapy and surgical operation(χ2=34.758,P<0.001). There was a significant difference in recurrence rate between endo-scopic surgery group and conservative pharmacotherapy group(χ2=40.211,P<0.001),as well as between surgical operation group and conservative pharmacotherapy group(χ2=26.785,P<0.001);there was no significant difference in recurrence rate between surgical oper-ation group and endoscopic surgery group(χ2=0.055,P=0.815),but endoscopic surgery had the advantages of minimal invasiveness, fast recovery,and low costs. Conclusion Age of onset of Lemmel′s syndrome is gradually increasing. MSCT,EUS,MRCP,and ERCP ap-plied alone or in combination are major diagnostic methods,and ERCP is the preferred therapeutic method for Lemmel′s syndrome.

Human gallbladder cancer (GBC) is a lethal aggressive malignant neoplasm. Identification of potential molecular biomarkers and development of targeted therapeutics for GBC patients is very necessary. In this study, we firstly investigated the correlation between ring finger protein 125 (RNF125) expression and the metastasis and prognosis of GBC, and the underlying molecular mechanism. RNF125 expression in a cohort of GBC tissues was examined; its correlation with clinicopathological and prognostic factors of GBC patients was analyzed. Moreover, the metastasis-related difference expressed genes in highly and lowly aggressive GBC cell lines were identified; and the influence of RNF125 knockdown on the metastatic phenotypes and characteristic EMT markers in highly aggressive GBC NOZ cells was detected. Furthermore, the underlying molecular mechanism of RNF125 effect was explored. The results showed that RNF125 was highly expressed in GBC tissues and related with aggressive characteristics such as Nevin stage (P = 0.041) etc. and unfavorable prognosis of GBC patients (P = 0.023, log-rank test). And, RNF125 was proved to a positive metastasis-related gene in vitro. RNF125 knockdown inhibited the invasion and migration, enhanced the adhesion, upregulated E-cadherin and β-catenin expression, and downregulated vimentin and N-cadherin expression (all P < 0.001) of NOZ cells in vitro. RNF125 promoting effect on GBC tumor progression was identified to relate with the activation of TGF-β1-SMAD3-ID1 signaling pathway. These findings firstly confirm that high RNF125 expression is related with aggressive characteristics and unfavorable prognosis of GBC patients; RNF125 promotes the invasion and metastasis of human GBCs via activating the TGF-β1-SMAD3-ID1 signaling pathway.

Vasculogenic mimicry (VM) is a tumor microcirculation pattern in highly aggressive gallbladder cancers (GBCs). We recently reported the anti‑VM activity of norcantharidin (NCTD) in highly aggressive GBC‑SD cells and xenografts. In this study, we further investigated that NCTD enhanced tissue inhibitor of matrix metalloproteinase‑2 (TIMP‑2) anti‑VM activity for GBCs and the underlying mechanisms. In vivo and in vitro experiments were performed to determine the effects of NCTD in combination with TIMP‑2 on tumor growth, host survival, VM formation, hemodynamic of GBC‑SD xenografts, and VM‑like networks and malignant phenotypes of GBC‑SD cells. Expression of matrix metalloproteinase (MMP)‑2 and membrane type 1‑MMP (MT1‑MMP) among human GBCs, GBC‑SD cells and xenografts were determined, respectively. The results showed that expression of MMP‑2 and MT1‑MMP in human GBCs, GBC‑SD cells and xenografts was significantly related to VM in GBCs; a shorter survival time of VM‑positive patients with high expression of MMP‑2 or MT1‑MMP compared to that of the patients with low expression. After treatment with NCTD+TIMP‑2, tumor growth, VM formation, VM hemodynamic of the xenografts in vivo were significantly inhibited as compared to control, NCTD or TIMP‑2 group, with a prolonged survival time of the xenograft mice (log‑rank test, P=0.0115); and these observations were confirmed by VM‑like networks by 3‑D matrices and showed that proliferation, apoptosis, invasion, migration of GBC‑SD cells in vitro were markedly affected. Furthermore, expression of MMP‑2 and MT1‑MMP in VM formation of the xenografts in vivo and GBC‑SD cells in vitro was downregulated as compared to control, NCTD or TIMP‑2 group. Thus, we concluded that NCTD enhances TIMP‑2 antitumor and anti‑VM activities in GBCs through downregulating MMP‑2 and MT1‑MMP.

Background: Tumor lymphangiogenesis plays an important role in promoting growth and metastasis of tumors, but no antilymphangiogenic agent is used clinically. Based on the effect of norcantharidin (NCTD) on lymphangiogenesis of human lymphatic endothelial cells (LECs), we firstly investigated the antilymphangiogenic activity of NCTD as a tumor lymphangiogenic inhibitor for human colonic adenocarcinomas (HCACs).Methods: In vivo and in vitro experiments to determine the effects of NCTD on tumor growth and lymphangiogenesis of the in-situ colonic xenografts in nude mice, and lymphatic tube formation of the three-dimensional (3-D) of the co-culture system of HCAC HT-29 cells and LECs were done. Proliferation, apoptosis, migration, invasion, Ki-67, Bcl-2 and cell cycle of LECs and the co-culture system in vitro were respectively determined. Streparidin-peroxidase staining, SABC, western blotting and RT-PCR were respectively used to examine the expression of LYVE-1, D2-40, CK20 (including their LMVD), and VEGF-A, VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in vitro and in vivo.Results: NCTD inhibited tumor growth and lymphangiogenesis of the in-situ colonic xenografts in vivo, and these observations were confirmed by facts that lymphatic tube formation, proliferation, apoptosis, migration, invasion, S-phase cell cycle, and Ki-67 and Bcl-2 expression in vitro, and LYVE-1, D2-40, CK20 expression and their LMVD in vitro and in vivo were inhibited and affected. Furthermore, the expression of VEGF-A, VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 at protein/mRNA levels in the process of lymphatic tube formation in vitro and tumor lymphangiogenesis in vivo was downregulated; NCTD in combination with mF4-31C1 or Sorafenib enhanced these effects.Conclusions: NCTD inhibits tumor growth and lymphangiogenesis of HCACs through "multi-points priming" mechanisms i.e. affecting related malignant phenotypes, inhibiting Ki-67 and Bcl-2 expression, inducing S-phase cell cycle arrest, and directly or indirectly downregulating VEGF-A,-C,-D/VEGFR-2,-3 signaling pathways. The present finding strongly suggests that NCTD could serve as a potential antilymphangiogenic agent for tumor lymphangiogenesis and is of importance to explore NCTD is used for antitumor metastatic comprehensive therapy for HCACs.

目的 评价ERCP联合ESWL治疗胰管结石的效果.方法 2008年1月～2009年12月在我院经影像学确诊的12例胰管结石患者接受了ERCP联合ESWL治疗.先行ERCP以了解胰管形态改变并放置胰管支架;续行ESWL,依结石形态及密度了解碎石效果,对碎石不满意者重复ESWL;6～8周后再行ERCP取石.结果 所有患者全部碎石成功(根据结石密度和体积变化);其中,1例行ESWL后结石完全排净,5例ESWL后经内镜治疗结石被完全清除,1例结石部分清除,1例取石失败,2例碎石后失访.治疗期间未出现严重并发症.结论 ESWL对胰管结石碎石效果好,但单纯ESWL仅部分患者结石可自行排出;ESWL后结合内镜取石治疗,能提高胰管结石清除效果.

Vasculogenic mimicry（VM）is a newly-defined tumor microcirculation pattern in highly aggressive malignant tumors.We recently reported tumor growth and VM formation of gallbladder cancers through the contribution of the ephrin type a receptor 2（EphA2）/focal adhesion kinase（FAK）/Paxillin signaling pathways.In this study,we further investigated the anti-VM activity of norcantharidin（NCTD）as a VM inhibitor for gallbladder cancers and the underlying mechanisms.In vivo and in vitro experiments to determine the effects of NCTD on tumor growth,host survival,VM formation of GBC-SD nude mouse xenografts,and vasculogenic-like networks,malignant phenotypes i.e.,proliferation,apoptosis,invasion and migration of GBC-SD cells.Expression of VM signaling-related markers EphA2,FAK and Paxillin in vivo and in vitro were examined by immunofluorescence,western blotting and real-time polymerase chain reaction（RT-PCR）,respectively.The results showed that after treatment with NCTD,GBCSD cells were unable to form VM structures when injecting into nude mouse,growth of the xenograft was inhibited and these observations were confirmed by facts that VM formation by three-dimensional（3-D）matrix,proliferation,apoptosis,invasion,migration of GBC-SD cells were affected;and survival time of the xenograft mice was prolonged.Furthermore,expression of EphA2,FAK and Paxillin proteins/mRNAs of the xenografts was downregulated.Thus,we concluded that NCTD has potential antiVM activity against human gallbladder cancers;one of the underlying mechanisms may be via blocking the EphA2/FAK/Paxillin signaling pathway.

BACKGROUND:Vasculogenic mimicry (VM) is a novel tumor blood supply in some highly aggressive malignant tumors. Recently, we reported VM existed in gallbladder carcinomas (GBCs) and the formation of the special passage through the activation of the PI3K/MMPs/Ln-5γ2 signaling pathway. GBC is a highly aggressive malignant tumor with disappointing treatments and a poor prognosis. Norcantharidin (NCTD) has shown to have multiple antitumor activities against GBCs, etc; however the exact mechanism is not thoroughly elucidated. In this study, we firstly investigated the anti-VM activity of NCTD as a VM inhibitor for GBCs and its underlying mechanisms.METHODS:In vitro and in vivo experiments to determine the effects of NCTD on proliferation, invasion, migration, VM formation, hemodynamic and tumor growth of GBC-SD cells and xenografts were respectively done by proliferation, invasion, migration assays, H&E staining and CD31-PAS double stainings, optic/electron microscopy, tumor assay, and dynamic micro-MRA. Further, immunohistochemistry, immunofluorescence, Western blotting and RT-PCR were respectively used to examine expression of VM signaling-related markers PI3-K, MMP-2, MT1-MMP and Ln-5γ2 in GBC-SD cells and xenografts in vitro and in vivo.RESULTS:After treatment with NCTD, proliferation, invasion, migration of GBC-SD cells were inhibited; GBC-SD cells and xenografts were unable to form VM-like structures; tumor center-VM region of the xenografts exhibited a decreased signal in intensity; then cell or xenograft growth was inhibited. Whereas all of untreated GBC-SD cells and xenografts formed VM-like structures with the same conditions; the xenograft center-VM region exhibited a gradually increased signal; and facilitated cell or xenograft growth. Furthermore, expression of MMP-2 and MT1-MMP products from sections/supernates of 3-D matrices and the xenografts, and expression of PI3-K, MMP-2, MM1-MMP and Ln-5γ2 proteins/mRNAs of the xenografts were all decreased in NCTD or TIMP-2 group; (all P < 0.01, vs. control group); NCTD down-regulated expression of these VM signaling-related markers in vitro and in vivo.CONCLUSIONS:NCTD inhibited tumor growth and VM of human GBCs in vitro and in vivo by suppression of the PI3-K/MMPs/Ln-5γ2 signaling pathway. It is firstly concluded that NCTD may be a potential anti-VM agent for human GBCs.

目的 总结并发肠梗阻盆位穿孔性阑尾炎的诊治经验.方法 对2010年1月至2012年12月摩洛哥赛达特哈桑二世医院收治的31例合并肠梗阻的盆位穿孔性阑尾炎患者的临床资料进行回顾性分析.结果 患者入院后均行剖腹探查、阑尾切除、腹腔引流手术,其中机械性肠梗阻8例,麻痹性肠梗阻23例,盆腔脓肿15例;围手术期感染性休克6例,多系统器官功能衰竭(MSOF)4例;术后腹腔残余感染和早期炎性肠梗阻5例,肺部感染3例,伤口感染7例.31例中治愈30例,死亡1例.结论 盆位阑尾炎症状不典型,容易延误诊治;并发肠梗阻的盆位阑尾穿孔可导致休克、MSOF等严重后果,需及时手术;螺旋CT对盆位阑尾穿孔引起的肠梗阻诊断具有一定价值.

Objective:To compare the complication and prognosis between open and laparoscopic repair of perforation of upper digestive tract in elderly patients.Methods:Clinical data of 72 elderly patients who had received surgical repair of perforation of upper digestive tract from Jan.2005 to Dec.2012 were analyzed retrospectively.34 patients received open repair and 38 patients received laparoscopic repair.Results:Sixty-nine cases were cured and 3 died.There were significant differences in post-operative incision infection(14.7% vs.0,P0.05) and pulmonary infection(26.5% vs.7.9%,P0.05) between open and laparoscopic groups.There was no statistical difference in post-operative intraperitoneal infection(14.7% vs.5.3%,P0.05) and mortality(5.9% vs.2.6%,P0.05) between the two groups.Conclusions:Laparoscopic repair of perforation of upper digestive tract can be safely carried out in elderly patients.Reduction of postoperative complications is the embodiment of the advantages of minimal invasion.

Objective To investigate the relationship between juxta-papilary duodenal diverticulum(JPD) and acute pancreatitis(AP).Methods Five hundred and forty patients underwent endoscopic retrograde cholangiopancreatography(ERCP).The correlation of JPD with age and acute pancreatitis was analyzed.Results The JPD was detected by ERCP in 125 patients with a prevalence rate of 23.2%.The average age of JPD group was significantly higher than that of non-JPD group(t=4.53,P0.0001).Significant difference was observed in detection rate of JPD between patients ≥61y and those ≤60y.Excluded the cases who complicated with common bile duct stones,the detection rate of JPD in AP group(23.8%,20/84) was significantly higher than that(8.6%,39/456) in non-AP group(P=0.0001).Conclusion JPD occurs more often in elderly patients,and closely correlated with AP,indicating that JPD might be a risk factor for AP.

As a novel mode of tumor neovascularization, vasculogenic mimicry (VM) has been reported to increase tumor-related mortality in many different solid tumors. In the present study, two established human gallbladder carcinoma (GBC) cell lines (highly aggressive GBC-SD and poorly aggressive SGC-996) cultured on a three-dimensional matrix were assessed for the ability of VM channel formation under normoxic or hypoxic conditions. In addition, the relationship between HIF-1α gene expression and VM channel formation of GBC cells in vitro was measured using the small interfering RNA (siRNA) technique, western blotting and real-time reverse transcription (RT)-PCR analysis. Furthermore, H&E and CD31/periodic acid-Schiff (PAS) staining were used to observe VM in GBC tissue samples. Additionally, all seventy-one specimens with VM and non-VM were stained for hypoxia inducible factor-1 α (HIF-1α) and its correlation with clinicopathological features and prognosis was analyzed simultaneously. We found that hypoxia could induce more VM channel formation and elevated HIF-1α expression in highly aggressive GBC-SD cells. HIF-1α siRNA efficiently knocked down HIF-1α expression and GBC VM networks under either normoxic or hypoxic conditions. VM was present in human primary GBC and overexpression of HIF-1α was significantly correlated with depth of invasion and perineural involvement in the non-VM group. Moreover, VM and HIF-1α were independent factors for the overall survival of GBC patients and correlated with decreased survival. In conclusion, VM was present in human GBC. As a critical mediator in VM formation, high expression of HIF-1α was associated with VM and tumor progression in GBC patients.

Astrocyte elevated gene-1 (AEG-1), as an HIV-1 or TNF-α-inducible transcript, is correlated with various aspects of tumor malignancy. However, the status of AEG-1 expression and its clinical significance in human gallbladder carcinoma (GBC) remains unknown. In the present study, we investigated AEG-1 expression in two GBC cell lines (GBC-SD and SGC-996) and GBC tissues by immunohistochemical, Western blot and real-time PCR analysis. We found that AEG-1 was highly expressed in GBC samples (63.4%, 26 of 41) compared with normal gallbladder mucosa (p=0.0003) and highly invasive GBC-SD cell lines at both the protein (p=0.0043) and mRNA levels (p=0.0001), and strongly correlated with differentiation degree (p=0.006), Nevin stage (p=0.0344), Ki-67 expression (p=0.0024) and liver infiltration (p=0.0332) in these patients. Multivariate analysis indicated that AEG-1 overexpression was an independent prognostic marker for GBC patients. Moreover, patients with high AEG-1 levels had shorter survival time (p=0.008). Our results suggest that the AEG-1 protein is a valuable marker of GBC progression and could be a potential therapeutic target.

Our objective was to explore the antiangiogenic activity of norcantharidin (NCTD) as an angiogenic inhibitor for gallbladder cancers. In vitro and in vivo experiments to determine the effects of NCTD on HUVECs, chicken CAM capillaries and gallbladder cancer xenograft angiogenesis in nude mice were respectively done. The MTT method was used to assay the cytotoxicity of NCTD on HUVECs. Immunofluorescence was used to evaluate HUVEC apoptosis. The scraping line method, matrigel invasion assay and tube formation assay were used to detect the migration, invasion and tube formation of HUVECs. A digital camera was used to observe chicken CAM capillaries. Experiments with NCTD in a xenograft model were used to observe the effect of NCTD on xenograft growth and survival of mice with xenografts. CD₃₄ immunohistochemistry, flow cytometry and micro-MRA were used, respectively, to determine MVD, cell apoptosis and hemodynamic analysis of the xenografts. Immunohistochemistry and RT-PCR were used, respectively, to detect the expression of VEGF, Ang-2, TSP, TIMP-2 proteins/mRNAs of the xenografts. The xenograft MVD associated with tumor volume, the PCNA/apoptosis ratio and related-protein expression was evaluated simultaneously. We found that NCTD effectively inhibited the proliferation, migration, invasion and capillary-like tube formation of HUVECs in vitro; it reduced angiogenesis and directly destroyed the formed CAM capillaries in vivo. In the experiments in mice, NCTD not only inhibited significantly xenograft proliferation and growth, prolonged survival time of mice with xenografts, decreased the xenograft MVD and vascular perfusion, but also, similarly to ES, decreased significantly the expression of VEGF or Ang-2 protein/mRNA, increased the expression of TSP or TIMP-2 protein/mRNA. Moreover, the xenograft MVD was positively related with tumor volume, PCNA/apoptosis ratio, and VEGF or Ang-2 expression, respectively (all P<0.05), but negatively correlated with TSP or TIMP-2 expression (both P<0.05). These data showed that NCTD could serve as a potential antiangiogenic agent for gallbladder cancers.

慢性胰腺炎(CP)能导致胰腺实质及胰管结构的破坏和内、外分泌功能的不可逆损害[1],常合并胰管结石及胰管狭窄,主要表现为腹痛、恶心、呕吐、脂肪泻、血糖升高等.对胰管结石的治疗以清除主胰管内结石,解除梗阻,通畅胰液引流为原则.随着技术的进步和发展,内镜下胰胆管逆行造影(ERCP)干预及体外震波碎石(extracorporeal shock wave lithotripsy,ESWL)治疗越来越受到关注.我们采用ERCP结合ESWL治疗10例胰管结石,现分析如下.

Objective To study the expression of transcriptional factor Sp1 in human pancreatic ductal carcinoma tissues and its prognostic significance.Methods Expression of Sp1 in 60 pancreatic ductal carcinoma cases with various clinical pathologic characteristics was detected by using immunohistochemistry.The significance of Sp1 expression on the survival of patients was evaluated.Results The positive expression rate of Sp1 in 60 pancreatic ductal carcinoma cases was 75%(45/60).In patients with portal vein and peripheral nerve invasion the positive rate of Sp1 expression was significantly higher than that in those without portal vein and peripheral nerve invasion.Expression of Sp1 had no relation with the location and differentiation of tumor,lymph metastasis,duodenum invasion and TNM stage.The medium survival time was 19 months in patients with negative Sp1 expression and 12 months for positive Sp1 expression tumor which was statistically significant.Conclusion Sp1 is over expressed in pancreatic ductal carcinoma and might be served as an independent prognostic factor in pancreatic ductal carcinoma.

Objective To study the relationships between expression of MMP-2 and TIMP-2 protein and clinical-pathological parameters in gallbladder carcinomas.Methods Carcinomas ( n =45) and polypoid lesions of the gallbladder ( n =15) were studied.Expression of MMP-2 and TIMP-2 protein was examined by immunohistochemical avidin-biotin-complex method and the image analysis.Clinical-pathological dates in patients with carcinomas of the gallbladder such as histological type,grade of differentiation,level of infiltration,liver invasion and lymph node involvement,etc were recorded.Results The average level (1.123±0.108 vs 1.0301±0.054,P =0.002) of MMP-2 expression was significantly higher in carcinoma of the gallbladder than in polypoid lesions of the gallbladder.The significant difference was found between the expression of MMP-2 in early stage and advanced tumors.But there are no correlations between MMP-2 in early stage and advanced tumors.But there are no correlations between MMP-2 protein expression and histological type,differentiation degree,infiltration level,lymph node involvement or liver invasion.Though correlation was not observed between TIMP-2 expression and histological type or differentiation degree,the significant relationship was found between TIMP-2 expression and different Nevin stage,infiltration level,local lymph node involvement or liver invasion in patients with carcinoma of the gallbladder ( P 0.05).Conclusion Expression of TIMP-2 protein could reflect more accurately biological character of gallbladder carcinomas when compared with MMP-2.If united examination,MMP-2 and TIMP-2 could help to differentiate malignant lesions from benign ones of the gallbladder and TIMP-2 might be a significant clinical directors in the judgment of invasion or metastasis and the estimating of prognosis in patients with carcinoma of the gallbladder.

AIM:To study the correlation between expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 and clinical-pathological parameters of patients with gallbladder carcinoma.METHODS:Carcinomas (n=45) and polypoid lesions (n=15) of the gallbladder were studied for the expression of MMP-2 and TIMP-2 protein by immunohistochemical avidin-biotin-complex method and image analysis. Clinical-pathological data of patients with gallbladder carcinoma such as histological type, grade of differentiation, level of infiltration, liver invasion and lymph node involvement, etc, were recorded.RESULTS:There was significant difference between the average level (1.123+/-0.108 vs 1.030+/-0.054, P=0.002) of MMP-2, the ratio (1.050+/-0.013 vs 0.937+/-0.078, P=0.003) of MMP-2/TIMP-2 in gallbladder carcinomas and in polypoid lesions of the gallbladder. Significant difference was found between the expression of MMP-2 in early stage and advanced tumors, but there was no correlation between MMP-2 protein expression and histological type, differentiation degree, infiltration level, lymph node involvement or liver invasion. Although no difference was observed between TIMP-2 expression and histological type or differentiation degree, significant difference was found between TIMP-2 expression and different Nevin stage, infiltration level, local lymph node involvement or liver invasion (1.168+/-0.067 vs 1.048+/-0.075, 1.170+/-0.062 vs 1.039+/-0.069, 1.039+/-0.076 vs 1.147+/-0.083, 1.048+/-0.074 vs 1.103+/-0.095, P<0.05). MMP-2/TIMP-2 ratio did not correlate with histological type, grade of differentiation and liver invasion, but significant differences were found between MMP-2/TIMP-2 ratio and different Nevin stage, infiltration level and lymph node involvement in patients with carcinoma of gallbladder.CONCLUSION:TIMP-2 and MMP-2/TIMP-2 ratio could reflect more accurately biological characteristic of gallbladder carcinoma and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis, in the judgment of invasion or metastasis and the estimate of prognosis in patients with gallbladder carcinomas.