肝窦内皮窗孔:洞察肝脏功能的视窗

肝窦内皮细胞是肝窦结构的基础,从某种意义上,正是由于肝窦内皮细胞支撑和"分割"才有了正常的肝窦结构,由于肝窦内皮结构的存在,为肝脏与来自肠道的血液之间设置了解剖层面上的屏障,参与了肝脏物质和免疫稳态的维持.曾经我们对肝窦内皮细胞的理解仅限于一群类"毛细血管内皮"样结构,仅在肝窦结构中起骨架作用,但随着研究的深入,越来越多的证据显示肝窦内皮具有特殊的结构和功能,其中"窗孔"的存在是肝窦内皮独特的结构,直到上世纪70年代我们首次通过电子显微镜观察到窦内皮窗孔的形态,这是一群直径150~175 nm,9~13个/um2、占据窦内皮表面的6%~8%的小孔结构,在不同的肝脏区域中其直径和密度略有差异.

急性心肌梗塞患者溶栓治疗后内皮素水平变化的观察

目的：探讨急性心肌梗塞（ＡＭＩ）患者溶栓治疗后内皮素（ＥＴ）变化规律，以及溶栓后冠状动脉（冠脉）再通与未通者ＥＴ变化的异同。方法：应用放免技术和酶法分别测定了ＡＭＩ常规治疗组（２１例）和溶栓组（１９例）患者梗塞后ＥＴ和肌酸激酶同功酶（ＣＫＭＢ）的动态变化。结果：溶栓组ＥＴ较常规治疗组提前４小时达峰值，且ＥＴ值高于常规治疗组。溶栓组ＣＫＭＢ峰值时间较常规治疗组提前２小时，而ＥＴ又比ＣＫＭＢ峰值时间提前４小时。溶栓冠脉再通组于梗塞后第８和第１０小时ＥＴ值均高于未通组，Ｐ均＜０．０５。再通组ＥＴ峰值时间较未通组提前２小时。ＡＭＩ有并发症组ＥＴ峰值和最大差值分别高于无并发症组，对应值间比较，Ｐ＜０．０１和Ｐ＜０．００１。结论：ＡＭＩ时ＥＴ升高，有并发症者升高更明显，溶栓冠脉再通后ＥＴ峰值提前。提示ＥＴ可能作为冠脉再通的评价指标之一。脉）再通与未通患者ＥＴ变化特点。１资料与方法１．１研究对象：①常规治疗组：２１例中男１４例，女７例；平均年龄（６２．４±２０．７）岁。②溶栓组：１９例中男１３例，女６例；平均年龄（５８．７±１７．１）岁。根据溶栓冠脉再通临床评定标准〔１〕，将本组１９例分为再通组（１２例）和未通组（７例）?

糖尿病视网膜病变患者血浆中ET-1和降钙素基因相关肽的变化

目的 探讨糖尿病视网膜病变 (DR)患者血浆中内皮素 - 1(endothelin- 1,ET- 1)和降钙素基因相关肽 (calcitonin in gene related- peptide,CGRP)水平的变化。方法 采用放射免疫分析法 ,测定糖尿病患者 (diabetic mellitus,DM)血浆中 ET- 1和 CGRP。结果 血浆中 ET- 1的水平在 DM患者明显高于对照组 (P<0 .0 0 1) ,并随 DR的出现及加重逐渐升高。DM患者血浆中 CGRP水平明显低于对照组 (P<0 .0 0 1)。结论 ET- 1和 CGRP可能与

Pepsinogen C Gene Expression in Epithelial Cells of Rat Stomach During Development

Pepsinogens are zymogens of pepsins,aspecific proteases working as digestive enzymes in vertebrate stomach,of which biological and molecular properties have been extensively studied.Several exhaustive studies have been performed in the pepsinogen producing cells in developing rat stomachs,but little is known about the expression of pepsinogen gene in these cells.In this study,the ontogeny of pepsinogen producing cells in rat fundic glands was studied by in situ hybridization using a digoxigenin-labeled RNA probe.The rat gastric epithelium was stratified but was morphologically undifferentiated at the stage of 18.5 days of gestation.The pepsinogen mRNA was expressed both in chief cells and mucous neck cells in adult rats,which was first detected by in situ hybridization in the stomach of the rats at 3.5 days after birth.The development of pepsinogen producing cells could be classified into four stages:(1) 18.5 days of gestation to 0.5 day after birth;(2) 3.5 days to 2 weeks after birth;(3) 3～4 weeks after birth;(4) 8 weeks after birth.Pepsinogen expression is strictly limited to these cells,the distribution of which shown a developmental stage-specific manner.We concluded the pepsinogen C could offer excellent molecular markers of differentiation during stomach epithelial cellulur development.

Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo

The hepatic sinusoids are lined by a unique population of hepatic sinusoidal endothelial cells (HSEC), which is one of the first hepatic cell populations to come into contact with blood components. However, HSEC are not simply barrier cells that restrict the access of blood- borne compounds to the parenchyma. They are func- tionally specialised endothelial cells that have complex roles, including not only receptor-mediated clearance of endotoxin, bacteria and other compounds, but also the regulation of inflammation, leukocyte recruitment and host immune responses to pathogens. Thus understand- ing the differentiation and function of HSEC is critical for the elucidation of liver biology and pathophysiology. This article reviews methods for isolating and studying human hepatic endothelial cell populations using in vitro models. We also discuss the expression and functions of phe- notypic markers, such as the presence of fenestrations and expression of VAP-1, Stabilin-1, L-SIGN, which can be used to identify sinusoidal endothelium and to permit discrimination from vascular and lymphatic endothelial cells.

Expression of Livin and vascular endothelial growth factor in different clinical stages of human esophageal carcinoma

AIM： To investigate the role of Livin and vascular endothelial growth factor （VEGF） in human esophageal carcinoma, and analyze its relationship to clinical stages.METHODS： Expression of Livin in fresh esophageal cancer tissues was detected by immunohistochemistry （IHC）, Western blotting and reverse transcriptasepolyrnerase chain reaction （RT-PCR）, and VEGF by Western blotting and RT-PCR. All statistical analyses were performed by SPSS version 11.0. RESULTS： Livin positivity was also significantly correlated with tumor stages, increasing with tumor progression. Expression of Livin and VEGF increased with the process of esophageal carcinoma. In the fourth clinical stage, expression of Livin and VEGF was the most significant. Expression of Livin was positively correlated with VEGF. CONCLUSION： Over-expression of Livin and VEGF contributes to the pathogenesis of esophageal carcinoma.

STI571 (Glivec) suppresses the expression of vascular endothelial growth factor in the gastrointestinal stromal tumor cell line,GIST-T1

AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor （SCF）. Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS： Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION： Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.

Correlative studies on uPA mRNA and uPAR mRNA expression with vascular endothelial growth factor, microvessel density, progression and survival time of patients with gastric cancer

AIM： To investigate the correlations between the expression of urokinase-type plasminogen activator （uPA） mRNA, uPA receptor （uPAR） mRNA and vascular endothelial growth factor （VEGF） protein and clinicopathologic features, microvessel density （MVD） and survival time. METHODS： In situ hybridization and immuno-histochemistry techniques were used to study the expressions of uPA mRNA, uPAR mRNA, VEGF and CD34 protein in 105 gastric carcinoma specimens. RESULTS： Expressions of uPA mRNA, uPAR mRNA and VEGF protein were observed in 61 （58.1%） cases, 70 （66.7%） cases and 67 （63.8%） cases, respectively. The uPA mRNA and uPAR mRNA positive expression rates in infiltrating-type cases （73.7%, 75.4%）, stage Ⅲ- Ⅳ （72.1%, 75.4%）, vessel invasion （63.2%, 69.9%）, lymphatic metastasis （67.1%, 74.4%） and distant metastasis （88.1%, 85.7%） were significantly higher than those of the expanding-type （χ^2 = 15.57, P = 0.001; χ^2 = 6.91, P = 0.046）, stage Ⅰ-Ⅱ （χ^2 = 19.22, P = 0.001; χ^2 = 16.75, P = 0.001）, non-vessel invasion （χ^2 = 11.92, P = 0.006; χ^2 = 14.15, P = 0.002）, non- lymphatic metastasis （χ^2 = 28.41, P = 0.001; χ^2 = 22.5, P = 0.005） and non-distant metastasis （χ^2 = 12.32, P = 0.004; χ^2 = 17.42, P = 0.002; χ^2 = 11.25, P = 0.012; χ^2 = 18.12, P = 0.002）.The VEGF positive expression rates in infiltrating-type cases （75.4%）, stage Ⅲ-Ⅳ （88.5%）, vessel invasion （82.9%）, lymphatic metastasis （84.3%） and distant metastasis （95.2%） were significantly higher than those of the expanding-type （χ^2 = 9.61, P = 0.021）,stage Ⅰ-Ⅱ （χ^2 = 16.66, P = 0.001）, non-vessel invasion （χ^2 = 29.38, P = 0.001）, non-lymphatic metastasis （χ^2 = 18.68, P = 0.005）, and non-distant metastasis （χ^2 = 22.72, P = 0.007; χ^2 = 21.62, P = 0.004）. The mean MVD in the specimens positive for the uPA mRNA, uPAR mRNA and VEGF protein was markedly higher than those with negative expression groups. Moreover, a positive relation between MVD and uPA mRNA （rs = 0.199, P = 0.042）, uPAR mRNA （rs = 0.278, P = 0.035）, and VEGF （rs = 0.398, P = 0.048） expressions was observed. The mean survival time in cases with positive uPA mRNA, uPAR mRNA and VEGF protein expression or MVD value ≥54.9 was significantly shorter than those in cases with negative expression or MVD value 〈 54.9. CONCLUSION： uPA and uPAR expressions are correlated with enhanced VEGF-induced tumor angiogenesis and may play a role in invasion and nodal metastasis of gastric carcinoma, thereby serving as prognostic markers of gastric cancer.

Analysis of p53 and vascular endothelial growth factor expression in human gallbladder carcinoma for the determination of tumor vascularity

AIM： To examine the expression of p53 and vascular endothelial growth factor （VEGF） as well as microvessel count （MVC） and to investigate the role of VEGF as an angiogenic marker and the possible role of p53 in the regulation of angiogenesis in human gallbladder carcinoma. METHODS： Surgically resected specimens of 49 gallbladder carcinomas were studied by immunohistochemical staining for p53 protein, VEGF, and factor VIII-related antigen. VEGF expression and mutant p53 expression were then correlated with Nevin stage, differentiation grade, MVC, and lymph node metastasis. RESULTS： Positive p53 protein and VEGF expressions were found in 61.2% and 63.3% of tumors, respectively. p53 and VEGF staining status was identical in 55.1% of tumors. The Nevin staging of p53- or VEGF-positive tumors was significantly later than that of negative tumors. The MVC in p53- or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-negative tumors was significantly lower than that in the other subgroups. CONCLUSION： Our findings suggest that pS3-VEGF pathway can regulate tumor angiogenesis in human gallbladder carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the tumor vascularity of gallbladder cancer.

Clinical significance of the expression of isoform 165 vascular endothelial growth factor mRNA in noncancerous liver remnants of patients with hepatocellular carcinoma

AIM: To investigate the prognostic role of isoform 165 vascular endothelial growth factor messenger RNA (VEGF165 mRNA)in noncancerous liver tissues from patients with primary hepatocellular carcinoma (HCC).METHODS: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA was determined prospectively in noncancerous liver tissues from 60 consecutive patients with HCC undergoing curative resection. We categorized the patients with VEGF165 mRNA over 0.500 in noncancerous liver tissues as group A, and those below 0.500 as group B.RESULTS: Among the isoforms of VEGF mRNA by multivariate analysis, a higher level of VEGF165 mRNA in noncancerous liver tissue correlated significantly with a higher risk of HCC recurrence (P = 0.039) and recurrence-related mortality (P= 0.048), but VEGF121 did not. The other significant predictors of recurrence consisted of vascular permeation (P = 0.022),daughter nodules (P = 0.033), cellular dedifferentiation (P = 0.033), an absent or incomplete capsule (P = 0.037).A significant variable of recurrence-related mortality was Vascular permeation (P= 0.012). As to the clinical manifestations of 16 patients who developed recurrence,the recurrent tumor number over 2, recurrent extent over two-liver segments, and the median survival after recurrence,all significantly correlated with group A patients (P = 0.043,0.043, and 0.048, respectively). However, the presence of extrahepatic metastasis was not (P＞0.05). The difference in recurrence after treatment between the two groups had no statistical significance (P＞0.05).CONCLUSION: The higher expression of isoform VEGF165mRNA in noncancerous liver remnant of patients with HCC may be a significant biological indicator of the invasiveness of postoperative recurrence.

Significance of VEGF and NF-κB Expression in Thyroid Carcinoma

OBJECTIVE To investigate the significance of vascular endothelial growth factor (VEGF) and nuclear factor-kappaB (NF-κB) expression in thyroid carcinoma. METHODS The expression of NF-κB and VEGF was determined by im- munohistochemistry in formalin-fixed and paraffin-embedded specimens obtained from 10 normal thyroid tissues (NT), 12 cases of thyroid adeno- ma (TA) and 68 cases of thyroid carcinoma (TC).Differences in expres- sion between NT, TA and TC were statistically analyzed. In addition, in cases of TC, the relationship of NF-κB and VEGF expression with various clinicopathological factors, including histological typing, clinical staging and lymph node metastasis, as well as the correlation between N F - κ B and VEGF expression was examined. RESULTS In contrast to the negative immunoreactivity for VEGF in NT, there was a significantly higher positive incidence (PI) in TA (41.7%, P= 0.040) and TC (75.0%, P<0.001), and a significant difference between TA and TC (P=0.036). Immunoreactivity for NF-κB in NT was negative and significantly higher in TC (63.2%, P<0.001),but not in TA (16.7%, P= 0.481). However the PI difference between TA and TC (P=0.003) was significant. Between the histological types of TC, a significantly higher PI was found in undifferentiated thyroid carcinoma (UTC),namely,100% for VEGF and 90.0% for NF-κB. We also found significant positive relation- ships of VEGF and N F - κ B expression with the clinical stage and lymph node metastasis. Furthermore, a significant positive correlation between VEGF and NF-κB expression in TC was observed. CONCLUSION Our data showed that the expression of VEGF and NF- ΚB/P65 was greater in TC and UTC, and documented their significant positive correlations with the clinical stage and lymph node metastasis in TC. In addition there was a significant positive relationship between their expression, suggesting that they have important roles in TC and that they may be potential targets for gene therapy in TC patients.

Activation of STAT3 signaling in human stomach adenocarcinoma drug-resistant cell line and its relationship with expression of vascular endothelial growth factor

AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STATS protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.

Upregulation of hypoxia inducible factor 1α mRNA is associated with elevated vascular endothelial growth factor expression and excessive angiogenesis and predicts a poor prognosis in gastric carcinoma

AIM： To investigate the implication of the hypoxia inducible factor HIF-1α mRNA in gastric carcinoma and its relation to the expression of vascular endothelial growth factor （VEGF） protein, tumor angiogenesis invasion/metastasis and the patient＇s survival. METHODS： In situ hybridization was used to examine expression of HIF-1α mRNA, and immunohistochemical staining was used to examine expression of VEGF protein and CD34 in 118 specimens from patients with gastric carcinoma. RESULTS： The positive rates of HIF-1α mRNA and VEGF protein were 49.15% and 55.92%, respectively. Positive expressions of HIF-1α and VEGF in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis were dramatically stronger than stage T1-T2 cases and those without vessel invasion, lymph node metastasis and distant metastasis. The mean microvascular density （MVD） in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis was significantly higher than stage T1-T2 tumors and those without vessel invasion, lymph node metastasis and distant metastasis. The mean MVD in tumors with positive HIF-1α and VEGF expression was significantly higher than that in tumors with negative HIF-1α and VEGF expression. The expression of HIF- 1α was positively correlated with VEGF protein. There were positive correlations between MVD and expression of HIF-1α and VEGF. The mean survival time and the S-year survival rate in cases with positive expression HIF-1α and VEGF and MVD value ≥ 41.5/0.72 mm^2 were significantly lower than those with negative expression of HIF-1α and VEGF and MVD value 〈 41.5/0.72 mm^2. CONCLUSION： Overexpression of HIF-1α is found in gastric carcinoma. HIF-1α may induce the angiogenesis in gastric carcinoma by upregulating the transcription of VEGF gene, and take part in tumor invasion and metastasis. They can be used as prognostic markers of gastric cancer in clinical practice.

Involvement of gene expressions in apoptosis of vascularendothelial cells induced by rattlesnake venom

Formation of apoptotic bodies is a typical character ofaPoptotic cell death, but how the processes are controlledis not known. In this study, we compared two apoptosisinducing systems in vascular endothelial cells (VEC). Wefound that the formation of aPoptotic bodies during apop-tosis induced by rattlesnake venom, which is an unique andspecific aPoptosis inducer to vascular endotheliaI cells, wasmuch faster than that induced by deprivation of survivalfactors (aFGF and serum). When we blocked the synthesisof mRNAs in cells treated with rattlesnake venom by DRB(5, 6- dichloro- 1 -β- D- rib ofur anosylb enzimidazole ), an in-hibitor of transcription, the formation of aPoptotic bodieswas dramatically inhibited. We examined the expressionof Psa gene and found that its expression was much higherin apoptosis induced by rattlesnake venom than that inaPoptosis induced by deprivation of aFGF and serum. Ourresults suggest that gene expression is important and P53gene may play a major role in inducing the formation ofapoptotic bodies in VEC.

Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

AIM： Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS： Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase （FAK） activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS： Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION： Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

Effects of endostatin on expression of vascular endothelial growth factor and its receptors and neovascularization in colonic carcinoma implanted in nude mice

AIM:To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS:Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups.Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested,the tumor volumes were determined,and the expressions of CD34,VEGF and FIk-1 were examined by immunohistochemical method. RESULTS:Tumor volume was significantly inhibited in the endostatin group(84.17%)and tumor weight was significantly inhibited in the endostatin group(0.197±0.049) compared to the control group(1.198±0.105)(F=22.56, P=0.001),microvessel density(MVD)was significantly decreased in the treated group(31.857±3.515)compared to the control group(100.143±4.290)(F=151.62,P<0.001). Furthermore,the expression of FIk-1 was significantly inhibited in the treated group(34.29%) ompared to the control group(8.57%)(X^2=13.745,P=0.001).However no significant decrease was observed in the expression of vascular endothelial growth factor(VEGF)between these two groups(X^2=0.119,P=0.730). CONCLUSION:Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway.This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.

Expression and correlation of CD44v6, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 in Krukenberg tumor

AIM： To explore the expression and correlation of CD44v6, vascular endothelial growth factor （VEGF）, matrix metalloproteinase （MMP）-2 and matrix metalloproteinase （MMP）-9 in Krukenberg and primary epithelial ovarian carcinoma. METHODS： The expressions of CD44v6, VEGF, MMP-2 and MMP-9 were detected by immunohistochemical method in 20 cases of normal ovarian tissues, 38 cases of Krukenberg tumor and 45 cases of primary epithelial ovarian carcinoma. RESULTS： The expression of CD44v6 （primary epithelial ovarian carcinoma tissue vs normal ovarian tissue： χ^2= 4.516, P= 0.034; Krukenberg tumor tissue vsnormal ovarian tissue： χ^2 = 19.537, P = 0.001） and VEGF （primary epithelial ovarian carcinoma tissue vs normal ovarian tissue： P = 0.026; Krukenberg tumor tissue vs normal ovarian tissue： χ^2 = 22.895, P = 0.001） was significantly higher in primary epithelial ovarian carcinoma tissue and Krukenberg tumor tissue than in normal ovarian tissue. The positive expression rate of MMP-2 and MMP-9 was 0% in the normal ovarian tissue. The positive expression rate of CD44v6 （ χ^2= 10.398, P= 0.001）, VEGF （ χ^2= 13.149, P = 0.001）, MMP-2 （ χ^2 = 33.668, P = 0.001） and MMP-9 （ χ^2= 38.839, P = 0.001） was remarkably higher in Krukenberg tumor than in primary epithelial ovarian carcinoma. The correlation of CD44v6, VEGF, MMP-2, and MMP-9 was observed in primary epithelial ovarian carcinoma and Krukenberg tumor. CONCLUSION： CD44v6, VEGF, MMP-2, and MMP-9 are involved in ovarian carcinoma, gastric cancer and Krukenberg tumor. Detection of CD44v6, VEGF, MMP-2 and MMP-9 may contribute to the diagnosis of ovarian carcinoma, gastric cancer, and Krukenberg tumor.

Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.