BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angioge...BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastas展开更多
Objectives To determine the pre-therapeutic serum level of vascular endothelial growth factor (VEGF) in patients with hepatocellular carcinoma (HCC) and to elucidate the relation between the serum level and clinical ...Objectives To determine the pre-therapeutic serum level of vascular endothelial growth factor (VEGF) in patients with hepatocellular carcinoma (HCC) and to elucidate the relation between the serum level and clinical characteristics and metastasis of HCC. Methods One-hundred and fifteen HCC patients, 40 patients with benign liver lesions, and 30 healthy control subjects were included in this study. The serum VEGF level was measured with the quantitative sandwich enzyme linked immunosorbent assay (ELISA, R&D systems). Results The serum VEGF levels in the HCC group (465.62±336.24 pg/ml) was significantly elevated as compared with those in patients with benign liver lesions (159.54±120.58 pg/ml) and those in normal controls (123.53±51.84 pg/ml). The VEGF levels were not significantly different between the patients with benign liver lesions and the normal controls. The serum VEGF levels showed a positive rate of 77.4%, 25%, and 3.3% in the HCC patients, benign liver lesion patients and normal controls, respectively. In the 115 HCC patients, the serum VEGF levels in patients with portal vein (PV) emboli (n=26, 582.76±441.89 pg/ml), with metastasis (n=43, 548.29±438.57 pg/ml) or with large HCC lesions (≥5 cm in diameter) (n=69, 554.43±369.99 pg/ml) were significantly higher than those without PV-emboli (n=89, 431.39±292.84 pg/ml), without metastasis (n=72, 416.24±247.27 pg/ml) or with small HCC lesions (n=42, 328.67±227.47 pg/ml). The serum VEGF levels in stage Ⅰ, Ⅱ, Ⅲ, Ⅳa and Ⅳb HCC patients were 340.6 pg/ml, 451.55±307.84 pg/ml, 397.44±257.18 pg/ml, 486.10±397.73 pg/ml and 647.93±344.56 pg/ml, respectively. Conclusion The pre-therapeutic serum VEGF levels in HCC patients appear to reflect the disease’s potential activity of vascular invasion and metastasis.展开更多
AIM: To study the expression of hypoxia-inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival. METHODS: Express...AIM: To study the expression of hypoxia-inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival. METHODS: Expressions of HIF-1α, VEGF and microvessel density (MVD) are studied through immunohistochemistry in 36 cases of HCC and the corresponding paraneoplastic tissue and 6 cases of normal liver tissue. The relationship of the expressions of HIF-1α and VEGF with the clinicopathological data and survival are analyzed. RESULTS: The positive rate of VEGF in HCC was 32/36, which is significantly higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of HIF-1aaaaaa in HCC tissue is 24/36, also higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of VEGF and HIF-1α in HCC with microscopic venous invasion is significantly higher than that in HCC without microscopic venous invasion (P<0.05). Spearman correlation analysis does not only show the expression of HIF-1α as correlated with the expression of VEGF (rs = 0.459, P<0.01), but it also shows the expression of HIF-1α and VEGF as correlated with MVD (rs=0.412 and 0.336, respectively, P<0.05). The differences of the survival rates among VEGF positive group and VEGF negative group are significant (P<0.05), whereas the differences of the survival rates among the HIF-1α negative group and positive group are not significant (P>0.05). CONCLUSION: HIF-1α plays important roles in neovascularization in HCC possibly through regulation of VEGF transcription.展开更多
AIM To investigate the correlation of iodine concentration(IC) generated by spectral computed tomography(CT) with micro-vessel density(MVD) and vascular endothelial growth factor(VEGF) expression in patients with adva...AIM To investigate the correlation of iodine concentration(IC) generated by spectral computed tomography(CT) with micro-vessel density(MVD) and vascular endothelial growth factor(VEGF) expression in patients with advanced gastric carcinoma(GC).METHODS Thirty-four advanced GC patients underwent abdominal enhanced CT in the gemstone spectral imaging mode. The IC of the primary lesion in the arterial phase(AP) and venous phase(VP) were measured, and were then normalized against that in the aorta to provide the normalized IC(nI C). MVD and VEGF were detected by immunohistochemical assays, using CD34 and VEGF-A antibodies, respectively. Correlations of nI C with MVD, VEGF, and clinical-pathological features were analyzed.RESULTS Both nI Cs correlated linearly with MVD and were higher in the primary lesion site than in the normal control site, but were not correlated with VEGF expression. After stratification by clinical-pathological subtypes, nI C-AP showed a statistically significant correlation with MVD, particularly in the group with tumors at stage T4, without nodular involvement, of a mixed Lauren type, where the tumor was located at the antrum site, and occurred in female individuals. nI C-VP showed a positive correlation with MVD in the group with the tumor at stage T4 and above, had nodular involvement, was poorly differentiated, was located at the pylorus site, of a mixed and diffused Lauren subtype, and occurred in male individuals. nI C-AP and nI C-VP showed significant differences in terms of histological differentiation and Lauren subtype.CONCLUSION The IC detected by spectral CT correlated with the MVD. n IC-AP and n IC-VP can reflect angiogenesis in different pathological subgroups of advanced GC.展开更多
AIM: To investigate the inhibitory effect of As2O3 on angiogenesis of tumor and expression of vascular endothelial growth factor (VEGF) in tumor cells in vivo and in vitro. METHODS: The solid tumor model was formed in...AIM: To investigate the inhibitory effect of As2O3 on angiogenesis of tumor and expression of vascular endothelial growth factor (VEGF) in tumor cells in vivo and in vitro. METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As2O3 was injected into the arsenic-treated groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected into the control group. Microvessel density (MVD) and expression of VEGF were detected with immunofluorescence laser confocal technology. Further expression of VEGF protein and VEGF mRNA was measured with Western bloting and fluorescence quantitative RT- PCR in SGC-7901 cells treated with As2O3. RESULTS: In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As2O3 respectively, about 50% and 30% tumor growth inhibition were observed correspondingly (P < 0.05, P < 0.05). Decrease in MVD appeared in As2O3-treated tumors compared with control group (P < 0.001, P < 0.001). MVD in tumors was significantly lower in 5 mg/kg group than in 2.5 mg/kg group (P < 0.01). The fluorescence intensity levels of VEGF in tumor cells were significantly lowered in the arsenic-treated groups (P < 0.01, P < 0.01). The fluorescence intensity level of VEGF in 5 mg/kg group was lower than that in 2.5 mg/ kg group (P < 0.01). In vitro, the expression of VEGF protein decreased in dose- and time-dependent manner after the treatment with As2O3, but in VEGF mRNA no significant difference was found between the control group and the treated groups. CONCLUSION: As2O3 can inhibit solid tumor growth by inhibiting the formation of new blood vessels. One of the mechanisms is that As2O3 can inhibit VEGF protein expression.展开更多
Objective To explore a new method for the therapy of avascular necrosis of the femoral head. Methods The recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head. The...Objective To explore a new method for the therapy of avascular necrosis of the femoral head. Methods The recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head. The expression of vascular endothelial growth factor (VEGF) was examined by RNA dot hybridization and immunohistochemical techniques. Repair of the femoral head was observed by histological and histomorphometric analysis.Results The expression of VEGF was detected in the femoral head transfected with the VEGF gene. The femoral head transfected with the VEGF gene showed a significant increase in angiogenesis 2 and 4 weeks after gene transfection and a significant increase in bone formation 6 and 8 weeks after gene transfection on histomorphometric analysis ( P <0.01).Conclusions Transfection of the VEGF gene enhances bone tissue angiogenesis. Repair of osteonecrosis could be accelerated accordingly,thus providing a potential method for therapy of osteonecrosis.展开更多
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 c...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.展开更多
Background Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hyper...Background Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension. Methods Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry. Results mPAP values were significantly higher than the control values after 7days of hypoxia [(18.4±0.4) mmHg, P<0.05]. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1α protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1α protein was markedly increased by day 3 (0.20±0.02, P<0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1α mRNA increased significantly after day 14 of hypoxia (0.20±0.02, P<0.05). VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15±0.02, P<0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1α mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1α mRNA was positively correlated with VEGF mRNA and protein (P<0.01). Conclusion HIF-1α and VEGF are both involved in the pathogenesis of hypoxia-induced pulm展开更多
AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing rec...AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.展开更多
ABM: Recent studies suggested that cyclooxygenase-2 (COX-2) enhances tumor angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Although COX-2 expression has been demonstrated in hepatocellular ...ABM: Recent studies suggested that cyclooxygenase-2 (COX-2) enhances tumor angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Although COX-2 expression has been demonstrated in hepatocellular carcinoma (HCC), the significance of COX-2 in progression of HCC remains unclear. This study evaluated the clinico-pathological correlation of COX-2 level and its relationship with VEGF level in HCC. METHODS: Fresh tumor tissues were obtained from 100 patients who underwent resection of HCC. COX-2 protein expression was examined by immunohistochemistry, and quantitatively by an enzyme immunometric assay (EIA) of tumor cytosolic COX-2 levels. Tumor cytosolic VEGF levels were measured by an ELISA. RESULTS: Immunostaining showed expression of COX-2 in tumor cells. Tumor cytosolic COX-2 levels correlated with VEGF levels (r = 0.469,P<0.001). Correlation with clinicopathological features showed significantly higher tumor cytosolic COX-2 levels in the presence of multiple tumors (P = 0.027), venous invasion (P = 0.030), microsatellite lesions (P=0.037) and advanced tumor stage (P = 0.008). Higher tumor cytosolic COX-2 levels were associated with worse patient survival. CONCLUSION: This study shows that elevated tumor COX-2 levels correlate with elevated VEGF levels and invasiveness in HCC, suggesting that COX-2 plays a significant role in the progression of HCC.展开更多
AIM: To test the hypothesis to block VEGF expression of SMMC-7721 hepatoma cells may inhibit tumor growth using the rat hepatoma model. METHODS: Amplify the 200 VEGF cDNA fragment and insert it into human U6 gene cass...AIM: To test the hypothesis to block VEGF expression of SMMC-7721 hepatoma cells may inhibit tumor growth using the rat hepatoma model. METHODS: Amplify the 200 VEGF cDNA fragment and insert it into human U6 gene cassette in the reverse orientation transcribing small antisense RNA which could specifically interact with VEGF165, and VEGF121 mRNA. Construct the retroviral vector containing this antisense VEGF U6 cassette and package the replication-deficient recombinant retrovirus. SMMC-7721 cells were transduced with these virus and positive clones were selected with G418. PCR and Southern blot analysis were performed to determine if U6 cassette integrated into the genomic DNA of positive clone. Transfected tumor cells were evaluated for RNA expression by ribonuclease protection assays. The VEGF protein in the supernatant of parental tumor cells and genetically modified tumor cells was determined with ELISA. In vitro and in vivo growth properties of antisense VEGF cell clone in nude mice were analyzed. RESULTS: Restriction enzyme digestion and PCR sequencing verified that the antisense VEGF RNA retroviral vector was successfully constructed.After G418 selection, resistant SMMC-7721 cell clone was picked up. PCR and Southern blot analysis suggested that U6 cassette was integrated into the cell genomic DNA. Stable SMMC-7721 cell clone transduced with U6 antisense RNA cassette could express 200 bp small antisense VEGF RNA and secrete reduced levels of VEGF in culture condition. Production of VEGF by antisense transgene-expressing cells was 65+/-10 ng/L per 10(6) cells, 42045 ng/L per 10(6) cells in sense group and 485+/-30 ng/L per 10(6) cells in the negative control group, (P【 0.05). The antisense-VEGF cell clone appeared phenotypically indistinguishable from SMMC-7721 cells and SMMC-7721 cells transfected sense VEGF. The growth rate of the antisense-VEGF cell clone was the same as the control cells. When S.C. was implanted into nude mice, growth of antisense-VEGF cell lines was greatly inhibited compared with co展开更多
Background Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1α and vascular endo...Background Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1α and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1α and VEGF play important roles in tumor angiogenesis. Methods HIF-1α mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1α and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1α protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD_ 34 immunostaining in colorectal carcinomas. Results Optical density values representing HIF-1α mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P<0.05) or in hypoxic conditions but treated with genistein (P<0.05). The levels of HIF-1α and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P<0.01, P<0.05, respectively) and hypoxia/genistein group (P<0.01, P<0.05, respectively). The positive expression rates of HIF-1α mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes’ stages (P<0.05). HIF-1α mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P<0.01). HIF-1α protein expression correlated significantly with VEGF protein expression and MVD.Conclusions Hypoxia induces the expression of HIF-1α and VEGF in colorectal adenocarcinomas. HIF-1α may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.展开更多
Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） including its protein, ligands, expression and pathophysiological significance. Data sources Inform...Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED （1997-2006） online resources using the key term LOX-1. Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. Results The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed. Conclusions Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.展开更多
Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS be...Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.展开更多
Objective： To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus （T2DM） rats and the effects of Panax Quinquefolius Saponin （PQS） of stem and leaf. Met...Objective： To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus （T2DM） rats and the effects of Panax Quinquefolius Saponin （PQS） of stem and leaf. Methods： The T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin （STZ, 35 mg/kg） plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose （SHG） group and fluctuant high blood glucose （FHG） group according to fasting blood glucose coefficient of variation （FBG-CV）, and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose： PQS 30 mg/（kg·d） group, PQS 60 mg/（kg·d） group, metformin hydrochloride control （MHC） group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control （NOR） group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor （HGF）, and serum nitric oxide （NO）, endothelin-1 （ET-1）, tumor necrosis factor α （TNF-α）, and soluble intercellular adhesion molecule 1 （slCAM-1） were measured. Results： In comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and slCAM-1 in SHG and FHG control groups were all significantly increased （P〈0.01）; in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and slCAM-1 in FHG group were all significantly increased further （P〈0.01 or P〈0.05）; meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF- α, and slCAM-1 in PQS and MHC groups were all decreased significantly （P〈0.01）. However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment. Conclusion： Blood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothel展开更多
AIM: To investigate the effect and mechanism of blockade of the CXC chemokine receptor-4 (CXCR4) signaling pathway by AMD3100, a small non-peptide CXCR4 inhibitor, on invasion and metastasis of colorectal cancer cells...AIM: To investigate the effect and mechanism of blockade of the CXC chemokine receptor-4 (CXCR4) signaling pathway by AMD3100, a small non-peptide CXCR4 inhibitor, on invasion and metastasis of colorectal cancer cells in vitro. METHODS: Human colorectal cancer cell line SW480 was treated with AMD3100 at different final concentrations. 3-(4,5-dimethylthiazole-2-yl)-2.5-dipheny-ltetrazolium bromide (MTT) assay was used to detect the effect of AMD3100 on cell proliferation. The invasion ability of SW480 cells was determined by cell invasion assay kit. In the presence of AMD3100, the CXCL12-mediated migratory response of SW480 cells was tested by classical chemotaxis assays. RT-PCR analysis and Western blotting were used to detect the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in SW480 cells. RESULTS: Cell viability was significantly suppressed by AMD3100 in a dose-dependent manner. AMD3100 (100 and 1000 ng/mL) significantly inhibited the invasion ability of SW480 cells. Treatment with AMD3100 markedly reduced the expression of VEGF and MMP-9 but not MMP-2 in SW480 cells. CONCLUSION: The CXCL12/CXCR4 system is an important mediator of proliferation and invasion of CXCR4-expressing colorectal cancer cells. AMD3100 inhibited invasion and metastasis activity of the colorectalcancer cell line SW480 through down-regulation of VEGF and MMP-9 expression.展开更多
Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the firs...Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.展开更多
基金This study was supported in part by grant from the KeyProject Foundation of Medical Sciences of Jiangsu province(RC2003100)
文摘BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastas
文摘Objectives To determine the pre-therapeutic serum level of vascular endothelial growth factor (VEGF) in patients with hepatocellular carcinoma (HCC) and to elucidate the relation between the serum level and clinical characteristics and metastasis of HCC. Methods One-hundred and fifteen HCC patients, 40 patients with benign liver lesions, and 30 healthy control subjects were included in this study. The serum VEGF level was measured with the quantitative sandwich enzyme linked immunosorbent assay (ELISA, R&D systems). Results The serum VEGF levels in the HCC group (465.62±336.24 pg/ml) was significantly elevated as compared with those in patients with benign liver lesions (159.54±120.58 pg/ml) and those in normal controls (123.53±51.84 pg/ml). The VEGF levels were not significantly different between the patients with benign liver lesions and the normal controls. The serum VEGF levels showed a positive rate of 77.4%, 25%, and 3.3% in the HCC patients, benign liver lesion patients and normal controls, respectively. In the 115 HCC patients, the serum VEGF levels in patients with portal vein (PV) emboli (n=26, 582.76±441.89 pg/ml), with metastasis (n=43, 548.29±438.57 pg/ml) or with large HCC lesions (≥5 cm in diameter) (n=69, 554.43±369.99 pg/ml) were significantly higher than those without PV-emboli (n=89, 431.39±292.84 pg/ml), without metastasis (n=72, 416.24±247.27 pg/ml) or with small HCC lesions (n=42, 328.67±227.47 pg/ml). The serum VEGF levels in stage Ⅰ, Ⅱ, Ⅲ, Ⅳa and Ⅳb HCC patients were 340.6 pg/ml, 451.55±307.84 pg/ml, 397.44±257.18 pg/ml, 486.10±397.73 pg/ml and 647.93±344.56 pg/ml, respectively. Conclusion The pre-therapeutic serum VEGF levels in HCC patients appear to reflect the disease’s potential activity of vascular invasion and metastasis.
文摘AIM: To study the expression of hypoxia-inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival. METHODS: Expressions of HIF-1α, VEGF and microvessel density (MVD) are studied through immunohistochemistry in 36 cases of HCC and the corresponding paraneoplastic tissue and 6 cases of normal liver tissue. The relationship of the expressions of HIF-1α and VEGF with the clinicopathological data and survival are analyzed. RESULTS: The positive rate of VEGF in HCC was 32/36, which is significantly higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of HIF-1aaaaaa in HCC tissue is 24/36, also higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of VEGF and HIF-1α in HCC with microscopic venous invasion is significantly higher than that in HCC without microscopic venous invasion (P<0.05). Spearman correlation analysis does not only show the expression of HIF-1α as correlated with the expression of VEGF (rs = 0.459, P<0.01), but it also shows the expression of HIF-1α and VEGF as correlated with MVD (rs=0.412 and 0.336, respectively, P<0.05). The differences of the survival rates among VEGF positive group and VEGF negative group are significant (P<0.05), whereas the differences of the survival rates among the HIF-1α negative group and positive group are not significant (P>0.05). CONCLUSION: HIF-1α plays important roles in neovascularization in HCC possibly through regulation of VEGF transcription.
基金Supported by the National Natural Science Foundation of China,No.81271573
文摘AIM To investigate the correlation of iodine concentration(IC) generated by spectral computed tomography(CT) with micro-vessel density(MVD) and vascular endothelial growth factor(VEGF) expression in patients with advanced gastric carcinoma(GC).METHODS Thirty-four advanced GC patients underwent abdominal enhanced CT in the gemstone spectral imaging mode. The IC of the primary lesion in the arterial phase(AP) and venous phase(VP) were measured, and were then normalized against that in the aorta to provide the normalized IC(nI C). MVD and VEGF were detected by immunohistochemical assays, using CD34 and VEGF-A antibodies, respectively. Correlations of nI C with MVD, VEGF, and clinical-pathological features were analyzed.RESULTS Both nI Cs correlated linearly with MVD and were higher in the primary lesion site than in the normal control site, but were not correlated with VEGF expression. After stratification by clinical-pathological subtypes, nI C-AP showed a statistically significant correlation with MVD, particularly in the group with tumors at stage T4, without nodular involvement, of a mixed Lauren type, where the tumor was located at the antrum site, and occurred in female individuals. nI C-VP showed a positive correlation with MVD in the group with the tumor at stage T4 and above, had nodular involvement, was poorly differentiated, was located at the pylorus site, of a mixed and diffused Lauren subtype, and occurred in male individuals. nI C-AP and nI C-VP showed significant differences in terms of histological differentiation and Lauren subtype.CONCLUSION The IC detected by spectral CT correlated with the MVD. n IC-AP and n IC-VP can reflect angiogenesis in different pathological subgroups of advanced GC.
基金Supported by the Science Fund of the Second Affiliated Hospital of Medical College, No. 2003-YL-35
文摘AIM: To investigate the inhibitory effect of As2O3 on angiogenesis of tumor and expression of vascular endothelial growth factor (VEGF) in tumor cells in vivo and in vitro. METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As2O3 was injected into the arsenic-treated groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected into the control group. Microvessel density (MVD) and expression of VEGF were detected with immunofluorescence laser confocal technology. Further expression of VEGF protein and VEGF mRNA was measured with Western bloting and fluorescence quantitative RT- PCR in SGC-7901 cells treated with As2O3. RESULTS: In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As2O3 respectively, about 50% and 30% tumor growth inhibition were observed correspondingly (P < 0.05, P < 0.05). Decrease in MVD appeared in As2O3-treated tumors compared with control group (P < 0.001, P < 0.001). MVD in tumors was significantly lower in 5 mg/kg group than in 2.5 mg/kg group (P < 0.01). The fluorescence intensity levels of VEGF in tumor cells were significantly lowered in the arsenic-treated groups (P < 0.01, P < 0.01). The fluorescence intensity level of VEGF in 5 mg/kg group was lower than that in 2.5 mg/ kg group (P < 0.01). In vitro, the expression of VEGF protein decreased in dose- and time-dependent manner after the treatment with As2O3, but in VEGF mRNA no significant difference was found between the control group and the treated groups. CONCLUSION: As2O3 can inhibit solid tumor growth by inhibiting the formation of new blood vessels. One of the mechanisms is that As2O3 can inhibit VEGF protein expression.
基金ThisstudywassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No 3 0 170 945 )
文摘Objective To explore a new method for the therapy of avascular necrosis of the femoral head. Methods The recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head. The expression of vascular endothelial growth factor (VEGF) was examined by RNA dot hybridization and immunohistochemical techniques. Repair of the femoral head was observed by histological and histomorphometric analysis.Results The expression of VEGF was detected in the femoral head transfected with the VEGF gene. The femoral head transfected with the VEGF gene showed a significant increase in angiogenesis 2 and 4 weeks after gene transfection and a significant increase in bone formation 6 and 8 weeks after gene transfection on histomorphometric analysis ( P <0.01).Conclusions Transfection of the VEGF gene enhances bone tissue angiogenesis. Repair of osteonecrosis could be accelerated accordingly,thus providing a potential method for therapy of osteonecrosis.
文摘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.
文摘Background Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension. Methods Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry. Results mPAP values were significantly higher than the control values after 7days of hypoxia [(18.4±0.4) mmHg, P<0.05]. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1α protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1α protein was markedly increased by day 3 (0.20±0.02, P<0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1α mRNA increased significantly after day 14 of hypoxia (0.20±0.02, P<0.05). VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15±0.02, P<0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1α mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1α mRNA was positively correlated with VEGF mRNA and protein (P<0.01). Conclusion HIF-1α and VEGF are both involved in the pathogenesis of hypoxia-induced pulm
文摘AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.
基金Supported by the Sun C.Y. Research Foundation for Hepatobiliary and Pancreatic Surgery of the University of Hong Kong
文摘ABM: Recent studies suggested that cyclooxygenase-2 (COX-2) enhances tumor angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Although COX-2 expression has been demonstrated in hepatocellular carcinoma (HCC), the significance of COX-2 in progression of HCC remains unclear. This study evaluated the clinico-pathological correlation of COX-2 level and its relationship with VEGF level in HCC. METHODS: Fresh tumor tissues were obtained from 100 patients who underwent resection of HCC. COX-2 protein expression was examined by immunohistochemistry, and quantitatively by an enzyme immunometric assay (EIA) of tumor cytosolic COX-2 levels. Tumor cytosolic VEGF levels were measured by an ELISA. RESULTS: Immunostaining showed expression of COX-2 in tumor cells. Tumor cytosolic COX-2 levels correlated with VEGF levels (r = 0.469,P<0.001). Correlation with clinicopathological features showed significantly higher tumor cytosolic COX-2 levels in the presence of multiple tumors (P = 0.027), venous invasion (P = 0.030), microsatellite lesions (P=0.037) and advanced tumor stage (P = 0.008). Higher tumor cytosolic COX-2 levels were associated with worse patient survival. CONCLUSION: This study shows that elevated tumor COX-2 levels correlate with elevated VEGF levels and invasiveness in HCC, suggesting that COX-2 plays a significant role in the progression of HCC.
基金Project supported by National Natural Science Foundation of China,No.863 Z2001-04
文摘AIM: To test the hypothesis to block VEGF expression of SMMC-7721 hepatoma cells may inhibit tumor growth using the rat hepatoma model. METHODS: Amplify the 200 VEGF cDNA fragment and insert it into human U6 gene cassette in the reverse orientation transcribing small antisense RNA which could specifically interact with VEGF165, and VEGF121 mRNA. Construct the retroviral vector containing this antisense VEGF U6 cassette and package the replication-deficient recombinant retrovirus. SMMC-7721 cells were transduced with these virus and positive clones were selected with G418. PCR and Southern blot analysis were performed to determine if U6 cassette integrated into the genomic DNA of positive clone. Transfected tumor cells were evaluated for RNA expression by ribonuclease protection assays. The VEGF protein in the supernatant of parental tumor cells and genetically modified tumor cells was determined with ELISA. In vitro and in vivo growth properties of antisense VEGF cell clone in nude mice were analyzed. RESULTS: Restriction enzyme digestion and PCR sequencing verified that the antisense VEGF RNA retroviral vector was successfully constructed.After G418 selection, resistant SMMC-7721 cell clone was picked up. PCR and Southern blot analysis suggested that U6 cassette was integrated into the cell genomic DNA. Stable SMMC-7721 cell clone transduced with U6 antisense RNA cassette could express 200 bp small antisense VEGF RNA and secrete reduced levels of VEGF in culture condition. Production of VEGF by antisense transgene-expressing cells was 65+/-10 ng/L per 10(6) cells, 42045 ng/L per 10(6) cells in sense group and 485+/-30 ng/L per 10(6) cells in the negative control group, (P【 0.05). The antisense-VEGF cell clone appeared phenotypically indistinguishable from SMMC-7721 cells and SMMC-7721 cells transfected sense VEGF. The growth rate of the antisense-VEGF cell clone was the same as the control cells. When S.C. was implanted into nude mice, growth of antisense-VEGF cell lines was greatly inhibited compared with co
基金ThisstudywassupportedbytheFundforKeyTechnologiesRandDProgrammeofHubeiProvince (No 2 0 0 3AA3 0 1CO3 )
文摘Background Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1α and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1α and VEGF play important roles in tumor angiogenesis. Methods HIF-1α mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1α and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1α protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD_ 34 immunostaining in colorectal carcinomas. Results Optical density values representing HIF-1α mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P<0.05) or in hypoxic conditions but treated with genistein (P<0.05). The levels of HIF-1α and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P<0.01, P<0.05, respectively) and hypoxia/genistein group (P<0.01, P<0.05, respectively). The positive expression rates of HIF-1α mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes’ stages (P<0.05). HIF-1α mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P<0.01). HIF-1α protein expression correlated significantly with VEGF protein expression and MVD.Conclusions Hypoxia induces the expression of HIF-1α and VEGF in colorectal adenocarcinomas. HIF-1α may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.
文摘Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED （1997-2006） online resources using the key term LOX-1. Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. Results The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed. Conclusions Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.
基金Supported by National Natural Science Foundation of China,No.81570555 and No.81770582
文摘Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.
基金Supported by the National Natural Science Foundation of China(No.81041038)
文摘Objective： To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus （T2DM） rats and the effects of Panax Quinquefolius Saponin （PQS） of stem and leaf. Methods： The T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin （STZ, 35 mg/kg） plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose （SHG） group and fluctuant high blood glucose （FHG） group according to fasting blood glucose coefficient of variation （FBG-CV）, and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose： PQS 30 mg/（kg·d） group, PQS 60 mg/（kg·d） group, metformin hydrochloride control （MHC） group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control （NOR） group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor （HGF）, and serum nitric oxide （NO）, endothelin-1 （ET-1）, tumor necrosis factor α （TNF-α）, and soluble intercellular adhesion molecule 1 （slCAM-1） were measured. Results： In comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and slCAM-1 in SHG and FHG control groups were all significantly increased （P〈0.01）; in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and slCAM-1 in FHG group were all significantly increased further （P〈0.01 or P〈0.05）; meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF- α, and slCAM-1 in PQS and MHC groups were all decreased significantly （P〈0.01）. However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment. Conclusion： Blood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothel
文摘AIM: To investigate the effect and mechanism of blockade of the CXC chemokine receptor-4 (CXCR4) signaling pathway by AMD3100, a small non-peptide CXCR4 inhibitor, on invasion and metastasis of colorectal cancer cells in vitro. METHODS: Human colorectal cancer cell line SW480 was treated with AMD3100 at different final concentrations. 3-(4,5-dimethylthiazole-2-yl)-2.5-dipheny-ltetrazolium bromide (MTT) assay was used to detect the effect of AMD3100 on cell proliferation. The invasion ability of SW480 cells was determined by cell invasion assay kit. In the presence of AMD3100, the CXCL12-mediated migratory response of SW480 cells was tested by classical chemotaxis assays. RT-PCR analysis and Western blotting were used to detect the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in SW480 cells. RESULTS: Cell viability was significantly suppressed by AMD3100 in a dose-dependent manner. AMD3100 (100 and 1000 ng/mL) significantly inhibited the invasion ability of SW480 cells. Treatment with AMD3100 markedly reduced the expression of VEGF and MMP-9 but not MMP-2 in SW480 cells. CONCLUSION: The CXCL12/CXCR4 system is an important mediator of proliferation and invasion of CXCR4-expressing colorectal cancer cells. AMD3100 inhibited invasion and metastasis activity of the colorectalcancer cell line SW480 through down-regulation of VEGF and MMP-9 expression.
文摘Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.
