AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vas...AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vascular endothelial cells.METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density (MVD) and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy. SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 + As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry.RESULTS: The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 μmol/L, respectively. Early apoptosis in the As2O3- treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls.CONCLUSION: Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.展开更多
Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we ...Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor (VEGF) and tissue factor (TF) to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned into prokaryotic expression plasmid pQE30 with a linker. The expression product recombinant VEGF-TF (rVEGF-TF) was purified and proved to have comparable enzyme activity to a commercial TF and the capability of specific binding to tumor vessels. Significant decrease of tumor growth was found in the mice administered with rVEGF-TF on Day 6 after initiated rVEGF-TF treatment (P<0.05), and the tumor masses in 2 of 10 mice were almost disappeared on Day 14 after the first treatment. In addition, valid thrombogenesis and tumor necrosis were observed in the tumor tissues injected with rVEGF-TF. Our results demonstrate that occlusion of tumor vasculature with rVEGF-TF is potentially an effective approach for cancer therapy.展开更多
Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, trans...Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, translation, and differential cellular localization of various isoforms. Recent advances in our understanding of post-transcriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi) technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.展开更多
Spondyloarthropathies (SPA) are commonly observed extra-intestinal manifestations of both Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel diseases ([BD). However, t...Spondyloarthropathies (SPA) are commonly observed extra-intestinal manifestations of both Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel diseases ([BD). However, the immunological link between these two clinical entities is still poorly understood. Several lines of evidence indicate that SpA may originate from the relocation to the joints of the immune process primarily induced in the gut. The transfer of the intestinal inflammatory process into the joints implicates that immune cells activated in the gut-draining lymph nodes can localize, at a certain point of the intestinal disease, either into the gut or into the joints. This is indicated by the overlapping expression of adhesion molecules observed on the surface of intestinal and synovial endothelial cells during inflammation. Moreover bacterial antigens and HLA-B27 expression may be implicated in the reactivation of T cells at the articular level. Finally, accumulating evidence indicates that a T helper 17 cell-mediated immune response may contribute to IBD and IBD-related SpA with a crucial role played by tumor necrosis factor-α in CD and to a lesser extent in UC.展开更多
AIM:To investigate the expression and potential prognostic role of vascular endothelial growth factor(VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors(GEP-NETs) . METHODS:Microvessel density(MVD) in ...AIM:To investigate the expression and potential prognostic role of vascular endothelial growth factor(VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors(GEP-NETs) . METHODS:Microvessel density(MVD) in GEP-NETs was evaluated using endoglin and CD31 immunohistochemistry.In addition,tissue levels of endoglin and VEGF were determined in homogenates by ELISA. RESULTS:Endoglin was highly expressed on tumor endothelial cells.CD31 MVD in GEP-NETs was significantly higher compared to endoglin MVD(P<0.01) .Two-tofour-fold higher tissue levels of endoglin and VEGF were seen in tumors compared to associated normal tissue. This increased endoglin tissue expression in tumors was significantly related to tumor size(P<0.01) ,presence of metastases(P=0.04) ,and a more advanced tumor stage(P=0.02) ,whereas expression of VEGF was not. CONCLUSION:We suggest that endoglin is a potential marker to indicate and predict metastases,which might be useful in the post-resection therapeutic approach of patients with GEP-NETs.展开更多
A 15-year-old girl was admitted to our hospital with a 9-month history of upper abdominal pain and loss of appetite. Her history showed no indication of hepatitis. Her abdomen appeared to be even and soft, and the liv...A 15-year-old girl was admitted to our hospital with a 9-month history of upper abdominal pain and loss of appetite. Her history showed no indication of hepatitis. Her abdomen appeared to be even and soft, and the liver and spleen could not be felt below the costal margin. Percussion pain in hepatic region was negative. Gastroscopy showed no abnormalities. An abdominal ultrasound examination revealed the presence of hepatic hypoechoic areas and an abdominal CT scan showed multiple roundlike low-density masses in both hepatic lobes. The edges of the focal lesions were smooth and continuous, with a heterogeneous center, the round-like edges were enhanced, but the enhancement in the focal lesions was not obvious.展开更多
AIM: To investigate the implication of angiogenin (ANG) in the neovascularizaton and growth of human gastric carcinoma (HGC). METHODS: ANG mRNA expression in HGC specimens obtained by surgical resection from pat...AIM: To investigate the implication of angiogenin (ANG) in the neovascularizaton and growth of human gastric carcinoma (HGC). METHODS: ANG mRNA expression in HGC specimens obtained by surgical resection from patients with HGC were examined by RT-PCR. ANG, Ki-67, VEGF protein expression and microvessel density (MVD) in HGC specimens were detected by immunohistochemistry. RESULTS: RT-PCR showed significantly higher ANG mRNA expression (0.482 ± 0.094) in HGC tissues than in the surrounding nontumorous tissues (0.276 ±0.019, P = 0.03). MVD within tumorous tissues increased significantly with ANG mRNA expression (r = 0.380, P = 0.001) and ANG protein expression (P 〈 0.01). The ANG expression levels of cancer tissues were positively correlated with VEGF (P 〈 0.01) and the proliferation index of cancer cells (P 〈 0.01). CONCLUSION: ANG is one of the neovascularization factors of HGC. ANG may work in coordination with VEGF, and promote the proliferation of HGC cells.展开更多
Objective: To observe the inhibition of intracranial glioma tumorigenesis by vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotide (ODN) in rats. Methods: Totally 20 μ1 Hank's liquid containing...Objective: To observe the inhibition of intracranial glioma tumorigenesis by vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotide (ODN) in rats. Methods: Totally 20 μ1 Hank's liquid containing 1×106 C6 glioma cells was seeded into rat right caudate putaraen in high-flow microinfusion with stereotactic technique. VEGF antisense ODN was simultaneously used with glioma cell. Each rat of the treated group Ⅰ and the treated group Ⅱ was treated with 1 000 μmol/L VEGF antisense ODN. Each rat of the treated group Ⅲ and the treated group Ⅳ was treated with 2 000 μmol/L VEGF antisense ODN. The experimental periods of the treated group Ⅰ , the treated group Ⅲ and the control group Ⅰ were 2 weeks, those of the treated group Ⅱ , the treated group Ⅳ and the control group Ⅱ were 3 weeks. Before sacrifice, MRI was performed on each rat. Tumor magnitude and pathologic examination were detected after samples were dissected. Results: The survival state of all treated rats was better, and that of the control rats was in severe danger. The tumor volumes of the treated group Ⅰ and the treated group Ⅱ were remarkably lessened. Tumor tissue could not be found macroscopically in the brain samples of the treated group Ⅲ and the treated group Ⅳ, but tumor nest could be found with microscopy. Tumors of the treated group I and the treated group Ⅱ had weak expressions of VEGF mRNA and VEGF, while normal brains and the samples of the treated group Ⅲ and the treated group Ⅳ had negative expressions, but tumors of the control groups had strong expressions. Conclusion: VEGF antisense ODN used early in situ can suppress angiogenesis and growth of rat intracranial glioma to retard tumorigenesis.展开更多
OBJECTIVE To analyze the effects of cryoablation on the mice bearing Rm-I prostate cancer through detecting tumor angiogenesis and cancer cell proliferation in the mice after cryoablation, and to explore the effects o...OBJECTIVE To analyze the effects of cryoablation on the mice bearing Rm-I prostate cancer through detecting tumor angiogenesis and cancer cell proliferation in the mice after cryoablation, and to explore the effects of cryoablation on vascular endothelium growth factor (VEGF), Ki67 protein expression and microvessel density (MVD) in the mice bearing prostate cancer. METHODS Sixty Rm-1 mouse models of prostate cancer were established. Experimental mice were randomized into 2 groups: the cryoablation group (n = 30) and the control group (n = 30). After file therap)4 tumor tissues of the mice in group A and B were obtained at day 0 (without cryoablation), 1st, 3rd, 5th, 7th, 14th day, respectivelj6 after cryoablation, and the expressions of MVD, VEGF and Ki67 proteins were detected at the same time points. RESULTS The expressions of MVD, VEGF and Ki67 proteins in group A were decreased. The lowest values of the factors were detected on the 3rd day after cryoablation, and increased slowly after that. The expressions of MVD, VEGF and Ki67 proteins in the control group were not changed. Significant changes of the expressions of MVD, VEGF and Ki67 proteins in the group A were found at different time points. Correlation analysis suggested a positive correlation between the expressions of VEGF and MVD proteins (r = 0.8793), a positive correlation between the expressions of Ki67 and MVD proteins (r = 0.7614), and a positive correlation between the expressions of VEGF and ki67 proteins (r = 0.6921). CONCLUSION After argon-helium cryoablation treatment for the mice bearing prostate cancer, the expressions of MVD, VEGF and Ki67 proteins in local tumor were reduced on the 1st day. The lowest values of the factors were detected on the 3rd day after cryoablation, and then increased after that. Cryoablation combined with other modalities of treatment may effectively improve the treatment effects of cryoablation for prostate cancer.展开更多
Contrast agents are increasingly being used to characterize the vasculature in an organ of interest,to better delineate benign from malignant pathology and to aid in staging and directing therapeutic procedures.We rev...Contrast agents are increasingly being used to characterize the vasculature in an organ of interest,to better delineate benign from malignant pathology and to aid in staging and directing therapeutic procedures.We review the mechanisms of action of first,second and third generation contrast agents and their use in various endoscopic procedures in the gastrointestinal tract.Various applications of contrast-enhanced endoscopic ultrasonography include differentiating benign from malignant mediastinal lymphadenopathy,assessment of depth of invasion of esophageal,gastric and gall bladder cancers and visualization of the portal venous system and esophageal varices.In addition,contrast agents can be used to differentiate pancreatic lesions.The use of color Doppler further increases the ability to diagnose and differentiate various pancreatic malignancies.The sensitivity of power Doppler sonography to depict tumor neovascularization can be increased by contrast agents.Contrast-enhanced harmonic imaging is a useful aid in identifying the tumor vasculature and studying pancreatic microperfusion.In the future,these techniques could potentially be used to quantify tumor perfusion,to assess and monitor the efficacy of antiangiogenic agents,to assist targeted drug delivery and allow molecular imaging.展开更多
Objective: The aim of the study was to detect the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in breast benign tissues and malignant tumors to clarify the relationship between...Objective: The aim of the study was to detect the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in breast benign tissues and malignant tumors to clarify the relationship between VEGF expression, angiogenesis and breast carcinoma occurrence. Methods: The expression of VEGF and MVD in 79 cases of invasive ductal breast carcinoma, 79 corresponding para-cancer normal tissues from primary invasive breast carcinomas, 35 breast carcinoma in situ, 23 breast atypical hyperplasia and 56 breast fibroid tumor were examined by immunohistochemistry staining (SP-method). Results: The positive rate of VEGF and MVD value increased significantly with the increase of the malignant degree of breast tissues (P = 0.000). In breast carcinoma group, the positive rate of VEGF and MVD value with lymph node metastasis were higher than those without lymph node metastasis (P = 0.011 and P = 0.023). A significant higher expression of VEGF and MVD value were observed as the clinical stage increased (P = 0.035 and P = 0.012). The MVD value was higher in VEGF positive group than negative group (P = 0.000). Conclusion: The combining detection of VEGF expression and MVD is helpful for evaluating malignant degree of breast carcinoma. Angiogenesis in breast tumors and occurrence of breast carcinoma might be correlated with the expression of VEGF.展开更多
Objective: As a novel blood supply pattern, vasculogenic mimicry(VM) has attracted increasingly attention in recent years, which may partly compensate for the absence of feeding and facilitate tumor perfusion. However...Objective: As a novel blood supply pattern, vasculogenic mimicry(VM) has attracted increasingly attention in recent years, which may partly compensate for the absence of feeding and facilitate tumor perfusion. However, anti-angiogenic drugs have little effect on VM. The grape seed proanthocyanidins(GSPs), a kind of promising bioactive phytochemical, has shown anti-carcinogenesis and anti-angiogenic in several tumor models. However, GSPs regulation of VM and its possible mechanisms in a H22 hepatoma carcinoma model remain not clear. The aim of this study was to examine the effects of GSPs on proliferation and VM in a H22 hepatoma carcinoma model and to investigate the underlying mechanism. Methods: Seventy-five mice were divided into the control group and experimental groups treated with different concentration of GSPs. CD34-PAS dual staining was employed to identify the VM structure. The immunohistochemical staining for investigating the expression of VEGF, Eph A2 and MMP-2 protein was performed. Results: Treatment of the H22 model with Endostar(4 mg/kg), 50, 100, 200 mg/kg of the GSPs resulted in 6.87%, 17.81%, 27.43%, 53.52% inhibition in tumor growth, respectively. The mean weight of tumors were significantly lower in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups than in the control group(all P < 0.01). Similarly, compared with the control group, the number of VM channels were significantly reduced in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups(all P < 0.01). Immunohistochemistry showed significant decreases in the expression levels of VEGF, Eph A2 and MMP-2 protein in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups when compared with control group(all P < 0.001). Conclusion: This is the first report providing evidence that GSPs inhibit the VM structure by regulation of the VEGF/Eph A2/MMPs signaling pathway. Therefore, we concluded that GSPs has the potential of being a clinical anti-VM inhibitor.展开更多
Objective:To explore the inhibitory effect of moxibustion on tumor growth and metastasis, and also its possible mechanism, in gastric tumor-bearing rats by investigating the expressions of vascular endothelial growth ...Objective:To explore the inhibitory effect of moxibustion on tumor growth and metastasis, and also its possible mechanism, in gastric tumor-bearing rats by investigating the expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Methods:Fifty healthy Sprague-Dawley (SD) rats (half male and half female) were routinely housed for 1 week. A total of 20 rats were randomly divided into a blank group and a sham operation group, with 10 rats in each group. The remaining 30 rats were used to make gastric cancer models by implantation of ascites-type Walker-256 cancer cells. After successful modeling, rats were randomly divided into a model group, a moxibustion group and an infrared group, with 10 rats in each group. From the day of modeling, the body weight of each group was weighed every 4 days. Warm moxibustion was alternately performed at two-group acupoints [Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) in one group, and bilateral Pishu (BL 20) and Weishu (BL 21) in another group] in the moxibustion group. The body surface projection area of the stomach was irradiated with short-wave infrared rays in the infrared group, once a day, 20 min per time for 21 d. At the end of the treatment, the gastric tumor was completely dissected, and the tumor volume and tumor growth inhibition rate were calculated. Then the gastric tumor cell metastasis was recorded. The levels of VEGF and EGF in rat gastric tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA). Results:Compared with the blank group, the body weight of the model group decreased significantly after modeling (P<0.05);compared with the model group, the rats in the moxibustion group had increased body weight during the middle and late stages (bothP<0.05). The tumor volumes of rats in the moxibustion group and the infrared group were smaller than the volume in the model group (bothP<0.05). The tumor growth inhibition rate in the moxibustion group was significantly higher than that in the infrared group (P<0.05). The case number of tumor metastasis in the moxibustion group was smaller than that in the model group and the infrared group. The VEGF level in the tumor tissues of the model group was statistically significantly higher than that in the blank group (P<0.05). Compared with the model group, the VEGF levels in the moxibustion group and the infrared group were statistically significantly lower (bothP<0.05). The EGF levels in the tumor tissues of the model group was statistically significantly lower than that in the blank group (P<0.05);compared with the model group, the EGF levels in the moxibustion group and the infrared group were statistically significantly increased (bothP<0.05). Conclusion:Moxibustion can increase the body weight, inhibit the tumor growth, invasion and metastasis in gastric tumor-bearing rats, which may be related to the regulation of VEGF and EGF expressions in tumor tissues.展开更多
This paper aims to the research of the impact of fluid shear stress on the adhesion between vascular endothelial cells and leukocyte induced by tumor necrosis factor-α(TNF-α) by microfliudic chip technology.Microflu...This paper aims to the research of the impact of fluid shear stress on the adhesion between vascular endothelial cells and leukocyte induced by tumor necrosis factor-α(TNF-α) by microfliudic chip technology.Microfluidic chip was fabricated by soft lithograph; Endothelial microfluidic chip was constructed by optimizing types of the extracellular matrix proteins modified in the microchannel and cell incubation time;human umbilical vein endothelial cells EA.Hy926 lined in the microchannel were exposed to fluid shear stress of 1.68 dynes/cm^2 and 8.4 dynes/cm^2 respectively.Meanwhile,adhesion between EA.Hy926 cells and leukocyte was induced by TNF-αunder a flow condition.EA.Hy926 cell cultured in the static condition was used as control group.The numbers of fluorescently-labeled leukocyte in microchannel were counted to quantize the adhesion level between EA.Hy926 cells and leukocyte; cell immunofluorescence technique was used to detect the intercellular adhesion molecule(ICAM-1) expression.The constructed endothelial microfluidic chip can afford to the fluid shear stress and respond to exogenous stimulus of TNF-α; compared with the adhesion numbers of leukocyte in control group,adhesion between EA.Hy926 cells exposed to low fluid shear stress and leukocyte was reduced under the stimulus of TNF-α at a concentration of 10 ng/ml(P<0.05); leukocyte adhesion with EA.Hy926 cells exposed to high fluid shear stress was reduced significantly than EA.Hy926 cells in control group and EA.1Hy926 cells exposed to low fluid shear stress(P<0.01); the regulation mechanism of fluid shear stress to the adhesion between EA.Hy926 cells and leukocyte induced by TNF-αwas through the way of ICAM-1.The endothelial microfluidic chip fabricated in this paper could be used to study the functions of endothelial cell in vitro and provide a new technical platform for exploring the pathophysiology of the related cardiovascular system diseases under a flow environment.展开更多
Objective:To observe the effects of herb-partitioned moxibustion and ginger-partitioned moxibustion on the growth of colon tumors in rats with colitis-associated colon cancer(CACC),and explore the mechanism of moxibus...Objective:To observe the effects of herb-partitioned moxibustion and ginger-partitioned moxibustion on the growth of colon tumors in rats with colitis-associated colon cancer(CACC),and explore the mechanism of moxibustion intervening CACC through the purinergic receptor P2X ligand-gated ion channel 7(P2X7R)/signal transducer and activator of transcription 3(STAT3)/vascular endothelial growth factor(VEGF)pathway.Methods:A total of 26 male Sprague-Dawley rats were selected.According to the random number table method,6 rats were selected as the normal group.The remaining 20 rats were injected intraperitoneally with azoxymethane(AOM)combined with oral dextran sodium sulfate(DSS)to prepare the CACC model.After the model was successfully established,2 rats were randomly selected for model identification.The remaining 18 rats which were successfully modeled were randomly divided into a model group,a herb-partitioned moxibustion group and a ginger-partitioned moxibustion group,with 6 rats in each group.Moxibustion intervention was performed in the herb-partitioned moxibustion group and the ginger-partitioned moxibustion group at Qihai(CV 6)and bilateral Tianshu(ST 25).Moxibustion was performed twice at each point each time,once a day,at a 1-day interval after 6 consecutive interventions,for a total of 30 interventions.After intervention,the colon tumor load,pathological change and histopathological score were observed.Immunohistochemistry was used to detect the expressions of VEGF,P2X7R,phospho-STAT3(p-STAT3),and nuclear factor-kappa B p65(NF-κB p65)proteins in rat colon tissue.Western blot was used to detect the levels of p-STAT3 and NF-κB p65 proteins in rat colon tissue.Results:Compared with the normal group,the colon tumor load and histopathological score in the model group were significantly increased(both P<0.001),and different grades of dysplasia were observed in colon tissue from the model group,reaching the degree of adenocarcinoma;the expression level of P2X7R protein in colon tissue was significantly decreased(P<0.001),and the expression levels of p-STAT3,NF-κB p65 and VEGF proteins were significantly increased(all P<0.001)in the model group.Compared with the model group,the colon tumor load,colon histopathological score and the levels of p-STAT3,NF-κB p65 and VEGF proteins in colon tissue were significantly decreased(all P<0.05)in the herb-partitioned moxibustion group and the ginger-partitioned moxibustion group while the expression levels of P2X7R protein in colon tissue were significantly increased(both P<0.05).Conclusion:Both herb-partitioned moxibustion and ginger-partitioned moxibustion can reduce the colon tumor load in CACC rats and delay the progression of colon adenomas.The mechanism may be mediated by the P2X7R/STAT3 pathway to inhibit STAT3 phosphorylation,thereby reducing VEGF protein expression.展开更多
OBJECTIVE: To investigate the effects and mecha- nisms of Erbanxiao solution in inhibiting tumor an- giogenesis. METHODS: We observed the effects and mecha- nisms of Chinese medicines on inhibiting tumor an- giogene...OBJECTIVE: To investigate the effects and mecha- nisms of Erbanxiao solution in inhibiting tumor an- giogenesis. METHODS: We observed the effects and mecha- nisms of Chinese medicines on inhibiting tumor an- giogenesis and studied the theories and results of treatment. Sixty patients with lung cancer were ran- domized into two groups (n=30). Patients in the control group were given compound Kushen injec- tion, and patients in the treatment group were giv- en Erbanxiao solution. The effect of Erbanxiao solu- tion on vascular endothelium growth factor (VEGF), basic fibroblast growth factor (bFGF), and tumor ne- crosis factor-α (TNF-α) was observed. RESULTS: The effective rate of the treatment group was 60% while the control group was 36%. There was a significant difference between the twogroups (P〈0.05). VEGF, bFGF, and TNF-a levels of the two groups were significantly different before and after treatment (P〈0.01). These Traditional Chi- nese Medicines significantly inhibited tumor angio- genesis, possibly by changing levels of VEGF, bFGF, and TNF-α. CONCLUSION: It is necessary to further explore the potential of Traditional Chinese Medicine in the treatment of angiogenesis in tumor patients.展开更多
基金Supported by The Science Fund of the Second Affiliated Hospital of the Medical College,No.2003-YL-35
文摘AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vascular endothelial cells.METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density (MVD) and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy. SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 + As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry.RESULTS: The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 μmol/L, respectively. Early apoptosis in the As2O3- treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls.CONCLUSION: Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.
基金the National Natural Science Foundation of China (Nos. 30560160 and 30560048)the New Century Excellent Talents in University of China (No. NCET-05-0757)the Education Department of Hainan Province, China (No. Hjkj200422)
文摘Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor (VEGF) and tissue factor (TF) to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned into prokaryotic expression plasmid pQE30 with a linker. The expression product recombinant VEGF-TF (rVEGF-TF) was purified and proved to have comparable enzyme activity to a commercial TF and the capability of specific binding to tumor vessels. Significant decrease of tumor growth was found in the mice administered with rVEGF-TF on Day 6 after initiated rVEGF-TF treatment (P<0.05), and the tumor masses in 2 of 10 mice were almost disappeared on Day 14 after the first treatment. In addition, valid thrombogenesis and tumor necrosis were observed in the tumor tissues injected with rVEGF-TF. Our results demonstrate that occlusion of tumor vasculature with rVEGF-TF is potentially an effective approach for cancer therapy.
文摘Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, translation, and differential cellular localization of various isoforms. Recent advances in our understanding of post-transcriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi) technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.
文摘Spondyloarthropathies (SPA) are commonly observed extra-intestinal manifestations of both Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel diseases ([BD). However, the immunological link between these two clinical entities is still poorly understood. Several lines of evidence indicate that SpA may originate from the relocation to the joints of the immune process primarily induced in the gut. The transfer of the intestinal inflammatory process into the joints implicates that immune cells activated in the gut-draining lymph nodes can localize, at a certain point of the intestinal disease, either into the gut or into the joints. This is indicated by the overlapping expression of adhesion molecules observed on the surface of intestinal and synovial endothelial cells during inflammation. Moreover bacterial antigens and HLA-B27 expression may be implicated in the reactivation of T cells at the articular level. Finally, accumulating evidence indicates that a T helper 17 cell-mediated immune response may contribute to IBD and IBD-related SpA with a crucial role played by tumor necrosis factor-α in CD and to a lesser extent in UC.
基金Supported by Centre for Biomedical Genetics and Dutch Cancer Society RUL2005-3371(Hawinkels LJAC)
文摘AIM:To investigate the expression and potential prognostic role of vascular endothelial growth factor(VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors(GEP-NETs) . METHODS:Microvessel density(MVD) in GEP-NETs was evaluated using endoglin and CD31 immunohistochemistry.In addition,tissue levels of endoglin and VEGF were determined in homogenates by ELISA. RESULTS:Endoglin was highly expressed on tumor endothelial cells.CD31 MVD in GEP-NETs was significantly higher compared to endoglin MVD(P<0.01) .Two-tofour-fold higher tissue levels of endoglin and VEGF were seen in tumors compared to associated normal tissue. This increased endoglin tissue expression in tumors was significantly related to tumor size(P<0.01) ,presence of metastases(P=0.04) ,and a more advanced tumor stage(P=0.02) ,whereas expression of VEGF was not. CONCLUSION:We suggest that endoglin is a potential marker to indicate and predict metastases,which might be useful in the post-resection therapeutic approach of patients with GEP-NETs.
文摘A 15-year-old girl was admitted to our hospital with a 9-month history of upper abdominal pain and loss of appetite. Her history showed no indication of hepatitis. Her abdomen appeared to be even and soft, and the liver and spleen could not be felt below the costal margin. Percussion pain in hepatic region was negative. Gastroscopy showed no abnormalities. An abdominal ultrasound examination revealed the presence of hepatic hypoechoic areas and an abdominal CT scan showed multiple roundlike low-density masses in both hepatic lobes. The edges of the focal lesions were smooth and continuous, with a heterogeneous center, the round-like edges were enhanced, but the enhancement in the focal lesions was not obvious.
基金Supported by the Natural Science Foundation of Fujian Province,No.C0110013Science and Technology KeyProgram Foundation of Fujian Province, No. 2002Y003
文摘AIM: To investigate the implication of angiogenin (ANG) in the neovascularizaton and growth of human gastric carcinoma (HGC). METHODS: ANG mRNA expression in HGC specimens obtained by surgical resection from patients with HGC were examined by RT-PCR. ANG, Ki-67, VEGF protein expression and microvessel density (MVD) in HGC specimens were detected by immunohistochemistry. RESULTS: RT-PCR showed significantly higher ANG mRNA expression (0.482 ± 0.094) in HGC tissues than in the surrounding nontumorous tissues (0.276 ±0.019, P = 0.03). MVD within tumorous tissues increased significantly with ANG mRNA expression (r = 0.380, P = 0.001) and ANG protein expression (P 〈 0.01). The ANG expression levels of cancer tissues were positively correlated with VEGF (P 〈 0.01) and the proliferation index of cancer cells (P 〈 0.01). CONCLUSION: ANG is one of the neovascularization factors of HGC. ANG may work in coordination with VEGF, and promote the proliferation of HGC cells.
文摘Objective: To observe the inhibition of intracranial glioma tumorigenesis by vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotide (ODN) in rats. Methods: Totally 20 μ1 Hank's liquid containing 1×106 C6 glioma cells was seeded into rat right caudate putaraen in high-flow microinfusion with stereotactic technique. VEGF antisense ODN was simultaneously used with glioma cell. Each rat of the treated group Ⅰ and the treated group Ⅱ was treated with 1 000 μmol/L VEGF antisense ODN. Each rat of the treated group Ⅲ and the treated group Ⅳ was treated with 2 000 μmol/L VEGF antisense ODN. The experimental periods of the treated group Ⅰ , the treated group Ⅲ and the control group Ⅰ were 2 weeks, those of the treated group Ⅱ , the treated group Ⅳ and the control group Ⅱ were 3 weeks. Before sacrifice, MRI was performed on each rat. Tumor magnitude and pathologic examination were detected after samples were dissected. Results: The survival state of all treated rats was better, and that of the control rats was in severe danger. The tumor volumes of the treated group Ⅰ and the treated group Ⅱ were remarkably lessened. Tumor tissue could not be found macroscopically in the brain samples of the treated group Ⅲ and the treated group Ⅳ, but tumor nest could be found with microscopy. Tumors of the treated group I and the treated group Ⅱ had weak expressions of VEGF mRNA and VEGF, while normal brains and the samples of the treated group Ⅲ and the treated group Ⅳ had negative expressions, but tumors of the control groups had strong expressions. Conclusion: VEGF antisense ODN used early in situ can suppress angiogenesis and growth of rat intracranial glioma to retard tumorigenesis.
文摘OBJECTIVE To analyze the effects of cryoablation on the mice bearing Rm-I prostate cancer through detecting tumor angiogenesis and cancer cell proliferation in the mice after cryoablation, and to explore the effects of cryoablation on vascular endothelium growth factor (VEGF), Ki67 protein expression and microvessel density (MVD) in the mice bearing prostate cancer. METHODS Sixty Rm-1 mouse models of prostate cancer were established. Experimental mice were randomized into 2 groups: the cryoablation group (n = 30) and the control group (n = 30). After file therap)4 tumor tissues of the mice in group A and B were obtained at day 0 (without cryoablation), 1st, 3rd, 5th, 7th, 14th day, respectivelj6 after cryoablation, and the expressions of MVD, VEGF and Ki67 proteins were detected at the same time points. RESULTS The expressions of MVD, VEGF and Ki67 proteins in group A were decreased. The lowest values of the factors were detected on the 3rd day after cryoablation, and increased slowly after that. The expressions of MVD, VEGF and Ki67 proteins in the control group were not changed. Significant changes of the expressions of MVD, VEGF and Ki67 proteins in the group A were found at different time points. Correlation analysis suggested a positive correlation between the expressions of VEGF and MVD proteins (r = 0.8793), a positive correlation between the expressions of Ki67 and MVD proteins (r = 0.7614), and a positive correlation between the expressions of VEGF and ki67 proteins (r = 0.6921). CONCLUSION After argon-helium cryoablation treatment for the mice bearing prostate cancer, the expressions of MVD, VEGF and Ki67 proteins in local tumor were reduced on the 1st day. The lowest values of the factors were detected on the 3rd day after cryoablation, and then increased after that. Cryoablation combined with other modalities of treatment may effectively improve the treatment effects of cryoablation for prostate cancer.
文摘Contrast agents are increasingly being used to characterize the vasculature in an organ of interest,to better delineate benign from malignant pathology and to aid in staging and directing therapeutic procedures.We review the mechanisms of action of first,second and third generation contrast agents and their use in various endoscopic procedures in the gastrointestinal tract.Various applications of contrast-enhanced endoscopic ultrasonography include differentiating benign from malignant mediastinal lymphadenopathy,assessment of depth of invasion of esophageal,gastric and gall bladder cancers and visualization of the portal venous system and esophageal varices.In addition,contrast agents can be used to differentiate pancreatic lesions.The use of color Doppler further increases the ability to diagnose and differentiate various pancreatic malignancies.The sensitivity of power Doppler sonography to depict tumor neovascularization can be increased by contrast agents.Contrast-enhanced harmonic imaging is a useful aid in identifying the tumor vasculature and studying pancreatic microperfusion.In the future,these techniques could potentially be used to quantify tumor perfusion,to assess and monitor the efficacy of antiangiogenic agents,to assist targeted drug delivery and allow molecular imaging.
基金Supported by a grant of Science and Technology Research and Development Program of Hebei Province (No. 0527611016)
文摘Objective: The aim of the study was to detect the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in breast benign tissues and malignant tumors to clarify the relationship between VEGF expression, angiogenesis and breast carcinoma occurrence. Methods: The expression of VEGF and MVD in 79 cases of invasive ductal breast carcinoma, 79 corresponding para-cancer normal tissues from primary invasive breast carcinomas, 35 breast carcinoma in situ, 23 breast atypical hyperplasia and 56 breast fibroid tumor were examined by immunohistochemistry staining (SP-method). Results: The positive rate of VEGF and MVD value increased significantly with the increase of the malignant degree of breast tissues (P = 0.000). In breast carcinoma group, the positive rate of VEGF and MVD value with lymph node metastasis were higher than those without lymph node metastasis (P = 0.011 and P = 0.023). A significant higher expression of VEGF and MVD value were observed as the clinical stage increased (P = 0.035 and P = 0.012). The MVD value was higher in VEGF positive group than negative group (P = 0.000). Conclusion: The combining detection of VEGF expression and MVD is helpful for evaluating malignant degree of breast carcinoma. Angiogenesis in breast tumors and occurrence of breast carcinoma might be correlated with the expression of VEGF.
文摘Objective: As a novel blood supply pattern, vasculogenic mimicry(VM) has attracted increasingly attention in recent years, which may partly compensate for the absence of feeding and facilitate tumor perfusion. However, anti-angiogenic drugs have little effect on VM. The grape seed proanthocyanidins(GSPs), a kind of promising bioactive phytochemical, has shown anti-carcinogenesis and anti-angiogenic in several tumor models. However, GSPs regulation of VM and its possible mechanisms in a H22 hepatoma carcinoma model remain not clear. The aim of this study was to examine the effects of GSPs on proliferation and VM in a H22 hepatoma carcinoma model and to investigate the underlying mechanism. Methods: Seventy-five mice were divided into the control group and experimental groups treated with different concentration of GSPs. CD34-PAS dual staining was employed to identify the VM structure. The immunohistochemical staining for investigating the expression of VEGF, Eph A2 and MMP-2 protein was performed. Results: Treatment of the H22 model with Endostar(4 mg/kg), 50, 100, 200 mg/kg of the GSPs resulted in 6.87%, 17.81%, 27.43%, 53.52% inhibition in tumor growth, respectively. The mean weight of tumors were significantly lower in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups than in the control group(all P < 0.01). Similarly, compared with the control group, the number of VM channels were significantly reduced in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups(all P < 0.01). Immunohistochemistry showed significant decreases in the expression levels of VEGF, Eph A2 and MMP-2 protein in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups when compared with control group(all P < 0.001). Conclusion: This is the first report providing evidence that GSPs inhibit the VM structure by regulation of the VEGF/Eph A2/MMPs signaling pathway. Therefore, we concluded that GSPs has the potential of being a clinical anti-VM inhibitor.
文摘Objective:To explore the inhibitory effect of moxibustion on tumor growth and metastasis, and also its possible mechanism, in gastric tumor-bearing rats by investigating the expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Methods:Fifty healthy Sprague-Dawley (SD) rats (half male and half female) were routinely housed for 1 week. A total of 20 rats were randomly divided into a blank group and a sham operation group, with 10 rats in each group. The remaining 30 rats were used to make gastric cancer models by implantation of ascites-type Walker-256 cancer cells. After successful modeling, rats were randomly divided into a model group, a moxibustion group and an infrared group, with 10 rats in each group. From the day of modeling, the body weight of each group was weighed every 4 days. Warm moxibustion was alternately performed at two-group acupoints [Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) in one group, and bilateral Pishu (BL 20) and Weishu (BL 21) in another group] in the moxibustion group. The body surface projection area of the stomach was irradiated with short-wave infrared rays in the infrared group, once a day, 20 min per time for 21 d. At the end of the treatment, the gastric tumor was completely dissected, and the tumor volume and tumor growth inhibition rate were calculated. Then the gastric tumor cell metastasis was recorded. The levels of VEGF and EGF in rat gastric tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA). Results:Compared with the blank group, the body weight of the model group decreased significantly after modeling (P<0.05);compared with the model group, the rats in the moxibustion group had increased body weight during the middle and late stages (bothP<0.05). The tumor volumes of rats in the moxibustion group and the infrared group were smaller than the volume in the model group (bothP<0.05). The tumor growth inhibition rate in the moxibustion group was significantly higher than that in the infrared group (P<0.05). The case number of tumor metastasis in the moxibustion group was smaller than that in the model group and the infrared group. The VEGF level in the tumor tissues of the model group was statistically significantly higher than that in the blank group (P<0.05). Compared with the model group, the VEGF levels in the moxibustion group and the infrared group were statistically significantly lower (bothP<0.05). The EGF levels in the tumor tissues of the model group was statistically significantly lower than that in the blank group (P<0.05);compared with the model group, the EGF levels in the moxibustion group and the infrared group were statistically significantly increased (bothP<0.05). Conclusion:Moxibustion can increase the body weight, inhibit the tumor growth, invasion and metastasis in gastric tumor-bearing rats, which may be related to the regulation of VEGF and EGF expressions in tumor tissues.
文摘This paper aims to the research of the impact of fluid shear stress on the adhesion between vascular endothelial cells and leukocyte induced by tumor necrosis factor-α(TNF-α) by microfliudic chip technology.Microfluidic chip was fabricated by soft lithograph; Endothelial microfluidic chip was constructed by optimizing types of the extracellular matrix proteins modified in the microchannel and cell incubation time;human umbilical vein endothelial cells EA.Hy926 lined in the microchannel were exposed to fluid shear stress of 1.68 dynes/cm^2 and 8.4 dynes/cm^2 respectively.Meanwhile,adhesion between EA.Hy926 cells and leukocyte was induced by TNF-αunder a flow condition.EA.Hy926 cell cultured in the static condition was used as control group.The numbers of fluorescently-labeled leukocyte in microchannel were counted to quantize the adhesion level between EA.Hy926 cells and leukocyte; cell immunofluorescence technique was used to detect the intercellular adhesion molecule(ICAM-1) expression.The constructed endothelial microfluidic chip can afford to the fluid shear stress and respond to exogenous stimulus of TNF-α; compared with the adhesion numbers of leukocyte in control group,adhesion between EA.Hy926 cells exposed to low fluid shear stress and leukocyte was reduced under the stimulus of TNF-α at a concentration of 10 ng/ml(P<0.05); leukocyte adhesion with EA.Hy926 cells exposed to high fluid shear stress was reduced significantly than EA.Hy926 cells in control group and EA.1Hy926 cells exposed to low fluid shear stress(P<0.01); the regulation mechanism of fluid shear stress to the adhesion between EA.Hy926 cells and leukocyte induced by TNF-αwas through the way of ICAM-1.The endothelial microfluidic chip fabricated in this paper could be used to study the functions of endothelial cell in vitro and provide a new technical platform for exploring the pathophysiology of the related cardiovascular system diseases under a flow environment.
文摘Objective:To observe the effects of herb-partitioned moxibustion and ginger-partitioned moxibustion on the growth of colon tumors in rats with colitis-associated colon cancer(CACC),and explore the mechanism of moxibustion intervening CACC through the purinergic receptor P2X ligand-gated ion channel 7(P2X7R)/signal transducer and activator of transcription 3(STAT3)/vascular endothelial growth factor(VEGF)pathway.Methods:A total of 26 male Sprague-Dawley rats were selected.According to the random number table method,6 rats were selected as the normal group.The remaining 20 rats were injected intraperitoneally with azoxymethane(AOM)combined with oral dextran sodium sulfate(DSS)to prepare the CACC model.After the model was successfully established,2 rats were randomly selected for model identification.The remaining 18 rats which were successfully modeled were randomly divided into a model group,a herb-partitioned moxibustion group and a ginger-partitioned moxibustion group,with 6 rats in each group.Moxibustion intervention was performed in the herb-partitioned moxibustion group and the ginger-partitioned moxibustion group at Qihai(CV 6)and bilateral Tianshu(ST 25).Moxibustion was performed twice at each point each time,once a day,at a 1-day interval after 6 consecutive interventions,for a total of 30 interventions.After intervention,the colon tumor load,pathological change and histopathological score were observed.Immunohistochemistry was used to detect the expressions of VEGF,P2X7R,phospho-STAT3(p-STAT3),and nuclear factor-kappa B p65(NF-κB p65)proteins in rat colon tissue.Western blot was used to detect the levels of p-STAT3 and NF-κB p65 proteins in rat colon tissue.Results:Compared with the normal group,the colon tumor load and histopathological score in the model group were significantly increased(both P<0.001),and different grades of dysplasia were observed in colon tissue from the model group,reaching the degree of adenocarcinoma;the expression level of P2X7R protein in colon tissue was significantly decreased(P<0.001),and the expression levels of p-STAT3,NF-κB p65 and VEGF proteins were significantly increased(all P<0.001)in the model group.Compared with the model group,the colon tumor load,colon histopathological score and the levels of p-STAT3,NF-κB p65 and VEGF proteins in colon tissue were significantly decreased(all P<0.05)in the herb-partitioned moxibustion group and the ginger-partitioned moxibustion group while the expression levels of P2X7R protein in colon tissue were significantly increased(both P<0.05).Conclusion:Both herb-partitioned moxibustion and ginger-partitioned moxibustion can reduce the colon tumor load in CACC rats and delay the progression of colon adenomas.The mechanism may be mediated by the P2X7R/STAT3 pathway to inhibit STAT3 phosphorylation,thereby reducing VEGF protein expression.
基金Supported by 5451 project of Health Science and Technology of Henan Province(No.201108)
文摘OBJECTIVE: To investigate the effects and mecha- nisms of Erbanxiao solution in inhibiting tumor an- giogenesis. METHODS: We observed the effects and mecha- nisms of Chinese medicines on inhibiting tumor an- giogenesis and studied the theories and results of treatment. Sixty patients with lung cancer were ran- domized into two groups (n=30). Patients in the control group were given compound Kushen injec- tion, and patients in the treatment group were giv- en Erbanxiao solution. The effect of Erbanxiao solu- tion on vascular endothelium growth factor (VEGF), basic fibroblast growth factor (bFGF), and tumor ne- crosis factor-α (TNF-α) was observed. RESULTS: The effective rate of the treatment group was 60% while the control group was 36%. There was a significant difference between the twogroups (P〈0.05). VEGF, bFGF, and TNF-a levels of the two groups were significantly different before and after treatment (P〈0.01). These Traditional Chi- nese Medicines significantly inhibited tumor angio- genesis, possibly by changing levels of VEGF, bFGF, and TNF-α. CONCLUSION: It is necessary to further explore the potential of Traditional Chinese Medicine in the treatment of angiogenesis in tumor patients.