糖尿病视网膜病变细胞因子及视网膜血流变化的意义

目的:探讨VEGF、细胞因子及视网膜血流状态与糖尿病视网膜病变(DR)的相关性。方法:将174例糖尿病患者根据视网膜病变情况分为无DR组(NDR,41例)、背景DR(NPDR,68例)及增殖期DR组(PDR,65例)三组,纳入健康志愿者30例作为对照组。对所有受试者血清VEGF、肿瘤坏死因子-α(TNF-α)、可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)及碱性成纤维细胞生长因子(bFGF)水平进行测定,并对其进行眼部彩色多普勒超声检查,测量视网膜中央动脉的各项血流动力学参数。结果:糖尿病患者血清VEGF,TNF-α,sICAM-1,sVCAM-1,bFGF水平显著高于对照组;PDR血清VEGF,TNF-α,sICAM-1,sVCAM-1,bFGF水平显著高于NDR和NPDR组,NPDR组血清VEGF,TNF-α,sICAM-1,sVCAM-1,bFGF水平又显著高于NDR(P<0.05)。糖尿病患者Vmax,Vmin,Vmean和PI显著低于对照组,RI显著高于对照组;PDR组Vmax,Vmin,Vmean和PI显著低于NDR和NPDR组,RI显著高于NDR和NPDR组;NPDR组Vmax,Vmin,Vmean和PI又显著低于NDR,RI则显著低于NDR和NPDR组(P<0.05)。结论:VEGF,TNF-α,sICAM-1,sVCAM-1,bFGF以及CRA血流动力学改变与DR的发生发展密切相关,在DR诊断和治疗中具有参考意义。

哮喘患者血清IL-13、TGF-β1、VEGF表达变化及与气道炎症、重塑的关系探讨

目的:本研究从细胞因子角度出发探讨白介素-13(Interleukin-13,IL-13)、转化生子因子-β1(Transforming growthfactor-β1,TGF-β1)、血管内皮生子因子(Vascular endothelial growth factor,VEGF)血清浓度是否在哮喘患者的气道慢性炎症及重塑的发病机制中起着调控作用及其可能途径。方法:选择哮喘急性发作期患者36例(中重度发作20例、轻度发作16例)、缓解期36例、健康体检者36例。取肘静脉血,用ELISA方法测定血清中IL-13、TGF-β1、VEGF水平;所有入试者均作肺功能检查,并对结果进行统计学分析。结果:血清IL-13、TGF-β1、VEGF的表达量在哮喘患者中存在显著的正相关性;同时三者血清浓度越高,肺功能检查指标第1 s用力呼气容积(Forced expiratory volume in the 1st s,FEV1)、第1 s用力呼气容积占用力肺活量的比值(Ratio of forced expiratory volume in 1 s to forced vital capacity,FEV1/FVC%)越小,提示哮喘的病情程度越重,血清IL-13、TGF-β1、VEGF的表达量与FEV1、FEV1/FVC%呈负相关性。结论:IL-13、TGF-β1、VEGF网络失衡是哮喘发病的主要机制之一,三者在哮喘发病中相互影响,相互促进,共同参与哮喘的气道炎症与重塑的过程;联合检测血清IL-13、TGF-β1、VEGF水平对判断哮喘患者病情严重程度及预后、辅助诊断及治疗具有重要价值。

Effect of acetyl L-carnitine on human retinal pigment epithelium-19 cells in hypoxic conditions

AIM:To investigate the effect of acetyl-L-carnitine(ALCAR)on cell viability,morphological integrity,and vascular endothelial growth factor(VEGF)expression in human retinal pigment epithelium(ARPE-19)cells using a hypoxic model.METHODS:In the first set of experiments,the optimal CoCl_(2) dose was determined by exposing ARPE-19 cell cultures to different concentrations.To evaluate the effect of ALCAR on cell viability,five groups of ARPE-19 cell culture were established that included a control group,a sham group(200μM CoCl_(2)),and groups that received 1,10 and 100 mM doses of ALCAR combined with 200μM CoCl_(2),respectively.The cell viability was measured by MTT assay.The morphological characteristics of cells were observed by an inverted phase contrast microscope.The levels of VEGF and HIF-1α secretion by ARPE-19 cells were detected by enzyme linked immunosorbent assay(ELISA)assay.RESULTS:ARPE-19 cells were exposed to different doses of CoCl_(2) in order to create a hypoxia model.Nevertheless,when exposed to a concentration of 200μM CoCl_(2),a notable decrease in viability to 83% was noted.ALCAR was found to increase the cell viability at 1 mM and 10 mM concentrations,while the highest concentration(100 mM)did not have an added effect.The cell viability was found to be significantly higher in the groups treated with a concentration of 1 mM and 10 mM ALCAR compared to the Sham group(P=0.041,P=0.019,respectively).The cell viability and morphology remained unaffected by the greatest dose of ALCAR(100 mM).The administration of 10 mM ALCAR demonstrated a statistically significant reduction in the levels of VEGF and HIF-1α compared with the Sham group(P=0.013,P=0.033,respectively).CONCLUSION:The findings from the current study indicate that ALCAR could represent a viable therapeutic option with the potential to open up novel treatment pathways for retinal diseases,particular relevance for age-related macular degeneration(AMD).However,to fully elucidate ALCAR’s application potential in retinal diseases,additional investigation is necessary to clearly define the exact mechanisms involved.

有氧运动联合牡蛎肽对自发性高血压大鼠血压及血清AngⅡ、ET-1、VEGF的影响

目的:研究有氧运动和补充牡蛎肽对自发性高血压大鼠(SHR)血压及血清AngⅡ、ET-1、VEGF含量的干预作用和交互作用。方法:对SHR和WKY大鼠进行8周有氧运动和补充牡蛎肽,检测各组大鼠血压,血管紧张素Ⅱ(AngⅡ)、内皮素-1(ET-1)和血管内皮生长因子(VEGF)含量。结果:有氧运动联合补充牡蛎肽对降低SHR血清ET-1、VEGF含量无显著的交互作用(P>0.05),但对降低SHR血压和血清AngⅡ含量均有显著的交互作用(P<0.01)。有氧运动对降低SHR血压和血清VEGF含量均有显著的效应(P<0.01);补充牡蛎肽对降低SHR血压和血清AngⅡ、ET-1、VEGF含量均有显著的效应(P<0.01)。结论:在高血压的发展过程中,不进行干预血压在一定程度上会持续升高;有氧运动联合补充牡蛎肽通过降低SHR血清AngⅡ、ET-1和VEGF含量,保护血管内皮,从而降低血压;有氧运动联合补充牡蛎肽对降低SHR血压具有协同效应。

Expression of vascular endothelial growth factors A and C in human pancreatic cancer

AIM： To study the expression of vascular endothelial growth factor A （VEGF-A） and VEGF-C and to determine whether the presence of VEGF-A and VEGF-C was associated with the clinicopathologic characteristics of pancreatic cancer. METHODS： VEGF-A and VEGF-C mRNA transcripts were examined by Northern blot in 6 human pancreatic cancer cell lines and 8 normal pancreatic tissues and 8 pancreatic carcinoma specimens. The expression of VEGF-A and VEGF-C proteins was examined by Western blot in the tested cell lines and by immunohistochemical stain in 50 pancreatic carcinoma samples. RESULTS： VEGF-A and VEGF-C mRNA transcripts were present in all the 6 human pancreatic cancer cell lines. Immunoblotting revealed the presence of VEGF-A and VEGF-C proteins in all the cell lines. Northern blot analysis of total RNA revealed 3.0-fold and 3.6-fold increase in VEGF-A and VEGF-C mRNA transcript in the cancer samples, respectively. Immunohistochemical analysis confirmed the expression of VEGF-A and VEGF-C in cancer cells within the tumor mass. Immunohistochemical analysis of 50 pancreatic cancer tissue samples revealed the presence of VEGF-A and VEGF-C immunoreactivity in 50% and 80% of the cancer tissue samples, respectively. The presence of VEGF-A in these cells was associated with larger tumor size and enhanced local spread （x^2= 6.690, P= 0.035〈0.05） but was not associated with decreased patient survival. However, the presence of VEGF-C in the cancer cells was associated with increased lymph node metastasis （x^2= 5.710, P= 0.017〈0.05）,but was not associated with decreased patient survival. There was no correlation between the expression of VEGF-A and VEGF-C in the same cancer cells. CONCLUSION： VEGF-A and VEGF-C are commonly overexpressed in human pancreatic cancer and may contribute to tumor growth and lymph node metastasis, There is no relationship between the expression of VEGF-A and VEGF-C in pancreatic cancer.

Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array

AIM： To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer （mCRC） with the aim of identifying prognostic markers.METHODS： The expression of 44 angiogenesis- secreted factors was measured by a novel cytokine antibody array methodology. The study evaluated vas- cular endothelial growth factor （VEGF） and its soluble vascular endothelial growth factor receptor （sVEGFR）-I protein levels by enzyme immunoassay （EIA） in a panel of 16 CRC cell lines, mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction （Q-RT-PCR） and vascular en- dothelial growth factor receptor （VEGFR）-2 expressionwas analyzed by flow cytometry.

Signaling pathway/molecular targets and new targeted agents under development in hepatocellular carcinoma

Advances in molecular cell biology over the last de- cade have clarified the mechanisms involved in can- cer growth, invasion, and metastasis, and enabled the development of molecular-targeted agents. To date, sorafenib is the only molecular-targeted agent whose survival benefit has been demonstrated in two global phase 111 randomized controlled trials, and has been approved worldwide. Phase 111 clinical trials of other molecular targeted agents comparing them with sorafenib as first-line treatment agents are ongoing. Those agents target the vascular endothelial growth factor, platelet-derived growth factor receptors, as well as target the epidermal growth factor receptor, insulin- like growth factor receptor and mammalian target of rapamycin, in addition to other molecules targeting other components of the signal transduction pathways. In addition, the combination of sorafenib with standard treatment, such as resection, ablation, transarterial em- bolization, and hepatic arterial infusion chemotherapy are ongoing. This review outlines the main pathways involved in the development and progression of hepato- cellular carcinoma and the new agents that target these pathways. Finally, the current statuses of clinical trials of new agents or combination therapy with sorafenib and standard treatment will also be discussed.

Targeted systemic therapies for hepatocellular carcinoma:Clinical perspectives,challenges and implications

Hepatocellular carcinoma （HCC） is a lethal disease in most patients, due to its aggressive course and a lack of effective systemic therapies for advanced disease. Surgical resection and liver transplantation remain the only curative options for a small subset of patients. Few patients with HCC are diagnosed early enough to be eli- gible for curative treatment. Angiogenesis inhibition is a natural therapeutic target for all solid tumors, but par- ticularly for the highly vascularized HCC tumors. With the approval of the targeted agent sorafenib, there are now additional options for patients with HCC. Although sorafenib does produce some improvement in survival in HCC patients, the responses are not durable. In addi- tion, there are significant dermatologic, gastrointestinal, and metabolic toxicities, and, as importantly, there is still limited knowledge of its usefulness in special sub- populations with HCC. Other angiogenesis inhibitors are in development to treat HCC both in the first-line set- ting and for use following sorafenib failure; the furthest in development is brivanib, a dual fibroblast growth factor pathway and vascular endothelial growth factor receptor inhibitor. Additional agents with antiangiogenic properties also in phase IT and Ⅲ development for the treatment of patients with HCC include bevacizumab, ramucirumab, ABT-869, everolimus and ARQ 197.

A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model

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.

Inhibition of tumor angiogenesis by TTF1 from extract of herbal medicine

AIM:To study the inhibition of tumor angiogenesis by 5,2,4'-trihydroxy-6,7,5'-trimethoxyflavone(TTF1) isolated from an extract of herbal medicine Sorbaria sorbifolia.METHODS:Angiogenic activity was assayed using the chick embryo chorioallantoic membrane(CAM) method.Microvessel density(MVD) was determined by staining tissue sections immunohistochemically for CD34 using the Weidner capillary counting method.The mRNA and protein levels of vascular endothelial growth factor(VEGF),vascular endothelialgrowth factor receptor 2(VEGFR2,Flk-1/KDR),basic fibroblast growth factor(bFGF),cyclo-oxygenase(COX)-2 and hypoxia-inducible factor(HIF)-1α were detected by quantitative real-time polymerase chain reaction and Western blotting analysis.RESULTS:The TTF1 inhibition rates for CAM were 30.8%,38.2% and 47.5% with treatment concentrations of 25,50 and 100 μg/embryo × 5 d,respectively.The inhibitory rates for tumor size were 43.8%,49.4% and 59.6% at TTF1 treatment concentrations of 5,10,and 20 μmol/kg,respectively.The average MVD was 14.2,11.2 and 8.5 at treatment concentrations of 5 μmol/kg,10 μmol/kg and 20 μmol/kg TTF1,respectively.The mRNA and protein levels of VEGF,KDR,bFGF,COX-2 and HIF-1α in mice treated with TTF1 were significantly decreased.CONCLUSION:TTF1 can inhibit tumor angiogenesis,and the mechanism may be associated with the down-regulation of VEGF,KDR,bFGF,HIF-1α and COX-2.

Effects of resistin-like molecule β over-expression on gastric cancer cells in vitro

AIM: To investigate the effects of resistin-like molecule β (RELMβ) over-expression on the invasion, metastasis and angiogenesis of gastric cancer cells. METHODS: Human RELMβ encoding expression vec tor was constructed and transfected into the RELMβ lowly-expressed gastric cancer cell lines SGC7901 and MKN-45. Gene expression was measured by Western blotting, reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR. Cell proliferation was measured by 2-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetry, colony formation and 5-ethynyl-20-deoxyuridine incorporation assays. The in vitro migration, invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenic capabilities of cancer cells were measured by tube formation of endothelial cells. RESULTS: Transfection of RELMβ vector into SGC-7901 and MKN-45 cells resulted in over-expression of RELMβ, which did not infl uence the cellular proliferation. However, over-expression of RELMβ suppressed the in vitro adhesion, invasion and metastasis of cancer cells, accompanied by decreased expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Moreover, transfection of RELMβ attenuated the expression of vascular endothelial growth factor and in vitro angiogenic capabilities of cancer cells. CONCLUSION: Over-expression of RELMβ abolishes the invasion, metastasis and angiogenesis of gastric cancer cells in vitro, suggesting its potentials as a novel therapeutic target for gastric cancer.

(-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer

AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activator of transcription 3 (Stat3) activity in gastric cancer. METHODS: Human gastric cancer (AGS) cells were treated with IL-6 (50 ng/mL) and EGCG at different concentrations. VEGF, total Stat3 and activated Stat3 protein levels in the cell lyses were examined by Western blotting, VEGF protein level in the conditionedmedium was measured by enzyme-linked immunosorbent assay, and the level of VEGF mRNA was evaluated by reverse transcription polymerase chain reaction (RTPCR). Stat3 nuclear translocation was determined by Western blotting with nuclear extract, and Stat3-DNA binding activity was examined with Chromatin immunoprecipitation (ChIP) assay. IL-6 induced endothelial cell proliferation was measured with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazoliumbromide assay, in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel, and IL-6-induced angiogenesis in vitro was measured with Matrigel plug assay. RESULTS: There was a basal expression and secretion of VEGF in AGS cells. After stimulation with IL-6, VEGF expression was apparently up-regulated and a 2.4-fold increase was observed. VEGF secretion in the conditioned medium was also increased by 2.8 folds. When treated with EGCG, VEGF expression and secretion were dose-dependently decreased. IL-6 also increased VEGF mRNA expression by 3.1 folds. EGCG treatment suppressed VEGF mRNA expression in a dose-dependent manner. EGCG dose-dependently inhibited Stat3 activation induced by IL-6, but did not change the total Stat3 expression. When treated with EGCG or AG490, VEGF expressions were reduced to the level or an even lower level in the tumor cells not stimulated with IL-6. However, PD98059 and LY294002 did not change VEGF expression induced by IL-6. EGCG inhibited Stat3 nucleus translocation, and Stat3-DNA binding activity was also markedly decreased by EGCG. Furthermore, EGCG inhibited IL-6 induced vascular endothelial cell proliferation and tube formation in vitro and angiogenesis in vitro . CONCLUSION: EGCG inhibits IL-6-induced VEGF expression and angiogenesis via suppressing Stat3 activity in gastric cancer, which has provided a novel mechanistic insight into the anti-angiogenic activity of EGCG.

Zinc Finger Protein-activating Transcription Factor Up-regulates Vascular Endothelial Growth Factor-A Expression in Vitro

Objective To construct the zinc finger protein-activating transcription factor (ZFP-ATF) plasmid and evaluate its efficacy in inducing vascular endothelial growth factor (VEGF) expression in EY.HY926 endothelial cells. Methods Firstly, we constructed the ZFP-ATF plasmid, then testified the quantity of VEGF protein in EY.HY926 endothelial cells after transfected with ZFP-ATP plasmid by Western blot, finally, we used the RT-PCR to testify whether the ZFP-ATF can stimulate expression of VEGF splice variants. Results The ZFP-ATF DNA sequences were located the multiclone sites of PVAX1 vector between the site of BamH Ⅰ and Xhol. Western blot result showed VEGF expression in EY.HY926 endothelial cells transfected with ZFP-ATF plasmid was significantly higher than that in cells transfected with VEGF165 (19.95±3.95 vs. 12.15±1.55 μg/μL, P<0.01). RT-PCR result showed VEGF-A mRNA expression level induced by ZFP-ATF was high than that induced by VEGF165. Conclusion ZFP-ATF can up-regulate the VEGF-A expression in comparison with VEGF165, which might have beneficial effects in angiogenesis process.

RNA interference against hypoxia inducible factor-1α inhibited growth of cervical cancer by limiting vascularization

Objective:Cervical cancer has become a major public health problem.The development of effective,systemic therapies for cervical cancer is highly desired.We show here that hypoxia inducible factor-1α(HIF-1α) was indicated as an attractive therapeutic molecular target for cervical cancer.Methods:Firstly,we observed the expressional level of HIF-1α in cervical cancer and Hela and Siha cell lines.Secondly,by constructuring HIF-1α shRNA targeting human HIF-1α mRNA common sequence and transfecting it with plasmid to cervical cell,we detected the changes of HIF-1α and its downstream genes levels VEGF.Then we injected selected stably transfected cell line into athymic nude mice to estimate its' antitumor effects.Results:We observed that HIF-1α inhibition was related to down-regulated VEGF resulting in prevention of angiogenesis,then leading to slower-growing tumors.Conclusion:The underlying concept of transfecting a HIF-1α shRNA expression vector to block the HIF-1α holds promise as the clinical potential of gene therapy for cervical cancer.

The effects of vascular endothelial growth factor and microvessel density in the fibromyoma uteri

Objective： To investigate vascular endothelial growth factor （VEGF） expression and microvessel density （MVD） on the fibromyoma uteri treated with mifepristone. Methods： VEGF expression and MVD were counted on 60 cases of the fibromyoma uteri by SP method, including 40 cases of mifepristone treated and 20 cases of untreated patients as controlled group. Results： VEGF positive expression rate and MVD in treated group were 3715% and 9.90 ＋ 5.95, which were lower than those in controlled group （80% and 16.36 ＋ 2.07; P 〈 0.05）. Meanwhile, in treated group, those in marked shrink in tumor size sub-group were lower than in not obvious sub-group （12.0% and 7.89 ＋ 4.36 vs. 80% and 11,29 ＋ 3.10; P 〈 0.05）. Conclusion： VEGF and MVD expression decreases in the fibromyoma uteri after treatment with mifepristone, suggesting that mifepristone could inhibit angiogenesis and blood supply resulting in tumor shrink.

Reinstate the Damaged VEGF Signaling Pathway with VEGF-activating Transcription Factor

Objective To investigate the role of vascular endothelial growth factor-activating transcriptional factor (VEGF-ATF) on the VEGF signaling pathway in diabetes mellitus. Methods Totally, 20 C57BL/6 mice fed with high fat diet was induced into diabetes mellitus. Ten diabetes mellitus mice received a lower limb muscle injection with VEGF-ATF plasmid, and another ten were as control. VEGF-ATF is an engineered transcription factor designed to increase VEGF expression. Three days later, mice were sacrificed and the injected gastrocnemius was used for analysis. VEGF mRNA and protein expressions were examined by real-time PCR and ELISA respectively. VEGF receptor 2 mRNA expression was tested with RT-PCR. Phosphorylated Akt, Akt, endothelial nitric oxide synthase (eNOS), and phosphorylated eNOS were assessed by western blot. Results At 3 days post-injection, in mice with diabetes mellitus, VEGF gene transfer increased VEGF mRNA copies and VEGF protein expression in injected muscles compared with control; and reinstated the impaired VEGF signaling pathway with increasing the ratios of phosphorylated Akt/Akt and phosphorylated eNOS/eNOS. However, it did not affect the expression of VEGF receptor 2 mRNA. Conclusion Gene transfer with VEGF-ATF is able to reinstate the impaired VEGF downstream pathway, and potentially promote therapeutic angiogenesis in mice with diabetes mellitus.

The expression of HIF-1α and VEGF as well as their correlation with angiogenesis in esophageal squamous cell carcinomas

Objective： To investigate the correlations among the expressions of hypoxia-inducible factor-1α （HIF-1α）, vascular endothelial cell growth factor （VEGF） and microvessel density （MVD）, and their relationships to the clinicopathologic characteristics of esophageal squamous cell carcinomas （ESCC）. Methods： The expressions of HIF-1α, VEGF and MVD were detected by immunohistochemical method in 45 cases of ESCC, 30 intraepithelial neoplasia and 35 normal esophageal mucosal epithelia tissues. The correlations among the expressions of HIF-1α, VEGF and MVD, and their relationships to the clinicopathologic features of ESCC were analyzed. Results： The rate of positive expression of HIF-1α and VEGF which were 80% and 84% in ESCC were significantly higher than those in intraepithelial neoplasia and normal esophageal mucosal epithelium tissues （P 〈 0.01） and so did the MVD value which was71.10 ±15.02 in ESCC （P 〈 0.01）. The expression of HIF-1α and VEGF were positively correlated with the depth of tumor invasion, lymph node metastasis and TNM staging of ESCC. The expressions of HIF-1α were positively correlated with the expressions of VEGF and the value of MVD. Conclusion： Overexpression of HIF-1α is found in ESCC. HIF-1α may induce the angiogenesis in ESCC by upregulating the transcription of VEGF gene. It may play an important role in the carcinogenesis and aggression in ESCC, HIF-1α, VEGF and MVD may be a useful marker for evaluating the biological behaviors of ESCC.

Expression levels of CXCR4 and VEGF correlate with blood-borne metastatic progression and outcome in patients with osteosarcoma

Objective:We determine whether chemokine receptor CXCR4 and vascular endothelial growth factor(VEGF) expression related to the metastasis and survival outcome of patients with osteosarcoma.Methods:Tissue microarray(TMA) was used to detect the expression of CXCR4 and VEGF in 56 osteosarcoma patient samples.Two-year follow-up was performed to observe the metastatic behavior and overall survival of osteosarcoma patients.Results:There was a significant correlation between the expression levels of CXCR4 and VEGF in 56 osteosarcoma patient samples(P = 0.002).Univariate analysis revealed the expression of CXCR4 and VEGF was not associated with age, gender and the level of ALP but associated with clinical stage.Conclusion:These data raises the possibility that VEGF could regulate the levels of CXCR4 to promote the migration of tumor cells to target organs.CXCR4 and VEGF expression are highly correlated with metastatic progression in patients with osteosarcoma and their immunohistochemical expression have predictive value for the metastatic development.

Expression of VEGF-C and b-FGF in Lung Cancer and Its Relationship with Cancer Progress

Objective： to observe expression of vascular endothelial growth factor-C （VEGF-C） and alkaline fibroblast growth factor （b-FGF） in tissues of lung cancer, and its relationship with cancer metastasis.Methods： to adopt immunohistochemical methods, analysis of 60 cases of lung tissue expression of VEGF-C and b-FGF in the situation.Result： positive rates of VEGF-C and b-FGF in lung cancer are respectively 56.67% and 63.33%; expression of VEGF-C and b-FGF in lung cancer is not related to pathological grades, pathologic stages or ages of patients （P 〉 0.05）,but closely related to TNM stages and existence of lymph node metastasis （P 〈 0.01）. IMVD in center of lung cancer tissues is obviously higher than surrounding area, with significant differences （P 〈 0.01）. Conclusion： expression of VEGF-C and b-FGF is related to lung cancer progress.

The Relationship of EGFR and VEGF mRNA Expression in Ovarian Carcinoma

OBJECTIVE Epidermal growth factor receptor (EGFR) isdysregulated in many human malignancies and is a potentialtarget for therapeutic intervention, but there is a majordisagreement among researchers about both the frequency andpossible clinical importance of EGFR overexpression in ovariancancer. We investigated the expression and significance of theEGFR mRNA and vascular endothelial growth factor (VEGF)mRNA in ovarian carcinoma.METHODS Reverse transcription polymerase chain reaction(RT-PCR) was employed to determine the expression of EGFRmRNA and VEGF mRNA in 79 ovarian specimen (including15 normal, 13 benign and 51 malignant, from 79 patients). Therelationship between EGFR and VEGF expression was analyzed.RESULTS The positive rates of the expression of EGFR mRNAand VEGF mRNA were significantly higher in the patientswith ovarian carcinoma than those in both the patients withbenign ovarian tumors and in the normal controls. There wascorrelation between EGFR mRNA expression and clinical stages.The positive rate of the expression of EGFR mRNA in Stage Ⅲ-Ⅳ was higher than that in Stage Ⅰ-Ⅱ of ovarian carcinoma (P <0.05). The expression of VEGF mRNA was correlated with theclinical stages and lymph node metastasis. The expression levelsof VEGF mRNA in Stage Ⅲ-Ⅳ and in the group with lymph nodemetastasis were significantly higher than those in Stage Ⅰ-Ⅱ and inthe group without lymph node metastasis, respectively (P < 0.05).The expression of EGFR mRNA was positively correlated with theexpression of VEGF mRNA (r = 0.438, P < 0.05).CONCLUSION The expressions of EGFR mRNA and VEGFmRNA are positively correlated to the occurrence of ovariancarcinoma and its metastasis. The detection of EGFR and VEGFmay be helpful for the targeted chemotherapy.