The objective of this study was to detect the expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma of newly diagnosed lymphoma patients, and analyze their possible relationships with clinicopathological characteristics and prognosis. The expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma from 86 newly diagnosed lymphoma patients were detected by enzyme-linked immunosorbent assay (ELISA). As a results, the multivariate analysis showed that VEGF-C level in non-Hodgkin's lymphoma patients was low, but high in Hodgkin's lymphoma patients; VEGFR-2 level was higher in patients > 60 years, while VEGF-D level was lower in patients with IPI > 2. The univariate analysis showed that VEGF-D level was lower in patients with IPI > 2, while VEGF-D and VEGF-C levels were higher in patients without B symptoms. Relationship analysis between these factors indicated that the relation of VEGF-D expression level with VEGFR-2 and VEGFR-3 was positive. It is concluded that VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 play important roles in the pathogenesis of lymphoma, and may be used as indicators of prognosis evaluation or even guide for the antiangiogenesis treatment of lymphoma.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymphoma ; blood ; diagnosis ; pathology ; Middle Aged ; Neoplasm Staging ; Prognosis ; Vascular Endothelial Growth Factor C ; blood ; Vascular Endothelial Growth Factor D ; blood ; Vascular Endothelial Growth Factor Receptor-2 ; blood ; Vascular Endothelial Growth Factor Receptor-3 ; blood ; Young Adult

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.
Aged ; Angiogenesis Inhibitors/pharmacology* ; Female ; Gene Expression Regulation ; Humans ; Intermittent Claudication/drug therapy* ; Ischemia/drug therapy* ; Lower Extremity/blood supply* ; Male ; Matrix Metalloproteinase 9/blood* ; Middle Aged ; Neovascularization, Pathologic ; Tissue Inhibitor of Metalloproteinase-1/blood* ; Tissue Inhibitor of Metalloproteinase-2/blood* ; Vascular Endothelial Growth Factor A/blood* ; Vascular Endothelial Growth Factor Receptor-1/blood* ; Vascular Endothelial Growth Factor Receptor-2/blood*

Tumor angiogenesis is a process leading to formation of blood vessels within tumors and is crucial for maintaining a supply of oxygen and nutrients to support tumor growth and metastasis. Vascular endothelial growth factor(VEGF) plays a key role in tumor angiogenesis including induction of endothelial cell proliferation, migration, survival and capillary tube formation. VEGF binds to two distinct receptors on endothelial cells. VEGFR-2 is considered to be the dominant signaling receptor for endothelial cell permeability, proliferation, and differentiation. Bevacizumab(Avastin, Genetech, USA) is a monoclonal antibody against vascular endothelial growth factor. It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels. The goal of this study is to identify the anti-tumor effect of Bevacizumab(Avastin) for oral squamous cell carcinoma cell lines. Human squamous cell carcinoma cell line(HN4) was used in this study. We examined the sensitivity of HN4 cell line to Bevacizumab(Avastin) by using in vitro proliferation assays. The results were as follows. 1. In the result of MTT assay according to concentration of Bevacizumab(Avastin), antiproliferative effect for oral squamous cell carcinoma cell lines was observed. 2. The growth curve of cell line showed the gradual growth inhibition of oral squamous cell carcinoma cell lines after exposure of Bevacizumab(Avastin). 3. In the apoptotic index, groups inoculated Bevacizumab(Avastin) were higher than control groups. 4. In condition of serum starvation, VEGFR-2 did not show any detectable autophosphorylation, whereas the addition of VEGF activated the receptor. Suppression of phosphorylated VEGFR-2 and phosphorylated MAPK was observed following treatment with Bevacizumab(Avastin) in a dose-dependent manner. 5. In TEM view, dispersed nuclear membrane, scattered many cytoplasmic vacuoles and localized chromosomal margination after Bevacizumab(Avastin) treatment were observed. These findings suggest that Bevacizumab(Avastin) has the potential to inhibit MAPK pathway in proliferation of oral squamous cell carcinoma cell lines via inhibition of VEGF-dependent tumor growth.
Blood Vessels ; Capillaries ; Carcinoma, Squamous Cell ; Cell Line ; Cytoplasm ; Endothelial Cells ; Humans ; Neoplasm Metastasis ; Nuclear Envelope ; Oxygen ; Permeability ; Starvation ; Vacuoles ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-2

OBJECTIVETo compare the histological morphology, hemodynamics and angiogenesis-related molecules between benign and malignant breast tumor and investigate their variation in different perfusion regions in the same type of tumors.

METHODSThirty patients with malignant breast carcinoma and 30 with breast fibroadenoma underwent contrast-enhanced ultrasound examination with time-intensity quantitative analysis. The perfusion indices including peak intensity (PI), area under the curve (AUC), time to peak (TTP) and wash-out time (WOT) were measured both inside and on the margin of the foci. The expressions of CD34, vascular endothelial growth factor (VEGF), and Flk-1/KDR in both groups were measured immuhistochemically.

RESULTSThe time-intensity curve (TIC) of malignant tumor group was characterized by rapid ascent and slow descent, while that of the benign group presented with slow ascent and rapid descent. The AUC and WOT of the malignant tumor group were significantly higher than those of the benign group, while the PI and TTP showed no significant difference. In malignant tumor group, PI, AUC and WOT on the margin of the foci were significantly higher those of the inside region, while TTP showed a reverse pattern. No significant differences were found in the perfusion parameters between the inside and outside of the foci in the benign group. The distribution of CD34 was heterogeneous in breast carcinoma, and the micro-vessels were densely distributed especially on the margin of the cancer nest. The microvessel density of the malignant group (34.48-/+8.34) was significantly higher than that of the benign group (18.65-/+4.69). Diffuse or focal high VEGF expression was found on the margin of the cancer nest and necrotic tissue, but hardly detected in the benign group. Flk-1/KDR expressed diffusely or focally in breast carcinoma with especial high expression on the margin of the cancer nest and necrotic tissue, but was virtually undetectable in the benign group.

CONCLUSIONThe perfusion pattern, TIC, mean perfusion parameter and variation of the regional perfusion parameters provide valuable evidence for differential diagnoses between benign and malignant breast tumors. Molecular imaging targeting VEGF and Flk-1/KD shed light on new approaches to early diagnosis of breast carcinoma.

Antigens, CD34 ; metabolism ; Breast Neoplasms ; blood supply ; diagnostic imaging ; metabolism ; pathology ; Fibroadenoma ; blood supply ; diagnostic imaging ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Hemodynamics ; Humans ; Immunohistochemistry ; Time Factors ; Ultrasonography ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo investigate the differences in the expression of angiogenesis-related molecules between benign and malignant breast neoplasms.

METHODSThirty breast cancer patients (33 foci) and 30 with benign breast neoplasms (34 foci) were examined for CD34, vascular endothelial growth factor (VEGF) and Flk-1/KDR expressions using immunohistochemistry.

RESULTSIn patients with breast cancer, the microvessels densely distributed around the cancer nest. The microvessel density (MVD) in the cancer patients was significantly higher than that in patients with benign tumors (34.48+/-8.34 vs 18.65+/-4.69, P<0.05). In the breast cancer patients, strong VEGF expression was found in the epithelial cells and vascular endothelial cells around the breast carcinoma, and Flk-1/KDR was also strongly expressed in the vascular endothelial cells. The expressions of VEGF and Flk-1/KDR were hardly detectable in the benign tumors.

CONCLUSIONVEGF is an important regulatory factor in promoting breast tumor angiogenesis.

Breast Neoplasms ; blood supply ; metabolism ; Carcinoma, Ductal, Breast ; blood supply ; metabolism ; Female ; Humans ; Neovascularization, Pathologic ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

Understanding the mechanisms of vascular remodeling could lead to more effective treatments for ischemic conditions. We aimed to compare between the abilities of both human Wharton jelly derived mesenchymal stem cells (hMSCs) and human cord blood endothelial progenitor cells (hEPCs) and CD34+ to induce angiogenesis in vitro. hMSCs, hEPCs, and CD34+ were isolated from human umbilical cord blood using microbead (MiniMacs). The cells characterization was assessed by flow cytometry following culture and real-time PCR for vascular endothelial growth factor receptor 2 (VEGFR2) and von Willebrand factor (vWF) to prove stem cells differentiation. The study revealed successful isolation of hEPCs, CD34+, and hMSCs. The hMSCs were identified by gaining CD29+ and CD44+ using FACS analysis. The hEPCs were identified by having CD133+, CD34+, and KDR. The potential ability of hEPCs and CD34+ to differentiate into endothelial-like cells was more than hMSCs. This finding was assessed morphologically in culture and by higher significant VEGFR2 and vWF genes expression (p<0.05) in differentiated hEPCs and CD34+ compared to differentiated hMSCs. hEPCs and CD34+ differentiation into endothelial-like cells were much better than that of hMSCs.
Fetal Blood ; Flow Cytometry ; Humans ; Mesenchymal Stromal Cells* ; Microspheres ; Real-Time Polymerase Chain Reaction ; Stem Cells* ; Vascular Endothelial Growth Factor Receptor-2 ; von Willebrand Factor ; Wharton Jelly

OBJECTIVETo investigate effects of exercise training on vascular regulators and discuss its antihypertensive mechanism.

METHODSRats were divided into three groups (n = 7): spontaneous hypertensive rats control group (SHR-C), training group (SHR-T) and normotensive wistar-kyoto control group (WKY-C). Aerobic exercise consisted of 10 weeks of swimming training for 5 days/week. Exercise duration was 40 min in the first week, then 50 min in the second week, from the third week to the end of training, duration was maintained at 60 min. After training, vascular endothelial growth factor (VEGF) and other biomarkers in soleus were measured by RT-PCR and immunoblotting.

RESULTSVEGF and endothelial NO synthase (eNOS) in SHR-C were lower than that in WKY-C (P < 0.05). Blood pressure in SHR-C and SHR-T were higher than that in WKY-C before training; After training, compared with SHR-C, VEGFR2, eNOS, VEGF and VEGF mRNA increased significantly in SHR-T paralleled with marked decreases in blood pressure and heart rate respectively (P < 0.05, P < 0.01).

CONCLUSIONAerobic exercise training lowered the blood pressure in spontaneous hypertensive rats, and promoted VEGF mRNA level and expressions of VEGF, VEGFR2 and eNOS. The up-regulations of these vascular regulators could benefit angiogenesis and contribute to the antihypertensive effects.

Animals ; Blood Pressure ; Hypertension ; metabolism ; therapy ; Male ; Muscle, Skeletal ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Inbred SHR ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVESTo investigate the expression of CD34, vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR in precancerous lesion, atypical hyperplasia (AH) and infiltrating carcinoma of breast cancer and to explore the correlation between angiogenesis abnormality and the tumor progression.

METHODSOne hundred and sixty cases of resected tissues from breast cancer patients were enrolled in the study and were divided into 5 groups: 30 cases as normal controls, 30 cases with simple hyperplasia, 30 cases with AH, 20 cases with intraductal carcinoma in situ and 50 cases with infiltrating ductal carcinoma. The expression of CD34, VEGF and its receptor, Flk-1/KDR in those tissues were determined with immunohistochemical techniques. The micro vascular density (MVD) in those tissues was determined with the expression of CD34.

RESULTSThe expression level of CD34, VEGF and Flk-1/KDR were different among the groups, with the highest expression in the infiltrating ductal carcinoma group. With the progression of breast cancer, the major indexes showed no significant changes in the early stage of progression, but the expression of VEGF and Flk-1/KDR increased significantly from AH stage. Meanwhile, the MVD increased in the same way. There was significant difference between AH and intraductal carcinoma group in the expression of VEGF and Flk-1/KDR (P<0.05), but not in the MVD (P>0.05).

CONCLUSIONSAbnormality in angiogenesis may be an early event in the tumorigenesis of breast cancer. Abnormal expression of VEGF and Flk-1/KDR may be the initiating factor of angiogenesis in the process of breast hyperplasia-AH-breast cancer, it could be the molecular target of early diagnosis and treatment.

Adult ; Aged ; Antigens, CD34 ; metabolism ; Breast ; metabolism ; pathology ; Breast Neoplasms ; blood supply ; metabolism ; pathology ; Case-Control Studies ; Disease Progression ; Female ; Humans ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo conduct a preliminary study on the effect of curcumol in promoting angiogenesis activity and its mechanism in zebrafishes, in order to provide basis for clinical prescription.

METHODZebrafishes biological model was established to, observe curcumol's effect on embryo blood vessel growth, blood vessel regeneration of adult fishes after tail-cutting and tissue regeneration of fish fries after tail-cutting. The relative fluorescence quantitative PCR method was adopted to determine the gene expression of vascular endothelial growth factor (VEGFA) and receptor VEGFR2 of fish fries after tail-cutting.

RESULTCurcumol contributed to angiogenesis of intersegmental blood vessels in zebrafishes embryos and speed up regeneration of blood vessels in adult fishes after tail-cutting. Furthermore, curcumol can increase the gene expression of VEGFA and VEGFR2 in fish fries.

CONCLUSIONCurcumol can promote angiogenesis in zebrafishes, and enhance the gene expression of VEGFA and VEGFR2 in fish fries after tail-cutting and speed up the regeneration of their tails.

Animals ; Embryo, Nonmammalian ; blood supply ; drug effects ; metabolism ; Gene Expression Regulation ; drug effects ; Neovascularization, Physiologic ; drug effects ; Sesquiterpenes ; pharmacology ; Vascular Endothelial Growth Factor A ; genetics ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; Zebrafish ; embryology ; genetics ; physiology

OBJECTIVETo study the effects of prolonged 75% oxygen exposure on the expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2) in the neonatal rat lungs and to elucidate the effects of prolonged exposure of high concentration of oxygen on lung vascular development and its relationship with bronchopulmonary dysplasia (BPD).

METHODSForty eight Sprague-Dawley rat pups were randomly exposed to air (control group) and 75% oxygen (experimental group) 12 hrs after birth. The rats were sacrificed 7, 14 and 21 days after exposure and their lungs were sampled. The lung sections were stained with hematoxylin and eosin for histological evaluation. Expression of VEGF, VEGFR1 and VEGFR2 protein and mRNA was detected by immunohistochemistry and RT-PCR.

RESULTSAfter being exposed to 75% oxygen for 21 days, lung tissues had pathological changes as 'new' BPD. Expressions of VEGF protein (10.9 + or - 2.7 vs 30.8 + or - 6.4), VEGFR1 protein (5.4 + or - 1.4 vs 15.6 + or - 3.4) and VEGFR2 protein (11.3 + or - 2.6 vs 21.7 + or - 4.5) on day 21 in the experimental group decreased significantly as compared with the control group (p<0.05). The expression of VEGF mRNA (1.6 vs 3.3), VEGFR1 mRNA (0.4 vs 6.6) and VEGFR2 mRNA (0.5 vs 4.9) on day 21 in the experimental group also decreased significantly as compared with the control group (p<0.05).

CONCLUSIONSProlonged exposure of high concentration of oxygen may cause BPD possibly by inhibiting lung vascular development in neonatal rats.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; etiology ; Female ; Humans ; Infant, Newborn ; Lung ; blood supply ; Male ; Oxygen ; toxicity ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; analysis ; genetics ; Vascular Endothelial Growth Factor Receptor-1 ; analysis ; genetics ; Vascular Endothelial Growth Factor Receptor-2 ; analysis ; genetics