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Sample records for ablation links vegf

  1. VEGFR1-mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy

    DEFF Research Database (Denmark)

    Cao, Renhai; Xue, Yuan; Hedlund, Eva-Maria;

    2010-01-01

    , and adenoviral vectors ablates pericytes from the mature retinal vasculature through the VEGF receptor 1 (VEGFR1)-mediated signaling pathway, leading to increased vascular leakage. In contrast, we demonstrate VEGF receptor 2 (VEGFR2) is primarily expressed in nonvascular photoreceptors and ganglion cells...

  2. The Vascular-Ablative Agent VEGF121/rGel Inhibits Pulmonary Metastases of MDA-MB-231 Breast Tumors

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    Sophia Ran

    2005-05-01

    Full Text Available VEGF121/rGel, a fusion protein composed of the growth factor VEGF121 and the recombinant toxin gelonin (rGel, targets the tumor neovasculature and exerts impressive cytotoxic effects by inhibiting protein synthesis. We evaluated the effect of VEGF121/rGel on the growth of metastatic MDA-MB-231 tumor cells in SCID mice. VEGF121/rGel treatment reduced surface lung tumor foci by 58% compared to controls (means were 22.4 and 53.3, respectively; P < .05 and the mean area of lung colonies by 50% (210 ± 37 m2vs 415 ± 10 m2 for VEGF121/rGel and control, respectively; P < .01. In addition, the vascularity of metastatic foci was significantly reduced: (198 ± 37 vs 388 ± 21 vessels/mm2 for treated and control, respectively. Approximately 62% of metastatic colonies from the VEGF121/rGel-treated group had fewer than 10 vessels per colony compared to 23% in the control group. The VEGF receptor Flk-1 was intensely detected on the metastatic vessels in the control but not in the VEGF121/rGel-treated group. Metastatic foci present in lungs had a three-fold lower Ki-67 labeling index compared to control tumors. Thus, the antitumor vascular-ablative effect of VEGF121/rGel may be utilized not only for treating primary tumors but also for inhibiting metastatic spread and vascularization of metastases.

  3. Evaluation of the efficacy of excimer laser ablation of cross-linked porcine cornea.

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    Shihao Chen

    Full Text Available BACKGROUND: Combination of riboflavin/UVA cross-linking (CXL and excimer laser ablation is a promising therapy for treating corneal ectasia. The cornea is strengthened by cross-linking, while the irregular astigmatism is reduced by laser ablation. This study aims to compare the efficacy of excimer laser ablation on porcine corneas with and without cross-linking. METHODS AND FINDINGS: The porcine cornea was de-epithelialized and treated with 0.1% riboflavin solution for 30 minutes. A half of the cornea was exposed to UVA-radiation for another 30 minutes while the controlled half of the cornea was protected from the UVA using a metal shield. Photo therapeutic keratectomy (PTK was then performed on the central cornea. Corneal thickness of 5 paired locations on the horizontal line, ± 0.5, ± 1.0, ± 1.5, ± 2.0, and ± 2.5 mm from the central spot, were measured using optical coherence tomography prior to and after PTK. The ablation depth was then determined by the corneal thickness. There was a 9% difference (P<0.001 in the overall ablation depth between the CXL-half corneas (158 ± 22 µm and the control-half corneas (174 ± 26 µm. The ablation depths of all 5 correspondent locations on the CXL-half were significantly smaller (P<0.001. CONCLUSION: The efficacy of the laser ablation seems to be lower in cross-linked cornea. Current ablation algorithms may need to be modified for cross-linked corneas.

  4. Combined and sequential delivery of bioactive VEGF165 and HGF from poly(trimethylene carbonate) based photo-cross-linked elastomers.

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    Chapanian, R; Amsden, B G

    2010-04-01

    The ability of trimethylene carbonate (TMC) based elastomers to release bioactive vascular endothelial growth factor (VEGF(165)) and hepatocyte growth factor (HGF) separately and in combined and sequential fashions using an osmotic release mechanism was investigated. A TMC-based elastomer was chosen since TMC degrades without producing potentially harmful acidic degradation products, and its mechanical properties can be tailored by copolymerizing with D,L-lactide (DLLA) and epsilon-caprolactone (epsilon-CL) and by controlling the cross-link density. The bioactivities of released VEGF(165) and HGF were assessed using the proliferation of human aortic endothelial (HAEC) and CCL 208 monkey lung epithelial cell lines. VEGF(165) and HGF were lyophilized separately or together with trehalose, rat serum albumin (RSA) and NaCl. No significant elastomer degradation occurred over the initial 8 weeks, during which the bulk of the embedded growth factors were released. The presence of a low concentration of NaCl in the release media did not affect the viability of HAEC and CCL 208 cells. The TMC-based elastomer was able to provide a sustained release of highly bioactive VEGF(165) and HGF for more than 10 days. When released in combination from the same device, VEGF(165) and HGF were released at similar rates. By preparing a dual-layered cylinder, in which VEGF(165) was in the outer layer and HGF in the inner layer, a constant release of VEGF alone was first obtained, followed by overlapping and constant release of the two growth factors after a period of 4days. This study demonstrates the potential of TMC-based elastomers combined with an osmotic mechanism to release acid-sensitive growth factors in bioactive form alone and in combination, in controlled rates and sequences. PMID:19961885

  5. Adipose VEGF Links the White-to-Brown Fat Switch With Environmental, Genetic, and Pharmacological Stimuli in Male Mice.

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    During, Matthew J; Liu, Xianglan; Huang, Wei; Magee, Daniel; Slater, Andrew; McMurphy, Travis; Wang, Chuansong; Cao, Lei

    2015-06-01

    Living in an enriched environment (EE) decreases adiposity, increases energy expenditure, causes resistance to diet induced obesity, and induces brown-like (beige) cells in white fat via activating a hypothalamic-adipocyte axis. Here we report that EE stimulated vascular endothelial growth factor (VEGF) expression in a fat depot-specific manner prior to the emergence of beige cells. The VEGF up-regulation was independent of hypoxia but required intact sympathetic tone to the adipose tissue. Targeted adipose overexpression of VEGF reproduced the browning effect of EE. Adipose-specific VEGF knockout or pharmacological VEGF blockade with antibodies abolished the induction of beige cell by EE. Hypothalamic brain-derived neurotrophic factor stimulated by EE regulated the adipose VEGF expression, and VEGF signaling was essential to the hypothalamic brain-derived neurotrophic factor-induced white adipose tissue browning. Furthermore, VEGF signaling was essential to the beige cells induction by exercise, a β3-adrenergic agonist, and a peroxisome proliferator-activated receptor-γ ligand, suggesting a common downstream pathway integrating diverse upstream mechanisms. Exploiting this pathway may offer potential therapeutic interventions to obesity and metabolic diseases. PMID:25763639

  6. Laser-induced corneal cross-linking upon photorefractive ablation with riboflavin

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    Kornilovskiy IM

    2016-04-01

    Full Text Available Igor M Kornilovskiy,1 Elmar M Kasimov,2 Ayten I Sultanova,2 Alexander A Burtsev1 1Department of Eye Diseases, Federal State Budgetary Institution “National Pirogov Medical Surgical Centre”, Ministry of Health, Moscow, Russia; 2Department of Eye Diseases, Zarifa Aliyeva National Ophthalmology Center, Ministry of Health, Baku, Azerbaijan Aim: To estimate the biomechanical effect of the laser-induced cross-linking resulting from photorefractive ablation of the cornea with riboflavin.Methods: Excimer laser ablation studies were performed ex vivo (32 eyes of 16 rabbits by phototherapeutic keratectomy (PTK and in vivo (24 eyes of 12 rabbits by transepithelial photorefractive keratectomy (TransPRK, with and without riboflavin saturation of the stroma. Then, we performed corneal optical coherence tomography on 36 eyes of 18 patients with varying degrees of myopia at different times after the TransPRK was performed with riboflavin saturation of the stroma.Results: Biomechanical testing of corneal samples saturated with riboflavin revealed cross-linking effect accompanied by the increase in tensile strength and maximum strength. PTK showed increase in tensile strength from 5.1±1.4 to 7.2±1.6 MPa (P=0.001, while TransPRK showed increase in tensile strength from 8.8±0.9 to 12.8±1.3 MPa (P=0.0004. Maximum strength increased from 8.7±2.5 to 12.0±2.8 N (P=0.005 in PTK and from 12.8±1.6 to 18.3±1.2 N (P=0.0004 in TransPRK. Clinical optical coherence tomography studies of the biomicroscopic transparent cornea at different times after TransPRK showed increased density in the surface layers of the stroma and membrane-like structure beneath the epithelium.Conclusion: Photorefractive ablation of the preliminary corneal stroma saturation with riboflavin causes the effect of laser-induced cross-linking, which is attended with an increase in corneal tensile strength, maximum strength, increased density in the surface layers of the stroma, and formation of

  7. Suppression of alpha-tocopherol ether-linked acetic acid in VEGF-induced angiogenesis and the possible mechanisms in human umbilical vein endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, Cheng-Hung, E-mail: chchuang@hk.edu.tw [Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, 1018 Sec. 6 Taiwan Boulevard, Taichung 43302, Taiwan, ROC (China); Liu, Chia-Hua [Department of Food Science and Biotechnology, National Chung-Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan, ROC (China); Lu, Ta-Jung [Department of Chemistry, Institute of Technology and Innovation Management, National Chung-Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan, ROC (China); Hu, Miao-Lin, E-mail: mlhuhu@dragon.nchu.edu.tw [Department of Food Science and Biotechnology, National Chung-Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan, ROC (China)

    2014-12-15

    Alpha-tocopherol ether-linked acetic acid (α-TEA) has been reported to exhibit both anti-tumor and anti-metastatic activities in cell culture and animal studies. However, it is unclear whether α-TEA possesses anti-angiogenic effects. In this study, we investigated the effect of α-TEA on vascular endothelial growth factor (VEGF)-induced angiogenesis and matrix metalloproteinase (MMP) expression both in vitro and ex vivo. We found that the α-TEA inhibited tube formation, invasion, and migration in human umbilical vein endothelial cells (HUVECs) and that such actions were accompanied by reduced expression of MMP-2. α-TEA also inhibited ex vivo angiogenesis, as indicated by chicken egg chorioallantoic membrane assay. We further showed that α-TEA attenuated protein expression of VEGF receptor-2 (VEGFR-2)-mediated p38 mitogen-activated protein kinase (p38), phosphorylated p38, and focal adhesion kinase (FAK). Moreover, α-TEA (30 μM) significantly up-regulated protein expression of tissue inhibitors of MMP (TIMP)-2 (by 138%) and the metastasis suppressor gene nm23-H1 (by 54%). These results demonstrate that the anti-angiogenic effect of α-TEA both in vitro and ex vivo and its possible mechanistic action appears to involve the inhibition of MMP-2 level through VEGFR-2-mediated FAK and p38 signaling pathways and through up-regulation of TIMP-2 and nm23-H1 expression. - Graphical abstract: Possible mechanisms of α-TEA on inhibited angiogenesis of human umbilical vein endothelial cells. Brief summary In the present study, we have demonstrated that VEGF-mediated angiogenesis is significantly inhibited by α-TEA, and that this effect involves inhibition of MMP-2 level through VEGFR-2-mediated FAK and p38 signaling pathways related to invasion and migration. - Highlights: • The anti-angiogenic effect and the mechanistic action of α-TEA were investigated. • α-TEA significantly inhibited VEGF-mediated angiogenesis both in vitro and ex vivo. • α-TEA down

  8. Miniaturizing VEGF: Peptides mimicking the discontinuous VEGF receptor-binding site modulate the angiogenic response.

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    De Rosa, Lucia; Finetti, Federica; Diana, Donatella; Di Stasi, Rossella; Auriemma, Sara; Romanelli, Alessandra; Fattorusso, Roberto; Ziche, Marina; Morbidelli, Lucia; D'Andrea, Luca Domenico

    2016-08-08

    The angiogenic properties of VEGF are mediated through the binding of VEGF to its receptor VEGFR2. The VEGF/VEGFR interface is constituted by a discontinuous binding region distributed on both VEGF monomers. We attempted to reproduce this discontinuous binding site by covalently linking into a single molecular entity two VEGF segments involved in receptor recognition. We designed and synthesized by chemical ligation a set of peptides differing in length and flexibility of the molecular linker joining the two VEGF segments. The biological activity of the peptides was characterized in vitro and in vivo showing a VEGF-like activity. The most biologically active mini-VEGF was further analyzed by NMR to determine the atomic details of its interaction with the receptor.

  9. Miniaturizing VEGF: Peptides mimicking the discontinuous VEGF receptor-binding site modulate the angiogenic response

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    De Rosa, Lucia; Finetti, Federica; Diana, Donatella; di Stasi, Rossella; Auriemma, Sara; Romanelli, Alessandra; Fattorusso, Roberto; Ziche, Marina; Morbidelli, Lucia; D’Andrea, Luca Domenico

    2016-08-01

    The angiogenic properties of VEGF are mediated through the binding of VEGF to its receptor VEGFR2. The VEGF/VEGFR interface is constituted by a discontinuous binding region distributed on both VEGF monomers. We attempted to reproduce this discontinuous binding site by covalently linking into a single molecular entity two VEGF segments involved in receptor recognition. We designed and synthesized by chemical ligation a set of peptides differing in length and flexibility of the molecular linker joining the two VEGF segments. The biological activity of the peptides was characterized in vitro and in vivo showing a VEGF-like activity. The most biologically active mini-VEGF was further analyzed by NMR to determine the atomic details of its interaction with the receptor.

  10. Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications.

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    Tortora, Giampaolo; Ciardiello, Fortunato; Gasparini, Giampietro

    2008-09-01

    Cellular heterogeneity, redundancy of molecular pathways and effects of the microenvironment contribute to the survival, motility and metastasis of cells in solid tumors. It is unlikely that tumors are entirely dependent on only one abnormally activated signaling pathway; consequently, treatment with an agent that interferes with a single target may be insufficient. Combined blockade of functionally linked and relevant multiple targets has become an attractive therapeutic strategy. The EGFR and ERBB2 (HER2) pathways and VEGF-dependent angiogenesis have a pivotal role in cancer pathogenesis and progression. Robust experimental evidence has shown that these pathways are functionally linked and has demonstrated a suggested role for VEGF in the acquired resistance to anti-ERBB drugs when these receptors are pharmacologically blocked. Combined inhibition of ERBB and VEGF signaling interferes with a molecular feedback loop responsible for acquired resistance to anti-ERBB agents and promotes apoptosis while ablating tumor-induced angiogenesis. To this aim, either two agents highly selective against VEGF and ERBB respectively, or, alternatively, a single multitargeted agent, can be used. Preclinical studies have proven the efficacy of both these approaches and early clinical studies have provided encouraging results. This Review discusses the experimental rationale for, preclinical studies of and clinical trials on combined blockade of ERBB and VEGF signaling.

  11. Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression.

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    Anton M Markovets

    Full Text Available UNLABELLED: The incidence of age-related macular degeneration (AMD, the main cause of blindness in older patients in the developed countries, is increasing with the ageing population. At present there is no effective treatment for the prevailing geographic atrophy, dry AMD, whereas antiangiogenic therapies successful used in managing the wet form of AMD. Recently we showed that mitochondria-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1 is able to prevent the development and moreover caused regression of pre-existing signs of the retinopathy in OXYS rats, an animal model of AMD. Here we examine the effects of SkQ1 on expression of key regulators of angiogenesis vascular endothelial growth factor A (VEGF and its antagonist pigment epithelium-derived factor (PEDF genes in the retina of OXYS rats as evidenced by real-time PCR and an ELISA test for VEGF using Wistar rats as control. Ophthalmoscopic examinations confirmed that SkQ1 supplementation (from 1.5 to 3 months of age, 250 nmol/kg prevented development while eye drops SkQ1 (250 nM, from 9 to 12 months caused some reduction of retinopathy signs in OXYS rats and did not reveal any negative effects on the control Wistar rat's retina. Prevention of premature retinopathy by SkQ1 was connected with an increase of VEGF mRNA and protein in OXYS rat's retina up to the levels corresponding to the Wistar rats, and did not involve changes in PEDF expression. In contrast the treatment with SkQ1 drops caused a decrease of VEGF mRNA and protein levels and an increase in the PEDF mRNA level in the middle-aged OXYS rats, but in Wistar rats the changes of gene expression were the opposite. CONCLUSIONS: The beneficial effects of SkQ1 on retinopathy connected with normalization of expression of VEGF and PEDF in the retina of OXYS rats and depended on age of the animals and the stage of retinopathy.

  12. A role for VEGF as a negative regulator of pericyte function and vessel maturation.

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    Greenberg, Joshua I; Shields, David J; Barillas, Samuel G; Acevedo, Lisette M; Murphy, Eric; Huang, Jianhua; Scheppke, Lea; Stockmann, Christian; Johnson, Randall S; Angle, Niren; Cheresh, David A

    2008-12-11

    Angiogenesis does not only depend on endothelial cell invasion and proliferation: it also requires pericyte coverage of vascular sprouts for vessel stabilization. These processes are coordinated by vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) through their cognate receptors on endothelial cells and vascular smooth muscle cells (VSMCs), respectively. PDGF induces neovascularization by priming VSMCs/pericytes to release pro-angiogenic mediators. Although VEGF directly stimulates endothelial cell proliferation and migration, its role in pericyte biology is less clear. Here we define a role for VEGF as an inhibitor of neovascularization on the basis of its capacity to disrupt VSMC function. Specifically, under conditions of PDGF-mediated angiogenesis, VEGF ablates pericyte coverage of nascent vascular sprouts, leading to vessel destabilization. At the molecular level, VEGF-mediated activation of VEGF-R2 suppresses PDGF-Rbeta signalling in VSMCs through the assembly of a previously undescribed receptor complex consisting of PDGF-Rbeta and VEGF-R2. Inhibition of VEGF-R2 not only prevents assembly of this receptor complex but also restores angiogenesis in tissues exposed to both VEGF and PDGF. Finally, genetic deletion of tumour cell VEGF disrupts PDGF-Rbeta/VEGF-R2 complex formation and increases tumour vessel maturation. These findings underscore the importance of VSMCs/pericytes in neovascularization and reveal a dichotomous role for VEGF and VEGF-R2 signalling as both a promoter of endothelial cell function and a negative regulator of VSMCs and vessel maturation. PMID:18997771

  13. SIGNIFICANCE OF INSPECTING SERUM VEGF DURING THERAPY OF TUMOR

    Institute of Scientific and Technical Information of China (English)

    薛文成; 孟冬娅; 杨婧; 罗军

    2002-01-01

    Objective: To investigate the clinical significance of the serum VEGF as amarker for monitoring the clinical course of tumor patients cured by surgery and radiotherapy. Methods: Enzyme linked immunosobent assay (ELISA) was used to detect serum levels of VEGF in the patients with carcinoma. Results: X-ray irradiation could induce the tumor cells to express and secret VEGF. Patients with elevated values of serum VEGF 60 days after radiotherapy had higher rate of tumor recurrence and metastasis. There was more chance of metastasis in lung cancer patients with higher level of VEGF after surgical resection (12/21). Less post-operation (3 months~4 years) patients without relapse or cancerometastasis showed elevated values of serum VEGF than those with relapse or cancerometastasis. There was negative correlation between the serum Hb and VEGF in the tumor patients (( =-0.289, P<0.01). In the 28 patients with normal Hb levels at pre-operation, 17 patients with decreased Hb levels had more chance getting higher VEGF after operation than the others (P<0.05). Conclusion: clinical manifestation should be considered in the application of serum VEGF as a tumor marker, a prognostic factor,and a recurrence indicator of tumor. To determine the levels of serum VEGF and Hb, correct the low level of Hb and block the effect of VEGF by special means may be helpful for tumor patients.

  14. VEGF Deficit is Involved in Endothelium Dysfunction in Preeclampsia

    Institute of Scientific and Technical Information of China (English)

    周琼; 刘海意; 乔福元; 吴媛媛; 徐京晶

    2010-01-01

    This study examined the association of expression of vascular endothelial growth factor(VEGF),a promoter of angiogenesis,with endothelium dysfunction in preeclampsia.The level of VEGF protein and mRNA in the placenta and peripheral blood samples of 30 preeclampsia patients and 30 normotensive pregnant women was measured by immunohistochemistry,real-time reverse transcriptase-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA),respectively.VEGF expression in the human umbilical vei...

  15. VEGF involvement in psoriasis.

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    Marina, Mihaela Elena; Roman, Iulia Ioana; Constantin, Anne-Marie; Mihu, Carmen Mihaela; Tătaru, Alexandru Dumitru

    2015-01-01

    Vascular endothelial growth factor (VEGF) is a key growth factor, regulating the neovascularization, during embryogenesis, skeletal growth, reproductive functions and pathological processes. The VEGF receptors (VEGFR) are present in endothelial cells and other cell types, such as vascular smooth muscle cells, hematopoietic stem cells, monocytes, neurons, macrophages, and platelets. Angiogenesis is initiated by the activation of vascular endothelial cells through several factors. The excess dermal vascularity and VEGF production are markers of psoriasis. The pathological role of VEGF/VEGFR signaling during the psoriasis onset and evolution makes it a promising target for the treatment of psoriasis. Antibodies and other types of molecules targeting the VEGF pathway are currently evaluated in arresting the evolution of psoriasis. PMID:26609252

  16. Screening and Improvement of an Anti-VEGF DNA Aptamer

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    Kazunori Ikebukuro

    2010-01-01

    Full Text Available To obtain an aptamer with a high affinity for vascular endothelial growth factor (VEGF, we focused on the receptor-binding domain (RBD of VEGF as a target epitope. Three rounds of screening gave Vap7, which bound to the VEGF isoforms VEGF121 and VEGF165 with KD values of 1.0 nM and 20 nM, respectively. Moreover, Vap7 showed specificity within the VEGF family. Secondary structure predictions and circular dicrhoism suggested that Vap7 folds into a G-quadruplex structure. We obtained a mutant aptamer that contains only this region of the aptamer sequence. This truncated mutant (V7t1 bound to both VEGF121 and VEGF165 with KD values of 1.1 nM and 1.4 nM, respectively. Its sequence was 5'-TGTGGGGGTGGACGGGCCGGGTAGA-3', and it appeared to form a G-quadruplex structure. We also produced an aptamer heterodimer consisting of our previously derived aptamer (del5-1, which binds to the heparin-binding domain of VEGF, linked to V7t1. The resulting heterodimer bound strongly to VEGF165 with a KD value of 4.7 × 102 pM.

  17. VEGF involvement in psoriasis

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    MARINA, MIHAELA ELENA; ROMAN, IULIA IOANA; CONSTANTIN, ANNE-MARIE; Carmen Mihaela MIHU; TĂTARU, ALEXANDRU DUMITRU

    2015-01-01

    Vascular endothelial growth factor (VEGF) is a key growth factor, regulating the neovascularization, during embryogenesis, skeletal growth, reproductive functions and pathological processes. The VEGF receptors (VEGFR) are present in endothelial cells and other cell types, such as vascular smooth muscle cells, hematopoietic stem cells, monocytes, neurons, macrophages, and platelets. Angiogenesis is initiated by the activation of vascular endothelial cells through several factors. The excess de...

  18. Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

    DEFF Research Database (Denmark)

    Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki;

    2016-01-01

    The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes...... of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte......, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the 'off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge...

  19. Relationship between Expression of beta-catenin and VEGFs(VEGFA,VEGF-C),VEGF Receptors-2(VEGFR-2)in Medulloblastoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-mei; ZHANG Xiong; LI Yu; MI Can

    2008-01-01

    Objective:To investigate the expression of beta-catenin and VEGFs(VEGF-A,VEGF-C)and VEGF receptor-2(VEGFR-2)protein in medulloblastoma.Methods:Immunohistochemical staining with SP method Was conducted to determine the expression of beta-eatenin and VEGFs(VEGF-A,VEGF-C)and VEGFR-2 in 33 cases of medulloblastoma and 10 normal cerebellar tissues. Results:The expression rate of beta-catenin,and VEGFs (VEGF-A,VEGF-C)and VEGFR-2 in medulloblastoma were significantly higher than that in normal tissue.A significant positive correlation was found between beta-catenin and VEGFs(VEGF-A,VEGF-C)and VEGFR-2 protein in medulloblastoma. Conclusion:There was a correlation between beta-catenin and VEGFs(VEGF-A,VEGF-C)and VEGFR-2 in medulloblastoma,which may play a role in the pathogenesis and development of medulloblastoma.

  20. Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer

    International Nuclear Information System (INIS)

    Insulin-like growth factor-I receptor (IGFIR) has been shown to regulate the tumor development. The objective of the current study is to determine the association of IGFIR with lymph node metastasis and to explore the related mechanism in human colorectal cancer in clinic. In a random series of 98 colorectal cancer patients, the expressions of IGFIR, vascular endothelial growth factor (VEGF) and VEGF-C were investigated by immunohistochemistry, and the association of these expressions with lymph node metastasis was statistically analyzed. The expressions of VEGF and VEGF-C in colorectal cancer cells stimulated with IGF-I were also examined by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Higher rates of IGFIR (46%), VEGF (53%), and VEGF-C (46%) expression were found in colorectal cancer tissues than in normal and colorectal adenoma tissues. These expressions were significantly associated with clinicopathologic factors and lymph node status. We also found the concomitant high expressions of IGFIR/VEGF (P < 0.001) and IGFIR/VEGF-C (P = 0.001) had a stronger correlation with lymph node metastasis than did each alone or both low expressions. In addition, IGF-I could effectively induce the VEGF and VEGF-C mRNA expression and protein secretion in colorectal cancer cells expressing IGFIR molecules. Moreover, Patients who had strong staining for IGFIR, VEGF and VEGF-C showed significantly less favorable survival rates compared with patients who had low staining for these molecules (P < 0.001). The survival rates of patients who were both high expression of IGFIR/VEGF and IGFIR/VEGF-C also were significantly lower compared with patients who were negative or one of high expression of these molecules (P < 0.001). Together the findings indicated for the first time that simultaneous examination of the expressions of IGFIR, VEGF and VEGF-C will benefit the diagnosis of lymph node metastasis in order to assay the

  1. Extracellular Matrix Stiffness Controls VEGF Signaling and Processing in Endothelial Cells.

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    Sack, Kelsey D; Teran, Madelane; Nugent, Matthew A

    2016-09-01

    Vascular endothelial growth factor A (VEGF) drives endothelial cell maintenance and angiogenesis. Endothelial cell behavior is altered by the stiffness of the substrate the cells are attached to suggesting that VEGF activity might be influenced by the mechanical cellular environment. We hypothesized that extracellular matrix (ECM) stiffness modifies VEGF-cell-matrix tethering leading to altered VEGF processing and signaling. We analyzed VEGF binding, internalization, and signaling as a function of substrate stiffness in endothelial cells cultured on fibronectin (Fn) linked polyacrylamide gels. Cell produced extracellular matrices on the softest substrates were least capable of binding VEGF, but the cells exhibited enhanced VEGF internalization and signaling compared to cells on all other substrates. Inhibiting VEGF-matrix binding with sucrose octasulfate decreased cell-internalization of VEGF and, inversely, heparin pre-treatment to enhance Fn-matrix binding of VEGF increased cell-internalization of VEGF regardless of matrix stiffness. β1 integrins, which connect cells to Fn, modulated VEGF uptake in a stiffness dependent fashion. Cells on hard surfaces showed decreased levels of activated β1 and inhibition of β1 integrin resulted in a greater proportional decrease in VEGF internalization than in cells on softer matrices. Extracellular matrix binding is necessary for VEGF internalization. Stiffness modifies the coordinated actions of VEGF-matrix binding and β1 integrin binding/activation, which together are critical for VEGF internalization. This study provides insight into how the microenvironment may influence tissue regeneration and response to injury and disease. J. Cell. Physiol. 231: 2026-2039, 2016. © 2016 Wiley Periodicals, Inc.

  2. VEGF121b and VEGF165b are weakly angiogenic isoforms of VEGF-A

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    Pio Ruben

    2010-12-01

    Full Text Available Abstract Background Different isoforms of VEGF-A (mainly VEGF121, VEGF165 and VEGF189 have been shown to display particular angiogenic properties in the generation of a functional tumor vasculature. Recently, a novel class of VEGF-A isoforms, designated as VEGFxxxb, generated through alternative splicing, have been described. Previous studies have suggested that these isoforms may inhibit angiogenesis. In the present work we have produced recombinant VEGF121/165b proteins in the yeast Pichia pastoris and constructed vectors to overexpress these isoforms and assess their angiogenic potential. Results Recombinant VEGF121/165b proteins generated either in yeasts or mammalian cells activated VEGFR2 and its downstream effector ERK1/2, although to a lesser extent than VEGF165. Furthermore, treatment of endothelial cells with VEGF121/165b increased cell proliferation compared to untreated cells, although such stimulation was lower than that induced by VEGF165. Moreover, in vivo angiogenesis assays confirmed angiogenesis stimulation by VEGF121/165b isoforms. A549 and PC-3 cells overexpressing VEGF121b or VEGF165b (or carrying the PCDNA3.1 empty vector, as control and xenotransplanted into nude mice showed increased tumor volume and angiogenesis compared to controls. To assess whether the VEGFxxxb isoforms are differentially expressed in tumors compared to healthy tissues, immunohistochemical analysis was conducted on a breast cancer tissue microarray. A significant increase (p xxxb and total VEGF-A protein expression in infiltrating ductal carcinomas compared to normal breasts was observed. A positive significant correlation (r = 0.404, p = 0.033 between VEGFxxxb and total VEGF-A was found. Conclusions Our results demonstrate that VEGF121/165b are not anti-angiogenic, but weakly angiogenic isoforms of VEGF-A. In addition, VEGFxxxb isoforms are up-regulated in breast cancer in comparison with non malignant breast tissues. These results are to be taken

  3. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

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    Fearnley, Gareth W.; Smith, Gina A.; Abdul-Zani, Izma; Yuldasheva, Nadira; Mughal, Nadeem A.; Homer-Vanniasinkam, Shervanthi; Kearney, Mark T.; Zachary, Ian C.; Tomlinson, Darren C.; Harrison, Michael A.; Wheatcroft, Stephen B.; Ponnambalam, Sreenivasan

    2016-01-01

    ABSTRACT Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes. PMID:27044325

  4. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2016-05-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145 promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.

  5. Regulating VEGF signaling in platelet concentrates via specific VEGF sequestering.

    Science.gov (United States)

    Belair, David G; Le, Ngoc Nhi; Murphy, William L

    2016-05-26

    Platelets contain an abundance of growth factors that mimic the composition of the wound healing milieu, and platelet-derived VEGF in particular can negatively influence wound healing if unregulated. Here, we sought to capture and regulate the activity of VEGF factor from human platelets using poly(ethylene glycol) microspheres. In this communication, we demonstrate that platelet freeze/thaw produced significantly higher levels of Vascular Endothelial Growth Factor (VEGF) than either calcium chloride treatment, protease activated receptor 1 activating peptide (PAR1AP) treatment, or thrombin treatment. PEG microspheres containing a VEGF-binding peptide (VBP), derived from VEGFR2, sequestered VEGF from platelet concentrate, prepared via freeze/thaw, and reduced the bioactivity of platelet concentrate in HUVEC culture, which suggests that VBP microspheres sequestered and reduced the activity of VEGF from patient-derived platelets. Here, we demonstrate the ability of VEGF sequestering microspheres to regulate the activity of VEGF derived from a growth factor-rich autologous human blood product. PMID:27010034

  6. CXCL7-Mediated Stimulation of Lymphangiogenic Factors VEGF-C, VEGF-D in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Minghuan Yu

    2010-01-01

    Full Text Available Increased expression of lymphangiogenesis factors VEGF-C/D and heparanase has been correlated with the invasion of cancer. Furthermore, chemokines may modify matrix to facilitate metastasis, and they are associated with VEGF-C and heparanase. The chemokine CXCL7 binds heparin and the G-protein-linked receptor CXCR2. We investigated the effect of CXCR2 blockade on the expression of VEGF-C/D, heparanase, and on invasion. CXCL7 siRNA and a specific antagonist of CXCR2 (SB225002 were used to treat CXCL7 stably transfected MCF10AT cells. Matrigel invasion assays were performed. VEGF-C/D expression and secretion were determined by real-time PCR and ELISA assay, and heparanase activity was quantified by ELISA. SB225002 blocked VEGF-C/D expression and secretion (P<.01. CXCL7 siRNA knockdown decreased heparanase (P<.01. Both SB225002 and CXCL7 siRNA reduced the Matrigel invasion (P<.01. The MAP kinase signaling pathway was not involved. The CXCL7/CXCR2 axis is important for cell invasion and the expression of VEGF-C/D and heparanase, all linked to invasion.

  7. Skeletal myofiber VEGF regulates contraction-induced perfusion and exercise capacity but not muscle capillarity in adult mice.

    Science.gov (United States)

    Knapp, Amy E; Goldberg, Daniel; Delavar, Hamid; Trisko, Breanna M; Tang, Kechun; Hogan, Michael C; Wagner, Peter D; Breen, Ellen C

    2016-07-01

    A single bout of exhaustive exercise signals expression of vascular endothelial growth factor (VEGF) in the exercising muscle. Previous studies have reported that mice with life-long deletion of skeletal myofiber VEGF have fewer capillaries and a severe reduction in endurance exercise. However, in adult mice, VEGF gene deletion conditionally targeted to skeletal myofibers limits exercise capacity without evidence of capillary regression. To explain this, we hypothesized that adult skeletal myofiber VEGF acutely regulates skeletal muscle perfusion during muscle contraction. A tamoxifen-inducible skeletal myofiber-specific VEGF gene deletion mouse (skmVEGF-/-) was used to reduce skeletal muscle VEGF protein by 90% in adult mice. Three weeks after inducing deletion of the skeletal myofiber VEGF gene, skmVEGF-/- mice exhibited diminished maximum running speed (-10%, P < 0.05) and endurance capacity (-47%; P < 0.05), which did not persist after 8 wk. In skmVEGF-/- mice, gastrocnemius complex time to fatigue measured in situ was 71% lower than control mice. Contraction-induced perfusion measured by optical imaging during a period of electrically stimulated muscle contraction was 85% lower in skmVEGF-/- than control mice. No evidence of capillary rarefication was detected in the soleus, gastrocnemius, and extensor digitorum longus (EDL) up to 8 wk after tamoxifen-induced VEGF ablation, and contractility and fatigue resistance of the soleus measured ex vivo were also unchanged. The force-frequency of the EDL showed a small right shift, but fatigue resistance did not differ between EDL from control and skmVEGF-/- mice. These data suggest myofiber VEGF is required for regulating perfusion during periods of contraction and may in this manner affect endurance capacity. PMID:27225953

  8. VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the reg- ulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS: The impact of high-level expression of the growth factor receptors EGFR and VEGF recep- tor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in hu- man CRC was investigated in 108 patients using immu- nohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS: Human CRC specimens and cell lines dis- played EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metas- tases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with ce- tuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION: In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab.

  9. VEGF Inhibitors for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Prakash S. Sukhramani

    2010-01-01

    Full Text Available Despite significant advances in systemic therapies, radiation oncology, and surgical techniques, many patients with cancer are still incurable. A novel therapeutic approach has been to target the vascular endothelial growth factors (VEGFs which are often mutated and/or over-expressed in many tumors. The ligands and receptors of VEGF family are well established as key regulators of angiogenesis and vasculogenesis processes. VEGF is a homodimeric, basic, 45 kDa glycoprotein specific for vascular endothelial cells. Specifically, VEGF participates in regulation of the female reproductive cycle, wound healing, inflammation, vascular permeability, vascular tone, hematopoiesis and also contributes to pathological angiogenesis disorders such as cancer, rheumatoid arthritis, diabetic retinopathy and the neovascular form of macular degeneration. Thus, the role of VEGF has been extensively studied in the pathogenesis and angiogenesis of human cancers. Clinical trials have anti-VEGF therapies are effective in reducing tumor size, metastasis and blood vessel formation. Clinically, this may result in increased progression free survival, overall patient survival rate and will expand the potential for combinatorial therapies. The aim of present review is on the cellular responses of VEGF inhibitors and their implications for cancer therapy.

  10. AlphaB-crystallin is involved in oxidative stress protection determined by VEGF in skeletal myoblasts.

    Science.gov (United States)

    Mercatelli, Neri; Dimauro, Ivan; Ciafré, Silvia Anna; Farace, Maria Giulia; Caporossi, Daniela

    2010-08-01

    Recent studies suggest that the effects of VEGF-A, the prototype VEGF ligand, may extend to a variety of cell types other than endothelial cells. The expression of VEGF-A and its main receptors, Flt-1/VEGFR-1 and KDR/Flk-1/VEGFR-2, was indeed detected in several cell types, including cardiac myocytes and regenerating myotubes. In addition to its proangiogenic activity, evidence indicates that VEGF-A can sustain skeletal muscle regeneration by enhancing the survival and migration of myogenic cells and by promoting the growth of myogenic fibers. In this study, our aim was to investigate whether VEGF could protect skeletal muscle satellite cells from apoptotic cell death triggered by reactive oxygen species and to identify the main molecular mechanisms. C2C12 mouse myoblasts, cultured in vitro in the presence of exogenous VEGF or stably transfected with a plasmid vector expressing VEGF-A, were subjected to oxidative stress and analyzed for cell growth and survival, induction of apoptosis, and molecular signaling. The results of our study demonstrated that VEGF protects C2C12 myoblasts from apoptosis induced by oxidative or hypoxic-like stress. This protection did not correlate with the modulation of the expression of VEGF receptors, but is clearly linked to the phosphorylation of the KDR/Flk-1 receptor, the activation of NF-kappaB, and/or the overexpression of the antiapoptotic protein alphaB-crystallin. PMID:20441791

  11. VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization

    Directory of Open Access Journals (Sweden)

    Sharon Lim

    2014-10-01

    Full Text Available Molecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC mobilization remain unknown. Here, we report that tumor VEGF markedly induced sinusoidal vasculature dilation in bone marrow (BM and BMC mobilization to tumors and peripheral tissues in mouse and human tumor models. Unexpectedly, anti-VEGFR2, but not anti-VEGFR1, treatment completely blocked VEGF-induced anemia and BMC mobilization. Genetic deletion of Vegfr2 in endothelial cells markedly ablated VEGF-stimulated BMC mobilization. Conversely, deletion of the tyrosine kinase domain from Vegfr1 gene (Vegfr1TK−/− did not affect VEGF-induced BMC mobilization. Analysis of VEGFR1+/VEGFR2+ populations in peripheral blood and BM showed no significant ratio difference between VEGF- and control tumor-bearing animals. These findings demonstrate that vascular dilation through the VEGFR2 signaling is the mechanism underlying VEGF-induced BM mobilization and anemia. Thus, our data provide mechanistic insights on VEGF-induced BMC mobilization in tumors and have therapeutic implications by targeting VEGFR2 for cancer therapy.

  12. VEGF-B: a thing of beauty

    Institute of Scientific and Technical Information of China (English)

    Xuri Li

    2010-01-01

    More than a decade ago, when we first embarked on our journey to delineate the biological function of vascular endothelial growth factor B (VEGF-B),we had a hard time comprehending why VEGF-B was needed. In mice, geneticdeletion of VEGF-B seemed to be harmless, since the VEGF-B null mice, to a large extent, can still live a fairly normal life [1].

  13. Antiangiogenic VEGF Isoform in Inflammatory Myopathies

    Directory of Open Access Journals (Sweden)

    Nila Volpi

    2013-01-01

    Full Text Available Objective. To investigate expression of vascular endothelial growth factor (VEGF antiangiogenic isoform A-165b on human muscle in idiopathic inflammatory myopathies (IIM and to compare distribution of angiogenic/antiangiogenic VEGFs, as isoforms shifts are described in other autoimmune disorders. Subjects and Methods. We analyzed VEGF-A165b and VEGF-A by western blot and immunohistochemistry on skeletal muscle biopsies from 21 patients affected with IIM (polymyositis, dermatomyositis, and inclusion body myositis and 6 control muscle samples. TGF-β, a prominent VEGF inductor, was analogously evaluated. Intergroup differences of western blot bands density were statistically examined. Endomysial vascularization, inflammatory score, and muscle regeneration, as pathological parameters of IIM, were quantitatively determined and their levels were confronted with VEGF expression. Results. VEGF-A165b was significantly upregulated in IIM, as well as TGF-β. VEGF-A was diffusely expressed on unaffected myofibers, whereas regenerating/atrophic myofibres strongly reacted for both VEGF-A isoforms. Most inflammatory cells and endomysial vessels expressed both isoforms. VEGF-A165b levels were in positive correlation to inflammatory score, endomysial vascularization, and TGF-β. Conclusions. Our findings indicate skeletal muscle expression of antiangiogenic VEGF-A165b and preferential upregulation in IIM, suggesting that modulation of VEGF-A isoforms may occur in myositides.

  14. Binding MR target contrast agent precursor-VEGF165- aptamer and VEGF165 in vitro%MR靶向对比剂前体——VEGF165-适配体与VEGF165体外结合实验研究

    Institute of Scientific and Technical Information of China (English)

    尤晓光; 白玉杰; 涂蓉

    2011-01-01

    目的 应用酶联免疫吸附实验 (ELISA)检测MR靶向对比剂前体--血管内皮生长因子165-适配体(VEGF165-aptamer)与VEGF165的体外结合能力,以了解其对VEGF的靶向性.方法 实验组采用亲和素96孔酶标板, 包被生物素化VEGF165-aptamer, 设置递减的浓度梯度(共9组)和空白对照组,采用组间方差分析.结果 实验组包被生物素化VEGF165-aptamer浓度在50~0.78 pmol/ μL时,实验组与空白组及实验各相邻组间差异有统计学意义(P0.05).结论 采用ELISA检测技术验证了VEGF165-aptamer与VEGF165间的体外结合能力,其有效最低小包被浓度为0.78 pmol/ μL, VEGF165-aptamer对VEGF165有良好的靶向性.%Objective To investigate the binding ability of MR target contrast agent precursor-vascular endothelial growth factor 165 (VEGF165)-aptamer with VEGF165 in vitro using enzyme-linked immunosorbent assay method.Methods In the test groups, the biotinylation VEGF165-aptamer was coated onto the 96 well plates with gradient concentrations from 50 pmol/μL to 0.195 pmol/μL. The corresponding control groups were also set up. The data were analyzed with One-way ANOVA. The binding bern een VEGF165-aptamer and VEGF165 was identified with ELISA method.Results When the concentraion of VEGF165-aptamerwas at range of 50 pmol/μL~0.78 pmol/μl,,tbere was significant difference in binding between the experimental and control groups (P<0.05). When the concentration was at 0.39 pmol/μL and 0.195 pmol/μL, there was no significant difference in binding between two groups (P>0.05). Conclusion The minimal concentration of VEGF165-aptamer that can synthesize detectable binding is at 0.78 pmol/μL. The vascular endothelial growth factor 165-adaplation body has favorable target tropism to the WEGF165.

  15. Functions of VEGF in female reproductive system

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    As a homodimeric glycoprotein, vascular en- dothelial growth factor (VEGF) is a highly specific mitogen of vascular endothelial cells. It can induce proliferation and migration, and inhibit apoptosis of endothelial cell. VEGF is involved in many processes in the female reproductive system, such as ovulation, periodical changes of endometrium, embryo implantation and development. VEGF plays important roles in some reproductive diseases, including preeclampsia and fetal hypoevolutism in uterus. Based on our studies on angiogenesis and its relevant factors in the female reproductive system these years, the functions of VEGF in female reproductive system are reviewed, and the research prospect and application of VEGF are also discussed.

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

    Institute of Scientific and Technical Information of China (English)

    Yao-guo Yang; Heng Guan; Chang-wei Liu; Yong-jun Li

    2009-01-01

    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 mcllitus.

  17. Experimental study of treatment for radiation-damaged mice by transgenic VEGF

    International Nuclear Information System (INIS)

    Objective: To study the effect of VEGF gene expression in the treatment of radiation damage, and to explore its molecular mechanism by transferring eukaryotic expression plasmid containing VEGF gene into irradiated mice cells. Methods: Normally Kunming mice were divided randomly into three groups as control group, irradiated group and transferred VEGF gene group. The mice were administered with 8 Gy X-ray exposure after intramuscular injection of VEGF recombinant plasmid in the transgenic group. The animals were killed at different times after X-ray exposure. Their clinical manifestation, mortality rate, pathology of tissues and in situ apoptosis in thymus and splenic cells were observed. Results: VEGF165 gene fragments were amplified from pSP73/HVEGF165 plasmid by PCR method, and then linked with pcDNA3.1 vector after incision by double enzyme. The recombinant plasmid pcDNA3.1/VEGF165 was constructed. Electrophoresis and sequencing showed that the recombinant plasmid sequence was exactly the same with the data in GenBank. The mortality of irradiated group and transgenic group 14 d post-irradiation was 64% and 36%, respectively, with the statistical difference (t=3.92, P165 was successfully constructed. Transgenic treatment with recombinant plasmid can remarkably decrease the mortality and apoptosis rate of thymus and spleen cells in mice suffering from severe radiation damage, and improve the pathologic change of immune organs. VEGF transgenic technique is one of the effective methods for treating severe radiation injury. (authors)

  18. Mechanical Forces Induce Changes in VEGF and VEGFR-1/sFlt-1 Expression in Human Chondrocytes

    Directory of Open Access Journals (Sweden)

    Rainer Beckmann

    2014-09-01

    Full Text Available Expression of the pro-angiogenic vascular endothelial growth factor (VEGF stimulates angiogenesis and correlates with the progression of osteoarthritis. Mechanical joint loading seems to contribute to this cartilage pathology. Cyclic equibiaxial strains of 1% to 16% for 12 h, respectively, induced expression of VEGF in human chondrocytes dose- and frequency-dependently. Stretch-mediated VEGF induction was more prominent in the human chondrocyte cell line C-28/I2 than in primary articular chondrocytes. Twelve hours of 8% stretch induced VEGF expression to 175% of unstrained controls for at least 24 h post stretching, in promoter reporter and enzyme-linked immunosorbent assay (ELISA studies. High affinity soluble VEGF-receptor, sVEGFR-1/sFlt-1 was less stretch-inducible than its ligand, VEGF-A, in these cells. ELISA assays demonstrated, for the first time, a stretch-mediated suppression of sVEGFR-1 secretion 24 h after stretching. Overall, strained chondrocytes activate their VEGF expression, but in contrast, strain appears to suppress the secretion of the major VEGF decoy receptor (sVEGFR-1/sFlt-1. The latter may deplete a biologically relevant feedback regulation to inhibit destructive angiogenesis in articular cartilage. Our data suggest that mechanical stretch can induce morphological changes in human chondrocytes in vitro. More importantly, it induces disturbed VEGF signaling, providing a molecular mechanism for a stress-induced increase in angiogenesis in cartilage pathologies.

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

    Institute of Scientific and Technical Information of China (English)

    Bao-He Zhu; Hua-Yun Chen; Wen-Hua Zhan; Cheng-You Wang; Shi-Rong Cai; Zhao Wang; Chang-Hua Zhang; Yu-Long He

    2011-01-01

    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 conditioned medium 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

  20. Where is VEGF in the body? A meta-analysis of VEGF distribution in cancer

    OpenAIRE

    Kut, C; Mac Gabhann, F.; Popel, A S

    2007-01-01

    Vascular endothelial growth factor (VEGF) is a major target for the inhibition of tumour vascularisation and the treatment of human cancer. Many tumours produce large quantities of VEGF, and as a result, diagnosis and prognosis of cancer may be predicted by measuring changes in VEGF concentrations in blood. In blood, the VEGF may be located in the plasma, or in the blood-borne cells and formed elements, in particular, platelets and leukocytes. In this study, we collate the measurements of VEG...

  1. TFF3 mediated induction of VEGF via hypoxia in human gastric cancer SGC-7901 cells.

    Science.gov (United States)

    Guleng, Bayasi; Han, Jia; Yang, Jin-Qiu; Huang, Qing-Wen; Huang, Jian-Kun; Yang, Xiao-Ning; Liu, Jing-Jing; Ren, Jian-Lin

    2012-04-01

    Increasing evidence indicates that in gastric epithelial cells, induction of TFF3 by hypoxia is mediated by HIF-1. Since VEGF is one of the most important angiogenic factors on cancer progression, we have started to investigate the possible link among HIF-1α, VEGF, and TFF3 in gastric cancer cells. We induced the hypoxic condition in SGC-7901cells using hypoxia-mimetic agent of CoCI2. SGC7901 cells were transfected with pcPUR + U6 plasmid carrying RNAi targeted to human TFF3 and selected puromycin-resistant pools to establish the stable knockdown of TFF3 cells. Our results showed the induction of HIF-1a via hypoxia and consequences of increased expressions of the TFF3 and VEGF in gastric cancer SGC-7901 cells. Overexpression of TFF3 upregulated the mRNA expressions of VEGF and HIF-1a induced by hypoxia, and stable knockdown of TFF3 impaired the mRNA upregulations of VEGF and HIF-1a induced by hypoxia. Furthermore, knockdown of TFF3 reduced the VEGF protein secretion: as VEGF secretion was increased time dependent manner in response to the hypoxia induction in TFF3-WT cells; however, VEGF production was significantly decreased in TFF3-KD cells (621 ± 89 vs. 264 ± 73 at 6 h and 969 ± 97 vs. 508 ± 69 at 12 h, P TFF3 mediated regulation of VEGF expression induced by hypoxia, and implicated that TFF3 might be applied as a potential anti-angiogenic target for treatment of gastric cancer.

  2. The relationship between corneal angiogenesis and lymphangiogenesis with VEGF-A and VEGF-C expression in the aqueous humor%角膜新生血管和淋巴管与房水中VEGF-A和VEGF-C表达量关系研究

    Institute of Scientific and Technical Information of China (English)

    赵玲; 周善璧; 杨洋; 唐德荣; 薛晓燕

    2013-01-01

    达量与角膜新生血管和角膜新生淋巴管数变化规律,为角膜病患者选择合适的角膜移植手术时机提供理论依据.方法 系统性回顾分析2011年4至10月期间因角膜病变在重庆医科大学附属第一医院眼科行穿透性角膜移植术的患者10例(10只眼).采用管腔内皮非特异受体CD31和淋巴管内皮细胞特异性抗体LYVE-1行免疫组织化学染色,定量检测角膜新生血管数目(Blood vessels counting,BVC)和角膜新生淋巴管的数目(Lymphatic vessels counting,LVC).将10个实验组样本和10个对照组(单纯年龄相关性白内障患者)的房水用酶联免疫吸附测定法(Enzyme linked immunosorbentassay,ELISA)对比试验,测出房水中VEGF-A和VEGF-C的表达量.结果采用配对t检验,Pearson相关检验进行统计学分析.结果 免疫组化染色结果10例实验组角膜都有新生血管,4例既有新生血管又有新生淋巴管.实验组和对照组房水中VEGF-A和VEGF-C表达量差异有统计学意义,角膜新生血管、新生淋巴管与其房水的VEGF-A和VEGF-C的表达量有明显的关系.结论 角膜病变后有角膜新生血管和新生淋巴管的患者,其房水中的VEGF-A和VEGF-C的表达量明显增高,且VEGF-A和角膜新生血管的数量呈正相关,VEGF-C和角膜新生淋巴管的数量也呈正相关,说明通过房水中VEGF-A和VEGF-C的检测可推知角膜新生血管和淋巴管的生长情况.

  3. Abnormal expression of vascular endothelial growth factor (VEGF) and its clinical features in tissues of human lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xinhua Wu; Dengfu Yao; Gongshen Shi; Liwei Qiu; Wei Wu; Songshi Ni; Xueguang Zhang

    2005-01-01

    Objective: Angiogennesis, the formation of new blood vessels from the existing vascular bed, is essential step for growth and invasion of primary tumor. Vascular endothelial growth-factor (VEGF) is known to play crucial role in tumor angiogenesis. In the present study, we investigate the expression of VEGF and VEGF-mRNA in the angiogennesis, metastasis and prognosis of lung cancer.Methods: The VEGF cellular distributions and expression in 38 specimens of patients with lung cancer were investigated with immunohistochemistry stain technology. The total RNAs in 38 tissues of lung cancer was measured, then the levels of VEGF-mRNA expression were analyzed by a reverse-transcription polymerase chain reaction (RT-PCR) assay. The levels of VEGF in sera of patients with lung cancer, benign lung diseases and healthy controls were detected through Enzyme linked immunosorbent assay (ELISA) method. Results: The VEGF positive stain was 76% in 38 cases of lung cancer specimens. The 89% rate of VEGF stain was found for clinical stage Ⅲ cases and 92%for stage Ⅳ lung cancers. The significantly higher expression of VEGF was evidenced in patients with lymph node metastasis (84 % ), distant metastasis (90%), and lung cancers with lower histological differentiation (89%), respectively. The expression level of total RNA was significantly higher in patients with lung cancers than that in their paracancerous or distant lung tissues. The VEGF expressions were tightly correlated with total RNA concentration of lung carcinoma ( P < 0.01 ). The predominant expressions of VEGF121 and VEGF165 gene fragments were found in lung cancer specimens by RT-PCR analysis. No significant difference of serum VEGF levels was detected between cases with lung cancer and patients with benign diseases. However, the VEGF level of cases with benign diseases was decreased significantly after patients with anti-inflammation medication. Conclusion: The present data suggested that the tumor tissue VEGF

  4. Using Anti-VEGF in Diabetic Retinopathy

    Science.gov (United States)

    Marashi, Ameen

    2016-01-01

    Vascular endothelium growth factor is the main pathological factor in diabetic retinopathy and diabetic macular edema (DME), Anti-VEGF agents are safe and effective in DME treatment, there are multiple Anti-VEGF agents, choosing between them is essential to individualize treatment for each patient to achieve the optimum results. PMID:27419238

  5. Over-expression of VEGF165 in the adipose tissue-derived stem cells via the lentiviral vector

    Institute of Scientific and Technical Information of China (English)

    SUN Xiang-zhou; LIU Gui-hua; WANG Zhuo-qing; ZHENG Fu-fu; BIAN Jun; HUANG Yan-ping; GAO Yong; ZHANG Ya-dong; DENG Chun-hua

    2011-01-01

    Background Many researchers studied the possibility of using stem cells as gene therapeutic vector. But few related reports on the adipose tissue-derived stem cells (ADSCs) are available. Therefore we intended to construct a lentiviral VEGF165 expression vector and then infect the ADSCs to produce therapeutic seed cells.Methods EHS1001-68950485313912 clone was mutated by PCR method to produce consensus fragment of VEGF165 transcript (NM_001025368). Lentivirus was enveloped with pGC-FU, pHelper 1.0 and pHelper 2.0 plasmids in 293T cells.And then the ADSCs (multiplicity of infection=20) were transfected with the vectors after titer determination. Stable expression of VEGF165 in ADSCs was confirmed by immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA) and Western blotting analysis.Results DNA sequencing and 293T transfection verified VEGF165 was linked to the GFP fused vector. The virus titer is up to 2x10a determined by quantitative PCR. VEGF165 transduced cells could show green fluorescence confirmed by immunofluorescence staining (almost 95%). ELISA analyses could detect out the density of VEGF was 850.86-1202.13pg/ml (mean (923.00±31.22) pg/ml) in the supernatant of VEGF16s-transduced cells but not detected in the GFP-transduced cells (P <0.001) and the Western blotting analyses also confirmed VEGF165 expression in VEGF165-transduced cells.Conclusions The VEGF165 over-expression ADSCs were obtained and may be used as a cell therapeutic tool and may be applied for vascular regeneration, especially in the treatment of erectile dysfunction.

  6. Proteasome inhibitor MG-132 regulates the expression of VEGF in human bronchial epithelial cell line, BEAS-2B

    Institute of Scientific and Technical Information of China (English)

    Xuefan Cui; Kaisheng Yin; Mao Huang; Linfu Zhou

    2005-01-01

    Objective: To explore the effects of MG-132 on the expression of VEGF in bronchial epithelial cell line, BEAS2B. Methods: Semi-quantitive RT-PCR for VEGF mRNA and enzyme-linked immunosorbent assay (ELISA) for VEGF protein were performed. Results: MG-132 increased the expression of VEGF mRNA and protein BEAS-2B cells in time-and concentration-dependent manners. After 24-h stimulation, 25 μmol/L MG-132 increased the maximal levels of VEGF protein in cell-conditioned medium. When the cells were stimulated with cycloheximide(CHX) before treatment with MG-132, the MG-132-induced production of VEGF protein was inhibited compared to the unstimulated cells. Supernatant of condition-medium treatment with MG-132 enhanced the growth of HUVEC.Conclusion: MG-132 induces VEGF gene expression in human bronchial epithelial cells line, BEAS-2B, and the MG-132-induced expression of VEGF may modulate lung tissue injury due to airway inflammation.

  7. Clinical value ofSerumTSH combined with 3 kinds ofVEGF determination in the early diagnosis of papillary thyroid carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming Zeng

    2015-01-01

    Objective:To discuss the clinical value of Serum TSH combined with 3 kinds of VEGF (VEGF-C, VEGF-D and VEGFR-3) determination in the early diagnosis of papillary thyroid carcinoma (PTC). Method:Selected 37 cases of patients with thyroid benign tumor (Benign group) and 37 cases of patients with PTC (PTC group), then collected the serum of these both groups, to determine the TSH, VEGF-C, VEGF-D and VEGFR-3 levels of all cases by chemiluminescence immunoassay and enzyme linked immunosorbent assay respectively. Through Logistic model, to calculate the curve area of TSH combined with 3 kinds of VEGF.Results:PTC group: VEGF-C, VEGFR-3 and TSH levels were obviously higher than that in Benign group (P<0.05); and VEGF-C, VEGFR-3 and TSH levels inⅢ-Ⅳ period patients were obviously higher than that in I-Ⅱ period patients (P<0.05); AUC area of VEGF-C, VEGFR-3 and TSH were respectively 0.805, 0.736 and 0.710, reached to significance level (P<0.05); AUC area of combined diagnosis was 0.859.Conclusion:VEGF-C, VEGFR-3 and TSH between papillary thyroid carcinoma and thyroid benign tumor had significant difference. Combined determination could improve the early diagnose rate of PTC, and could be regarded as one of the important auxiliary index of PTC early diagnosis.

  8. Studies of ablation pressure, ablative acceleration and ablative implosions

    International Nuclear Information System (INIS)

    Time and space resolved X-ray spectroscopy have been used to measure ablation rate and ablation pressure on plane targets irradiated by the first and second harmonics of Nd glass laser light. Streaked X-ray shadowgraphy has been applied to the study of ablatively imploded spherical shell targets uniformly irradiated by six 1.05 μm laser beams. The results give a direct measurement of shell acceleration and thus of ablation pressure and show evidence of fluid instability increasing as the shell ratio is varied from 10 to 100. A direct determination of implosion core density is also obtained. (author)

  9. Determination of vascular endothelial growth factor (VEGF) in circulating blood: significance of VEGF in various leucocytes and platelets

    DEFF Research Database (Denmark)

    Werther, K; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2002-01-01

    contained considerable amounts of VEGF. In isolated lymphocytes and monocytes, VEGF was not present in measurable amounts. The number of neutrophils was significantly (p<0.0001) correlated to VEGF concentrations in lysed whole blood, but not to VEGF concentrations in plasma or serum. The number of platelets...... clotting. CONCLUSION: Circulating neutrophils contain considerable amounts of VEGF that contribute to high VEGF levels in lysed whole blood. VEGF in circulating platelets contributes to high VEGF levels in serum and lysed whole blood. Allowing whole blood samples to clot for between 2 and 6 h before serum......AIM: The sources of increased vascular endothelial growth factor (VEGF) concentrations in peripheral blood from cancer patients are not known in detail. The aim of the present study was to evaluate correlations between the VEGF content in isolated leucocyte subpopulations and VEGF concentrations in...

  10. Abnormal expression of VEGF and its gene transcription status as diagnostic indicators in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Yun Shi; Yang Shi; Xuli Yang; Jianrong Chen; Qi Qian; Dengfu Yao; Guangzhou Wu

    2015-01-01

    Objective Angiogenesis is known to be essential for the survival, growth, invasion, and metastasis of lung cancer cells. Vascular endothelial growth factor (VEGF) is an important factor regulating angiogenesis of non-small cell lung cancer (NSCLC); however, its pathologic features and significance are unclear. In this study, the tissue VEGF expression levels and its gene transcriptional status, as well as circulating VEGF levels, were investigated in patients with lung disease.Methods VEGF protein and mRNA expression levels in 38 lung tissue samples were analyzed by immu-nohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Circulating VEGF levels were detected quantitatively by an enzyme linked immuno-sorbent assay. Results The level of VEGF expression was significantly higher in lung cancer tissue than in the corre-sponding paracancerous or non-cancerous tissues. The average level of VEGF-positive staining was 76% in tissue samples from NSCLC patients; the levels were 89% in tissue samples from stage Ⅲ patients and 92% in stage Ⅳ patients. High VEGF expression was also evident in cases with lymph node metastasis (84%), distant metastasis (90%), and lower differentiation degree (89%). VEGF mRNA in cancerous tis-sues was represented predominantly by the VEGF121 and VEGF165 isoforms. Circulating VEGF levels were significantly higher in NSCLC patients [(840 ± 324) pg/mL] than in patients with benign lung diseases [(308 ± 96) pg/mL] or in healthy individuals serving as controls [(252 ± 108) pg/mL]. Conclusion The over-expression of lung VEGF and its gene transcription status should be useful mo-lecular indicators for NSCLC diagnosis.

  11. VEGF, which is elevated in the CSF of patients with hydrocephalus, causes ventriculomegaly and ependymal changes in rats.

    Science.gov (United States)

    Shim, Joon W; Sandlund, Johanna; Han, Carin H; Hameed, Mustafa Q; Connors, Susan; Klagsbrun, Michael; Madsen, Joseph R; Irwin, Nina

    2013-09-01

    Hydrocephalus is a condition characterized primarily by excessive accumulation of fluid in the ventricles of the brain for which there is currently no effective pharmacological treatment. Surgery, often accompanied by complications, is the only current treatment. Extensive research in our laboratory along with work from others has suggested a link between hydrocephalus and vascular function. We hypothesized that vascular endothelial growth factor (VEGF), the major angiogenic factor, could play a role in the pathogenesis of hydrocephalus. We tested this hypothesis by examining two predictions of such a link: first, that VEGF is present in many cases of clinical hydrocephalus; and second, that exogenous VEGF in an animal model could cause ventricular enlargement and tissue changes associated with hydrocephalus. Our results support the idea that VEGF elevation can potentiate hydrocephalus. The clinical relevance of this work is that anti-angiogenic drugs may be useful in patients with hydrocephalus, either alone or in combination with the currently available surgical treatments.

  12. Expression of vascular endothelial growth factor (VEGF) and VEGF-C in serum and tissue of Wilms tumor

    Institute of Scientific and Technical Information of China (English)

    WANG Lei; ZHANG Da; CHEN Xin-rang; FAN Yu-xia; WANG Jia-xiang

    2011-01-01

    Background Angiogenesis and lymphogenesis which were promoted by vascular endothelial growth factor (VEGF)and VEGF-C are important in the growth and metastasis of solid tumors.The high level of VEGF and VEGF-C were distributed in numerous types of cancers,but their distribution and expression in Wilms tumor,the most common pediatric tumor of the kidney,was unclear.Methods To learn about the distribution,mass spectroscopy and immunohistochemistry were used to measure the level of VEGF and VEGF-C in serum and tissue of Wilms tumor.Results The expression level of VEGF in serum of Wilms tumor was the same as in pre-surgery and control,so it was the same case of VEGF-C.Both of these factors were chiefly located in Wilms tumor tissue,but not in borderline and normal.In addition,the higher clinical staging and histopathologic grading were important elements in high expression of VEGF and VEGF-C.Gender,age and the size of tumor have not certainly been implicated in expression level of VEGF and VEGF-C.Conclusions The lymph node metastasis and growth of tumors resulted from angiogenesis and lymphogenesis which were promoted by VEGF and VEGF-C in Wilms tumor.The autocrine and paracrine process of VEGF and VEGF-C were the principal contributor to specific tissues of Wilms tumor but not to the entire body.

  13. VEGF regulates TRPC6 channels in podocytes

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Loddenkemper, Christoph;

    2012-01-01

    BACKGROUND: Both, increased plasma concentrations of vascular endothelial growth factor (VEGF) and increased expression of transient receptor potential canonical type 6 (TRPC6) channels in podocytes have been associated with proteinuric kidney diseases. Now, we investigated the hypothesis that VE...

  14. VEGF: a potential target for hydrocephalus.

    Science.gov (United States)

    Shim, Joon W; Sandlund, Johanna; Madsen, Joseph R

    2014-12-01

    Growth factors are primarily responsible for the genesis, differentiation and proliferation of cells and maintenance of tissues. Given the central role of growth factors in signaling between cells in health and in disease, it is understandable that disruption of growth factor-mediated molecular signaling can cause diverse phenotypic consequences including cancer and neurological conditions. This review will focus on the specific questions of enlarged cerebral ventricles and hydrocephalus. It is also well known that angiogenic factors, such as vascular endothelial growth factor (VEGF), affect tissue permeability through activation of receptors and adhesion molecules; hence, recent studies showing elevations of this factor in pediatric hydrocephalus led to the demonstration that VEGF can induce ventriculomegaly and altered ependyma when infused in animals. In this review, we discuss recent findings implicating the involvement of biochemical and biophysical factors that can induce a VEGF-mimicking effect in communicating hydrocephalus and pay particular attention to the role of the VEGF system as a potential pharmacological target in the treatment of some cases of hydrocephalus. The source of VEGF secretion in the cerebral ventricles, in periventricular regions and during pathologic events including hydrocephalus following hypoxia and hemorrhage is sought. The review is concluded with a summary of potential non-surgical treatments in preclinical studies suggesting several molecular targets including VEGF for hydrocephalus and related neurological disorders.

  15. Radiation-induced VEGF-C expression and endothelial cell proliferation in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Hsuan [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University, Pharmacological Institute, College of Medicine, Taipei (China); Pan, Shiow-Lin; Wang, Jing-Chi; Teng, Che-Ming [National Taiwan University, Pharmacological Institute, College of Medicine, Taipei (China); Kuo, Sung-Hsin [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University College of Medicine, Department of Internal Medicine, Taipei (China); Cheng, Jason Chia-Hsien [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University College of Medicine, Graduate Institute of Clinical Medicine, Taipei (China)

    2014-12-15

    The present study was undertaken to investigate whether radiation induces the expression of vascular endothelial growth factor C (VEGF-C) through activation of the PI3K/Akt/mTOR pathway,subsequently affecting endothelial cells. Radiotherapy-induced tumor micro-lymphatic vessel density (MLVD) was determined in a lung cancer xenograft model established in SCID mice. The protein expression and phosphorylation of members of the PI3K/Akt/mTOR pathway and VEGF-C secretion and mRNA expression in irradiated lung cancer cells were assessed by Western blot analysis, enzyme-linked immunosorbent assays (ELISAs), and reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, specific chemical inhibitors were used to evaluate the role of the PI3K/Akt/mTOR signaling pathway. Conditioned medium (CM) from irradiated control-siRNA or VEGF-C-siRNA-expressing A549 cells was used to evaluate the proliferation of endothelial cells by the MTT assay. Radiation increased VEGF-C expression in a dose-dependent manner over time at the protein but not at the mRNA level. Radiation also up-regulated the phosphorylation of Akt, mTOR, 4EBP, and eIF4E, but not of p70S6K. Radiation-induced VEGF-C expression was down-regulated by LY294002 and rapamycin (both p < 0.05). Furthermore, CM from irradiated A549 cells enhanced human umbilical vein endothelial cell (HUVEC) and lymphatic endothelial cell (LEC) proliferation, which was not observed with CM from irradiated VEGF-C-siRNA-expressing A549 cells. Radiation-induced activation of the PI3K/Akt/mTOR signaling pathway increases VEGF-C expression in lung cancer cells, thereby promoting endothelial cell proliferation. (orig.) [German] Die vorliegende Studie untersucht, ob die Strahlung die Expression von VEGF-C (vascular endothelial growth factor C) mittels Aktivierung des PI3K/Akt/mTOR-Signalwegs induziert und anschliessend die endothelialen Zellen beeinflusst. Die durch Strahlentherapie induzierte Mikrolymphgefaessdichte (MLVD) im Tumor wurde in

  16. Comparative Phosphoproteomics Analysis of VEGF and Angiopoietin-1 Signaling Reveals ZO-1 as a Critical Regulator of Endothelial Cell Proliferation.

    Science.gov (United States)

    Chidiac, Rony; Zhang, Ying; Tessier, Sylvain; Faubert, Denis; Delisle, Chantal; Gratton, Jean-Philippe

    2016-05-01

    VEGF and angiopoietin-1 (Ang-1) are essential factors to promote angiogenesis through regulation of a plethora of signaling events in endothelial cells (ECs). Although pathways activated by VEGF and Ang-1 are being established, the unique signaling nodes conferring specific responses to each factor remain poorly defined. Thus, we conducted a large-scale comparative phosphoproteomic analysis of signaling pathways activated by VEGF and Ang-1 in ECs using mass spectrometry. Analysis of VEGF and Ang-1 networks of regulated phosphoproteins revealed that the junctional proteins ZO-1, ZO-2, JUP and p120-catenin are part of a cluster of proteins phosphorylated following VEGF stimulation that are linked to MAPK1 activation. Down-regulation of these junctional proteins led to MAPK1 activation and accordingly, increased proliferation of ECs stimulated specifically by VEGF, but not by Ang-1. We identified ZO-1 as the central regulator of this effect and showed that modulation of cellular ZO-1 levels is necessary for EC proliferation during vascular development of the mouse postnatal retina. In conclusion, we uncovered ZO-1 as part of a signaling node activated by VEGF, but not Ang-1, that specifically modulates EC proliferation during angiogenesis. PMID:26846344

  17. Pharmacokinetics and pharmacodynamics of VEGF-neutralizing antibodies

    Directory of Open Access Journals (Sweden)

    Finley Stacey D

    2011-11-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF is a potent regulator of angiogenesis, and its role in cancer biology has been widely studied. Many cancer therapies target angiogenesis, with a focus being on VEGF-mediated signaling such as antibodies to VEGF. However, it is difficult to predict the effects of VEGF-neutralizing agents. We have developed a whole-body model of VEGF kinetics and transport under pathological conditions (in the presence of breast tumor. The model includes two major VEGF isoforms VEGF121 and VEGF165, receptors VEGFR1, VEGFR2 and co-receptors Neuropilin-1 and Neuropilin-2. We have added receptors on parenchymal cells (muscle fibers and tumor cells, and incorporated experimental data for the cell surface density of receptors on the endothelial cells, myocytes, and tumor cells. The model is applied to investigate the action of VEGF-neutralizing agents (called "anti-VEGF" in the treatment of cancer. Results Through a sensitivity study, we examine how model parameters influence the level of free VEGF in the tumor, a measure of the response to VEGF-neutralizing drugs. We investigate the effects of systemic properties such as microvascular permeability and lymphatic flow, and of drug characteristics such as the clearance rate and binding affinity. We predict that increasing microvascular permeability in the tumor above 10-5 cm/s elicits the undesired effect of increasing tumor interstitial VEGF concentration beyond even the baseline level. We also examine the impact of the tumor microenvironment, including receptor expression and internalization, as well as VEGF secretion. We find that following anti-VEGF treatment, the concentration of free VEGF in the tumor can vary between 7 and 233 pM, with a dependence on both the density of VEGF receptors and co-receptors and the rate of neuropilin internalization on tumor cells. Finally, we predict that free VEGF in the tumor is reduced following anti-VEGF treatment when

  18. Lung Ablation: Whats New?

    Science.gov (United States)

    Xiong, Lillian; Dupuy, Damian E

    2016-07-01

    Lung cancer had an estimated incidence of 221,200 in 2015, making up 13% of all cancer diagnoses. Tumor ablation is an important treatment option for nonsurgical lung cancer and pulmonary metastatic patients. Radiofrequency ablation has been used for over a decade with newer modalities, microwave ablation, cryoablation, and irreversible electroporation presenting as additional and possibly improved treatment options for patients. This minimally invasive therapy is best for small primary lesions or favorably located metastatic tumors. These technologies can offer palliation and sometimes cure of thoracic malignancies. This article discusses the current available technologies and techniques available for tumor ablation. PMID:27050331

  19. Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology.

    OpenAIRE

    Banks, R E; Forbes, M. A.; Kinsey, S E; Stanley, A; Ingham, E; Walters, C; Selby, P J

    1998-01-01

    Vascular endothelial growth factor (VEGF) is a potent angiogenic factor with a key role in several pathological processes, including tumour vascularization. Our preliminary observations indicated higher VEGF concentrations in serum samples than in matched plasma samples. We have now demonstrated that this difference is due to the presence of VEGF within platelets and its release upon their activation during coagulation. In eight healthy volunteers, serum VEGF concentrations ranged from 76 to ...

  20. Expression of vascular endothelial growth factor (VEGF) in locally invasive prostate cancer is prognostic for radiotherapy outcome

    International Nuclear Information System (INIS)

    Purpose: Vascular endothelial growth factor (VEGF) is an important hypoxia-inducible pro-angiogenic protein that has been linked with an adverse survival outcome after radiotherapy in other cancer types: we hypothesized that this may also occur in prostate cancer. A retrospective study was, therefore, carried out to evaluate the potential of tumor VEGF expression to predict radiotherapy outcome in patients with high-risk prostate cancer. Methods and Materials: Fifty patients with locally advanced (T3 N0 M0) tumors of Gleason score ≥6, and who received radiotherapy alone as primary treatment for their disease, were studied. Vascular endothelial growth factor expression was assessed on pretreatment diagnostic tumor biopsies using a semiquantitative immunohistochemical scoring system. The results were analyzed in relation to clinicopathologic factors and patient outcome including biochemical failure and disease-specific mortality. Results: High VEGF expression was associated with a poor prognosis: in univariate log rank analysis, VEGF was the only significant prognostic factor for disease-specific survival (p = 0.035). High VEGF expression also associated with increased Gleason score (p = 0.02), but not posttreatment biochemical failure. Conclusion: High tumor expression of VEGF identified patients at high risk of failure of treatment with radiotherapy. These patients might benefit from additional treatment approaches incorporating anti-angiogenic or hypoxia-specific agents

  1. VEGF system, a multi therapeutic target [Sistema VEGF, um alvo multi-terapêutico

    Directory of Open Access Journals (Sweden)

    Daniel L. M. de Aguiar

    2009-08-01

    Full Text Available The ability to modulate the vascular endothelial growth factor system (VEGF is fundamental in thetreatment of several pathophysiologies and in the maintenance of homeostasis. Here, some strategies ofcontrol are discussed, e.g. extracellular actions, monoclonal antibodies and aptamers acting as inhibitors ofVEGF and its receptors (VEGFR. In addition, in the cytoplasm one must include inhibitors of the tyrosine kinasedomain.

  2. VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2–dependent Ca2+ signaling

    Science.gov (United States)

    Favia, Annarita; Desideri, Marianna; Gambara, Guido; D’Alessio, Alessio; Ruas, Margarida; Esposito, Bianca; Del Bufalo, Donatella; Parrington, John; Ziparo, Elio; Palombi, Fioretta; Galione, Antony; Filippini, Antonio

    2014-01-01

    Vascular endothelial growth factor (VEGF) and its receptors VEGFR1/VEGFR2 play major roles in controlling angiogenesis, including vascularization of solid tumors. Here we describe a specific Ca2+ signaling pathway linked to the VEGFR2 receptor subtype, controlling the critical angiogenic responses of endothelial cells (ECs) to VEGF. Key steps of this pathway are the involvement of the potent Ca2+ mobilizing messenger, nicotinic acid adenine-dinucleotide phosphate (NAADP), and the specific engagement of the two-pore channel TPC2 subtype on acidic intracellular Ca2+ stores, resulting in Ca2+ release and angiogenic responses. Targeting this intracellular pathway pharmacologically using the NAADP antagonist Ned-19 or genetically using Tpcn2−/− mice was found to inhibit angiogenic responses to VEGF in vitro and in vivo. In human umbilical vein endothelial cells (HUVECs) Ned-19 abolished VEGF-induced Ca2+ release, impairing phosphorylation of ERK1/2, Akt, eNOS, JNK, cell proliferation, cell migration, and capillary-like tube formation. Interestingly, Tpcn2 shRNA treatment abolished VEGF-induced Ca2+ release and capillary-like tube formation. Importantly, in vivo VEGF-induced vessel formation in matrigel plugs in mice was abolished by Ned-19 and, most notably, failed to occur in Tpcn2−/− mice, but was unaffected in Tpcn1−/− animals. These results demonstrate that a VEGFR2/NAADP/TPC2/Ca2+ signaling pathway is critical for VEGF-induced angiogenesis in vitro and in vivo. Given that VEGF can elicit both pro- and antiangiogenic responses depending upon the balance of signal transduction pathways activated, targeting specific VEGFR2 downstream signaling pathways could modify this balance, potentially leading to more finely tailored therapeutic strategies. PMID:25331892

  3. VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-dependent Ca2+ signaling.

    Science.gov (United States)

    Favia, Annarita; Desideri, Marianna; Gambara, Guido; D'Alessio, Alessio; Ruas, Margarida; Esposito, Bianca; Del Bufalo, Donatella; Parrington, John; Ziparo, Elio; Palombi, Fioretta; Galione, Antony; Filippini, Antonio

    2014-11-01

    Vascular endothelial growth factor (VEGF) and its receptors VEGFR1/VEGFR2 play major roles in controlling angiogenesis, including vascularization of solid tumors. Here we describe a specific Ca(2+) signaling pathway linked to the VEGFR2 receptor subtype, controlling the critical angiogenic responses of endothelial cells (ECs) to VEGF. Key steps of this pathway are the involvement of the potent Ca(2+) mobilizing messenger, nicotinic acid adenine-dinucleotide phosphate (NAADP), and the specific engagement of the two-pore channel TPC2 subtype on acidic intracellular Ca(2+) stores, resulting in Ca(2+) release and angiogenic responses. Targeting this intracellular pathway pharmacologically using the NAADP antagonist Ned-19 or genetically using Tpcn2(-/-) mice was found to inhibit angiogenic responses to VEGF in vitro and in vivo. In human umbilical vein endothelial cells (HUVECs) Ned-19 abolished VEGF-induced Ca(2+) release, impairing phosphorylation of ERK1/2, Akt, eNOS, JNK, cell proliferation, cell migration, and capillary-like tube formation. Interestingly, Tpcn2 shRNA treatment abolished VEGF-induced Ca(2+) release and capillary-like tube formation. Importantly, in vivo VEGF-induced vessel formation in matrigel plugs in mice was abolished by Ned-19 and, most notably, failed to occur in Tpcn2(-/-) mice, but was unaffected in Tpcn1(-/-) animals. These results demonstrate that a VEGFR2/NAADP/TPC2/Ca(2+) signaling pathway is critical for VEGF-induced angiogenesis in vitro and in vivo. Given that VEGF can elicit both pro- and antiangiogenic responses depending upon the balance of signal transduction pathways activated, targeting specific VEGFR2 downstream signaling pathways could modify this balance, potentially leading to more finely tailored therapeutic strategies. PMID:25331892

  4. Laser ablation principles and applications

    CERN Document Server

    1994-01-01

    Laser Ablation provides a broad picture of the current understanding of laser ablation and its many applications, from the views of key contributors to the field. Discussed are in detail the electronic processes in laser ablation of semiconductors and insulators, the post-ionization of laser-desorbed biomolecules, Fourier-transform mass spectroscopy, the interaction of laser radiation with organic polymers, laser ablation and optical surface damage, laser desorption/ablation with laser detection, and laser ablation of superconducting thin films.

  5. Platelet VEGF and serum TGF-β1 levels predict chemotherapy response in non-small cell lung cancer patients.

    Science.gov (United States)

    Fu, Bao-Hong; Fu, Zhan-Zhao; Meng, Wei; Gu, Tao; Sun, Xiao-Dong; Zhang, Zhi

    2015-08-01

    We examined the levels of platelet vascular endothelial growth factor (VEGF(PLT)) and serum level of transforming growth factor beta 1 (TGF-β1) in non-small cell lung cancer (NSCLC) patients before and after chemotherapy to assess their clinical value as biomarkers. A total of 115 subjects were recruited at the First Hospital of Qinhuangdao between July 2012 and October 2013, including 65 NSCLC patients receiving chemotherapy (NSCLC group) and 50 healthy controls (control group). All NSCLC patients received gemcitabine plus cisplatin (GP regimen) for a total of two courses. VEGF(PLT) and serum TGF-β1 levels were measured before and after chemotherapy using enzyme-linked immunosorbent assay (ELISA). Platelet count was obtained using the Abbott CD-1600 auto blood analyzer. NSCLC group was categorized into complete response (CR) plus partial response (PR) group and stable disease (SD) plus progressive disease (PD) group based on the results of CT scans obtained 1 week after chemotherapy. Our results revealed that VEGF(PLT) and serum TGF-β1 levels were significantly higher in NSCLC group before chemotherapy, compared to the control group (VEGF(PLT), 0.813 ± 0.072 vs. 0.547 ± 0.024; t = 26.48; P VEGF(PLT) and serum TGF-β1 levels decreased significantly after chemotherapy in CR + PR group in comparison with before chemotherapy (VEGF(PLT), 0.453 ± 0.078 vs. 0.814 ± 0.127; t = 15.51; P VEGF(PLT) and serum TGF-β1 levels were markedly higher after chemotherapy in the SD + PD group in comparison with before chemotherapy (VEGF(PLT), 0.816 ± 0.043 vs. 1.065 ± 0.016; t = 22.38; P VEGF(PLT) and serum TGF-β1 levels, and VEGF(PLT) and TGF-β1 levels correlate with chemotherapy response to GP regimen. Therefore, VEGF(PLT) and serum TGF-β1 levels are valuable biomarkers in clinical monitoring of NSCLC patients. PMID:25820820

  6. The Relationship between Serum VEGF Expression and PET/CT Images in TNM-staging of Lung Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To analyze the relationship between the characteristics of PET/CT images for lung carcinoma (LC) TNM staging and the expression of serum VEGF protein.METHODS PET/CT examinations were performed before treatment of 53 patients with LC. The expression of serum VEGF protein was examined using a quantitative sandwich enzyme-linked immunosorbent assay (ELISA R and D system). The relationship was analyzed between PET/CT images for LC T-staging and metastasis (lymph nodes and distance) and serum VEGF expression.RESULTS Based on PET/CT images for LC T-staging, 11 cases were staged as T1, 9 as T2, 18 as T3 and 15 as T4. Mediastinal nodal metastases were found in 22 patients, and distance metastasis in 9. The serum VEGF level in the LC patients was (378.02±180.79) ng/L, showing that there was a significant difference between the patients and healthy subjects (P<0.05).There was no significant difference in the level of serum VEGF between different low T-staged (T1, T2) patients. However, the level of serum VEGF was significantly different between the low T-staged (T1, T2) and high T-staged (T3, T4) patients (P<0.05). The level of the serum VEGF protein in the patients with mediastinal nodal metastasis was (561.50±104.55) ng/L, and indicating that there was a statistical significance (t=12.21, P<0.05) compared to those in the non-metastatic group. The level of serum VEGF in the patients with distance metastasis was (614.11±158.81) ng/L, demonstrating that there was a significant difference (t=5.30, P<0.05) compared to those in the nondistant metastatic group.CONCLUSION ①There is a high level of serum VEGF xpression in LC patients. ②There is a correlation between metastases (lymph nodes and distance) and the level of serum VEGF. ③With an upgrade of the TNM-stage, the level of serum VEGF protein is elevated.

  7. The VEGF signaling pathway in cancer: the road ahead

    Institute of Scientific and Technical Information of China (English)

    Steven A.Stacker; Marc G.Achen

    2013-01-01

    The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology.The members of the family,VEGF-A (also known as VEGF),VEGF-B,VEGF-C,VEGF-D,and placenta growth factor (PIGF),play important roles in vascular biology in both normal physiology and pathology.The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab,also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target.Other members of the VEGF family are now being targeted,and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic.Here,we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.

  8. VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells

    International Nuclear Information System (INIS)

    There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo. Although VEGF did not affect the property of CSCs in vitro, the injection of mouse brains with VEGF-expressing CSCs led to the massive expansion of vascular-rich GBM, tumor-associated hemorrhage, and high morbidity, suggesting that VEGF promoted tumorigenesis via angiogenesis. These results revealed that VEGF induced the proliferation of VEC in the vascular-rich tumor environment, the so-called stem cell niche

  9. An Antagonistic Vascular Endothelial Growth Factor (VEGF) Variant Inhibits VEGF-Stimulated Receptor Autophosphorylation and Proliferation of Human Endothelial Cells

    Science.gov (United States)

    Siemeister, Gerhard; Schirner, Michael; Reusch, Petra; Barleon, Bernhard; Marme, Dieter; Martiny-Baron, Georg

    1998-04-01

    Vascular endothelial growth factor (VEGF) is a potent mitogen with a unique specificity for endothelial cells and a key mediator of aberrant endothelial cell proliferation and vascular permeability in a variety of human pathological situations, such as tumor angiogenesis, diabetic retinopathy, rheumatoid arthritis, or psoriasis. VEGF is a symmetric homodimeric molecule with two receptor binding interfaces lying on each pole of the molecule. Herein we report on the construction and recombinant expression of an asymmetric heterodimeric VEGF variant with an intact receptor binding interface at one pole and a mutant receptor binding interface at the second pole of the dimer. This VEGF variant binds to VEGF receptors but fails to induce receptor activation. In competition experiments, the heterodimeric VEGF variant antagonizes VEGF-stimulated receptor autophosphorylation and proliferation of endothelial cells. A 15-fold excess of the heterodimer was sufficient to inhibit VEGF-stimulated endothelial cell proliferation by 50%, and a 100-fold excess resulted in an almost complete inhibition. By using a rational approach that is based on the structure of VEGF, we have shown the feasibility to construct a VEGF variant that acts as an VEGF antagonist.

  10. The VEGF receptor, neuropilin-1, represents a promising novel target for chronic lymphocytic leukemia patients.

    Science.gov (United States)

    Piechnik, Agnieszka; Dmoszynska, Anna; Omiotek, Marcin; Mlak, Radosław; Kowal, Małgorzata; Stilgenbauer, Stephan; Bullinger, Lars; Giannopoulos, Krzysztof

    2013-09-15

    Angiogenesis has been shown to substantially contribute to the progression of chronic lymphocytic leukemia (CLL). Neuropilin-1 (NRP1) represents a receptor for vascular endothelial growth factor (VEGF), which has been reported to be overexpressed in several malignancies. In our study, we characterized mRNA levels of VEGF receptors including NRP1 in a large cohort of CLL patients (n = 114), additionally we performed a detailed characterization of NRP1 expression on B cells, plasmacytoid dendritic cells (PDCs) and regulatory T cells (Tregs). The expression of NRP1 was significantly higher on leukemic lymphocytes compared to control B lymphocytes on mRNA and protein levels (22.72% vs. 0.2%, p = 0.0003, respectively), Tregs (42.6% vs. 16.05%, p = 0.0003) and PDCs (100% vs. 98% p < 0.0001). In functional studies, we found higher NRP1 expression on CLL cells after stimulation with VEGF. The correlation between expression of VEGF receptors: FLT1, NRP1 and FOXP3 expression (r(2) = 0.53, p < 0.0001 and r(2) = 0.49, p < 0.0001, respectively) was observed. Earlier we described the specific Treg reduction during the therapy with thalidomide in vivo. Now we observe the reduction of the NRP1 expression on Tregs in vitro, thereby suggesting a possible target of thalidomide action. In conclusion, NRP1 might represent an interesting link between angiogenesis and tolerance mechanisms and represents interesting target for therapy.

  11. Anthrax lethal toxin suppresses high glucose induced VEGF over secretion through a post-translational mechanism

    Institute of Scientific and Technical Information of China (English)

    Wei-Wei; Zhang; Xin; Wang; Ping; Xie; Song-Tao; Yuan; Qing-Huai; Liu

    2015-01-01

    AIM: To prove anthrax lethal toxin(Le Tx) blocks the mitogen activated protein kinases(MAPKs) activation by degrading the MAPK/ERK kinases(MEKs) to suppress vascular endothelial growth factor(VEGF) secretion.METHODS: Human adult retinal pigmented epithelium(ARPE) cells were cultured and treated with normal glucose, high glucose or high glucose with Le Tx for additional 24, 48 or 72 h for viable cell count. Total RNA from the ARPE was isolated for reverse transcription polymerase chain reaction(RT-PCR). The conditioned medium of ARPE cells treated in different group for 48 h was filtered and diluted to detect the concentration of VEGF by enzyme-linked immunosorbant assays.Evaluate the role of MEK/MAPK pathway in the secretion of VEGF by immunoblotting. RESULTS: In this study, we proved high glucose induced activation of the MAPK extracellular signal-regulated kinase(ERK1/2) and p38 in the ARPE cell line was blocked by anthrax Le Tx. Le Tx also inhibited high glucose induced ARPE cell over proliferation.CONCLUSION: Le Tx suppressed high glucose induced VEGF over secretion in the ARPE cells, mainly through a post-translational mechanism.

  12. COX-2, VEGF and tumour angiogenesis.

    LENUS (Irish Health Repository)

    Toomey, D P

    2009-06-01

    Epidemiological evidence suggests a protective effective of regular NSAID use against developing cancer. Cyclooxygenase-2, a target of NSAIDs, is upregulated in many cancers and has been associated with increased VEGF production and angiogenesis. Angiogenesis is the formation of new vessels from existing vasculature and as an essential process for tumour development represents an important therapeutic target. Following an extensive review of the literature this article details the current knowledge on the role of COX-2 in tumorigenesis focusing on its relationship to angiogenesis and VEGF production by tumour cells. While COX-2 is clearly detrimental to prognosis and NSAIDs have a beneficial effect, the possibility of COX-2 independent effects being partly or wholly responsible for this benefit cannot be excluded.

  13. Tendon lesion and VEGF-111 injection

    OpenAIRE

    Kaux, Jean-François; Drion, Pierre; Libertiaux, Vincent; Pascon, Frédéric; Colige, Alain; Le Goff, Caroline; Lambert, Charles; Janssen, Lauriane; Nusgens, Betty; Gothot, André; CESCOTTO, Serge; Defraigne, Jean-Olivier; Rickert, Markus; Crielaard, Jean-Michel

    2010-01-01

    Introduction: Tendon lesion is one of the most frequent pathology in sports and by physical workers. This pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Injection of platelet-rich plasma (PRP) seems to be a promising one by releasing growth factors (GF) locally. Among all the GF released by activated platelets, the vascular endothelial growth factor-A (VEGF-A) is known to induce positive effects on vascular function and angiogenesis, and could b...

  14. Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma.

    Science.gov (United States)

    Pritchard-Jones, R O; Dunn, D B A; Qiu, Y; Varey, A H R; Orlando, A; Rigby, H; Harper, S J; Bates, D O

    2007-07-16

    Malignant melanoma is the most lethal of the skin cancers and the UK incidence is rising faster than that of any other cancer. Angiogenesis - the growth of new vessels from preexisting vasculature - is an absolute requirement for tumour survival and progression beyond a few hundred microns in diameter. We previously described a class of anti-angiogenic isoforms of VEGF, VEGF(xxx)b, that inhibit tumour growth in animal models, and are downregulated in some cancers, but have not been investigated in melanoma. To determine whether VEGF(xxx)b expression was altered in melanoma, PCR and immunohistochemistry of archived human tumour samples were used. In normal epidermis and in a proportion of melanoma samples, VEGF(xxx)b staining was seen. Some melanomas had much weaker staining. Subsequent examination revealed that expression was significantly reduced in primary melanoma samples (both horizontal and vertical growth phases) from patients who subsequently developed tumour metastasis compared with those who did not (analysis of variance (ANOVA) Pxxx)b expression appears to predict metastatic spread in patients with primary melanoma. These results suggest that there is a switch in splicing as part of the metastatic process, from anti-angiogenic to pro-angiogenic VEGF isoforms. This may form part of a wider metastatic splicing phenotype.

  15. Intravoxel Incoherent Motion Diffusion Weighted MR Imaging for Monitoring the Instantly Therapeutic Efficacy of Radiofrequency Ablation in Rabbit VX2 Tumors without Evident Links between Conventional Perfusion Weighted Images.

    Directory of Open Access Journals (Sweden)

    Ziyi Guo

    Full Text Available To investigate the intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI as a potential valuable marker to monitor the therapy responses of VX2 to radiofrequency ablation (RF Ablation.The institutional animal care and use committee approved this study. In 10 VX2 tumor-bearing rabbits, IVIM-DWI examinations were performed with a 3.0T imaging unit by using 16 b values from 0 to 800 sec/mm2. The true diffusion coefficient (D, pseudodiffusion coefficient (D* and perfusion fraction (f of tumors were compared between before and instantly after RF Ablation treatment. The differences of D, D* and f and conventional perfusion parameters (from perfusion CT and dynamic enhanced magnetic resonance imaging, DCE-MRI in the coagulation necrosis area, residual unablated area, untreated area, and normal control had been calculated by compared t-test. The correlation between f or D* with perfusion weighted CT including blood flow, BF (milliliter per 100 mL/min, blood volume, BV (milliliter per 100 mL/min, and capillary permeability-surface area, PMB (as a fraction or from DCE-MRI: transfer constant (Ktrans, extra-vascular extra-cellular volume fraction (Ve and reflux constant (Kep values had been analyzed by region-of-interest (ROI methods to calculate Pearson's correlation coefficients.In the ablated necrosis areas, f and D* significantly decreased and D significantly increased, compared with residual unblazed areas or untreated control groups and normal control groups (P < 0.001. The IVIM-DWI derived f parameters showed significant increases in the residual unablated tumor area. There was no significant correlations between f or D* and conventional perfusion parameters.The IVIM-DW derived f, D and D* parameters have the potential to indicate therapy response immediately after RF Ablation treatment, while no significant correlations with classical tumor perfusion metrics were derived from DCE-MRI and perfusion-CT measurements.

  16. Radiofrequency ablation in dermatology

    Directory of Open Access Journals (Sweden)

    Sachdeva Silonie

    2007-01-01

    Full Text Available Radiofreqeuency ablation is a versatile dermatosurgical procedure used for surgical management of skin lesions by using various forms of alternating current at an ultra high frequency. The major modalities in radiofrequency are electrosection, electrocoagulation, electrodessication and fulguration. The use of radiofrequency ablation in dermatosurgical practice has gained importance in recent years as it can be used to treat most of the skin lesions with ease in less time with clean surgical field due to adequate hemostasis and with minimal side effects and complications. This article focuses on the major tissue effects and factors influencing radiofrequency ablation and its application for various dermatological conditions.

  17. Microwave Ablation of Hepatic Malignancy

    OpenAIRE

    Lubner, Meghan G.; Brace, Christopher L.; Ziemlewicz, Tim J.; Hinshaw, J. Louis; Lee, Fred. T.

    2013-01-01

    Microwave ablation is an extremely promising heat-based thermal ablation modality that has particular applicability in treating hepatic malignancies. Microwaves can generate very high temperatures in very short time periods, potentially leading to improved treatment efficiency and larger ablation zones. As the available technology continues to improve, microwave ablation is emerging as a valuable alternative to radiofrequency ablation in the treatment of hepatic malignancies. This article rev...

  18. Expression of VEGF, b-FGF, and their receptors after injection of VEGF on ischemic heart muscle

    Institute of Scientific and Technical Information of China (English)

    XU Xun-yu; SUN Lin; HAN Tao; CHEN Wen-hong; CUI Yong; LI Yan

    2004-01-01

    Objective: To study the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) and their receptors after injection of external VEGF on ischemic heart muscle and to investigate the mechanism of therapeutic myocardial angiogenesis of VEGF. Methods: Standard experimental pigs underwent placement of a left circumflex artery ameroid occluder. Six weeks later, the animals in the experimental group were treated with VEGF (20μg) by direct epicardial injection ( n = 8) and other animals in the control group did not receive any treatment ( n = 8).Four weeks after therapy, the animals were evaluated with regard to mRNA and protein expression of VEGF and b-FGF and their receptors by RT-PCR and Western blotting. Results: The mRNA expression of VEGF and b-FGF and their receptors by RT-PCR expressing as percentage of density ratio to the GAPDH control was increased in experimental group versus control group. The protein expression of VEGF and b-FGF and their receptors by Western blot expressing as percentage of density ratio to the Commassie Blue control was increased in experimental group versus control Group. Conclusion: Exogenous VEGF can induce the expression of endogenous VEGF, b-FGF, and their receptors; b-FGF may play a role in the angiogenesis of VEGF.

  19. Preparation and in vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(D,L-lactic-co-glycolic acid) microspheres using a double emulsion/solvent evaporation technique.

    Science.gov (United States)

    Karal-Yılmaz, Okşan; Serhatlı, Müge; Baysal, Kemal; Baysal, Bahattin M

    2011-01-01

    Biodegradable Poly(lactic-co-glycolic acid; PLGA), microspheres encapsulating the angiogenic protein recombinant human vascular endothelial growth factor (rhVEGF) were formed to achieve VEGF release in a sustained manner. These microspheres are a promising delivery system which can be used for therapeutic angiogenesis. The PLGA microspheres incorporating two different initial loading amounts of rhVEGF have been prepared by a modified water-in-oil-in-water (w/o/w) double emulsion/solvent evaporation technique. The microspheres have been characterized by particle size distribution, environmental scanning electron microscopy (ESEM), light microscopy, encapsulation efficiency and their degradation was studied in vitro. The rhVEGF released from microspheres was quantified by the competitive enzyme-linked immunosorbent assay (ELISA) and human umbilical vein endothelial cell (HUVEC) proliferation assay was used to assess biological activity of the released VEGF. The microspheres were spherical with diameters of 10-60 µm and the encapsulation efficiency was between 46% and 60%. The release kinetics of rhVEGF was studied for two different amounts: 5 µg VEGF (V5) and 50 µg VEGF (V50) per 500 mg starting polymer. The total protein (VEGF:BSA) release increased up to 4 weeks for two rhVEGF concentrations. The ELISA results showed that the burst release for V5 and V50 microspheres were 4 and 27 ng/mL, respectively. For V5, the microspheres showed an initial burst release, followed by a higher steady-state release until 14 days. VEGF release increased up to 2 weeks for V50 microsphere. HUVEC proliferation assay showed that endothelial cells responded to bioactive VEGF by proliferating and migrating.

  20. Moldable cork ablation material

    Science.gov (United States)

    1977-01-01

    A successful thermal ablative material was manufactured. Moldable cork sheets were tested for density, tensile strength, tensile elongation, thermal conductivity, compression set, and specific heat. A moldable cork sheet, therefore, was established as a realistic product.

  1. Anti-VEGF Cancer Therapy in Nephrology Practice

    Directory of Open Access Journals (Sweden)

    Hassan Izzedine

    2014-01-01

    Full Text Available Expanded clinical experience with the antivascular endothelial growth factor (VEGF agents has come with increasing recognition of their renal adverse effects. Although renal histology is rarely sought in antiangiogenic-treated cancer patients, kidney damage related to anti-VEGF is now established. Its manifestations include hypertension, proteinuria, and mainly glomerular thrombotic microangiopathy. Then, in nephrology practice, should we continue to perform kidney biopsy, and what should be done with the anti-VEGF agents in case of renal toxicity?

  2. Leptin, BMI, and a Metabolic Gene Expression Signature Associated with Clinical Outcome to VEGF Inhibition in Colorectal Cancer.

    Science.gov (United States)

    Pommier, Aurélien J C; Farren, Matthew; Patel, Bhavika; Wappett, Mark; Michopoulos, Filippos; Smith, Neil R; Kendrew, Jane; Frith, Jeremy; Huby, Russell; Eberlein, Catherine; Campbell, Hayley; Womack, Christopher; Smith, Paul D; Robertson, Jane; Morgan, Shethah; Critchlow, Susan E; Barry, Simon T

    2016-01-12

    VEGF (vascular endothelial growth factor) signaling inhibitors are widely used in different cancer types; however, patient selection remains a challenge. Analyses of samples from a phase III clinical trial in metastatic colorectal cancer testing chemotherapy versus chemotherapy with the small molecule VEGF receptors inhibitor cediranib identified circulating leptin levels, BMI, and a tumor metabolic and angiogenic gene expression signature associated with improved clinical outcome in patients treated with cediranib. Patients with a glycolytic and hypoxic/angiogenic profile were associated with increased benefit from cediranib, whereas patients with a high lipogenic, oxidative phosphorylation and serine biosynthesis signature did not gain benefit. These findings translated to pre-clinical tumor xenograft models where the same metabolic gene expression profiles were associated with in vivo sensitivity to cediranib as monotherapy. These findings suggest a link between patient physiology, tumor biology, and response to antiangiogenics, which may guide patient selection for VEGF therapy in the future. PMID:26626460

  3. Genetic variations in VEGF and VEGFR2 and glioblastoma outcome

    DEFF Research Database (Denmark)

    Sjöström, S; Wibom, C; Andersson, U;

    2010-01-01

    collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs......Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases...

  4. Genetic variations in VEGF and VEGFR2 and glioblastoma outcome

    DEFF Research Database (Denmark)

    Sjöström, S; Wibom, C; Andersson, U;

    2011-01-01

    collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs......Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases...

  5. Hypoxia promotes adipose-derived stem cell proliferation via VEGF

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2016-01-01

    Full Text Available Adipose-derived stem cells (ADSCs are a promising mesenchymal stem cell source with therapeutic applications. Recent studies have shown that ADSCs could be expanded in vitro without phenotype changes. This study aimed to evaluate the effect of hypoxia on ADSC proliferation in vitro and to determine the role of vascular endothelial growth factor (VEGF in ADSC proliferation. ADSCs were selectively cultured from the stromal vascular fraction obtained from adipose tissue in DMEM/F12 medium supplemented with 10% fetal bovine serum and 1% antibiotic-antimycotic. ADSCs were cultured under two conditions: hypoxia (5% O2 and normal oxygen (21% O2. The effects of the oxygen concentration on cell proliferation were examined by cell cycle and doubling time. The expression of VEGF was evaluated by the ELISA assay. The role of VEGF in ADSC proliferation was studied by neutralizing VEGF with anti-VEGF monoclonal antibodies. We found that the ADSC proliferation rate was significantly higher under hypoxia compared with normoxia. In hypoxia, ADSCs also triggered VEGF expression. However, neutralizing VEGF with anti-VEGF monoclonal antibodies significantly reduced the proliferation rate. These results suggest that hypoxia stimulated ADSC proliferation in association with VEGF production. [Biomed Res Ther 2016; 3(1.000: 476-482

  6. Correlation of the Appearances of DSA with VEGF Expression and Its Clinical Significance in Patients with Primary Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    CHEN Fangman; JIAO Xudong; DU Fang

    2006-01-01

    Objective: To investigate the relationship between the appearances of digital subtraction angiography (DSA) and the serum level of vascular endothelial growth factor (VEGF) in patients with primary hepatocellular carcinoma (HCC). Methods: 24 HCC patients, 30 times DSA were examined, serum VEGF level was measured with the quantitative enzyme linked immunosorbent assay (ELISA) in patients and healthy control subjects in this study. Results: Among DSA for 24 patients with HCC, 18 of 24 cases showed hepatic artery blood supply of tumor. Four of 24 cases showed portal vein blood supply of tumor,1 of 24 cases showed superior mesenteric artery blood supply of tumor and artery-venous shunt formation, and there was no blood supply to tumor in one case. Serum VEGF level in HCC[(χ+s)194.5±14.2] ng/L was significant elevated to those in patients comparing with those of the normal controls (132.4±47.9)ng/L and marked differences (P<0.01). Conclusion: During the cases for plenty blood supply or arteryvenous shunt formation in patients with HCC, serum VEGF level markedly elevated in the patients of HCC. VEGF expression was significantly related to intrahepatic dissemination, recurrence and metastasis in patients with HCC.

  7. VEGF is deposited in the subepithelial matrix at the leading edge of branching airways and stimulates neovascularization in the murine embryonic lung.

    Science.gov (United States)

    Healy, A M; Morgenthau, L; Zhu, X; Farber, H W; Cardoso, W V

    2000-11-01

    We used whole lung cultures as a model to study blood vessel formation in vitro and to examine the role that epithelial-mesenchymal interactions play during embryonic pulmonary vascular development. Mouse lungs were isolated at embryonic day 11.5 (E11.5) and cultured for up to 4 days prior to blood vessel analysis. Platelet endothelial cell adhesion molecule-1 (PECAM/CD31) and thrombomodulin (TM/CD141) immunolocalization demonstrate that vascular development occurs in lung cultures. The vascular structures identified in lung cultures first appear as a loosely associated plexus of capillary-like structures that with time surround the airways. To investigate the potential role of vascular endothelial cell growth factor (VEGF) during pulmonary neovascularization, we immunolocalized VEGF in embryonic lungs. Our data demonstrate that VEGF is uniformly present in the airway epithelium and the subepithelial matrix of E11.5 lungs. At later time points, E13.5 and E15.5, VEGF is no longer detected in the proximal airways, but is restricted to the branching tips of airways in the distal lung. RT-PCR analysis reveals that VEGF(164) is the predominant isoform expressed in lung cultures. Grafting heparin-bound VEGF(164) beads onto lung explants locally stimulates a marked neovascular response within 48 hr in culture. Semi-quantitative RT-PCR reveals an 18% increase in PECAM mRNA in VEGF(164)-treated whole lung cultures as compared with untreated cultures. The restricted temporal and spatial expression of VEGF suggests that matrix-associated VEGF links airway branching with blood vessel formation by stimulating neovascularization at the leading edge of branching airways. PMID:11066091

  8. The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice.

    NARCIS (Netherlands)

    Rennel, E.; Waine, E.; Guan, H.; Schuler, Y.; Leenders, W.P.J.; Woolard, J.; Sugiono, M.; Gillatt, D.; Kleinerman, E.; Bates, D.; Harper, S.

    2008-01-01

    Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the

  9. Novel VEGF decoy receptor fusion protein conbercept targeting multiple VEGF isoforms provide remarkable anti-angiogenesis effect in vivo.

    Directory of Open Access Journals (Sweden)

    Qin Wang

    Full Text Available VEGF family factors are known to be the principal stimulators of abnormal angiogenesis, which play a fundamental role in tumor and various ocular diseases. Inhibition of VEGF is widely applied in antiangiogenic therapy. Conbercept is a novel decoy receptor protein constructed by fusing VEGF receptor 1 and VEGF receptor 2 extracellular domains with the Fc region of human immunoglobulin. In this study, we systematically evaluated the binding affinity of conbercept with VEGF isoforms and PlGF by using anti-VEGF antibody (Avastin as reference. BIACORE and ELISA assay results indicated that conbercept could bind different VEGF-A isoforms with higher affinity than reference. Furthermore, conbercept could also bind VEGF-B and PlGF, whereas Avastin showed no binding. Oxygen-induced retinopathy model showed that conbercept could inhibit the formation of neovasularizations. In tumor-bearing nude mice, conbercept could also suppress tumor growth very effectively in vivo. Overall, our study have demonstrated that conbercept could bind with high affinity to multiple VEGF isoforms and consequently provide remarkable anti-angiogenic effect, suggesting the possibility to treat angiogenesis-related diseases such as cancer and wet AMD etc.

  10. Aberrant, ectopic expression of VEGF and VEGF receptors 1 and 2 in malignant colonic epithelial cells. Implications for these cells growth via an autocrine mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Ahluwalia, Amrita [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States); Jones, Michael K. [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States); Department of Medicine, University of California, Irvine, CA (United States); Szabo, Sandor [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States); Department of Pathology, University of California, Irvine, CA (United States); Tarnawski, Andrzej S., E-mail: amrita.ahluwalia@va.gov [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States); Department of Medicine, University of California, Irvine, CA (United States)

    2013-08-09

    Highlights: •Malignant colonic epithelial cells express VEGF and its receptors. •Cultured colon cancer cells secrete VEGF into the medium. •Inhibition of VEGF receptor significantly decreases colon cancer cell proliferation. •VEGF is critical for colon cancer cell growth. -- Abstract: Vascular endothelial growth factor A (referred to as VEGF) is implicated in colon cancer growth. Currently, the main accepted mechanism by which VEGF promotes colon cancer growth is via the stimulation of angiogenesis, which was originally postulated by late Judah Folkman. However, the cellular source of VEGF in colon cancer tissue; and, the expression of VEGF and its receptors VEGF-R1 and VEGF-R2 in colon cancer cells are not fully known and are subjects of controversy. Material and methods: We examined and quantified expression of VEGF, VEGF-R1 and VEGF-R2 in three different human colonic tissue arrays containing sections of adenocarcinoma (n = 43) and normal mucosa (n = 41). In human colon cancer cell lines HCT116 and HT29 and normal colon cell lines NCM356 and NCM460, we examined expression of VEGF, VEGF-R1 and VEGF-R2 mRNA and protein, VEGF production and secretion into the culture medium; and, the effect of a potent, selective inhibitor of VEGF receptors, AL-993, on cell proliferation. Results: Human colorectal cancer specimens had strong expression of VEGF in cancer cells and also expressed VEGF-R1 and VEGF-R2.In vitro studies showed that human colon cancer cell lines, HCT116 and HT29, but not normal colonic cell lines, express VEGF, VEGF-R1 and VEGF-R2 and secrete VEGF into the medium up to a concentration 2000 pg/ml within 48 h. Furthermore, we showed that inhibition of VEGF receptors using a specific VEGF-R inhibitor significantly reduced proliferation (by >50%) of cultured colon cancer cell lines. Conclusions: Our findings support the contention that VEGF generated by colon cancer cells stimulates their growth directly through an autocrine mechanism that is

  11. Exercise-Induced VEGF Transcriptional Activation in Brain, Lung and Skeletal Muscle

    OpenAIRE

    Tang, Kechun; Xia, Feng Cheng; Wagner, Peter D.; Breen, Ellen C.

    2009-01-01

    Muscle VEGF expression is upregulated by exercise. Whether this VEGF response is regulated by transcription and/or post-transcriptional mechanisms is unknown. Hypoxia may be responsible: myocyte PO2 falls greatly during exercise and VEGF is a hypoxia-responsive gene. Whether exercise induces VEGF expression in other organs important to acute physical activity is also unknown. To address these questions, we created a VEGF/Luciferase reporter mouse and measured VEGF transcription, mRNA and prot...

  12. VEGF165b in the developing vasculatures of the fetal human eye

    Science.gov (United States)

    Baba, Takayuki; McLeod, D. Scott; Edwards, Malia M.; Merges, Carol; Sen, Tanusree; Sinha, Debasish; Lutty, Gerard A.

    2016-01-01

    VEGF165b is an anti-angiogenic form of VEGF165 produced by alternative splicing. The localization of pro-angiogenic VEGF165 and anti-angiogenic VEGF165b was investigated during development of the vasculatures in fetal human eyes from 7 to 21 weeks gestation (WG). The fetal vasculature of vitreous, which includes tunica vasculosa lentis (TVL), had moderate VEGF165 immunoreactivity at 7WG and very little VEGF165b. Both forms were elevated at 12WG. VEGF165 then decreased around 17WG when the TVL regresses but VEGF165b remained elevated. In choroid, VEGF165 was present in forming choriocapillaris (CC) and retinal pigment epithelium (RPE) at 7WG while VEGF165b was present in CC and mesenchymal precursors within the choroidal stroma. By 21WG, both forms were elevated in RPE and choroidal blood vessels but VEGF165b was apical and VEGF165 basal in RPE. Diffuse VEGF165 immunoreactivity was prominent in 12WG innermost retina where blood vessels will form while VEGF165b was present in most CXCR4+ progenitors in the inner neuroblastic layer and migrating angioblasts in the putative nerve fiber layer. By 21WG, VEGF165 was present in nerve fibers and VEGF165b in inner Muller cell process. The localization of VEGF165b was distinctly different from VEGF165 both spatially and temporally and it was often associated with nucleus in progenitors. PMID:22275161

  13. Transient Ablation of Teflon Hemispheres

    Science.gov (United States)

    Arai, Norio; Karashima, Kei-ichi; Sato, Kiyoshi

    1997-01-01

    For high-speed entry of space vehicles into atmospheric environments, ablation is a practical method for alleviating severe aerodynamic heating. Several studies have been undertaken on steady or quasi-steady ablation. However, ablation is a very complicated phenomenon in which a nonequilibrium chemical process is associated with an aerodynamic process that involves changes in body shape with time. Therefore, it seems realistic to consider that ablation is an unsteady phenomenon. In the design of an ablative heat-shield system, since the ultimate purpose of the heat shield is to keep the internal temperature of the space vehicle at a safe level during entry, the transient heat conduction characteristics of the ablator may be critical in the selection of the material and its thickness. This note presents an experimental study of transient ablation of Teflon, with particular emphasis on the change in body shape, the instantaneous internal temperature distribution, and the effect of thermal expansion on ablation rate.

  14. Power Laser Ablation Symposia

    CERN Document Server

    Phipps, Claude

    2007-01-01

    Laser ablation describes the interaction of intense optical fields with matter, in which atoms are selectively driven off by thermal or nonthermal mechanisms. The field of laser ablation physics is advancing so rapidly that its principal results are seen only in specialized journals and conferences. This is the first book that combines the most recent results in this rapidly advancing field with authoritative treatment of laser ablation and its applications, including the physics of high-power laser-matter interaction. Many practical applications exist, ranging from inertial confinement fusion to propulsion of aerostats for pollution monitoring to laser ignition of hypersonic engines to laser cleaning nanoscale contaminants in high-volume computer hard drive manufacture to direct observation of the electronic or dissociative states in atoms and molecules, to studying the properties of materials during 200kbar shocks developed in 200fs. Selecting topics which are representative of such a broad field is difficu...

  15. Changing paradigms of anti-VEGF in the Indian scenario

    Directory of Open Access Journals (Sweden)

    P Mahesh Shanmugam

    2014-01-01

    Full Text Available Anti-vascular endothelial growth factors (VEGF agents have revolutionized the treatment of retinal diseases. Use of anti-VEGF agents in the Indian Scenario present some unique challenges considering the absence of compounding pharmacies, poor penetrance of health insurance and limited affordability of the citizens of a developing economy. To study the changing paradigms of anti-VEGF use in the Indian scenario, all articles published by Indian authors, data from web-based surveys amongst Indian vitreo-retinal specialists were reviewed. In the paucity of compounding pharmacies in India, fractionation and injection techniques differ from those of developed countries. Frequent anti-VEGF monotherapy offers the best anatomical and visual results, but economics of scale do not allow the same in the Indian scenario, resulting in PRN dosing and combination of anti-VEGF with laser photocoagulation, being the commonly employed treatment protocols.

  16. Osmotic release of bioactive VEGF from biodegradable elastomer monoliths is the same in vivo as in vitro.

    Science.gov (United States)

    Chapanian, Rafi; Tse, Man Y; Pang, Stephen C; Amsden, Brian G

    2012-02-01

    The feasibility of generating an extended period of linear release of therapeutic proteins from photo-cross-linked, biodegradable elastomer monolithic devices in vitro has been previously demonstrated. The release is driven primarily by the osmotic pressure generated upon the dissolution of the encapsulated particles within the polymer. The osmotic pressure is provided by co-incorporation into the particle of trehalose as an osmotigen. Herein, we demonstrate that the release rate of a therapeutic protein, vascular endothelial growth factor (VEGF), by this osmotic pressure mechanism is the same in vivo as found in vitro. (125) I-VEGF was colyophilized with trehalose and serum albumin and distributed as particles throughout a photo-cross-linked elastomer composed of trimethylene carbonate, ε-caprolactone, and d,l-lactide. The release of VEGF from the device was monitored by measuring the decrease in radioactivity within the devices in vitro and within explanted devices that had been implanted subcutaneously in the dorsal area of Wistar rats. The released VEGF remained bioactive in vivo, inducing the formation of blood vessels that contained red blood cells. Furthermore, the released trehalose was well tolerated by the surrounding tissue. PMID:21976136

  17. Optical-vortex laser ablation

    OpenAIRE

    Hamazaki, Junichi; Morita, Ryuji; Chujo, Keisuke; Kobayashi, Yusuke; Tanda, Satoshi; Omatsu, Takashige

    2010-01-01

    Laser ablation of Ta plates using nanosecond optical vortex pulses was carried out, for the first time. It was suggested that owing to orbital angular momentum of optical vortex, clearer and smoother processed surfaces were obtained with less ablation threshold fluence, in comparison with the ablation by a nonvortex annular beam modified from a spatially Gaussian beam.

  18. Clinical effect observation of VEGF expression interfered by Thalidomide combined with radiotherapy in esophageal cancer treatment

    International Nuclear Information System (INIS)

    Objective: To prospectively study the dynamic variation of vascular endothelial growth factor (VEGF), the short-term efficiency and the tolerability of the esophageal cancer patients treated by radiotherapy combined with thalidomide. Methods: The serum samples of 86 esophageal cancer patients were collected before, during and after the radiotherapy. The VEGF levels were assayed by enzyme-linked immunosorbent assay (ELISA). 3 patients interrupted the treatment because of intolerance radiotherapy. Based on the changes of VEGF level, 32 esophageal cancer cases whose VEGF levels increased or remained were assigned to the group to which thalidomide was given during the whole course of radiotherapy. The rest 51 patients whose VEGF level decreased received radiotherapy without thalidomide during the whole course.In addition,30 healthy cases were included in control group. Then the efficiency and safety of the introduction of thalidomide in radiotherapy were investigated. Results: The VEGF levels of 86 esophageal cancer cases were significantly higher than the 30 healthy control cases (t=5.07, P<0.01), which were also correlated with the primary tumor size (t=4.55, P<0.01), lymph node metastasis (t=7.50, P<0.01), histological type (F=3.40, P<0.01) and clinical stage (t=2.52, P<0.01). However, it was irrelevant to the lesion site,distant metastasis, X-ray pathologic type, gender or age (P>0.05). For the thalidomide involved group, the VEGF level after radiotherapy was significantly lower than during radiotherapy (t=2.37, P<0.05) with an effective rate of 71.88%. For the rest 51 cases without using thalidomide, the effective rate was 78.43% yet there was no significant difference between the VEGF levels during and after radiotherapy (t=0.18, P>0.05). 62.50% patients reported symptoms of dizzy and burnout after using thalidomide, while this incidence was 15.69% for the rest patients (χ2=19.28, P=0.000). For the groups with or without thalidomide combination, the sleepiness

  19. Engineered Conformation-dependent VEGF Peptide Mimics Are Effective in Inhibiting VEGF Signaling Pathways

    OpenAIRE

    Vicari, Daniele; Foy, Kevin C.; Liotta, Eric M.; Kaumaya, Pravin T.P.

    2011-01-01

    Angiogenesis, or formation of new blood vessels, is crucial to cancer tumor growth. Tumor growth, progression, and metastasis are critically influenced by the production of the pro-angiogenic vascular endothelial growth factor (VEGF). Promising anti-angiogenic drugs are currently available; however, their susceptibilities to drug resistance and long term toxicity are serious impediments to their use, thus requiring the development of new therapeutic approaches for safe and effective angiogeni...

  20. Tumor ablations in IMRI

    Institute of Scientific and Technical Information of China (English)

    Roberto Blanco Sequeiros

    2002-01-01

    @@ IntroductionMagnetic resonance imaging based guidance control and monitoring of minimally invasive intervention has developed from a hypothetical concept to a practical possibility. Magnetic-resonance-guided interstitial therapy in principle is defined as a treatment technique for ablating deepseated tumors in the human body.

  1. Spark ablation device

    NARCIS (Netherlands)

    Schmidt-Ott, A.; Pfeiffer, T.V.

    2013-01-01

    A spark ablation device for generating nanoparticles comprising a spark generator; the spark generator comprising first and second electrodes, wherein the spark generator further comprises at least one power source which is arranged to be operative at a first energy level for maintaining a discharge

  2. Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells

    International Nuclear Information System (INIS)

    Vascular endothelial growth factor-a (VEGF)-targeted therapies have become an important treatment for a number of human malignancies. The VEGF inhibitors are actually effective in several types of cancers, however, the benefits are transiently, and the vast majority of patients who initially respond to the therapies will develop resistance. One of possible mechanisms for the acquired resistance may be the direct effect(s) of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGFR). Thus, we investigated here the direct effect of chronic VEGF inhibition on phenotype changes in human colorectal cancer (CRC) cells. To chronically inhibit cancer cell-derived VEGF, human CRC cell lines (HCT116 and RKO) were chronically exposed (2 months) to an anti-VEGF monoclonal antibody (mAb) or were disrupted the Vegf gene (VEGF-KO). Effects of VEGF family members were blocked by treatment with a VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI). Hypoxia-induced apoptosis under VEGF inhibited conditions was measured by TUNEL assay. Spheroid formation ability was assessed using a 3-D spheroid cell culture system. Chronic inhibition of secreted/extracellular VEGF by an anti-VEGF mAb redundantly increased VEGF family member (PlGF, VEGFR1 and VEGFR2), induced a resistance to hypoxia-induced apoptosis, and increased spheroid formation ability. This apoptotic resistance was partially abrogated by a VEGFR-TKI, which blocked the compensate pathway consisted of VEGF family members, or by knockdown of Vegf mRNA, which inhibited intracellular function(s) of all Vegf gene products. Interestingly, chronic and complete depletion of all Vegf gene products by Vegf gene knockout further augmented these phenotypes in the compensate pathway-independent manner. These accelerated phenotypes were significantly suppressed by knockdown of hypoxia-inducible factor-1α that was up-regulated in the VEGF-KO cell lines. Our findings suggest that chronic inhibition of tumor cell-derived VEGF

  3. Measurement of circulating levels of VEGF-A,-C,and -D and their receptors,VEGFR-1 and -2 in gastric adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Mansour S Al-Houndhd; A Al-Shukaili; M Al-Nabhani; B Al-Bahrani; IA Burney; A Rizivi; SS Ganguly

    2008-01-01

    AIM: To analyze the serum levels and prognostic significance of vascular endothelial growth factor (VEGF) -A,-C,and -D,and their receptors,VEGFR-1 and -2 in gastric adenocarcinomas.METHODS: The serum levels of VEGF family members were measured in 76 control subjects and 76 patients with gastric adenocarcinoma using an enzyme-linked immunosorbent assay (ELISA).These measurements were correlated with clinco-pathological features and survival rates.RESULTS: The serum levels of VEGF-A and its receptor,VEGFR-1,were significantly higher in patients with gastric cancer than in healthy donors (t = 2.3,P = 0.02 and t = 4.2,P<0.0001,respectively).In contrast,the serum levels of VEGF-D were significantly higher in control subjects than in patients (t = 2.9,P = 0.004).There was no significant difference in serum levels of VEGF-C and VEGFR-2 between patients and controls.VEGF-C was associated with advanced tumor stage and presence of metastasis.VEGFR-1 was associated with metastasis,advanced overall stage,tumor differentiation and survival.VEGFR-2 levels were associated with poor tumor differentiation.There was no significant prognostic value for any of the VEGF family members or their receptors except for VEGFR-1 where high levels were associated with a poor overall survival.CONCLUSION: Serum VEGF levels vary significantly in the same cohort of patients with variable clinicopathological features and prognostic values.The simultaneous measurement of VFGF receptors levels in sera may overcome the limitations of a single biomarker assay.

  4. VEGF-specific siRNAs modified with 2′-deoxy effectively suppress VEGF expression and inhibit growth of nasopharyngeal carcinoma xenograft in a mouse model

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Vascular endothelial growth factor (VEGF) is up-regulated in the vast majority of human tumors. The up-regulation of VEGF not only plays important roles in tumor angiogenesis, but also provides a target for tumor treatment with small interfering RNA (siRNA) that targets VEGF; however, it is unclear whether a quite high up-regulation of VEGF will affect the efficiency of RNA interference strategies targeting VEGF. A high level expression of VEGF was found in CNE cells from a nasopharyngeal carcinoma cell line. In this study, we investigate whether VEGF-specific siRNAs can effectively suppress VEGF expression in CNE cells, and study the methods for the use of VEGF-specific siRNAs as potential therapeutic agents. CNE cells with high VEGF expression induced by hypoxia were transfected with VEGF-specific siRNAs. The expression of VEGF was effectively suppressed by VEGF-specific siRNAs, measured by ELISA, Western blot analysis and RT-PCR. Furthermore, experiments in nude mice bearing nasopharyngeal carcinoma xenograft were initiated 5 d after injection of CNE cells. VEGF-specific siRNAs were modified with 2′-deoxy, then injected into the tumors, and a liposome-mediated siRNA transfection system and ultrasound exposure were used to help delivery of the siRNAs. Tumor growth was reduced significantly after 3 weeks’ treatment. These studies suggest that VEGF-specific siRNAs still can effectively suppress VEGF expression even in tumor cell lines with a relatively high level of VEGF expression, such as CNE, and VEGF-specific siRNAs modified with 2′-deoxy can be used as potential agents for tumor therapy.

  5. VEGF stimulates intramembranous bone formation during craniofacial skeletal development.

    Science.gov (United States)

    Duan, Xuchen; Bradbury, Seth R; Olsen, Bjorn R; Berendsen, Agnes D

    2016-01-01

    Deficiency of vascular endothelial growth factor A (VEGF) has been associated with severe craniofacial anomalies in both humans and mice. Cranial neural crest cell (NCC)-derived VEGF regulates proliferation, vascularization and ossification of cartilage and membranous bone. However, the function of VEGF derived from specific subpopulations of NCCs in controlling unique aspects of craniofacial morphogenesis is not clear. In this study a conditional knockdown strategy was used to genetically delete Vegfa expression in Osterix (Osx) and collagen II (Col2)-expressing NCC descendants. No major defects in calvaria and mandibular morphogenesis were observed upon knockdown of VEGF in the Col2(+) cell population. In contrast, loss of VEGF in Osx(+) osteoblast progenitor cells led to reduced ossification of calvarial and mandibular bones without affecting the formation of cartilage templates in newborn mice. The early stages of ossification in the developing jaw revealed decreased initial mineralization levels and a reduced thickness of the collagen I (Col1)-positive bone template upon loss of VEGF in Osx(+) precursors. Increased numbers of proliferating cells were detected within the jaw mesenchyme of mutant embryos. Explant culture assays revealed that mandibular osteogenesis occurred independently of paracrine VEGF action and vascular development. Reduced VEGF expression in mandibles coincided with increased phospho-Smad1/5 (P-Smad1/5) levels and bone morphogenetic protein 2 (Bmp2) expression in the jaw mesenchyme. We conclude that VEGF derived from Osx(+) osteoblast progenitor cells is required for optimal ossification of developing mandibular bones and modulates mechanisms controlling BMP-dependent specification and expansion of the jaw mesenchyme. PMID:26899202

  6. Anti-VEGF antibody treatment accelerates polycystic kidney disease.

    Science.gov (United States)

    Raina, Shagun; Honer, Michael; Krämer, Stefanie D; Liu, Yang; Wang, Xueqi; Segerer, Stephan; Wüthrich, Rudolf P; Serra, Andreas L

    2011-10-01

    Polycystic kidney growth implies expansion of the vasculature, suggesting that vascular endothelial growth factor (VEGF)-dependent processes play a critical role and that VEGF is a putative therapeutic target. Whether an anti-VEGF antibody improves renal cystic disease has not been determined. We administrated 5 mg/kg B20.4.1, an anti-VEGF-A antibody, or vehicle intraperitoneally twice weekly to 4-wk-old male normal (+/+) and cystic (Cy/+) Han:SPRD rats for 6 wk. Renal function, urinary protein excretion, organ/body weight ratios, cyst volume, tubular epithelial cell (TEC) proliferation, renal VEGF, hypoxia-inducible factor (HIF)-1α and -2α expression, renal histology, and kidney hypoxia visualized by [(18)F]fluoromisonidazole positron emission tomography were assessed. The treated compared with untreated +/+ rats had lower TEC proliferation rates, whereas Cy/+ rats receiving B20.4.1 displayed an increased proximal TEC proliferation rate, causing enhanced cyst and kidney growth. The +/+ and Cy/+ rats receiving B20.4.1 had severe renal failure and extensive glomerular damage. Proteinuria, which was highest in anti-VEGF-treated Cy/+ and lowest in untreated normal littermates, was positively correlated with renal HIF-1α and negatively correlated with VEGF expression. The untreated Cy/+ vs. +/+ rats had higher overall [(18)F]fluoromisonidazole uptake. The +/+ rats receiving B20.4.1 vs. untreated had increased [(18)F]fluoromisonidazole uptake, whereas the uptake was unchanged among treated vs. untreated Cy/+ animals. In conclusion, B20.4.1 caused an exaggerated cystic response of the proximal tubules in cystic rats and severe kidney injury that was associated with low renal VEGF and high HIF-1α levels. Anti-VEGF drug therapy may therefore not be a treatment option for polycystic kidney disease. PMID:21677148

  7. Joint Effect of Urinary Total Arsenic Level and VEGF-A Genetic Polymorphisms on the Recurrence of Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Shu-Mei Yang

    Full Text Available The results of our previous study suggested that high urinary total arsenic levels were associated with an increased risk of renal cell carcinoma (RCC. Germline genetic polymorphisms might also affect cancer risk and clinical outcomes. Vascular endothelial growth factor (VEGF plays an important role in vasculogenesis and angiogenesis, but the combined effect of these factors on RCC remains unclear. In this study, we explored the association between the VEGF-A -2578C>A, -1498T>C, -1154G>A, -634G>C, and +936C>T gene polymorphisms and RCC. We also evaluated the combined effects of the VEGF-A haplotypes and urinary total arsenic levels on the prognosis of RCC. This case-control study was conducted with 191 RCC patients who were diagnosed with renal tumors on the basis of image-guided biopsy or surgical resections. An additional 376 age- and gender-matched controls were recruited. Concentrations of urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotyping was investigated using fluorescent-based TaqMan allelic discrimination. We observed no significant associations between VEGF-A haplotypes and RCC risk. However, the VEGF-A ACGG haplotype from VEGF-A -2578, -1498, -1154, and -634 was significantly associated with an increased recurrence of RCC (OR = 3.34, 95% CI = 1.03-10.91. Urinary total arsenic level was significantly associated with the risk of RCC in a dose-response manner, but it was not related to the recurrence of RCC. The combination of high urinary total arsenic level and VEGF-A risk haplotypes affected the OR of RCC recurrence in a dose-response manner. This is the first study to show that joint effect of high urinary total arsenic and VEGF-A risk haplotypes may influence the risk of RCC recurrence in humans who live in an area without obvious arsenic exposure.

  8. Gene Expression of VEGF-A and VEGF-C in Peripheral Blood Mononuclear Cells of Iranian Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Aliparasti

    2013-06-01

    Full Text Available OBJECTIVE: The crucial role of angiogenesis in the pathophysiology of acute myeloid leukemia (AML has been proposed. One of the key regulators of angiogenesis is the vascular endothelial growth factor (VEGF. Among the VEGF family, it has been observed that VEGF-A and VEGF-C are expressed by AML cells and mediate leukemic cell proliferation, survival, and resistance to chemotherapy. Emerging evidence, however, suggests that elevated levels of VEGF or a proangiogenic phenotype may impede, rather than promote, early tumor development and progression. As the significance of VEGF-A and VEGF-C levels in the pathogenesis of AML has not been clarified well, the aim of this study is to evaluate gene expression of these angiogenesis promoters and its possible prognostic value in peripheral blood mononuclear cells of Iranian patients with AML. METHODS: We investigated the mRNA expression of VEGF-A and VEGF-C in peripheral blood mononuclear cells of 27 patients with newly diagnosed AML and 28 healthy controls by quantitative real-time PCR. RESULTS: Expression of VEGF-C mRNA was significantly lower in AML patients than in healthy controls (p<0.001. However, there was no significant decrement in expression of VEGF-A mRNA of AML patients compared to the control group (p=0.861. VEGF-A and VEGF-C expression were not able to predict clinical outcome. CONCLUSION: Our data showed that AML is associated with a decreased expression of VEGF-C mRNA. However, expression levels did not influence the clinical outcome in our study. It seems that angiogenesis is affected by different cytokines other than VEGF-C or VEGF-A, and VEGF is also affected by different cytokines. Taken together, these findings help to provide new insights into the investigation of other angiogenic factors and cytokines that may play roles in the pathogenesis of AML.

  9. Analysis of diabetic retinopathy biomarker VEGF gene by computational approaches

    OpenAIRE

    Jayashree Sadasivam; Ramesh, N; Vijayalakshmi, K.; Vinni Viridi; Shiva prasad

    2012-01-01

    Diabetic retinopathy, the most common diabetic eye disease, is caused by changes in the blood vessels of the retina which remains the major cause. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. One of the biomarker for Diabetic retinopathy has been identified as Vascular Endothelial Growth Factor ( VEGF )gene by computational analysis. VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors...

  10. Lesion size in relation to ablation site during radiofrequency ablation

    DEFF Research Database (Denmark)

    Petersen, H H; Chen, X; Pietersen, A;

    1998-01-01

    convective cooling by induction of a flow around the electrode tip increases lesion dimensions and power consumptions. Furthermore we conclude that for the given target temperature the power consumption is positively correlated with lesion volume (p ...This study was designed to investigate the effect of the convective cooling of the tip of the ablation electrode during temperature controlled radiofrequency ablation. In vivo two different application sites in the left ventricle of anaesthetised pigs were ablated and in vitro ablation...... larger for septal applications than apical applications (p convective cooling by induction of flow yielded larger lesion volume, depth and width (p

  11. Thrombospondin-1 and VEGF in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Canan Alkim

    2012-01-01

    Full Text Available Angiogenesis is an important process in the pathogenesis of chronic inflammation. We aimed to study the angiogeneic balance in inflammatory bowel disease (IBD by evaluating the expression of vascular endothelial growth factor (VEGF and thrombospondin-1 (TSP-1 on colonic epithelial cells, together with the expression of inducible nitric oxide synthase (iNOS.Twenty-one ulcerative colitis (UC, 14 Crohn's disease (CD, 11 colorectal cancer patients, and 11 healthy controls colonic biopsy samples were evaluated immunohistochemically.The expressions of TSP-1, VEGF, and iNOS in UC and CD groups were higher than expression in healthy control group, all with statistical significance. However, in colorectal cancer group, VEGF and iNOS expressions were increased importantly, but TSP-1 expression was not statistically different from healthy control group's expression. Both TSP-1 and VEGF expressions were correlated with iNOS expression distinctly but did not correlate with each other.Both pro-angiogeneic VEGF and antiangiogeneic TSP-1 expressions were found increased in our IBD groups, but in colorectal cancer group, only VEGF expression was increased. TSP-1 increases in IBD patients as a response to inflammatory condition, but this increase was not enough to suppress pathologic angiogenesis and inflammation in IBD.

  12. Bone and Soft Tissue Ablation

    OpenAIRE

    Foster, Ryan C.B.; Joseph M Stavas

    2014-01-01

    Bone and soft tissue tumor ablation has reached widespread acceptance in the locoregional treatment of various benign and malignant musculoskeletal (MSK) lesions. Many principles of ablation learned elsewhere in the body are easily adapted to the MSK system, particularly the various technical aspects of probe/antenna design, tumoricidal effects, selection of image guidance, and methods to reduce complications. Despite the common use of thermal and chemical ablation procedures in bone and soft...

  13. Basal and apical regulation of VEGF-A and placenta growth factor in the RPE/choroid and primary RPE

    Science.gov (United States)

    Kaya, Leyla; Flach, Janina; Lassen, Jens; Treumer, Felix; Roider, Johann

    2015-01-01

    Purpose Members of the vascular endothelial growth factor (VEGF) family are strongly involved in pathological processes in the retina, such as age-related macular degeneration and diabetic retinopathy. Cells of the retinal pigment epithelium (RPE) constitutively secrete VEGF-A, and the secretion of placental growth factor (PlGF) has also been described. RPE cells are strongly polarized cells with different secretome at the apical and basal side. In this study, we evaluated the basal and apical regulation of VEGF-A and PlGF secretion in RPE/choroid explants and primary RPE cells. Methods RPE/choroid tissue explants were prepared from porcine eyes and cultivated in modified Ussing chambers, separating apical (RPE) and basal (choroid) supernatant. Primary RPE cells were also prepared from porcine eyes and cultivated on Transwell plates. Explants and cells were treated with inhibitors for VEGFR-2 (SU1498), p38 (SB203580), and the transcription factors nuclear factor-kappa B (NF-κB) and SP-1 (mithramycin), respectively. VEGF-A and PlGF content was evaluated with enzyme-linked immunosorbent assay (ELISA). In addition, western blots were performed. Results In the RPE/choroid, VEGF-A can initially be found on the apical and basal sides with significantly more pronounced secretion on the basal side. VEGF-A secretion is differentially regulated on the apical and basal sides, with the inhibition of SP-1 and NF-κB showing strong effects apically and basally after 24 h and 48 h, the inhibition of p38 displaying its effect mainly on the basal side with some effect apically after 48 h, and the inhibition of VEGFR-2 reducing the secretion of VEGF only on the apical side at 24 h and 48 h. In the RPE cell culture, similar effects were found, with inhibition of NF-κB or SP-1 displaying a strong decrease in VEGF-A on both sides, and p38 inhibition displaying only an inhibitory effect on the basal side. In contrast, an apical effect of VEGFR-2 inhibition was not found. However, the

  14. Radiofrequency ablation of pulmonary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Crocetti, Laura, E-mail: l.crocetti@med.unipi.i [Division of Diagnostic Imaging and Intervention, Department of Liver Transplants, Hepatology and Infectious Diseases, Pisa University School of Medicine (Italy); Lencioni, Riccardo [Division of Diagnostic Imaging and Intervention, Department of Liver Transplants, Hepatology and Infectious Diseases, Pisa University School of Medicine (Italy)

    2010-07-15

    The development of image-guided percutaneous techniques for local tumor ablation has been one of the major advances in the treatment of solid tumors. Among these methods, radiofrequency (RF) ablation is currently established as the primary ablative modality at most institutions. RF ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma when liver transplantation or surgical resection are not suitable options and is considered as a viable alternate to surgery for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer. Recently, RF ablation has been demonstrated to be a safe and valuable treatment option for patients with unresectable or medically inoperable lung malignancies. Resection should remain the standard therapy for non-small cell lung cancer (NSCLC) but RF ablation may be better than conventional external-beam radiation for the treatment of the high-risk individual with NSCLC. Initial favourable outcomes encourage combining radiotherapy and RF ablation, especially for treating larger tumors. In the setting of colorectal cancer lung metastases, survival rates provided by RF ablation in selected patients, are substantially higher than those obtained with any chemotherapy regimens and provide indirect evidence that RF ablation therapy improves survival in patients with limited lung metastatic disease.

  15. Formation of VEGF isoform-specific spatial distributions governing angiogenesis: computational analysis

    Directory of Open Access Journals (Sweden)

    Mac Gabhann Feilim

    2011-05-01

    Full Text Available Abstract Background The spatial distribution of vascular endothelial growth factor A (VEGF is an important mediator of vascular patterning. Previous experimental studies in the mouse hindbrain and retina have suggested that VEGF alternative splicing, which controls the ability of VEGF to bind to heparan sulfate proteoglycans (HSPGs in the extracellular matrix (ECM, plays a key role in controlling VEGF diffusion and gradients in tissues. Conversely, proteolysis notably by matrix metalloproteinases (MMPs, plays a critical role in pathological situations by releasing matrix-sequestered VEGF and modulating angiogenesis. However, computational models have predicted that HSPG binding alone does not affect VEGF localization or gradients at steady state. Results Using a 3D molecular-detailed reaction-diffusion model of VEGF ligand-receptor kinetics and transport, we test alternate models of VEGF transport in the extracellular environment surrounding an endothelial sprout. We show that differences in localization between VEGF isoforms, as observed experimentally in the mouse hindbrain, as well as the ability of proteases to redistribute VEGF in pathological situations, are consistent with a model where VEGF is endogenously cleared or degraded in an isoform-specific manner. We use our predictions of the VEGF distribution to quantify a tip cell's receptor binding and gradient sensing capacity. A novel prediction is that neuropilin-1, despite functioning as a coreceptor to VEGF165-VEGFR2 binding, reduces the ability of a cell to gauge the relative steepness of the VEGF distribution. Comparing our model to available in vivo vascular patterning data suggests that vascular phenotypes are most consistently predicted at short range by the soluble fraction of the VEGF distributions, or at longer range by matrix-bound VEGF detected in a filopodia-dependent manner. Conclusions Isoform-specific VEGF degradation provides a possible explanation for numerous examples

  16. VEGF111b, a new member of VEGFxxxb isoforms and induced by mitomycin C, inhibits angiogenesis

    International Nuclear Information System (INIS)

    Highlights: •We discovered a new member of VEGFxxxb family-VEGF111b. •We found VEGF111b mRNA and protein can be induced by mitomycin C. •We confirmed VEGF111b over-expression inhibits angiogenesis. •VEGF111b inhibits angiogenesis through inhibiting VEGF-R2/PI3K/Akt and VEGF-R2/ERK1/2 phosphorylation. -- Abstract: Vascular endothelial growth factor (VEGF-A) stimulating angiogenesis is required for tumor growth and progression. The conventional VEGF-A isoforms have been considered as pro-angiogenic factors. Another family of VEGF-A isoforms generated by alternative splicing, termed VEGFxxxb isoforms, has anti-angiogenic property, exemplified by VEGF165b. Here, we identify a new number of VEGFxxx family-VEGF111b induced by mitomycin C, although not detected in mitomycin C-unexposed ovarian cancer cells. SKOV3 cells were transfected with pcDNA3.1 empty vector, pcDNA3.1-VEGF111b or pcDNA3.1-VEGF165b to collect conditioned mediums respectively. VEGF111b overexpression inhibits proliferation, migration and tube formation of endothelial cell by inhibiting VEGF-R2 phosphorylation and its downstream signaling, similar to VEGF165b but slightly lower than VEGF165b. The anti-angiogenic property depends on the six amino acids of exon 8b of the VEGFxxxb isoforms. Our results show that VEGF111b is a novel potent anti-angiogenic agent that can target the VEGF-R2 and its signaling pathway to inhibit ovarian tumor growth

  17. Endoscopic ultrasound guided radiofrequency ablation in pancreas

    DEFF Research Database (Denmark)

    Seicean, Andrada; Tefas, Cristian; Ungureanu, Bogdan;

    2014-01-01

    Radiofrequency ablation of the pancreas represents a more effective tumor-destruction method compared to other ablation techniques. The endoscopic ultrasound guided radiofrequency ablation is indicated for locally advanced, non-metastatic pancreatic adenocarcinoma, without the need of general...

  18. Differential regulation of angiogenesis using degradable VEGF-binding microspheres.

    Science.gov (United States)

    Belair, David G; Miller, Michael J; Wang, Shoujian; Darjatmoko, Soesiawati R; Binder, Bernard Y K; Sheibani, Nader; Murphy, William L

    2016-07-01

    Vascular endothelial growth factor (VEGF) spatial and temporal activity must be tightly controlled during angiogenesis to form perfusable vasculature in a healing wound. The native extracellular matrix (ECM) regulates growth factor activity locally via sequestering, and researchers have used ECM-mimicking approaches to regulate the activity of VEGF in cell culture and in vivo. However, the impact of dynamic, affinity-mediated growth factor sequestering has not been explored in detail with biomaterials. Here, we sought to modulate VEGF activity dynamically over time using poly(ethylene glycol) microspheres containing VEGF-binding peptides (VBPs) and exhibiting varying degradation rates. The degradation rate of VBP microspheres conferred a differential ability to up- or down-regulate VEGF activity in culture with primary human endothelial cells. VBP microspheres with fast-degrading crosslinks reduced VEGF activity and signaling, while VBP microspheres with no inherent degradability sequestered and promoted VEGF activity in culture with endothelial cells. VBP microspheres with degradable crosslinks significantly reduced neovascularization in vivo, but neither non-degradable VBP microspheres nor bolus delivery of soluble VBP reduced neovascularization. The covalent incorporation of VBP to degradable microspheres was required to reduce neovascularization in a mouse model of choroidal neovascularization in vivo, which demonstrates a potential clinical application of degradable VBP microspheres to reduce pathological angiogenesis. The results herein highlight the ability to modulate the activity of a sequestered growth factor by changing the crosslinker identity within PEG hydrogel microspheres. The insights gained here may instruct the design and translation of affinity-based growth factor sequestering biomaterials for regenerative medicine applications. PMID:27061268

  19. The expression of VEGF and its receptors in the human ductus arteriosus.

    Science.gov (United States)

    Weber, Sven C; Rheinlaender, Cornelia; Sarioglu, Nanette; Peiser, Christian; Rüdiger, Mario; Obladen, Michael; Koehne, Petra S

    2008-10-01

    Programmed proliferative degeneration of the human fetal ductus arteriosus (DA) preceding definite postnatal closure has a large developmental variability and is controlled by several signaling pathways. Among these vascular endothelial growth factor (VEGF) and its receptors (VEGF-Rs) play an important role. Until now, gestational age dependent expression of VEGF and its receptors has not been investigated in a large number of human DA tissue specimens. We examined protein expression of VEGF and the three VEGF-Rs immunohistochemically in 63 human fetal autopsy DA specimens of 11-38 wk gestation. Specimens were classified into different maturity stages according to their histologic appearance. VEGF and VEGF-Rs-staining was detected in all maturity stages. VEGF-staining was localized perinuclearly in all vascular layers and did not change during development. VEGF-R1 and VEGF-R3 expression was marked in the endothelium in early maturity stages and decreased during development. In contrast, -R2 predominated in the media in later developmental stages. Our results emphasize the importance of VEGF as a mediator during programmed proliferative degeneration of fetal DA and support the hypothesis that VEGF-R1 and VEGF-R3 are required for normal blood vessel development during embryogenesis. In contrast, VEGF-R2 is the predominant receptor in later angiogenic signaling.

  20. Construction and Identification of Recombinant Adenovirus Vector Containing the hVEGF165 Gene

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To construct the recombinant adenovirus vector containing the cDNA for human vascular endothelial growth factor (hVEGF165), the cDNA for hVEGF165 was subcloned into pACCMV·pLpA. Subsequently, this recombinant pACCMV·hVEGF was co-transfected into 293 cells together with pJM17 to obtain the replication-deficient recombinant adenovirus containing hVEGF gene-AdCMV·hVEGF. The VEGF gene expression was detected by using RT-PCR and Western blot in rabbit aorta vascular smooth muscle cells (VSMC) infected with AdCMV·hVEGF. Cultured human umbilical vein endothelial cells (HUVEC) were incubated with the conditioned medium (CM) from above mentioned VSMC infected with AdCMV·hVEGF to observe the effect of VEGF on proliferation of HUVEC. 48 h after the infection with AdCMV·hVEGF, VSMC demonstrated VEGF expression, and the expressed VEGF could stimulate the proliferation of HUVEC in vitro. Successfully prepared AdCMV·hVEGF165 could express biologically active VEGF in infected VSMC, and stimulate proliferation of HUVEC.

  1. LASER ABLATION STUDIES OF CONCRETE

    Science.gov (United States)

    Laser ablation was studied as a means of removing radioactive contaminants from the surface and near-surface regions of concrete. We present the results of ablation tests on cement and concrete samples using a 1.6 kW pulsed Nd:YAG laser with fiber optic beam delivery. The laser-s...

  2. Radiofrequency ablation of osteoid osteoma

    NARCIS (Netherlands)

    Vanderschueren, Geert Maria Joris Michael

    2009-01-01

    The main purpose of this thesis was to evaluate the effectiveness and safety of CT-guided radiofrequency ablation for the treatment of spinal and non-spinal osteoid osteomas. Furthermore, the technical requirements needed for safe radiofrequency ablation and the clinical outcome after radiofrequency

  3. Investigation of Antiangiogenic Tumor Therapy Potential of Microencapsulated HEK293 VEGF165b Producing Cells

    Directory of Open Access Journals (Sweden)

    Fatemeh Afkhami

    2010-01-01

    encapsulated and non-encapsulated cells was similar. The effect of VEGF165b harvested from encapsulated cells on Human Umbilical Vein Endothelial cells (HUVECs proliferation were also examined.The same inhibitory effects on HUVECs proliferation was seen when the cells were incubated with a mixture of VEGF165b and a 2-fold VEGF165b or with VEGF165b and 2-fold excess VEGF165b released from encapsulated cells. Subcutaneous injection of microencapsulated VEGF165b producing cells in tumor site of nude mice resulted in the reduction of the number of vessels around the tumors.

  4. VEGF Spliced Variants: Possible Role of Anti-Angiogenesis Therapy

    Directory of Open Access Journals (Sweden)

    Caroline Hilmi

    2012-01-01

    Full Text Available Angiogenesis has been targeted in retinopathies, psoriasis, and a variety of cancers (colon, breast, lung, and kidney. Among these tumour types, clear cell renal cell carcinomas (RCCs are the most vascularized tumours due to mutations of the von Hippel Lindau gene resulting in HIF-1 alpha stabilisation and overexpression of Vascular Endothelial Growth Factor (VEGF. Surgical nephrectomy remains the most efficient curative treatment for patients with noninvasive disease, while VEGF targeting has resulted in varying degrees of success for treating metastatic disease. VEGF pre-mRNA undergoes alternative splicing generating pro-angiogenic isoforms. However, the recent identification of novel splice variants of VEGF with anti-angiogenic properties has provided some insight for the lack of current treatment efficacy. Here we discuss an explanation for the relapse to anti-angiogenesis treatment as being due to either an initial or acquired resistance to the therapy. We also discuss targeting angiogenesis via SR (serine/arginine-rich proteins implicated in VEGF splicing.

  5. Pharmacokinetics of Anti-VEGF Agent Aflibercept in Cancer Predicted by Data-Driven, Molecular-Detailed Model.

    Science.gov (United States)

    Finley, S D; Angelikopoulos, P; Koumoutsakos, P; Popel, A S

    2015-11-01

    Mathematical models can support the drug development process by predicting the pharmacokinetic (PK) properties of the drug and optimal dosing regimens. We have developed a pharmacokinetic model that includes a biochemical molecular interaction network linked to a whole-body compartment model. We applied the model to study the PK of the anti-vascular endothelial growth factor (VEGF) cancer therapeutic agent, aflibercept. Clinical data is used to infer model parameters using a Bayesian approach, enabling a quantitative estimation of the contributions of specific transport processes and molecular interactions of the drug that cannot be examined in other PK modeling, and insight into the mechanisms of aflibercept's antiangiogenic action. Additionally, we predict the plasma and tissue concentrations of unbound and VEGF-bound aflibercept. Thus, we present a computational framework that can serve as a valuable tool for drug development efforts. PMID:26783500

  6. Rapamycin increases pCREB, Bcl-2, and VEGF-A through ERK under normoxia

    Institute of Scientific and Technical Information of China (English)

    Yudong Liu; Qixin Zheng; Hongbin Wu; Xiaodong Guo; Jingfeng Li; Shaofei Hao

    2013-01-01

    Rapamycin may serve as a new anti-osteosarcoma (OSA) agent due to its ability to inhibit the metastatic behavior of OSA.However,only limited benefit is observed in rodent studies and clinical trials using rapamycin as a single agent in the treatment of OSA.The target of rapamycin,mammalian target of rapamycin has multiple biological functions and may be linked with the kinases that mediate the phosphorylation of cyclic AMP-responsive element-binding (CREB) protein,an import factor in tumor progression.By employing an OSA cell line MG-63,we investigated how rapamycin regulates the phosphorylation of CREB (pCREB) at Ser133 and the expressions of two putative CREB targets,B-cell lymphoma 2 (Bcl-2)and vascular endothelial growth factor-A (VEGF-A).Under normoxia,we found that rapamycin (100nM)induced an increase of pCREB that was prevented by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126 or cAMP-dependent protein kinase (PKA) inhibitor H89.However,H89 enhanced Akt phosphorylation and did not decrease the cell viability upon rapamycin treatment.In contrast,U0126 did not enhance Akt phosphorylation and decreased the cell viability upon rapamycin treatment.Moreover,U0126 prevented the rapamycin-induced increase of Bcl-2 and VEGF-A levels.Under hypoxia,rapamycin effectively prevented the hypoxia-induced increase of pCREB,Bcl-2,and VEGF-A.Our study demonstrated that rapamycin might be less effective in treating OSA cells under normoxia and provided the rationale for a combination of rapamycin and MEK/ERK inhibitor in the treatment of OSA.

  7. Intracellular autocrine VEGF signaling promotes EBDC cell proliferation, which can be inhibited by Apatinib.

    Science.gov (United States)

    Peng, Sui; Zhang, Yanyan; Peng, Hong; Ke, Zunfu; Xu, Lixia; Su, Tianhong; Tsung, Allan; Tohme, Samer; Huang, Hai; Zhang, Qiuyang; Lencioni, Riccardo; Zeng, Zhirong; Peng, Baogang; Chen, Minhu; Kuang, Ming

    2016-04-10

    Tumor cells produce vascular endothelial growth factor (VEGF) which can interact with membrane or cytoplasmic VEGF receptors (VEGFRs) to promote cell growth. We aimed to investigate the role of extracellular/intracellular autocrine VEGF signaling and Apatinib, a highly selective VEGFR2 inhibitor, in extrahepatic bile duct cancer (EBDC). We found conditioned medium or recombinant human VEGF treatment promoted EBDC cell proliferation through a phospholipase C-γ1-dependent pathway. This pro-proliferative effect was diminished by VEGF, VEGFR1 or VEGFR2 neutralizing antibodies, but more significantly suppressed by intracellular VEGFR inhibitor. The rhVEGF induced intracellular VEGF signaling by promoting nuclear accumulation of pVEGFR1/2 and enhancing VEGF promoter activity, mRNA and protein expression. Internal VEGFR2 inhibitor Apatinib significantly inhibited intracellular VEGF signaling, suppressed cell proliferation in vitro and delayed xenograft tumor growth in vivo, while anti-VEGF antibody Bevacizumab showed no effect. Clinically, overexpression of pVEGFR1 and pVEGFR2 was significantly correlated with poorer overall survival (P = .007 and P = .020, respectively). In conclusion, the intracellular autocrine VEGF loop plays a predominant role in VEGF-induced cell proliferation. Apatinib is an effective intracellular VEGF pathway blocker that presents a great therapeutic potential in EBDC. PMID:26805764

  8. VEGF promotes gastric cancer development by upregulating CRMP4

    Science.gov (United States)

    Peng, Jianjun; Zhai, Ertao; He, Yulong; Wu, Hui; Chen, Chuangqi; Ma, Jinping; Wang, Zhao; Cai, Shirong

    2016-01-01

    This study aimed to investigate the precise role of CRMP4 in gastric tumor growth and patient survival. The mRNA and protein expression levels of CRMP4, VEGF and VEGFR2 were validated by qRT-PCR and immunohistochemistry. We investigated the effects on tumor growth of overexpression and knockdown of CRMP4 both in vitro and in vivo by constructing stable gastric cell lines using lentiviral-mediated transduction and shRNA interference-mediated knockdown of CRMP4 expression. We further validated the role of the ERK/AKT signaling pathways in VEGF and CRMP4 expression using ERK and PI3K inhibitors. Increased expression of VEGF and CRMP4 were observed in gastric cancer tissues compared with tumor-adjacent tissue. We found that higher CRPM4 expression was associated with lymph node metastasis, TNM stage, tumor differentiation and poorer prognosis in gastric cancer patients. In HGC27 and SGC7901 gastric cancer cells, VEGF upregulated CRMP4 in time and dose-dependent manners. Overexpression of CRMP4 increased cell proliferation, migration and invasion, whereas knockdown of CRMP4 expression had opposite effects. VEGF activated CRMP4 expression in gastric cancer cells, and this effect was significantly inhibited by MAPK and PI3K inhibitors (PD98059 and LY294002). In mice, CRMP4 overexpression also resulted in increased tumor growth. These results suggest that increased CRMP4 expression mediated by the activation of VEGF signaling facilitates gastric tumor growth and metastasis, which may have clinical implications associated with a reduced survival rate in gastric cancer patients. PMID:26934554

  9. Notch, IL-1 and leptin crosstalk outcome (NILCO is critical for leptin-induced proliferation, migration and VEGF/VEGFR-2 expression in breast cancer.

    Directory of Open Access Journals (Sweden)

    Shanchun Guo

    Full Text Available High levels of pro-angiogenic factors, leptin, IL-1, Notch and VEGF (ligands and receptors, are found in breast cancer, which is commonly correlated with metastasis and lower survival of patients. We have previously reported that leptin induces the growth of breast cancer and the expression of VEGF/VEGFR-2 and IL-1 system. We hypothesized that Notch, IL-1 and leptin crosstalk outcome (NILCO plays an essential role in the regulation of leptin-mediated induction of proliferation/migration and expression of pro-angiogenic molecules in breast cancer. To test this hypothesis, leptin's effects on the expression and activation of Notch signaling pathway and VEGF/VEGFR-2/IL-1 were determined in mouse (4T1, EMT6 and MMT breast cancer cells. Remarkably, leptin up-regulated Notch1-4/JAG1/Dll-4, Notch target genes: Hey2 and survivin, together with IL-1 and VEGF/VEGFR-2. RNA knockdown and pharmacological inhibitors of leptin signaling significantly abrogated activity of reporter gene-luciferase CSL (RBP-Jk promoter, showing that it was linked to leptin-activated JAK2/STAT3, MAPK, PI-3K/mTOR, p38 and JNK signaling pathways. Interestingly, leptin upregulatory effects on cell proliferation/migration and pro-angiogenic factors Notch, IL-1 and VEGF/VEGFR-2 were abrogated by a γ-secretase inhibitor, DAPT, as well as siRNA against CSL. In addition, blockade of IL-1R tI inhibited leptin-induced Notch, Hey2 and survivin as well as VEGF/VEGFR-2 expression. These data suggest leptin is an inducer of Notch (expression/activation and IL-1 signaling modulates leptin effects on Notch and VEGF/VEGFR-2. We show for the first time that a novel unveiled crosstalk between Notch, IL-1 and leptin (NILCO occurs in breast cancer. Leptin induction of proliferation/migration and upregulation of VEGF/VEGFR-2 in breast cancer cells were related to an intact Notch signaling axis. NILCO could represent the integration of developmental, pro-inflammatory and pro-angiogenic signals

  10. Relationship of VEGF/VEGFR with immune and cancer cells:staggering or forward?

    Institute of Scientific and Technical Information of China (English)

    Yu-Ling Li; Hua Zhao; Xiu-Bao Ren

    2016-01-01

    Vascular endothelial growth factor (VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors (VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells (DCs), macrophages, and lymphocytes further express certain types of VEGF receptors. VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness. This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.

  11. Insight into 144 patients with ocular vascular events during VEGF antagonist injections

    DEFF Research Database (Denmark)

    Mansour, Ahmad M; Shahin, Maha; Kofoed, Peter K;

    2012-01-01

    To record ocular vascular events following injections of vascular endothelium growth factor (VEGF) antagonists.......To record ocular vascular events following injections of vascular endothelium growth factor (VEGF) antagonists....

  12. Recombinant Goat VEGF164 Increases Hair Growth by Painting Process on the Skin of Shaved Mouse.

    Science.gov (United States)

    Bao, Wenlei; Yin, Jianxin; Liang, Yan; Guo, Zhixin; Wang, Yanfeng; Liu, Dongjun; Wang, Xiao; Wang, Zhigang

    2014-09-01

    To detect goat vascular endothelial growth factor (VEGF)-mediated regrowth of hair, full-length VEGF164 cDNA was cloned from Inner Mongolia cashmere goat (Capra hircus) into the pET-his prokaryotic expression vector, and the recombinant plasmid was transferred into E. coli BL21 cells. The expression of recombinant 6×his-gVEGF164 protein was induced by 0.5 mM isopropyl thio-β-D-galactoside at 32°C. Recombinant goat VEGF164 (rgVEGF164) was purified and identi ed by western blot using monoclonal anti-his and anti-VEGF antibodies. The rgVEGF164 was smeared onto the dorsal area of a shaved mouse, and we noted that hair regrowth in this area was faster than in the control group. Thus, rgVEGF164 increases hair growth in mice. PMID:25178380

  13. EUV ablation of organic polymers at a high fluence

    Institute of Scientific and Technical Information of China (English)

    Chiara; Liberatore; Klaus; Mann; Matthias; Mller; Ladislav; Pina; Libor; Juha; Jorge; J.Rocca; Akira; Endo; Tomas; Mocek

    2014-01-01

    A preliminary investigation on short-wavelength ablation mechanisms of poly(methyl methacrylate)(PMMA) and poly(1,4-phenylene ether ether-sulfone)(PPEES) by extreme ultraviolet(EUV) radiation at 13.5 nm using a table-top laserproduced plasma from a gas-puff target at LLG(Gttingen) and at 46.9 nm by a 10 Hz desktop capillary discharge laser operated at the Institute of Physics(Prague) is presented.Ablation of polymer materials is initiated by photoinduced polymer chain scissions.The ablation occurs due to the formation of volatile products by the EUV radiolysis removed as an ablation plume from the irradiated material into the vacuum.In general,cross-linking of polymer molecules can compete with the chain decomposition.Both processes may influence the efficiency and quality of micro(nano)structuring in polymer materials.Wavelength is a critical parameter to be taken into account when an EUV ablation process occurs,because different wavelengths result in different energy densities in the near-surface region of the polymer exposed to nanosecond pulses of intense EUV radiation.

  14. Vascular endothelial growth factor A (VEGF-A) decreases expression and secretion of pleiotrophin in a VEGF receptor-independent manner.

    Science.gov (United States)

    Poimenidi, Evangelia; Theodoropoulou, Christina; Koutsioumpa, Marina; Skondra, Lamprini; Droggiti, Eirini; van den Broek, Marloes; Koolwijk, Pieter; Papadimitriou, Evangelia

    2016-05-01

    Vascular endothelial growth factor A (VEGF-A) is a key molecule in angiogenesis acting through VEGF receptors (VEGFRs), ανβ3 integrin, receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and cell surface nucleolin (NCL). Pleiotrophin (PTN) stimulates endothelial cell migration and limits the angiogenic effects of VEGF-A165 to the levels of its own effect, possibly acting as a VEGF-A165 modifier. Since PTN and VEGF-A165 share receptors and actions on endothelial cells, in the present work we studied whether and how VEGF-A165 affects PTN expression or secretion. VEGF-A165 decreased PTN mRNA and protein levels acting at the transcriptional level. Bevacizumab, a selective VEGFR2 tyrosine kinase inhibitor and down-regulation of VEGFR2 expression by siRNA did not affect this decrease, suggesting that it is VEGFR-independent. VEGF-A121 also decreased PTN mRNA and protein levels, suggesting that heparin binding of VEGF-A165 is not involved. Blockage of cell surface NCL, lack of expression or mutation of β3 integrin and down-regulation of RPTPβ/ζ abolished the inhibitory effect of VEGF-A165 on PTN expression and secretion. Down-regulation of endogenous PTN in endothelial cells enhanced VEGF-A165-induced increase in migration and tube formation on matrigel. Collectively, these data suggest that VEGF-A down-regulates PTN expression and secretion through the RPTPβ/ζ-ανβ3-NCL axis to enhance its own effect on cell migration and further highlight the role of RPTPβ/ζ in VEGF-A actions. PMID:26924457

  15. VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema

    OpenAIRE

    Yoon, Young-sup; Murayama, Toshinori; Gravereaux, Edwin; Tkebuchava, Tengiz; Silver, Marcy; Curry, Cynthia; Wecker, Andrea; Kirchmair, Rudolf; Hu, Chun Song; Kearney, Marianne; Ashare, Alan; Jackson, David G.; Kubo, Hajime; Isner, Jeffrey M.; Losordo, Douglas W.

    2003-01-01

    Although lymphedema is a common clinical condition, treatment for this disabling condition remains limited and largely ineffective. Recently, it has been reported that overexpression of VEGF-C correlates with increased lymphatic vessel growth (lymphangiogenesis). However, the effect of VEGF-C–induced lymphangiogenesis on lymphedema has yet to be demonstrated. Here we investigated the impact of local transfer of naked plasmid DNA encoding human VEGF-C (phVEGF-C) on two animal models of lymphed...

  16. The biophysical property of A549 cells transferred by VEGF-D.

    Science.gov (United States)

    Wang, Zhen; Wu, Xiu-Li; Wang, Xu; Tian, Hong-Xia; Chen, Zhi-Hong; Li, Yang-Qiu

    2014-01-01

    Vascular endothelial growth factor-D (VEGF-D) together with VEGF-C is considered to be associated with lymphangiogenesis and angiogenesis and involve in tumorization. This study aims to investigate the influence of exogenous VEGF-D gene on the biophysical property of cell surface of lung adenocarcinoma cell line. A panel of lung adenocarcinoma cell lines were examined the expression of VEGF-D and VEGF-C by real-time PCR. The VEGF-D recombinant plasmid containing enhanced green fluorescence protein (EGFP) was constructed and transfected to the cell line with no expression of VEGF-D and confirmed by real-time PCR and Western blot analysis. Topographic images of cells were obtained by using atomic force microscope (AFM) in contact mode. Unlike VEGF-C, VEGF-D was found to have a very low expression or undetectable expression in lung adenocarcinoma cell lines. The VEGF-D recombinant plasmid had been constructed successfully and was transferred into the human lung adenocarcinoma cell line A549 cells which had no endogenous expression of VEGF-D, and exogenous VEGF-D could be detected in mRNA and protein expression levels in the gene modified cells, while the VEGF-C gene expression had no change after VEGF-D transfection. After transfection, the irregular microspikes or nano clusters could observe on the surface of A549 cells, and VEGF-D transfected A549 cells became more rigid. The exogenous VEGF-D gene might cause the remarkable biophysical architectural changes in the A549 cells, which might as a novel biomarker for evaluation of its biological function. PMID:23526563

  17. Angiopoietin-1/Tie-2 activation contributes to vascular survival and tumor growth during VEGF blockade

    OpenAIRE

    Huang, Jianzhong; Bae, Jae-O; Tsai, Judy P.; Kadenhe-Chiweshe, Angela; Papa, Joey; Lee, Alice; Zeng, Shan; Kornfeld, Z. Noah; Ullner, Paivi; Zaghloul, Nibal; Ioffe, Ella; Nandor, Sarah; Burova, Elena; Holash, Jocelyn; Thurston, Gavin

    2009-01-01

    Approval of the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab by the FDA in 2004 reflected the success of this vascular targeting strategy in extending survival in patients with advanced cancers. However, consistent with previous reports that experimental tumors can grow or recur during VEGF blockade, it has become clear that many patients treated with VEGF inhibitors will ultimately develop progressive disease. Previous studies have shown that disruption of VEGF signali...

  18. VEGF-dependent mechanism of anti-angiogenic action of diamond nanoparticles in Glioblastoma Multiforme tumor

    DEFF Research Database (Denmark)

    Grodzik, M.; Sawosz, E.; Wierzbicki, M.;

    2012-01-01

    of diamond nanoparticle on VEGF level and inhibition of the brain tumor angiogenesis. We evaluated interaction of VEGF-A and VEGF-receptor proteins with diamond nanoparticles (TEM), visualized lower the permeability of blood vessels after diamond nanoparticles treatment and determined localization...

  19. Elevated expressions of Survivin and VEGF proteins are strong independent predictors of survival in squamous carcinoma of larynx%凋亡抑制蛋白Survivin和血管内皮生长因子高表达是喉鳞状细胞癌生存预后的独立预测因子

    Institute of Scientific and Technical Information of China (English)

    Rong Luo; Weijia Kong; Yanjun Wang

    2008-01-01

    Objective: To study the relationship between Survivin and VEGF proteins in a subgroup of patients with squamous carcinoma of larynx. Methods: 108 cases of squamous carcinoma of larynx with clinical data were collected and expressions of Survivin and VEGF in peripheral blood were investigated by enzyme-linked immunosorbent assay (ELISA). Results: Expressions of Survivin and VEGF were significantly associated with T stage, N stage and metastasis of squamous carcinoma of larynx. The patients with Survivin or VEGF over-expressions presented lower survival rate, respectively, as compared to those of low-expression (P < 0.05). The survival rate in squamous carcinoma of larynx patients with Survivin and VEGF dual over-expressions was significantly lower than that of patients with dual low-expression (P < 0.05). Multivariate analysis indicated that both Survivin and VEGF over-expressions in squamous carcinoma of larynx peripheral blood samples were strong independent factors of poor prognosis in squamous carcinoma of larynx patients. Conclusion: Survivin and VEGF over-expressions are independent prognostic factors for the patients with squamous carcinoma of larynx. These results also suggest that peripheral blood Survivin and VEGF expressions are valuable prognostic markers for prognosis prediction in squamous carcinoma of larynx patients.

  20. Field enhancement induced laser ablation

    DEFF Research Database (Denmark)

    Fiutowski, Jacek; Maibohm, Christian; Kjelstrup-Hansen, Jakob;

    Sub-diffraction spatially resolved, quantitative mapping of strongly localized field intensity enhancement on gold nanostructures via laser ablation of polymer thin films is reported. Illumination using a femtosecond laser scanning microscope excites surface plasmons in the nanostructures...

  1. Effects of Rosuvastatin and MiR-126 on Myocardial Injury Induced by Acute Myocardial Infarction in Rats: Role of Vascular Endothelial Growth Factor A (VEGF-A).

    Science.gov (United States)

    Fei, Ling; Zhang, Jun; Niu, Heping; Yuan, Chen; Ma, Xiaoli

    2016-01-01

    BACKGROUND The present study investigated the effects of VEGF-A targeted by miR-126 on myocardial injury after acute myocardial infarction (AMI) in rats, along with the contributions of rosuvastatin to the synergic effect. MATERIAL AND METHODS SD rats were obtained to construct AMI models by ligating their left anterior descending coronary arteries (LAD). We conducted echocardiography to check the 6 involved indexes: left ventricular ejection fractions (LVEF), fractional shortening (FS), left ventricular end-systolic volume (LVV), left ventricular end-diastolic volume (LVVd), cardiac output (CO), and heart rate (HR). Moreover, antibody sandwich enzyme-linked immunosorbent assay was carried out to determine MI markers: creatine kinase (CK), CK Isoenzyme (CK-MB), and Troponin I (cTn I). Dual-Luciferase Reporter Assay was performed to confirm the targeting of miR-126 and VEGF-A. MTT assay provided insight into the proliferation of myocardial fibroblasts. Finally, RT-RCR and Western blot were used for the detection of miR-126 and VEGF-A expressions in vivo and in vitro. RESULTS Luciferase activity assay showed that miR-126 transfection significantly decreased the relative luciferase activity in HEK293T cells when it was bound to normal 3' UTR of VEGF-A (P<0.05). In comparison to the control group, rats in the AMI model group had significantly lower LVEF, FS, and CO, and substantially higher LVVs, LVVd, HR, CK/U, CK-MB/U, and cTn-1/U (all P<0.05). Down-regulated miR-126 and up-regulated VEGF-A were also observed in MI models (P<0.05). CONCLUSIONS miR-126 and rosuvastatin have protective effects on AMI risk, and VEGF-A antagonizes effects on AMI is imposed by. PMID:27376405

  2. Ablative Approaches for Pulmonary Metastases.

    Science.gov (United States)

    Boyer, Matthew J; Ricardi, Umberto; Ball, David; Salama, Joseph K

    2016-02-01

    Pulmonary metastases are common in patients with cancer for which surgery is considered a standard approach in appropriately selected patients. A number of patients are not candidates for surgery due to a medical comorbidities or the extent of surgery required. For these patients, noninvasive or minimally invasive approaches to ablate pulmonary metastases are potential treatment strategies. This article summarizes the rationale and outcomes for non-surgical treatment approaches, including radiotherapy, radiofrequency and microwave ablation, for pulmonary metastases.

  3. Laser ablation in analytical chemistry.

    Science.gov (United States)

    Russo, Richard E; Mao, Xianglei; Gonzalez, Jhanis J; Zorba, Vassilia; Yoo, Jong

    2013-07-01

    In 2002, we wrote an Analytical Chemistry feature article describing the Physics of Laser Ablation in Microchemical Analysis. In line with the theme of the 2002 article, this manuscript discusses current issues in fundamental research, applications based on detecting photons at the ablation site (LIBS and LAMIS) and by collecting particles for excitation in a secondary source (ICP), and directions for the technology. PMID:23614661

  4. Recombinant Goat VEGF164 Increases Hair Growth by Painting Process on the Skin of Shaved Mouse

    OpenAIRE

    Bao, Wenlei; Yin, Jianxin; Liang, Yan; Guo, Zhixin; Wang, Yanfeng; Liu, Dongjun; Wang, Xiao; Wang, Zhigang

    2014-01-01

    To detect goat vascular endothelial growth factor (VEGF)-mediated regrowth of hair, full-length VEGF164 cDNA was cloned from Inner Mongolia cashmere goat (Capra hircus) into the pET-his prokaryotic expression vector, and the recombinant plasmid was transferred into E. coli BL21 cells. The expression of recombinant 6×his-gVEGF164 protein was induced by 0.5 mM isopropyl thio-β-D-galactoside at 32°C. Recombinant goat VEGF164 (rgVEGF164) was purified and identi ed by western blot using monoclonal...

  5. Transcriptional regulation of the VEGF gene in dependence of individual genomic variations.

    Science.gov (United States)

    Metzger, Carmen S; Koutsimpelas, Dimitrios; Brieger, Juergen

    2015-12-01

    Overexpression of the vascular endothelial growth factor (VEGF) gene has been associated with advanced stage and poor survival in several cancers. The majority of disease-associated VEGF-single nucleotide polymorphisms (SNPs) locate within regulatory regions. Therefore, an influence of SNPs located in the promoter/5'-untranslated region (5'UTR) on transcription factor binding (TFB) and gene expression seems feasible. We reviewed the literature investigating a potential connection of VEGF-SNPs and transcriptional regulation of the VEGF gene. In addition, we employed transcription factor databases to search for VEGF-SNPs which have already been associated with diseases. The objective of this review is to gain an overview about an association of VEGF-SNPs and the transcription factor dependent regulation of the VEGF gene. A decreasing binding specificity of the transcription factor MZF1 in presence of the VEGF-SNP +405 C-allele has been reported. TF databases indicated a potential HIF binding site for the -2578 C-allele representing an important potential inducer of VEGF expression. Additionally, linkage disequilibrium of the -2578 A-allele and an 18 bp insertion increases the number of potential TFB sites. For the VEGF promoter SNP -1154 A/G an interaction with the HRE under participation of the SNP +405 C/G was supposed. The comprehension of the association of specific SNPs and TFB could be an essential part in our understanding of individual differences of VEGF regulation and course of diseases. PMID:26209503

  6. The interaction of heparan sulfate proteoglycans with endothelial transglutaminase-2 limits VEGF165-induced angiogenesis.

    Science.gov (United States)

    Beckouche, Nathan; Bignon, Marine; Lelarge, Virginie; Mathivet, Thomas; Pichol-Thievend, Cathy; Berndt, Sarah; Hardouin, Julie; Garand, Marion; Ardidie-Robouant, Corinne; Barret, Alain; Melino, Gerry; Lortat-Jacob, Hugues; Muller, Laurent; Monnot, Catherine; Germain, Stephane

    2015-07-14

    Sprouting angiogenesis is stimulated by vascular endothelial growth factor (VEGF165) that is localized in the extracellular matrix (ECM) and binds to heparan sulfate (HS)-bearing proteins known as heparan sulfate proteoglycans (HSPGs). VEGF165 presentation by HSPGs enhances VEGF receptor-2 (VEGFR2) signaling. We investigated the effect of TG2, which binds to HSPGs, on the interaction between VEGF165 and HS and angiogenesis. Mice with tg2 deficiency showed transiently enhanced retina vessel formation and increased vascularization of VEGF165-containing Matrigel implants. In addition, endothelial cells in which TG2 was knocked down exhibited enhanced VEGF165-induced sprouting and migration, which was associated with increased phosphorylation of VEGFR2 at Tyr(951) and its targets Src and Akt. TG2 knockdown did not affect the phosphorylation of VEGFR2 at Tyr(1175) or cell proliferation in response to VEGF165 and sprouting or signaling in response to VEGF121. Decreased phosphorylation of VEGFR2 at Tyr(951) was due to ECM-localized TG2, which reduced the binding of VEGF165 to endothelial ECM in a manner that required its ability to bind to HS but not its catalytic activity. Surface plasmon resonance assays demonstrated that TG2 impeded the interaction between VEGF165 and HS. These results show that TG2 controls the formation of VEGF165-HSPG complexes and suggest that this regulation could be pharmacologically targeted to modulate developmental and therapeutic angiogenesis. PMID:26175493

  7. The carboxyl terminus of VEGF-A is a potential target for anti-angiogenic therapy.

    Science.gov (United States)

    Carter, James G; Gammons, Melissa V R; Damodaran, Gopinath; Churchill, Amanda J; Harper, Steven J; Bates, David O

    2015-01-01

    Anti-VEGF-A therapy has become a mainstay of treatment for ocular neovascularisation and in cancer; however, their effectiveness is not universal, in some cases only benefiting a minority of patients. Anti-VEGF-A therapies bind and block both pro-angiogenic VEGF-Axxx and the partial agonist VEGF-Axxxb isoforms, but their anti-angiogenic benefit only comes about from targeting the pro-angiogenic isoforms. Therefore, antibodies that exclusively target the pro-angiogenic isoforms may be more effective. To determine whether C-terminal-targeted antibodies could inhibit angiogenesis, we generated a polyclonal antibody to the last nine amino acids of VEGF-A165 and tested it in vitro and in vivo. The exon8a polyclonal antibody (Exon8apab) did not bind VEGF-A165b even at greater than 100-fold excess concentration, and dose dependently inhibited VEGF-A165 induced endothelial migration in vitro at concentrations similar to the VEGF-A antibody fragment ranibizumab. Exon8apab can inhibit tumour growth of LS174t cells implanted in vivo and blood vessel growth in the eye in models of age-related macular degeneration, with equal efficacy to non-selective anti-VEGF-A antibodies. It also showed that it was the VEGF-Axxx levels specifically that were upregulated in plasma from patients with proliferative diabetic retinopathy. These results suggest that VEGF-A165-specific antibodies can be therapeutically useful. PMID:25274272

  8. Cancer-derived VEGF plays no role in malignant ascites formation in the mouse

    Institute of Scientific and Technical Information of China (English)

    Bayasi Guleng; Tsuneo Ikenoue; Yasushi Fukushima; Keita Morikane; Makoto Miyagishi; Kazunari Taira; Takao Kawabe; Masao Omata; Keisuke Tateishi; Fumihiko Kanai; Amarsanaa Jazag; Miki Ohta; Yoshinari Asaoka; Hideaki Ijichi; Yasuo Tanaka; Jun Imamura

    2005-01-01

    AIM: Vascular endothelial growth factor (VEGF) is a potent mediator of peritoneal fluid accumulation following tumor progression. This study investigated the role of VEGF secreted by cancerous cells in the formation of malignant ascites.METHODS: VEGF expression was eliminated byknockdown in the pancreas cancer cell-line PancO2 using vector-based short-hairpin type RNA interference (RNAi).Malignant ascites formation in the mouse was analyzed by intraperitoneal injection of PancO2 cells expressing VEGF or with expression knockdown.RESULTS: The VEGF knockdown PancO2 cell was successfully established. Knockdown of VEGF did not affect cancer cell proliferation in vitro or in vivo. The volume of ascites following peritoneal expansion of the tumor in VEGF knockdown cells and control cells did not differ statistically in this in vivo study. Moreover, the VEGF concentration in the ascites did not differ statistically.CONCLUSION: Malignant ascites formation might be mediated by VEGF production in noncancerous tissues,such as stromal compartments. An anti-VEGF strategy against malignant ascites could be applied to various tumors regardless of whether they secrete VEGF.

  9. PEA3 activates VEGF transcription in T47D and SKBR3 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Dong Hua; Bobin Chen; Mei Bai; Hao Yu; Xiaohong Wu; Wei Jin

    2009-01-01

    Vascular endothelial growth factor(VEGF)is a potent stimulator of angiogenesis and a prognostic factor for many tumors,including those of endocrine-responsive tissues such as the breast and uterus.In this study,we found that overexpression of PEA3 could increase VEGF mRNA levels and VEGF promoter activity in human T47D and SKBR3 breast cancer cells.Chromatin immunoprecipitation assay demonstrated that PEA3 could bind to the VEGF promoter in the cells transfected with PEA3 expression vector.PEA3 small interfering RNA attenuated VEGF promoter activity and the binding of PEA3 to the VEGF promoter in T47D and SKBR3 cells.These results indicated that PEA3 could activate VEGF promoter transcription.

  10. Angiogenic Effects of Collagen/Mesoporous Nanoparticle Composite Scaffold Delivering VEGF165

    Science.gov (United States)

    Kim, Tae-Hyun; Kang, Min Sil

    2016-01-01

    Vascularization is a key issue for the success of tissue engineering to repair damaged tissue. In this study, we report a composite scaffold delivering angiogenic factor for this purpose. Vascular endothelial growth factor (VEGF) was loaded on mesoporous silica nanoparticle (MSN), which was then incorporated within a type I collagen sponge, to produce collagen/MSN/VEGF (CMV) scaffold. The CMV composite scaffold could release VEGF sustainably over the test period of 28 days. The release of VEGF improved the cell proliferation. Moreover, the in vivo angiogenesis of the scaffold, as studied by the chick chorioallantoic membrane (CAM) model, showed that the VEGF-releasing scaffold induced significantly increased number of blood vessel complexes when compared with VEGF-free scaffold. The composite scaffold showed good biocompatibility, as examined in rat subcutaneous tissue. These results demonstrate that the CMV scaffold with VEGF-releasing capacity can be potentially used to stimulate angiogenesis and tissue repair.

  11. The expression and function of VEGF at embryo implanta- tion "window" in the mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that plays a critical role in angiogenesis. Recent reports indicated that VEGF was closely involved in embryo implantation and embryonic vasculogenesis. However, very little information is available about the detailed expression and function of VEGF at implantation "window". In this work, VEGFs were primarily present on uterine epithelial cell monolayer and blastocysts including the outgrew trophoblasts at implantation window. VEGF antibodies decreased the number of mice embryos implanted and the percentage of blastocysts with attachment and outgrowth in a co-culture model in a dose-dependant manner. These findings demonstrate that VEGF is one of the essential cytokines for embryo implantation in mouse. VEGF may act as a local mediator to regulate the maternal-fetal interaction, and facilitate blastocyst implantation.

  12. Ablation of Solid Hydrogen in a Plasma

    DEFF Research Database (Denmark)

    Jørgensen, L. W.; Sillesen, Alfred Hegaard

    1979-01-01

    Several hydrogen pellet ablation models based on the formation of a shielding neutral cloud have been reported by different authors. The predicted ablation rates are shown to follow almost the same scaling law and this is used to explain the authors' ablation experiment.......Several hydrogen pellet ablation models based on the formation of a shielding neutral cloud have been reported by different authors. The predicted ablation rates are shown to follow almost the same scaling law and this is used to explain the authors' ablation experiment....

  13. Esophageal papilloma: Flexible endoscopic ablation byradiofrequency

    Institute of Scientific and Technical Information of China (English)

    Gianmattia del Genio; Federica del Genio; Pietro Schettino; Paolo Limongelli; Salvatore Tolone; Luigi Brusciano; Manuela Avellino; Chiara Vitiello; Giovanni Docimo; Angelo Pezzullo; Ludovico Docimo

    2015-01-01

    Squamous papilloma of the esophagus is a rare benignlesion of the esophagus. Radiofrequency ablation is anestablished endoscopic technique for the eradication ofBarrett esophagus. No cases of endoscopic ablation ofesophageal papilloma by radiofrequency ablation (RFA)have been reported. We report a case of esophagealpapilloma successfully treated with a single sessionof radiofrequency ablation. Endoscopic ablation ofthe lesion was achieved by radiofrequency using anew catheter inserted through the working channelof endoscope. The esophageal ablated tissue wasremoved by a specifically designed cup. Completeablation was confirmed at 3 mo by endoscopy withbiopsies. This case supports feasibility and safety of asa new potential indication for BarrxTM RFA in patientswith esophageal papilloma.

  14. Galectin-3 in patients undergoing ablation of atrial fibrillation

    OpenAIRE

    Nicolas Clementy; Eric Piver; Nazih Benhenda; Anne Bernard; Bertrand Pierre; Edouard Siméon; Laurent Fauchier; Jean-Christophe Pagès; Dominique Babuty

    2014-01-01

    Background: Mechanisms of maintenance of atrial fibrillation are known to include fibrosis. Galectin-3, as a biomarker of fibrosis, may be a valuable marker of atrial remodeling. We sought to find whether there was a link between clinical features and higher galectin-3 levels in patients with atrial fibrillation. Methods: Serum concentrations of Galectin-3 were determined in a consecutive series of patients addressed for ablation of atrial fibrillation. Results: One-hundred-and-eighty-s...

  15. Response to anti-VEGF-A treatment of endothelial cells in vitro.

    Science.gov (United States)

    Puddu, Alessandra; Sanguineti, Roberta; Traverso, Carlo Enrico; Viviani, Giorgio L; Nicolò, Massimo

    2016-05-01

    This study was conducted to compare the effects of two anti-VEGF-A drugs, Ranibizumab and Aflibercept, on the expression and secretion of VEGFs family members, and on their influence in proliferation and migration of endothelial cells (HECV) in vitro. HECV cells were exposed 24 h (T1), 4 days (T2) and 6 days (T3) to Ranibizumab or Aflibercept at pharmacodynamically relevant concentrations (Ranibizumab: 12.5 μg/ml and 125 μg/ml; Aflibercept: 50 μg/ml and 500 μg/ml). Cell viability and then expression and secretion of VEGF-A, VEGF-B, VEGF-C and PlGF were evaluated respectively by Real Time-PCR and ELISA. Intracellular signaling activated by VEGF-A and VEGF-C was investigated evaluating phosphorylation of VEGFR2. Influence in would healing was evaluated through scratch assay. In general no differences were observed among the tested concentrations of anti-vegf drugs. Ranibizumab and Aflibercept did not affect HECV cell viability in all experimental times. At T1, Ranibizumab decreased mRNA levels of VEGF-A, induced VEGF-C secretion, abrogated phosphorylation of VEGFR2 stimulated by VEGF-A, and impaired ability of HECV cells to repair wound healing. Aflibercept decreased mRNA levels of VEGF-A, -B and PlGF; slightly increased basal level of phVEGFR2, and completely abrogated phosphorylation stimulated by VEGF-A and VEGF-C. No effects on secretion of VEGF-B and on would healing were observed after exposure to Aflibercept. Prolonged exposure to anti-VEGFs decreased expression and secretion of VEGF-A and VEGF-B, up-regulated VEGF-C mRNA levels and its secretion, and increased basal phosphorylation of VEGFR2. Acute treatment with Ranibizumab or Aflibercept evoked different responses on endothelial cells, however these differences were lost after prolonged exposure. Scratch test results suggest that treatment with Ranibizumab may be more effective than Aflibercept in reducing angiogenic potential of endothelial cells in vitro.

  16. Femtosecond laser ablation of enamel

    Science.gov (United States)

    Le, Quang-Tri; Bertrand, Caroline; Vilar, Rui

    2016-06-01

    The surface topographical, compositional, and structural modifications induced in human enamel by femtosecond laser ablation is studied. The laser treatments were performed using a Yb:KYW chirped-pulse-regenerative amplification laser system (560 fs and 1030 nm) and fluences up to 14 J/cm2. The ablation surfaces were studied by scanning electron microscopy, grazing incidence x-ray diffraction, and micro-Raman spectroscopy. Regardless of the fluence, the ablation surfaces were covered by a layer of resolidified material, indicating that ablation is accompanied by melting of hydroxyapatite. This layer presented pores and exploded gas bubbles, created by the release of gaseous decomposition products of hydroxyapatite (CO2 and H2O) within the liquid phase. In the specimen treated with 1-kHz repetition frequency and 14 J/cm2, thickness of the resolidified material is in the range of 300 to 900 nm. The micro-Raman analysis revealed that the resolidified material contains amorphous calcium phosphate, while grazing incidence x-ray diffraction analysis allowed detecting traces of a calcium phosphate other than hydroxyapatite, probably β-tricalcium phosphate Ca3), at the surface of this specimen. The present results show that the ablation of enamel involves melting of enamel's hydroxyapatite, but the thickness of the altered layer is very small and thermal damage of the remaining material is negligible.

  17. The impact of hyperbaric oxygen therapy on serological values of vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF

    Directory of Open Access Journals (Sweden)

    Ziebura Thomas

    2010-12-01

    Full Text Available Abstract Background Hyperbaric oxygen (HBO therapy is an effective adjunct treatment for ischemic disorders such as chronic infection or chronic wounds. It combines hyperoxic effects with the stimulating potential of post-therapeutic reactive hypoxia. As its crucial effects, stimulation of fibroblast growth, induction of collagen synthesis and the initiation of angiogenesis are discussed. Angiogenesis is a multistage process resulting in the growth of blood vessels. It includes degradation of extracellular matrix, proliferation and migration of different cell populations and finally formation of new vessel structures. This complex chain of procedures is orchestrated by different cytokines and growth factors. Crucial mediators of angiogenesis are basic fibroblast growth factor (bFGF and vascular endothelial growth factor (VEGF; their in-vivo function is still not fully understood. Methods Forty-three patients suffering from sudden sensorineural hearing loss or tinnitus were treated with HBO. The therapy included 10 sessions of 90 minutes each, one session a day. Serological levels of bFGF and VEGF were assessed by enzyme-linked immunosorbent assays performed according to the manufacturer's instructions on day 1, 2, 5 and 10 of HBO therapy and were compared to mean values of the control group, related to the patient's age and sex, and their development observed over the ten days of HBO. Results There was no sex- or age dependency of bFGF observed in the present study, whereas under HBO our results showed a significant mitigation of the bFGF concentration. In the present data, there was no connection between the VEGF concentration and the patients' ages. Women showed significantly higher levels of VEGF. There was no significant change of VEGF concentration or the VEGF/bFGF ratio during HBO. All scored results varied within the range of standard values as described in the current literature. Conclusions A significant effect of HBO on serum

  18. VEGF Levels in Plasma in Relation to Platelet Activation, Glycemic Control, and Microvascular Complications in Type 1 Diabetes

    OpenAIRE

    Schlingemann, Reinier O.; van Noorden, Cornelis J. F.; Diekman, Mattheus J.M.; Tiller, Anna; Meijers, Joost C.M.; Koolwijk, Pieter; Wiersinga, Wilmar M.

    2013-01-01

    OBJECTIVE Increased levels of vascular endothelial growth factor (VEGF) in human plasma samples have suggested that circulating VEGF is a cause of endothelial dysfunction in diabetes mellitus. However, artificial release of VEGF from platelets as a source of VEGF in plasma samples, as also occurs in serum samples, has not been ruled out in these studies. RESEARCH DESIGN AND METHODS We determined VEGF levels in plasma collected in both citrate and PECT, a medium that inactivates platelets, in ...

  19. Anti-VEGF Therapy and the Retina: An Update

    Directory of Open Access Journals (Sweden)

    Vikas Tah

    2015-01-01

    Full Text Available Ocular angiogenesis and macular oedema are major causes of sight loss across the world. Aberrant neovascularisation, which may arise secondary to numerous disease processes, can result in reduced vision as a result of oedema, haemorrhage, and scarring. The development of antivascular endothelial growth factor (anti-VEGF agents has revolutionised the treatment of retinal vasogenic conditions. These drugs are now commonly employed for the treatment of a plethora of ocular pathologies including choroidal neovascularisation, diabetic macular oedema, and retinal vein occlusion to name a few. In this paper, we will explore the current use of anti-VEGF in a variety of retinal diseases and the impact that these medications have had on visual outcome for patients.

  20. Microwave ablation of hepatocellular carcinoma.

    Science.gov (United States)

    Poggi, Guido; Tosoratti, Nevio; Montagna, Benedetta; Picchi, Chiara

    2015-11-01

    Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s', RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s', showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA. PMID:26557950

  1. Femtosecond laser ablation of dentin

    International Nuclear Information System (INIS)

    The surface morphology, structure and composition of human dentin treated with a femtosecond infrared laser (pulse duration 500 fs, wavelength 1030 nm, fluences ranging from 1 to 3 J cm-2) was studied by scanning electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The average dentin ablation threshold under these conditions was 0.6 ± 0.2 J cm-2 and the ablation rate achieved in the range 1 to 2 µm/pulse for an average fluence of 3 J cm-2. The ablation surfaces present an irregular and rugged appearance, with no significant traces of melting, deformation, cracking or carbonization. The smear layer was entirely removed by the laser treatment. For fluences only slightly higher than the ablation threshold the morphology of the laser-treated surfaces was very similar to the dentin fracture surfaces and the dentinal tubules remained open. For higher fluences, the surface was more porous and the dentin structure was partially concealed by ablation debris and a few resolidified droplets. Independently on the laser processing parameters and laser processing method used no sub-superficial cracking was observed. The dentin constitution and chemical composition was not significantly modified by the laser treatment in the processing parameter range used. In particular, the organic matter is not preferentially removed from the surface and no traces of high temperature phosphates, such as the β-tricalcium phosphate, were observed. The achieved results are compatible with an electrostatic ablation mechanism. In conclusion, the high beam quality and short pulse duration of the ultrafast laser used should allow the accurate preparation of cavities, with negligible damage of the underlying material. (paper)

  2. Microwave ablation of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Although surgical resection is still the optimal treatmentoption for early-stage hepatocellular carcinoma(HCC) in patients with well compensated cirrhosis,thermal ablation techniques provide a valid nonsurgicaltreatment alternative, thanks to their minimalinvasiveness, excellent tolerability and safety profile,proven efficacy in local disease control, virtuallyunlimited repeatability and cost-effectiveness. Differentenergy sources are currently employed in clinics asphysical agents for percutaneous or intra-surgicalthermal ablation of HCC nodules. Among them, radiofrequency(RF) currents are the most used, whilemicrowave ablations (MWA) are becoming increasinglypopular. Starting from the 90s', RF ablation (RFA) rapidlybecame the standard of care in ablation, especially inthe treatment of small HCC nodules; however, RFAexhibits substantial performance limitations in thetreatment of large lesions and/or tumors located nearmajor heat sinks. MWA, first introduced in the FarEastern clinical practice in the 80s', showing promisingresults but also severe limitations in the controllabilityof the emitted field and in the high amount of poweremployed for the ablation of large tumors, resultingin a poor coagulative performance and a relativelyhigh complication rate, nowadays shows better resultsboth in terms of treatment controllability and of overallcoagulative performance, thanks to the improvementof technology. In this review we provide an extensiveand detailed overview of the key physical and technicalaspects of MWA and of the currently available systems,and we want to discuss the most relevant published dataon MWA treatments of HCC nodules in regard to clinicalresults and to the type and rate of complications, both inabsolute terms and in comparison with RFA.

  3. Surgical Ablation of Atrial Fibrillation.

    Science.gov (United States)

    Ramlawi, Basel; Abu Saleh, Walid K

    2015-01-01

    The Cox-maze procedure for the restoration of normal sinus rhythm, initially developed by Dr. James Cox, underwent several iterations over the years. The main concept consists of creating a series of transmural lesions in the right and left atria that disrupt re-entrant circuits responsible for propagating the abnormal atrial fibrillation rhythm. The left atrial appendage is excluded as a component of the Maze procedure. For the first three iterations of the Cox- maze procedure, these lesions were performed using a surgical cut-and-sew approach that ensured transmurality. The Cox-Maze IV is the most currently accepted iteration. It achieves the same lesion set of the Cox- maze III but uses alternative energy sources to create the transmural lesions, potentially in a minimally invasive approach on the beating heart. High-frequency ultrasound, microwave, and laser energy have all been used with varying success in the past. Today, bipolar radiofrequency heat or cryotherapy cooling are the most accepted sources for creating linear lesions with consistent safety and transmurality. The robust and reliable nature of these energy delivery methods has yielded a success rate reaching 90% freedom from atrial fibrillation at 12 months. Such approaches offer a significant long-term advantage over catheter-based ablation, especially in patients having longstanding, persistent atrial fibrillation with characteristics such as dilated left atrial dimensions, poor ejection fraction, and failed catheter ablation. Based on these improved results, there currently is significant interest in developing a hybrid ablation strategy that incorporates the superior transmural robust lesions of surgical ablation, the reliable stroke prevention potential of epicardial left atrial appendage exclusion, and sophisticated mapping and confirmatory catheter-based ablation technology. Such a minimally invasive hybrid strategy for ablation may lead to the development of multidisciplinary "Afib teams" to

  4. Intravitreal anti-VEGF therapy in retinopathy of prematurity

    OpenAIRE

    GÜNAY, Murat; ÇELİK, Gökhan

    2015-01-01

    Retinopathy of prematurity (ROP) is the retinal vascular developmental disorder of the premature infants and it is a leading cause of childhood blindness. Hypoxia secondary to the immature retina with subsequent release of some mediators establish the characteristic feature of ‘progressive retinopathy’. The most promoter one among these mediators is vascular endothelial growth factor (VEGF). The screening and treatment criteria were identified in past literature and successful treatment resul...

  5. VEGF blockade inhibits angiogenesis and reepithelialization of endometrium

    OpenAIRE

    Fan, Xiujun; Krieg, Sacha; Kuo, Calvin J.; Wiegand, Stanley J; Rabinovitch, Marlene; Druzin, Maurice L.; Brenner, Robert M.; Giudice, Linda C.; Nayak, Nihar R.

    2008-01-01

    Despite extensive literature on vascular endothelial growth factor (VEGF) expression and regulation by steroid hormones, the lack of clear understanding of the mechanisms of angiogenesis in the endometrium is a major limitation for use of antiangiogenic therapy targeting endometrial vessels. In the current work, we used the rhesus macaque as a primate model and the decidualized mouse uterus as a murine model to examine angiogenesis during endometrial breakdown and regeneration. We found that ...

  6. MR靶向对比剂前体——VEGF165-适配体与VEGF165体外结合实验研究

    Institute of Scientific and Technical Information of China (English)

    尤晓光; 白玉杰; 涂蓉

    2011-01-01

    目的应用酶联免疫吸附实验(ELISA)检测MR靶向对比剂前体——血管内皮生长因子165-适配体(VEGF165-aptamer)与VEGF165的体外结合能力,以了解其对VEGF的靶向性。方法实验组采用亲和素96孔酶标板,包被生物素化VEGF165-aptamer,设置递减的浓度梯度(共9组)和空白对照组,采用组间方差分析。结果实验组包被生物素化VEGF165-aptamer浓度在50~0.78pmol/μL时,实验组与空白组及实验各相邻组间差异有统计学意义(P0.05)。结论采用ELISA检测技术验证了VEGF165-aptamer与VEGF165间的体外结合能力,其有效最低小包被浓度为0.78pmol/μL,VEGF165-aptamer对VEGF165有良好的靶向性。

  7. Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in colon carcinomas

    Directory of Open Access Journals (Sweden)

    Li Jing

    2011-06-01

    Full Text Available Abstract Background HER-2/neu and VEGF expression is correlated with disease behaviors in various cancers. However, evidence for their expression in colon cancer is rather contradictory both for the protein expression status and prognostic value. HER-2/neu is found to participate in VEGF regulation, and has known correlation with VEGF expression in some tumors. In this study, we investigated HER-2/neu and VEGF expression in Chinese colon patients and explored whether there was any correlation between their expression patterns. Methods HER-2/neu and VEGF were investigated immunohistochemically using tumor samples obtained from 317 colon cancer patients with all tumor stages. Correlation of the degree of staining with clinicopathological parameters and survival was investigated. Results Positive expression rates of HER-2/neu and VEGF in colon cancer were 15.5% and 55.5% respectively. HER-2/neu expression was significantly correlated with tumor size and distant metastases (P (P > 0.05. Expression of VEGF was significantly correlated with tumor size, tumor stage, lymph node metastases, and distant metastases (P (P = 0.146. No correlation between HER-2/neu and VEGF expression was detected (P = 0.151. Conclusions HER-2/neu and VEGF are not important prognostic markers of colon cancer. The present results do not support any association between HER2/neu and VEGF expression in this setting.

  8. Transhemangioma Ablation of Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

  9. Transhemangioma Ablation of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei, E-mail: druei@yahoo.com [Tan Tock Seng Hospital, Department of Diagnostic Radiology (Singapore)

    2012-12-15

    Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

  10. VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo

    Directory of Open Access Journals (Sweden)

    E Wernike

    2010-02-01

    Full Text Available Bone formation and osseointegration of biomaterials are dependent on angiogenesis and vascularization. Angiogenic growth factors such as vascular endothelial growth factor (VEGF were shown to promote biomaterial vascularization and enhance bone formation. However, high local concentrations of VEGF induce the formation of malformed, nonfunctional vessels. We hypothesized that a continuous delivery of low concentrations of VEGF from calcium phosphate ceramics may increase the efficacy of VEGF administration.VEGF was co-precipitated onto biphasic calcium phosphate (BCP ceramics to achieve a sustained release of the growth factor. The co-precipitation efficacy and the release kinetics of the protein were investigated in vitro. For in vivo investigations BCP ceramics were implanted into critical size cranial defects in Balb/c mice. Angiogenesis and microvascularization were investigated over 28 days by means of intravital microscopy. The formation of new bone was determined histomorphometrically. Co-precipitation reduced the burst release of VEGF. Furthermore, a sustained, cell-mediated release of low concentrations of VEGF from BCP ceramics was mediated by resorbing osteoclasts. In vivo, sustained delivery of VEGF achieved by protein co-precipitation promoted biomaterial vascularization, osseointegration, and bone formation. Short-term release of VEGF following superficial adsorption resulted in a temporally restricted promotion of angiogenesis and did not enhance bone formation. The release kinetics of VEGF appears to be an important factor in the promotion of biomaterial vascularization and bone formation. Sustained release of VEGF increased the efficacy of VEGF delivery demonstrating that a prolonged bioavailability of low concentrations of VEGF is beneficial for bone regeneration.

  11. Catheter ablation of parahisian premature ventricular complex.

    Science.gov (United States)

    Kim, Jun; Kim, Jeong Su; Park, Yong Hyun; Kim, June Hong; Chun, Kook Jin

    2011-12-01

    Catheter ablation is performed in selected patients with a symptomatic premature ventricular complex (PVC) or PVC-induced cardiomyopathy. Ablation of PVC from the His region has a high risk of inducing a complete atrioventricular block. Here we report successful catheter ablation of a parahisian PVC in a 63-year-old man.

  12. Soft thrombus formation in radiofrequency catheter ablation

    NARCIS (Netherlands)

    Demolin, JM; Eick, OJ; Munch, K; Koullick, E; Nakagawa, H; Wittkampf, FHM

    2002-01-01

    During RF catheter ablation, local temperature elevation can result in coagulum formation on the ablation electrode, resulting in impedance rise. A recent study has also demonstrated the formation of a so-called soft thrombus during experimental ablations. This deposit poorly adhered to the catheter

  13. Ablated tektite from the central Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Glass, B.P.; Chapman, D.R.; ShyamPrasad, M.

    A well-preserved ablated (button-shaped) tektite recovered from the surface sediments of the central Indian Ocean lacks flow ridges and has apparently undergone ablation of 6.9 to 7.9 mm. The lack of flow ridges and amount of ablation indicate that...

  14. Designer Leptin Receptor Antagonist Allo-aca Inhibits VEGF Effects in Ophthalmic Neoangiogenesis Models

    Science.gov (United States)

    Coroniti, Roberta; Fario, Rafal; Nuno, Didier J.; Otvos, Laszlo; Scolaro, Laura; Surmacz, Eva

    2016-01-01

    Experimental and clinical data suggest that pro-angiogenic, pro-inflammatory and mitogenic cytokine leptin can be implicated in ocular neovascularization and other eye pathologies. At least in part, leptin action appears to be mediated through functional interplay with vascular endothelial growth factor (VEGF). VEGF is a potent regulator of neoangiogenesis and vascular leakage with a proven role in conditions such as proliferative diabetic retinopathy, age-related macular degeneration and diabetic macular edema. Accordingly, drugs targeting VEGF are becoming mainstream treatments for these diseases. The crosstalk between leptin and VEGF has been noted in different tissues, but its involvement in the development of eye pathologies is unclear. Leptin is coexpressed with VEGF during ocular neovascularization and can potentiate VEGF synthesis and angiogenic function. However, whether or not VEGF regulates leptin expression or signaling has never been studied. Consequently, we addressed this aspect of leptin/VEGF crosstalk in ocular models, focusing on therapeutic exploration of underlying mechanisms. Here we show, for the first time, that in retinal (RF/6A) and corneal (BCE) endothelial cells, VEGF (100 ng/mL, 24 h) stimulated leptin mRNA synthesis by 70 and 30%, respectively, and protein expression by 56 and 28%, respectively. In parallel, VEGF induced RF/6A and BCE cell growth by 33 and 20%, respectively. In addition, VEGF upregulated chemotaxis and chemokinesis in retinal cells by ~40%. VEGF-dependent proliferation and migration were significantly reduced in the presence of the leptin receptor antagonist, Allo-aca, at 100–250 nmol/L concentrations. Furthermore, Allo-aca suppressed VEGF-dependent long-term (24 h), but not acute (15 min) stimulation of the Akt and ERK1/2 signaling pathways. The efficacy of Allo-aca was validated in the rat laser-induced choroidal neovascularization model where the compound (5 μg/eye) significantly reduced pathological

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

    Institute of Scientific and Technical Information of China (English)

    Junichi Takino; Shoichi Yamagishi; Masayoshi Takeuchi

    2012-01-01

    AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs)on hepatocellular carcinoma (HCC) cells.METHODS:Two HCC cell lines (Hep3B and HepG2cells) and human umbilical vein endothelial cells (HUVEC) were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs (RAGE) protein was detected in Hep3B and HepG2 cells.HepG2 cells were not affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor (VEGF) mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin (BSA)treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00 ± 0.10 vs 1.92± 0.09 (P < 0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63 ± 0.04ng/mL vs 2.28 ± 0.17 ng/mL for the 24 h treatment and 3.36 ± 0.10 ng/mL vs 4.79 ± 0.31 ng/mL for the 48 h treatment,respectively (P < 0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4% ± 9.0% vs 144.5% ± 11.3% for cell viability,4.29 ± 1.53 vs 6.78 ± 1.84 for migration indices,and 71.0 ± 7.5 vs 112.4 ± 8.0 for the number of branching points,respectively (P < 0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

  16. Up-regulation of VEGF-C secreted by cancer cells and not VEGF-A correlates with clinical evaluation of lymph node metastasis in esophageal squamous cell carcinoma (ESCC).

    Science.gov (United States)

    Krzystek-Korpacka, Malgorzata; Matusiewicz, Malgorzata; Diakowska, Dorota; Grabowski, Krzysztof; Blachut, Katarzyna; Banas, Teresa

    2007-05-01

    Tissue expression of VEGF-C correlates with lymph node involvement (LNI) in ESCC and serum VEGF-C (sVEGF-C) in a non-small cell lung cancer has been more accurate marker of LNI than chest CT. Despite LNI importance in ESCC, the usefulness of serum VEGF-C (sVEGF-C) as a disease and LNI marker in ESCC has not been investigated yet. We found elevated sVEGF-C in ESCC (17.40 vs. 10.57 ng/ml in controls, pmarker than described elsewhere: CEA, CA19-9 and SCC-Ag, with: sensitivity--70%, specificity--81%, accuracy--83.7%. Analysis of sVEGF-C correlation with clinico-pathological cancer features revealed relation to LNI (N0: 15.77 vs. N1: 21.78 ng/ml, p=0.02), especially in advanced cancers. Serum VEGF-C as a marker of LNI was characterized by: sensitivity--76%, specificity--58%, accuracy--64.4%. No relation was observed between LNI and sVEGF-A or sVEGF-A/platelets (PLT). Because sVEGF-C was higher in N0 cancers (ptumor presence also up-regulates sVEGF-C. We found sVEGF-C correlation with PLT and WBC: R=0.36 and R=0.32 (pcancer features implies that elevation of sVEGF-C in N1 cancers is not related to them.

  17. Modern Advances in Ablative TPS

    Science.gov (United States)

    Venkatapathy, Ethiraj

    2013-01-01

    Topics covered include: Physics of Hypersonic Flow and TPS Considerations. Destinations, Missions and Requirements. State of the Art Thermal Protection Systems Capabilities. Modern Advances in Ablative TPS. Entry Systems Concepts. Flexible TPS for Hypersonic Inflatable Aerodynamic Decelerators. Conformal TPS for Rigid Aeroshell. 3-D Woven TPS for Extreme Entry Environment. Multi-functional Carbon Fabric for Mechanically Deployable.

  18. Method development to quantify Bv8 expression in circulating CD11b+ cells in patients with neovascular age-related macular degeneration (nvAMD) exhibiting Anti-VEGF refractoriness.

    Science.gov (United States)

    Catchpole, Timothy; Daniels, Tad; Perkins, Jill; Csaky, Karl G

    2016-07-01

    A subset of neovascular age-related macular degeneration (nvAMD) subjects appears to be refractory to the effects of anti-VEGF treatment and require frequent intravitreal injections. Prokineticin-2 (Bv8) expression in CD11b(+) cells has been linked to anti-VEGF response. We have developed a reproducible method to quantify gene expression in circulating CD11b + cells. Utilizing this method we tested the hypothesis that high Bv8 expression in circulating CD11b(+) cells is associated with anti-VEGF refractoriness in nvAMD patients. Two groups of nvAMD subjects undergoing treatment with anti-VEGF agents were recruited and classified as refractory or non-refractory to anti-VEGF treatment (n = 33 for each group). Two blood draws were obtained from each subject 1-9 months apart. Peripheral blood mononuclear cells (PBMCs) were isolated and CD11b(+) cells were purified via magnetic bead separation. RNA was purified, and relative expression of Bv8 among the subjects was compared via quantitative PCR analysis. Utilizing this approach no significant difference was detected in the mean LogRQ values between the first and second blood draws (t-test, p = 0.826) indicating low intra-patient variability and demonstrating good reproducibility of the assay. There was no significant difference in Bv8 expression between nvAMD subjects classified as refractory versus non-refractory. We were unable to find a correlation between Bv8 expression in CD11b + cells and anti-VEGF refractoriness in human nvAMD subjects. Relatively high expression in Bv8 in these subjects did not correlate with clinical treatment history, as measured by the frequency of injections. Utilizing this well characterized technique, studies are underway to examine alternative gene expression profiles in various circulating cell populations that may contribute to anti-VEGF refractoriness. PMID:27256991

  19. Contraction induced secretion of VEGF from skeletal muscle cells is mediated by adenosine

    DEFF Research Database (Denmark)

    Høier, Birgitte; Olsen, Karina; Nyberg, Michael Permin;

    2010-01-01

    The role of adenosine and contraction for secretion of VEGF in skeletal muscle was investigated in human subjects and rat primary skeletal muscle cells. Microdialysis probes were inserted into the thigh muscle of seven male subjects and dialysate was collected at rest, during infusion of adenosine...... and contraction caused secretion of VEGF (pcontraction induced secretion of VEGF protein was abolished by the A(2B) antagonist enprofyllin and markedly reduced by inhibition of PKA or MAPK. The results demonstrate that adenosine causes secretion of VEGF from human skeletal muscle cells...... and that the contraction induced secretion of VEGF is partially mediated via adenosine acting on A(2B) adenosine receptors. Moreover, the contraction induced secretion of VEGF protein from muscle is dependent on both PKA and MAPK activation, but only the MAPK pathway appears to be adenosine dependent....

  20. A numerical simulation of ablation controlled arcs

    Energy Technology Data Exchange (ETDEWEB)

    Godin, D.; Trepanier, J.Y. [Ecole Polytechnique, Dept. of Mechanical Engineering, Montreal, PQ (Canada); Eby, S.D. [Ecole Polytechnique, Centre de Recherche en Calcul Applique, Montreal, PQ (Canada); Robin-Jouan, P. [GEC-Alsthom T and D, Villeurbanne, (France)

    1998-09-01

    An approach to model the ablation phenomenon of ablation controlled arcs using computational fluid dynamics was presented. Ablation controlled arcs are found in high voltage electrical equipment such as fuses and circuit-breakers. A qualitative prediction of the ablation level is critical from an industrial point of view because deliberate use of ablation is made to increase the pressure in a circuit-breaker chamber to allow for an efficient extinction when the current returns to zero. The numerical model was validated by comparing results of published experimental data. 7 refs., 10 figs.

  1. Circulating VEGF as a biological marker in patients with rheumatoid arthritis? Preanalytical and biological variability in healthy persons and in patients

    DEFF Research Database (Denmark)

    Hetland, Merete Lund; Christensen, Ib Jarle; Lottenburger, Tine;

    2008-01-01

    and contamination of plasma with cellular elements lead to significant increases in VEGF levels, whereas storage for up to 2 years at -80 degrees C or up to 10 freeze/thaw cycles did not affect VEGF levels. Serum VEGF levels were 7-10 fold higher than plasma VEGF levels. Reference intervals for VEGF (plasma: 45 pg...

  2. VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

    International Nuclear Information System (INIS)

    Research highlights: → Bone marrow-derived mast cells (BMMCs) secrete functional VEGF but do not degranulate after Cobalt chloride-induced hypoxia. → CoCl2-induced VEGF secretion in mast cells occurs by a Ca2+-insensitive but brefeldin A and Tetanus toxin-sensitive mechanism. → Trolox and N-acetylcysteine inhibit hypoxia-induced VEGF secretion but only Trolox inhibits FcεRI-dependent anaphylactic degranulation in mast cells. → Src family kinase Fyn activation after free radical production is necessary for hypoxia-induced VEGF secretion in mast cells. -- Abstract: Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl2) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl2 promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl2-induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl2-induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl2 in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals-dependent Fyn kinase activation.

  3. Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF) gene therapy

    OpenAIRE

    Haninec Pavel; Kaiser Radek; Bobek Vladimír; Dubový Petr

    2012-01-01

    Abstract Background Vascular endothelial growth factor (VEGF) is not only a potent angiogenic factor but it also promotes axonal outgrowth and proliferation of Schwann cells. The aim of the present study was to quantitatively assess reinnervation of musculocutaneous nerve (MCN) stumps using motor and primary sensory neurons after plasmid phVEGF transfection and end-to-end (ETE) or end-to-side (ETS) neurorrhaphy. The distal stump of rat transected MCN, was transfected with plasmid phVEGF, plas...

  4. Platelet Activation Determines Angiopoietin-1 and VEGF Levels in Malaria: Implications for Their Use as Biomarkers

    OpenAIRE

    Judith Brouwers; Rintis Noviyanti; Rob Fijnheer; de Groot, Philip G.; Leily Trianty; Siti Mudaliana; Mark Roest; Din Syafruddin; Andre van der Ven; Quirijn de Mast

    2013-01-01

    INTRODUCTION: The angiogenic proteins angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor (VEGF) are regulators of endothelial inflammation and integrity. Since platelets store large amounts of Ang-1 and VEGF, measurement of circulation levels of these proteins is sensitive to platelet number, in vivo platelet activation and inadvertent platelet activation during blood processing. We studied plasma Ang-1, Ang-2 and VEGF levels in malaria patients, taking the necessary precautio...

  5. VEGF-induced angiogenesis following localized delivery via injectable, low viscosity poly(trimethylene carbonate).

    Science.gov (United States)

    Amsden, Brian G; Timbart, Laurianne; Marecak, Dale; Chapanian, Rafi; Tse, M Yat; Pang, Stephen C

    2010-07-14

    The purpose of this study was to examine the potential of low molecular weight poly(trimethylene carbonate) for localized vascular endothelial growth factor (VEGF) delivery. Poly(trimethylene carbonate) of various molecular weights was prepared by ring-opening polymerization initiated by 1-octanol. The resultant polymers were liquid at room temperature with low glass transition temperatures and viscosities at 37 degrees C that permitted their injection through an 18 (1/2) G 1.5'' needle. Particles consisting of VEGF co-lyophilized with trehalose were mixed into the polymers and the rate of release of VEGF was assessed in vitro. With a 1% particle loading, VEGF was released from the polymer at a rate of 20 ng/day over a period of 3 weeks. This release behavior was independent of the molecular weight of polymer used. Increasing the VEGF content in the lyophilized particles did not increase the VEGF release rate, an effect attributed to the solubility limit of VEGF in the solution formed upon dissolution of the particles. The VEGF released retained its bioactivity at greater than 95% of that of as-lyophilized VEGF, as assessed using a human aortic endothelial cell proliferation assay. This high bioactivity was supported by in vivo release experiments, wherein VEGF containing polymer implants induced the generation of significantly greater numbers of blood vessels towards the polymer implant than controls. The blood vessels did not remain stable and were reduced in number by three weeks, due to the unsustained and low concentration of VEGF released. This formulation approach, of using a low viscosity polymer delivery vehicle, is potentially useful for localized delivery of acid-sensitive proteins, such as VEGF. PMID:20381557

  6. Activation of protease-activated receptor 2 induces VEGF independently of HIF-1

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Grøndahl; Riis, Simone Elkjær; Frøbert, Ole;

    2012-01-01

    Human adipose stem cells (hASCs) can promote angiogenesis through secretion of proangiogenic factors such as vascular endothelial growth factor (VEGF). In other cell types, it has been shown that induction of VEGF is mediated by both protease activated receptor 2 (PAR2) and hypoxia inducible fact...... 1(HIF-1). The present study hypothesized that PAR2 stimulation through activation of kinase signaling cascades lead to induction of HIF-1 and secretion of VEGF....

  7. PGC-1alpha mediates exercise-induced skeletal muscle VEGF expression in mice

    DEFF Research Database (Denmark)

    Leick, Lotte; Hellsten, Ylva; Fentz, Joachim;

    2009-01-01

    The aim of the present study was to test the hypothesis that PGC-1alpha is required for exercise-induced VEGF expression in both young and old mice and that AMPK activation leads to increased VEGF expression through a PGC-1alpha-dependent mechanism. Whole body PGC-1alpha knockout (KO) and litterm...... content. Furthermore, the findings suggest an AMPK-mediated regulation of VEGF expression through PGC-1alpha....

  8. Transgenic overexpression of VEGF-C induces weight gain and insulin resistance in mice

    Science.gov (United States)

    Karaman, Sinem; Hollmén, Maija; Yoon, Sun-Young; Alkan, H. Furkan; Alitalo, Kari; Wolfrum, Christian; Detmar, Michael

    2016-01-01

    Obesity comprises great risks for human health, contributing to the development of other diseases such as metabolic syndrome, type 2 diabetes and cardiovascular disease. Previously, obese patients were found to have elevated serum levels of VEGF-C, which correlated with worsening of lipid parameters. We recently identified that neutralization of VEGF-C and -D in the subcutaneous adipose tissue during the development of obesity improves metabolic parameters and insulin sensitivity in mice. To test the hypothesis that VEGF-C plays a role in the promotion of the metabolic disease, we used K14-VEGF-C mice that overexpress human VEGF-C under control of the keratin-14 promoter in the skin and monitored metabolic parameters over time. K14-VEGF-C mice had high levels of VEGF-C in the subcutaneous adipose tissue and gained more weight than wildtype littermates, became insulin resistant and had increased ectopic lipid accumulation at 20 weeks of age on regular mouse chow. The metabolic differences persisted under high-fat diet induced obesity. These results indicate that elevated VEGF-C levels contribute to metabolic deterioration and the development of insulin resistance, and that blockade of VEGF-C in obesity represents a suitable approach to alleviate the development of insulin resistance. PMID:27511834

  9. Effect of antisence VEGF on the radiosensitivity of esophageal cancer cells in vitro

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of' antisense VEGF on the cell proliferation, VEGF protein expression and radiosensitivity of esophageal cancer cells in vitro. Methods: Fragments of antisense cDNA, empty vector plasmid DNA and antisense oligodeoxynucleotide of VEGF were transfected into esophageal cancer (TE-1) cells mediated with lipofectamine, respectively. Cell proliferating rate and apoptotic rate of these groups were edetected by MIT and FCM methods, respectively. After irradiation, the expression of VEGF in transfected cells were detected by using RT-PCR and Western blotting. The radiosensitivity of transfected cells were analyzed with colony forming assay. Results: After antisense cDNA plasmid and antisense oligodeoxynucleotide of VEGF were transfected successfully into TE-1 cells, expressions of VEGF protein decreased, however, the changes in cell growth rate and distribution of cell cycle, and the apoptotic rate were not observed in these transfected cells. After irradiation, the radiosensitivity of transfected TE-1 cells were increased, but there was no significant difference in cell growth rate among groups. The apoptotic rates in antisense groups increased slightly compared to TE-1 and TE-1-E groups. Conclusions: Expression of VEGF mRNA and VEGF protein were significantly suppressed in TE-1 cells transfected by antisense cDNA and antisense oligodeoxynucleotide of VEGF. After irradiation, the radiosensitivity of the transfected TE-1 cells was increased. (authors)

  10. Semaphorin 3A suppresses VEGF-mediated angiogenesis yet acts as a vascular permeability factor.

    Science.gov (United States)

    Acevedo, Lisette M; Barillas, Samuel; Weis, Sara M; Göthert, Joachim R; Cheresh, David A

    2008-03-01

    Semaphorin 3A (Sema3A), a known inhibitor of axonal sprouting, also alters vascular patterning. Here we show that Sema3A selectively interferes with VEGF- but not bFGF-induced angiogenesis in vivo. Consistent with this, Sema3A disrupted VEGF- but not bFGF-mediated endothelial cell signaling to FAK and Src, key mediators of integrin and growth factor signaling; however, signaling to ERK by either growth factor was unperturbed. Since VEGF is also a vascular permeability (VP) factor, we examined the role of Sema3A on VEGF-mediated VP in mice. Surprisingly, Sema3A not only stimulated VEGF-mediated VP but also potently induced VP in the absence of VEGF. Sema3A-mediated VP was inhibited either in adult mice expressing a conditional deletion of endothelial neuropilin-1 (Nrp-1) or in wild-type mice systemically treated with a function-blocking Nrp-1 antibody. While both Sema3A- and VEGF-induced VP was Nrp-1 dependent, they use distinct downstream effectors since VEGF- but not Sema3A-induced VP required Src kinase signaling. These findings define a novel role for Sema3A both as a selective inhibitor of VEGF-mediated angiogenesis and a potent inducer of VP. PMID:18180379

  11. A Biomimic Reconstituted High Density Lipoprotein Nanosystem for Enhanced VEGF Gene Therapy of Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Xiaotian Sun

    2015-01-01

    Full Text Available A biomimic reconstituted high density lipoprotein (rHDL based system, rHDL/Stearic-PEI/VEGF complexes, was fabricated as an advanced nanovector for delivering VEGF plasmid. Here, Stearic-PEI was utilized to effectively condense VEGF plasmid and to incorporate the plasmid into rHDL. The rHDL/Stearic-PEI/VEGF complexes with diameter under 100 nm and neutral surface charge demonstrated enhanced stability under the presence of bovine serum albumin. Moreover, in vitro cytotoxicity and transfection assays on H9C2 cells further revealed their superiority, as they displayed lower cytotoxicity with much higher transfection efficiency when compared to PEI 10K/VEGF and Lipos/Stearic-PEI/VEGF complexes. In addition, in vivo investigation on ischemia/reperfusion rat model implied that rHDL/Stearic-PEI/VEGF complexes possessed high transgene capacity and strong therapeutic activity. These findings indicated that rHDL/Stearic-PEI/VEGF complexes could be an ideal gene delivery system for enhanced VEGF gene therapy of myocardial ischemia, which might be a new promising strategy for effective myocardial ischemia treatment.

  12. Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction†

    OpenAIRE

    Jarvis, Ashley; Allerston, Charles K.; Jia, Haiyan; Herzog, Birger; Garza-Garcia, Acely; Winfield, Natalie; Ellard, Katie; Aqil, Rehan; Lynch, Rosemary; Chapman, Chris; Hartzoulakis, Basil; Nally, James; Stewart, Mark; Cheng, Lili; Menon, Malini

    2010-01-01

    We report the molecular design and synthesis of EG00229, 2, the first small molecule ligand for the VEGF-A receptor neuropilin 1 (NRP1) and the structural characterization of NRP1−ligand complexes by NMR spectroscopy and X-ray crystallography. Mutagenesis studies localized VEGF-A binding in the NRP1 b1 domain and a peptide fragment of VEGF-A was shown to bind at the same site by NMR, providing the basis for small molecule design. Compound 2 demonstrated inhibition of VEGF-A binding to NRP1 an...

  13. Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation.

    Science.gov (United States)

    Heitrich, Mauro; García, Daiana Maria de Los Ángeles; Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Aguirre, María Victoria

    2016-08-01

    Sepsis remains the most important cause of acute kidney injury (AKI) and acute lung injury (ALI) in critically ill patients. The cecal ligation and puncture (CLP) model in experimental mice reproduces most of the clinical features of sepsis. Erythropoietin (EPO) is a well-known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and pro-angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO protection through the expression of the EPO/EPO receptor (EPO-R) and VEGF/VEF-R2 systems in kidneys and lungs of mice undergoing CLP-induced sepsis. Male inbred Balb/c mice were divided in three experimental groups: Sham, CLP, and CLP+EPO (3000IU/kg sc). Assessment of renal functional parameters, survival, histological examination, immunohistochemistry and/or Western blottings of EPO-R, VEGF and VEGF-R2 were performed at 18h post-surgery. Mice demonstrated AKI by elevation of serum creatinine and renal histologic damage. EPO treatment attenuates renal dysfunction and ameliorates kidney histopathologic changes. Additionally, EPO administration attenuates deleterious septic damage in renal cortex through the overexpression of EPO-R in tubular interstitial cells and the overexpression of the pair VEGF/VEGF-R2. Similarly CLP- induced ALI, as evidenced by parenchymal lung histopathologic alterations, was ameliorated through pulmonary EPO-R, VEGF and VEGF-R2 over expression suggesting and improvement in endothelial survival and functionality. This study demonstrates that EPO exerts protective effects in kidneys and lungs in mice with CLP-induced sepsis through the expression of EPO-R and the regulation of the VEGF/VEGF-R2 pair. PMID:27470403

  14. In vivo characterization of {sup 68}Ga-NOTA-VEGF{sub 121} for the imaging of VEGF receptor expression in U87MG tumor xenograft models

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Choong Mo; Koo, Hyun-Jung; Lee, Kyung-Han; Choe, Yearn Seong [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Sung-Min; Yim, Min Su; Ryu, Eun Kyoung [Korea Basic Science Institute, Division of Magnetic Resonance Research, Chungbuk (Korea, Republic of)

    2013-02-15

    Vascular endothelial growth factor receptors (VEGFRs) are associated with tumor growth and induction of tumor angiogenesis and are known to be overexpressed in various human tumors. In the present study, we prepared and evaluated {sup 68}Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid-benzyl (NOTA)-VEGF{sub 121} as a positron emission tomography (PET) radioligand for the in vivo imaging of VEGFR expression. {sup 68}Ga-NOTA-VEGF{sub 121} was prepared by conjugation of VEGF{sub 121} and p-SCN-NOTA, followed by radiolabeling with {sup 68}GaCl{sub 3} and then purification using a PD-10 column. Human aortic endothelial cell (HAEC) binding of {sup 68}Ga-NOTA-VEGF{sub 121} was measured as a function of time. MicroPET and biodistribution studies of U87MG tumor xenografted mice were performed at 1, 2, and 4 h after injection of {sup 68}Ga-NOTA-VEGF{sub 121}. The tumor tissues were then sectioned and subjected to immunostaining. The decay-corrected radiochemical yield of {sup 68}Ga-NOTA-VEGF{sub 121} was 40 {+-} 4.5 % and specific activity was 243.1 {+-} 104.6 GBq/{mu}mol (8.6 {+-} 3.7 GBq/mg). {sup 68}Ga-NOTA-VEGF{sub 121} was avidly taken up by HAECs in a time-dependent manner, and the uptake was blocked either by 32 % with VEGF{sub 121} or by 49 % with VEGFR2 antibody at 4 h post-incubation. In microPET images of U87MG tumor xenografted mice, radioactivity was accumulated in tumors (2.73{+-}0.32 %ID/g at 2 h), and the uptake was blocked by 40 % in the presence of VEGF{sub 121}. In biodistribution studies, tumor uptake (1.84{+-}0.14 %ID/g at 2 h) was blocked with VEGF{sub 121} at a similar level (52 %) to that of microPET images. Immunostaining analysis of U87MG tumor tissues obtained after the microPET imaging showed high levels of VEGFR2 expression. These results demonstrate that {sup 68}Ga-NOTA-VEGF{sub 121} has potential for the in vivo imaging of VEGFR expression. In addition, our results also suggest that the in vivo characteristics of radiolabeled VEGF depend on the

  15. Corneal avascularity is due to soluble VEGF receptor-1.

    Science.gov (United States)

    Ambati, Balamurali K; Nozaki, Miho; Singh, Nirbhai; Takeda, Atsunobu; Jani, Pooja D; Suthar, Tushar; Albuquerque, Romulo J C; Richter, Elizabeth; Sakurai, Eiji; Newcomb, Michael T; Kleinman, Mark E; Caldwell, Ruth B; Lin, Qing; Ogura, Yuichiro; Orecchia, Angela; Samuelson, Don A; Agnew, Dalen W; St Leger, Judy; Green, W Richard; Mahasreshti, Parameshwar J; Curiel, David T; Kwan, Donna; Marsh, Helene; Ikeda, Sakae; Leiper, Lucy J; Collinson, J Martin; Bogdanovich, Sasha; Khurana, Tejvir S; Shibuya, Masabumi; Baldwin, Megan E; Ferrara, Napoleone; Gerber, Hans-Peter; De Falco, Sandro; Witta, Jassir; Baffi, Judit Z; Raisler, Brian J; Ambati, Jayakrishna

    2006-10-26

    Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea. PMID:17051153

  16. The link in Linking

    Science.gov (United States)

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-01-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block. PMID:23840106

  17. Corneal avascularity is due to soluble VEGF receptor-1

    OpenAIRE

    Ambati, Balamurali K.; Nozaki, Miho; Singh, Nirbhai; Takeda, Atsunobu; Jani, Pooja D.; Suthar, Tushar; Albuquerque, Romulo J. C.; Richter, Elizabeth; Sakurai, Eiji; Newcomb, Michael T.; Kleinman, Mark E.; Caldwell, Ruth B.; Lin, Qing; OGURA, Yuichiro; Orecchia, Angela

    2006-01-01

    Corneal avascularity—the absence of blood vessels in the cornea—is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders1-4. But the molecular underpinnings of the avascular phenotype have until now remained obscure5-10 and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and th...

  18. Percutaneous thermal ablation of renal neoplasms

    International Nuclear Information System (INIS)

    Due to modern examination techniques such as multidetector computed tomography and high-field magnetic resonance imaging, the detection rate of renal neoplasms is continually increasing. Even though tumors exceeding 4 cm in diameter rarely metastasize, all renal lesions that are possible neoplasms should be treated. Traditional treatment techniques include radical nephrectomy or nephron-sparing resection, which are increasingly performed laparoscopically. Modern thermal ablation techniques such as hyperthermal techniques like radiofrequency ablation RFA, laser induced thermal ablation LITT, focused ultrasound FUS and microwave therapy MW, as well as hypothermal techniques (cryotherapy) may be a useful treatment option for patients who are unfit for or refuse surgical resection. Cryotherapy is the oldest and best known thermal ablation technique and can be performed laparoscopically or percutaneously. Since subzero temperatures have no antistyptic effect, additional maneuvers must be performed to control bleeding. Percutaneous cryotherapy of renal tumors is a new and interesting method, but experience with it is still limited. Radiofrequency ablation is the most frequently used method. Modern probe design allows volumes between 2 and 5 cm in diameter to be ablated. Due to hyperthermal tract ablation, the procedure is deemed to be safe and has a low complication rate. Although there are no randomized comparative studies to open resection, the preliminary results for renal RFA are promising and show RFA to be superior to other thermal ablation techniques. Clinical success rates are over 90% for both, cryo- and radiofrequency ablation. Whereas laser induced thermal therapy is established in hepatic ablation, experience is minimal with respect to renal application. For lesions of more than 2 cm in diameter, additional cooling catheters are required. MR thermometry offers temperature control during ablation. Microwave ablation is characterized by small ablation volumes

  19. Stretch-induced hypertrophy activates NFkB-mediated VEGF secretion in adult cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Anna Leychenko

    Full Text Available Hypertension and myocardial infarction are associated with the onset of hypertrophy. Hypertrophy is a compensatory response mechanism to increases in mechanical load due to pressure or volume overload. It is characterized by extracellular matrix remodeling and hypertrophic growth of adult cardiomyocytes. Production of Vascular Endothelial Growth Factor (VEGF, which acts as an angiogenic factor and a modulator of cardiomyocyte function, is regulated by mechanical stretch. Mechanical stretch promotes VEGF secretion in neonatal cardiomyocytes. Whether this effect is retained in adult cells and the molecular mechanism mediating stretch-induced VEGF secretion has not been elucidated. Our objective was to investigate whether cyclic mechanical stretch induces VEGF secretion in adult cardiomyocytes and to identify the molecular mechanism mediating VEGF secretion in these cells. Isolated primary adult rat cardiomyocytes (ARCMs were subjected to cyclic mechanical stretch at an extension level of 10% at 30 cycles/min that induces hypertrophic responses. Cyclic mechanical stretch induced a 3-fold increase in VEGF secretion in ARCMs compared to non-stretch controls. This increase in stretch-induced VEGF secretion correlated with NFkB activation. Cyclic mechanical stretch-mediated VEGF secretion was blocked by an NFkB peptide inhibitor and expression of a dominant negative mutant IkBα, but not by inhibitors of the MAPK/ERK1/2 or PI3K pathways. Chromatin immunoprecipitation assays demonstrated an interaction of NFkB with the VEGF promoter in stretched primary cardiomyocytes. Moreover, VEGF secretion is increased in the stretched myocardium during pressure overload-induced hypertrophy. These findings are the first to demonstrate that NFkB activation plays a role in mediating VEGF secretion upon cyclic mechanical stretch in adult cardiomyocytes. Signaling by NFkB initiated in response to cyclic mechanical stretch may therefore coordinate the hypertrophic

  20. Identification of an exonic splicing silencer in exon 6A of the human VEGF gene

    Directory of Open Access Journals (Sweden)

    Crystal Ronald G

    2009-11-01

    Full Text Available Abstract Background The different isoforms of vascular endothelial growth factor (VEGF play diverse roles in vascular growth, structure and function. Alternative splicing of the VEGF gene results in the expression of three abundant isoforms: VEGF121, VEGF165 and VEGF189. The mRNA for VEGF189 contains the alternatively spliced exon 6A whereas the mRNA for VEGF165 lacks this exon. The objective of this study was to identify the cis elements that control utilization of exon 6A. A reporter minigene was constructed (pGFP-E6A containing the coding sequence for GFP whose translation was dependent on faithful splicing for removal of the VEGF exon 6A. To identify cis-acting splicing elements, sequential deletions were made across exon 6A in the pGFP-E6A plasmid. Results A candidate cis-acting exonic splicing silencer (ESS comprising nucleotides 22-30 of exon 6A sequence was identified corresponding to the a silencer consensus sequence of AAGGGG. The function of this sequence as an ESS was confirmed in vivo both in the context of the reporter minigene as a plasmid and in the context of a longer minigene with VEGF exon 6A in its native context in an adenoviral gene transfer vector. Further mutagenesis studies resulted in the identification of the second G residue of the putative ESS as the most critical for function. Conclusion This work establishes the identity of cis sequences that regulate alternative VEGF splicing and dictate the relative expression levels of VEGF isoforms.

  1. A two-compartment model of VEGF distribution in the mouse.

    Directory of Open Access Journals (Sweden)

    Phillip Yen

    Full Text Available Vascular endothelial growth factor (VEGF is a key regulator of angiogenesis--the growth of new microvessels from existing microvasculature. Angiogenesis is a complex process involving numerous molecular species, and to better understand it, a systems biology approach is necessary. In vivo preclinical experiments in the area of angiogenesis are typically performed in mouse models; this includes drug development targeting VEGF. Thus, to quantitatively interpret such experimental results, a computational model of VEGF distribution in the mouse can be beneficial. In this paper, we present an in silico model of VEGF distribution in mice, determine model parameters from existing experimental data, conduct sensitivity analysis, and test the validity of the model. The multiscale model is comprised of two compartments: blood and tissue. The model accounts for interactions between two major VEGF isoforms (VEGF(120 and VEGF(164 and their endothelial cell receptors VEGFR-1, VEGFR-2, and co-receptor neuropilin-1. Neuropilin-1 is also expressed on the surface of parenchymal cells. The model includes transcapillary macromolecular permeability, lymphatic transport, and macromolecular plasma clearance. Simulations predict that the concentration of unbound VEGF in the tissue is approximately 50-fold greater than in the blood. These concentrations are highly dependent on the VEGF secretion rate. Parameter estimation was performed to fit the simulation results to available experimental data, and permitted the estimation of VEGF secretion rate in healthy tissue, which is difficult to measure experimentally. The model can provide quantitative interpretation of preclinical animal data and may be used in conjunction with experimental studies in the development of pro- and anti-angiogenic agents. The model approximates the normal tissue as skeletal muscle and includes endothelial cells to represent the vasculature. As the VEGF system becomes better characterized in

  2. Detection of VEGF-A(xxx)b isoforms in human tissues.

    Science.gov (United States)

    Bates, David O; Mavrou, Athina; Qiu, Yan; Carter, James G; Hamdollah-Zadeh, Maryam; Barratt, Shaney; Gammons, Melissa V; Millar, Ann B; Salmon, Andrew H J; Oltean, Sebastian; Harper, Steven J

    2013-01-01

    Vascular Endothelial Growth Factor-A (VEGF-A) can be generated as multiple isoforms by alternative splicing. Two families of isoforms have been described in humans, pro-angiogenic isoforms typified by VEGF-A165a, and anti-angiogenic isoforms typified by VEGF-A165b. The practical determination of expression levels of alternative isoforms of the same gene may be complicated by experimental protocols that favour one isoform over another, and the use of specific positive and negative controls is essential for the interpretation of findings on expression of the isoforms. Here we address some of the difficulties in experimental design when investigating alternative splicing of VEGF isoforms, and discuss the use of appropriate control paradigms. We demonstrate why use of specific control experiments can prevent assumptions that VEGF-A165b is not present, when in fact it is. We reiterate, and confirm previously published experimental design protocols that demonstrate the importance of using positive controls. These include using known target sequences to show that the experimental conditions are suitable for PCR amplification of VEGF-A165b mRNA for both q-PCR and RT-PCR and to ensure that mispriming does not occur. We also provide evidence that demonstrates that detection of VEGF-A165b protein in mice needs to be tightly controlled to prevent detection of mouse IgG by a secondary antibody. We also show that human VEGF165b protein can be immunoprecipitated from cultured human cells and that immunoprecipitating VEGF-A results in protein that is detected by VEGF-A165b antibody. These findings support the conclusion that more information on the biology of VEGF-A165b isoforms is required, and confirm the importance of the experimental design in such investigations, including the use of specific positive and negative controls.

  3. Tumor Ablation with Irreversible Electroporation

    OpenAIRE

    Al-Sakere, Bassim; André, Franck,; Bernat, Claire; Connault, Elisabeth; Opolon, Paule; Davalos, Rafael V.; Rubinsky, Boris; Mir, Lluis M.

    2007-01-01

    We report the first successful use of irreversible electroporation for the minimally invasive treatment of aggressive cutaneous tumors implanted in mice. Irreversible electroporation is a newly developed non-thermal tissue ablation technique in which certain short duration electrical fields are used to permanently permeabilize the cell membrane, presumably through the formation of nanoscale defects in the cell membrane. Mathematical models of the electrical and thermal fields that develop dur...

  4. Caries selective ablation: the handpiece

    Science.gov (United States)

    Hennig, Thomas; Rechmann, Peter; Holtermann, Andreas

    1995-05-01

    Caries selective ablation is fixed to a window of fluences predicted by the ablation thresholds of carious and healthy dentin, respectively. The aim of the study was to develop a dental handpiece which guarantees homogeneous fluence at the irradiated tooth surface. Furthermore the point of treatment should be cooled down without energy losses due to the cooling system. We suggest the direct coupling of the laser radiation into a laminar stream of liquid, which acts in turn as a lengthened beam guide. The impacts of the laser radiation and of the cooling medium fall exactly into the same point. Hot ablation debris is removed out of the crater by the flush of the water jet. Fluences are constant if the handpiece is used in contact mode or at a distance. Normally the surface of a bare fiber working in contact mode is destroyed after a few shots. Coupling the laser radiation into a stream of liquid prevents this destruction. Putting together the benefits of this special handpiece short overall treatment times seem to be possible. High average power can be applied to the tooth without the threat of thermal damage. Furthermore no time consuming cutting of the fiber prolongs the treatment time.

  5. Multikinase inhibitor sorafenib transiently promotes necrosis after radiofrequency ablation in rat liver but activates growth signals

    International Nuclear Information System (INIS)

    Aim: To investigate the effects of sorafenib when combined with radiofrequency ablation treatment in liver tissue, the necrosis volume, tissue repair and hepatocellular growth signals were analyzed in rats. Radiofrequency ablation (RFA) is a widely applied treatment for hepatocellular carcinoma (HCC). Radiofrequency ablation is combined with the multi-tyrosinkinase-inhibitor sorafenib in ongoing clinical trials. Whether this combination treatment affects liver tissue repair is unknown. Materials and methods: Male Sprague Dawley (SD) rats received RFA or sham puncture with concomitant sorafenib (5 mg/kg qd from day 2) or vehicle. Necrosis volume was calculated from resected specimens. Proliferation and micro vessel density were determined by Ki67 and CD31 immunofluorescence, respectively. mRNA expression of hepatocyte growth factor (HGF), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) was quantified. Results: While ablation size was identical in all treatment groups at day 1, sorafenib treated animals showed sustained necroses (219 ± 24 vs. 88 ± 52 mm3 in controls; P = 0.03), elevated alanine aminotransferase (ALT) and elevated glutamate dehydrogenase (GLDH) (76 ± 37 vs. 47 ± 58 mm3; P = 0.50) at day 3. By day 7 necrosis volumes equalized for the treatment groups. Ki67 and CD31 staining showed reduced proliferation and micro vessel density at days 1 and 3 following sorafenib. Growth factors HGF and EGF were significantly overexpressed in liver tissue after sorafenib. Conclusion: Sorafenib initially promotes necrosis after RFA in liver tissue. The delay in tissue repair is overcome at day 7 presumably by transient compensatory overexpression of growth signals. Based on these data from animal studies further investigation of adjuvant sorafenib in humans is warranted.

  6. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

    Directory of Open Access Journals (Sweden)

    Villegas VM

    2014-05-01

    for advanced Coats’ disease presenting with exudative retinal detachment.Keywords: Coats’ disease, bevacizumab, anti-VEGF, laser ablation, retina

  7. Explosive character of the atheroma plaques ablation

    International Nuclear Information System (INIS)

    At the present time, ischemia (heart disease) is a main cause of the death in the world; a promising method for its treatment is the use of the technology of the laser light of raised power for the ablation of the atherosclerosis plaques. In this paper, the thermodynamic processes will be studied at the beginning and during atheroma ablation using Nd-YAG (10-50 w) and Argon (4-10 w) lasers of a theoretical point of view. The spatial distribution of the temperature during the ablation has been modelated by the method of finite volumes. The manifestation of the raised temperature of the tissue at the threshold of the ablation, which describes the explosive nature of the ablation by laser (popcorn effect), is observed and discussed. The results indicate the quantitative differences in the ablation behavior between the two used lasers, which can have important clinical implications particularly in the reduction of thermal damages to surrounding normal tissue. (author)

  8. Transient Ablation Regime in Circuit Breakers

    Institute of Scientific and Technical Information of China (English)

    Alexandre MARTIN; Jean-Yves TREPANIER; Marcelo REGGIO; GUO Xue-yan

    2007-01-01

    Nozzle wall ablation caused by high temperature electric arcs is studied in the context of high voltage SF6 circuit breakers.The simplified ablation model used in litterature has been updated to take into account the unsteady state of ablation.Ablation rate and velocity are now calculated by a kinetic model using two layers of transition,between the bulk plasma and the ablating wall.The first layer (Knudsen layer),right by the wall,is a kinetic layer of a few mean-free path of thickness.The second layer is collision dominated and makes the transition between the kinetic layer and the plasma bulk.With this new coupled algorithm,it is now possible to calculate the temperature distribution inside the wall,as well as more accurate ablation rates.

  9. Proteomic analysis of Vascular Endothelial Growth Factor (VEGF) signalling: studies of the mechanism of VEGF-induced Heat Shock Protein 27 phosphorylation and its role in endothelial cell signalling and function

    OpenAIRE

    Britton, G.

    2010-01-01

    Vascular Endothelial Growth Factor (VEGF) is essential for angiogenesis and endothelial function. Proteomic analysis of Human Umbilical Vein Endothelial Cells (HUVEC) identified Heat Shock Protein 27 (Hsp27) as a major VEGF-regulated protein. Hsp27 is implicated in actin organization, cell survival and migration, and is a potential mediator of these VEGF functions in the endothelium. Studies of pharmacological inhibitors indicated that VEGF-stimulated Hsp27 serine 82 (S82) phos...

  10. VEGF-C Is a Thyroid Marker of Malignancy Superior to VEGF-A in the Differential Diagnostics of Thyroid Lesions.

    Directory of Open Access Journals (Sweden)

    Kosma Woliński

    Full Text Available Thyroid nodular goiter is one of the most common medical conditions affecting even over a half of adult population. The risk of malignancy is rather small but noticeable-estimated by numerous studies to be about 3-10%. The definite differentiation between benign and malignant ones is a vital issue in endocrine practice. The aim of the current study was to assess the expression of vascular endothelial growth factor A (VEGF-A and VEGF-C on the mRNA level in FNAB washouts in case of benign and malignant thyroid nodules and to evaluate the diagnostic value of these markers of malignancy.Patients undergoing fine-needle aspiration biopsy (FNAB in our department between January 2013 and May 2014 were included. In case of all patients who gave the written consent, after ultrasonography (US and fine-needle aspiration biopsy (FNAB performed as routine medical procedure the needle was flushed with RNA Later solution, the washouts were frozen in -80 Celsius degrees. Expression of VEGF-A and VEGF-C and GADPH (reference gene was assessed in washouts on the mRNA level using the real-time PCR technique. Probes of patients who underwent subsequent thyroidectomy and were diagnosed with differentiated thyroid cancer (DTC; proved by post-surgical histopathology were analyzed. Similar number of patients with benign cytology were randomly selected to be a control group.Thirty one DTCs and 28 benign thyroid lesions were analyzed. Expression of VEGF-A was insignificantly higher in patients with DTCs (p = 0.13. Expression of VEGF-C was significantly higher in patients with DTC. The relative expression of VEGF-C (in comparison with GAPDH was 0.0049 for DTCs and 0.00070 for benign lesions, medians - 0.0036 and 0.000024 respectively (p<0.0001.Measurement of expression VEGF-C on the mRNA level in washouts from FNAB is more useful than more commonly investigated VEGF-A. Measurement of VEGF-C in FNAB washouts do not allow for fully reliable differentiation of benign and

  11. Functional Modification of Fibrous PCL Scaffolds with Fusion Protein VEGF-HGFI Enhanced Cellularization and Vascularization.

    Science.gov (United States)

    Zhao, Liqiang; Ma, Shaoyang; Pan, Yiwa; Zhang, Qiuying; Wang, Kai; Song, Dongmin; Wang, Xiangxiang; Feng, Guowei; Liu, Ruming; Xu, Haijin; Zhang, Jun; Qiao, Mingqiang; Kong, Deling

    2016-09-01

    The lack of efficient vascularization within frequently used poly(ε-caprolactone) (PCL) scaffolds has hindered their application in tissue engineering. Hydrophobin HGFI, an amphiphilic protein, can form a self-assembly layer on the surface of PCL scaffolds and convert their wettability. In this study, a fusion protein consisting of HGFI and vascular endothelial growth factor (VEGF) is prepared by Pichia pastoris expression system. Sodium dodecyl sulface-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting confirm that the VEGF-HGFI is successfully isolated and purified. Transmission electron microscope and water contact angle measurement demonstrate that VEGF-HGFI can form a self-assembly layer with about 25 nm in thickness on electrospun PCL fibers and increase their hydrophilicity. VEGF-HGFI modification can effectively enhance the adhesion, migration, and proliferation of human umbilical vein endothelial cells. Near-infrared fluorescence imaging shows that the VEGF-HGFI modification on PCL scaffolds can exist at least 21 d in vitro and at least 14 d in vivo. Bioluminescence imaging shows that VEGF-HGFI can effectively activate vascular endothelial growth factor receptor 2 receptors. Subcutaneous implantation in mice and rats reveal that cellularization and vascularization are significantly improved in VEGF-HGFI modified PCL scaffolds. These results suggest that VEGF-HGFI is a useful molecule for functional modification of scaffolds to enhance cellularization and vascularization in tissue engineering. PMID:27391702

  12. Anti-VEGF agents in metastatic colorectal cancer (mCRC: are they all alike?

    Directory of Open Access Journals (Sweden)

    Saif MW

    2013-06-01

    Full Text Available Muhammad Wasif Saif GI Oncology Program, Tufts University School of Medicine, Boston, MA, USA Abstract: Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States, VEGF receptors (eg, ramucirumab, and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors. The goal of the current review was to identify comparative preclinical data for the currently available VEGF-targeted therapies. Sources were compiled using PubMed searches (2007 to 2012, using search terms including, but not limited to: “bevacizumab,” “aflibercept,” “ramucirumab,” and “IMC-18F1.” Two preclinical studies were identified that compared bevacizumab and the newer agent, aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis therapies should help further expand treatment options for colorectal and other cancers. Comparative preclinical data on these agents is currently lacking. Keywords: aflibercept, antiangiogenesis, metastatic colorectal cancer (mCRC, tyrosine kinase inhibitor (TKI, vascular endothelial growth factor (VEGF

  13. RNA interference inhibits expression of vascular endothelial growth factor (VEGF) in human retinal pigment epithelial cells

    Institute of Scientific and Technical Information of China (English)

    CAI Chun-mei; SUN Bao-chen; LIU Xu-yang; WANG Jin-jin; LI Jun-fa; HAN Song; WANG Ning-li; LU Qing-jun

    2005-01-01

    @@ Choroidal neovascularization (CNV), a major cause of vision loss, is the result of the increased vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells. It is important to inhibit the expression of VEGF protein in RPE cells.

  14. Correlation of VEGF and COX-2 Expression with VM in Malignant Melanomas

    Institute of Scientific and Technical Information of China (English)

    BaocunSun; ShiwuZhang; XiulanZhao; YanxueLiu; ChunshengNi; DanfangZhang; HongQi; ZhiyongLiu; XishanHao

    2004-01-01

    OBJECTIVE To investigate the relationship between vascular epithelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in melanomas and the expressive difference of VEGF and COX-2 between melanomas with and without vasculogenic mimicry(VM).METHODS Sixty cases of malignant melanomas emoeaaea In paraffin were studied. The tumors were divided into a high-grade malignant group and a low-grade malignant group based on their tumor type, atypia and survival time of the patient. Then tissue microarrays were produced from these paraffin-embedded tumor tissues which were stained for VEGF, COX-2 and PAS. The difference in expression between VEGF and COX-2 in the malignant melanomas was compared using a grid-count. In addition, the tumors were also divided into mimicry and non-mimicry groups based on their PAS staining. Then the differences between the PAS positive and negative areas of the 2 groups were compared.RESULTS In malignant melanomas with VM, VEGF and COX-2 expression was less in tumors in which VM was absent, but VEGF, COX-2 expression in high-grade malignant melanomas was higher than that in low-grade grade malignant melanomas. Expression of VEGF was correlated with COX-2 expression.CONCLUSION VM exists in some high-grade malignant melanomas. The differences and relations between VEGF and COX-2 showed that some high-grade malignant melanomas possess a unique molecular-mechanism of tumor metastasis and blood supply.

  15. Pulmonary Large Cell Carcinoma Displays High Expression of EMMPRIN and VEGF

    Institute of Scientific and Technical Information of China (English)

    Yushuang Zheng; Miao Yu; Huachuan Zheng; Yifu Guan; Yasuo Takano

    2008-01-01

    OBJECTIVE To investigate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and vascular endothelial growth factor (VEGF) in lung carcinomas,and to clarify their roles in carcinoma progression.METHODS Expression of EMMPRIN and VEGF was examined with tissue microarrays (TMAs) of lung carcinomas (n = 181),and their suppression in adjacent normal lung samples (n = 40) were determined by immunohistochemistry.The results were compared with clinicopathological findings for the same tumors.RESULTS Both EMMPRIN and VEGF were occasionally expressed in pseudostratified columnar epithelium and frequently in lung carcinomas.Histologically,EMMPRIN and VEGF displayed higher levels in large (LCC) cell carcinomas than adenocarcinoma (AD),squamous (SQ) and small cell carcinomas (SCC) (P < 0.05).EMMPRIN was more highly expressed in SQ as compared with AD (P < 0.05),while the converse was true for VEGF (P < 0.05).Binding was generally more intense for EMMPRIN in samples from male compared to female patients (P < 0.05),whereas the latter tended to exhibit more VEGF expression (P < 0.05).Positive associations of VEGF expression with the TNM stage and amounts of EMMPRIN were noted in the lung carcinomas (P < 0.05).CONCLUSION EMMPRIN and VEGF possibly contribute to physiological repair of normal lung and histogenesis of lung carcinoma.Both proteins might be involved in the molecular basis for differences in the incidence of lung carcinoma between men and women.

  16. Effect of VEGF, P53 and telomerase on angiogenesis of gastric carcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    Yan-Fang Yu; Yong Zhang; Na Shen; Rui-Ying Zhang; Xin-Qing Lu

    2014-01-01

    Objective: To investigate the effect of vascular endothelial growth factor (VEGF), P53 and telomerase on angiogenesis in gastric carcinoma tissue. Methods: A total of 95 surgical resection samples of gastric cancer tissue after pathological diagnosis are collected to observe the VEGF, P53 and telomerase expression using immunohistochemical methods. Relationship between their expression and its influence on angiogenesis in gastric carcinoma tissue were analyzed. Results:Microvascular density (MVD) and the expression of VEGF, P53 and telomerase were positively correlated. Expression of VEGF and P53 protein were related to tumor type and lymph metastasis, and also a correlation was observed between P53 and VEGF. The telomerase expression had no correlation with VEGF, and P53. Conclusions: VEGF angiogenesis has a angiogenesis promoting effect on gastric cancer tissue development and plays an important role in tumor generation and metastasis. Mutant P53 promotes the tumor angiogenesis generation by adjusting VEGF. Telomerase has a certain role in promoting activity of angiogenesis through different way rather than P53.

  17. Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues.

    Science.gov (United States)

    Honek, Jennifer; Seki, Takahiro; Iwamoto, Hideki; Fischer, Carina; Li, Jingrong; Lim, Sharon; Samani, Nilesh J; Zang, Jingwu; Cao, Yihai

    2014-10-14

    Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti- VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.

  18. Nucleolin Promotes Heat Shock-Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis.

    Science.gov (United States)

    Morfoisse, Florent; Tatin, Florence; Hantelys, Fransky; Adoue, Aurelien; Helfer, Anne-Catherine; Cassant-Sourdy, Stephanie; Pujol, Françoise; Gomez-Brouchet, Anne; Ligat, Laetitia; Lopez, Frederic; Pyronnet, Stephane; Courty, Jose; Guillermet-Guibert, Julie; Marzi, Stefano; Schneider, Robert J; Prats, Anne-Catherine; Garmy-Susini, Barbara H

    2016-08-01

    The vascular endothelial growth factor VEGF-D promotes metastasis by inducing lymphangiogenesis and dilatation of the lymphatic vasculature, facilitating tumor cell extravasion. Here we report a novel level of control for VEGF-D expression at the level of protein translation. In human tumor cells, VEGF-D colocalized with eIF4GI and 4E-BP1, which can program increased initiation at IRES motifs on mRNA by the translational initiation complex. In murine tumors, the steady-state level of VEGF-D protein was increased despite the overexpression and dephosphorylation of 4E-BP1, which downregulates protein synthesis, suggesting the presence of an internal ribosome entry site (IRES) in the 5' UTR of VEGF-D mRNA. We found that nucleolin, a nucleolar protein involved in ribosomal maturation, bound directly to the 5'UTR of VEGF-D mRNA, thereby improving its translation following heat shock stress via IRES activation. Nucleolin blockade by RNAi-mediated silencing or pharmacologic inhibition reduced VEGF-D translation along with a subsequent constriction of lymphatic vessels in tumors. Our results identify nucleolin as a key regulator of VEGF-D expression, deepening understanding of lymphangiogenesis control during tumor formation. Cancer Res; 76(15); 4394-405. ©2016 AACR. PMID:27280395

  19. A nanobody directed to a functional epitope on VEGF, as a novel strategy for cancer treatment

    DEFF Research Database (Denmark)

    Farajpour, Zahra; Rahbarizadeh, Fatemeh; Kazemi, Bahram;

    2014-01-01

    Compelling evidence suggests that vascular endothelial growth factor (VEGF), due to its essential role in angiogenesis, is a critical target for cancer treatment. Neutralizing monoclonal antibodies against VEGF are important class of drugs used in cancer therapy. However, the cost of production...

  20. Identification and in vitro characterization of phage-displayed VHHs targeting VEGF

    DEFF Research Database (Denmark)

    Farajpour, Zahra; Rahbarizadeh, Fatemeh; Kazemi, Bahram;

    2014-01-01

    Vascular endothelial growth factor (VEGF) is a potential target for cancer treatment because of its role in angiogenesis and its overexpression in most human cancers. Currently, anti-VEGF antibodies have been shown to be promising tools for therapeutic applications. However, large size, poor tumo...

  1. Tumor-associated fibroblasts as "Trojan Horse" mediators of resistance to anti-VEGF therapy.

    Science.gov (United States)

    Francia, Giulio; Emmenegger, Urban; Kerbel, Robert S

    2009-01-01

    While targeting VEGF has shown success against a number of human cancers, drug resistance has resulted in compromised clinical benefits. In this issue of Cancer Cell, Crawford et al. (2009) report that tumors resistant to anti-VEGF therapy stimulate tumor-associated fibroblasts to express proangiogenic PDGF-C, implicating it as a potential therapeutic target.

  2. Expression profiling of ETS and MMP factors in VEGF-activated endothelial cells: role of MMP-10 in VEGF-induced angiogenesis.

    Science.gov (United States)

    Heo, Sun-Hee; Choi, Young-Jin; Ryoo, Hyun-Mo; Cho, Je-Yoel

    2010-09-01

    In the process of angiogenesis, working of many transcription factors at the proper time is important to activate angiogenesis-related genes such as cytokine, matrix protease and adhesion molecules. In this study, we searched for Ets transcription factors and matrix metalloproteinases (MMPs) that respond to VEGF in endothelial cells. We first analyzed the expression of 27 human Ets factors and 15 human MMPs in VEGF-treated human umbilical vein endothelial cells (HUVEC) using quantitative RT-PCR. The most abundant Ets factors in HUVEC were ETS-1, Fli-1, ERP/NET/ELK3, and ERG. MMP-1, -2, -10, -11, -14, -15, and -16 were also detected in HUVEC. We also found that ETV-1, Fli-1, ERG, MMP-1, -3, -7, -8, -9, -10, -13, and -19 expression is up-regulated more than 1.5-fold in HUVEC after 2 h of VEGF treatment. In addition, the expression of MMP-10 induced by VEGF remained twofold higher for 24 h compared to non-treated control. The elevation of MMP10 mRNA and protein levels was confirmed to be both time- and dosage-dependent. In addition, MMP-10 transcription was mediated by Ets-1 but not ERP/NET/ELK3. The inhibition of PI3K and MAPK inhibited VEGF-induced MMP-10 expression. Furthermore, transfection of MMP-10 siRNA inhibited VEGF-induced migration and tube formation in HUVEC, and it also inhibited vessel formation in matrigel plugs in vivo. In conclusion, our study demonstrated induction of MMP-10 by VEGF in HUVEC and supports an angiogenic role for MMP-10 in response to VEGF stimulation in vitro and in vivo. PMID:20432469

  3. Computer-aided hepatic tumour ablation

    CERN Document Server

    Voirin, D; Amavizca, M; Leroy, A; Letoublon, C; Troccaz, J; Voirin, David; Payan, Yohan; Amavizca, Miriam; Leroy, Antoine; Letoublon, Christian; Troccaz, Jocelyne

    2001-01-01

    Surgical resection of hepatic tumours is not always possible. Alternative techniques consist in locally using chemical or physical agents to destroy the tumour and this may be performed percutaneously. It requires a precise localisation of the tumour placement during ablation. Computer-assisted surgery tools may be used in conjunction to these new ablation techniques to improve the therapeutic efficiency whilst benefiting from minimal invasiveness. This communication introduces the principles of a system for computer-assisted hepatic tumour ablation.

  4. Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy

    Science.gov (United States)

    Bolinger, Mark T.; Antonetti, David A.

    2016-01-01

    Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models. Finally, novel drug targets including components of the kinin–kallikrein system and emerging treatments such as anti-HPTP (human protein tyrosine phosphatase) β antibodies are discussed. Recognition of non-VEGF contributions to disease pathogenesis may lead to novel therapeutics to enhance existing treatments for patients who do not respond to anti-VEGF therapies. PMID:27618014

  5. Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Mark T. Bolinger

    2016-09-01

    Full Text Available Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models. Finally, novel drug targets including components of the kinin–kallikrein system and emerging treatments such as anti-HPTP (human protein tyrosine phosphatase β antibodies are discussed. Recognition of non-VEGF contributions to disease pathogenesis may lead to novel therapeutics to enhance existing treatments for patients who do not respond to anti-VEGF therapies.

  6. Exercise induced capillary growth in human skeletal muscle and the dynamics of VEGF

    DEFF Research Database (Denmark)

    Høier, Birgitte; Hellsten, Ylva

    2014-01-01

    In skeletal muscle, growth of capillaries is an important adaptation to exercise training that secures adequate diffusion capacity for oxygen and nutrients even at high intensity exercise when increases in muscle blood flow are profound. Mechanical forces present during muscle activity......, such as shear stress and passive stretch, lead to cellular signalling, enhanced expression of angiogenic factors and initiation of capillary growth. The most central angiogenic factor in skeletal muscle capillary growth is vascular endothelial growth factor (VEGF). During muscle contraction, VEGF increases...... in the muscle interstitium, acts on VEGF receptors on the capillary endothelium and thereby stimulates angiogenic processes. A primary source of muscle interstitial VEGF during exercise is the skeletal muscle fibers which contain large stores of VEGF within vesicles. We propose that, during muscle activity...

  7. Expression and significance of VEGF and p53 in degenerate intervertebral disc tissue

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yu Lu; Xiao-Hong Ding; Li-Jun Zhong; Hong Xia; Xiao-Dong Chen; Hai Huang

    2013-01-01

    Objective: To investigate the mechanism of expression and significance of vascular endothelial growth factor (VEGF) and p53 in degenerate intervertebral disc tissue. Methods: Pathological sections collected from 156 patients with lumbar disc herniation after surgery were tested by immunohistochemistry method, for evaluation of the expression of VEGF and p53 in degenerate intervertebral disc tissue. Results: 98 cases (62.8%) with vascular infiltration phenomenon are found, and positive rates of VEGF and p53 in degenerate intervertebral disc tissue are 73.42%(116/156) and 58.97% (92/156); co-expression rate is 53.2%(83/156); the expression rates of VEFG and p53 are significantly higher in the tissue with blood vessel infiltration than in the tissue without infiltration; there is a close relationship of VEGF with p53. Conclusions: VEGF and p53 gene synergetic express in degenerate intervertebral disc tissue, working together in neovascularization and infiltration, and accelerating intervertebral disc tissue degeneration.

  8. Metformin inhibits development of diabetic retinopathy through inducing alternative splicing of VEGF-A

    Science.gov (United States)

    Yi, Quan-Yong; Deng, Gang; Chen, Nan; Bai, Zhi-Sha; Yuan, Jian-Shu; Wu, Guo-Hai; Wang, Yu-Wen; Wu, Shan-Jun

    2016-01-01

    Previous studies have shown that metformin, an AMP-activated protein kinase activator widely prescribed for type 2 diabetes, is especially beneficial in cases of diabetic retinopathy (DR) with undetermined mechanisms. Here, we used a streptozotocin-induced diabetes model in mice to study the effects of metformin on the development of DR. We found that 10 weeks after STZ treatment, DR was induced in STZ-treated mice, regardless treatment of metformin. However, metformin alleviated the DR, seemingly through attenuating the retina neovascularization. The total vascular endothelial cell growth factor A (VEGF-A) in eyes was not altered by metformin, but the phosphorylation of the VEGF receptor 2 (VEGFR2) was decreased, which inhibited VEGF signaling. Further analysis showed that metformin may induce VEGF-A mRNA splicing to VEGF120 isoform to reduce its activation of the VEGFR2. These findings are critical for generating novel medicine for DR treatment.

  9. Cardiac Remodeling After Atrial Fibrillation Ablation

    Directory of Open Access Journals (Sweden)

    Li-Wei Lo, MD; Shih-Ann Chen, MD

    2013-06-01

    Full Text Available Radiofrequency catheter ablation procedures are considered a reasonable option for patients with symptomatic, drug refractory atrial fibrillation (AF. Ablation procedures have been reported to effectively restore sinus rhythm and provide long-term relief of symptoms. Both electrical and structural remodeling occurs with AF. A reversal of the electrical remodeling develops within 1 week after restoration to sinus rhythm following the catheter ablation. The recovery rate is faster in the right atrium than the left atrium. Reverse structural remodeling takes longer and is still present 2 to 4 months after restoration of sinus rhythm. The left atrial transport function also improves after successful catheter ablation of AF. Left atrial strain surveys from echocardiography are able to identify patients who respond to catheter ablation with significant reverse remodeling after ablation. Pre-procedural delayed enhancement magnetic resonance imaging is also able to determine the degree of atrial fibrosis and is another tool to predict the reverse remodeling after ablation. The remodeling process is complex if recurrence develops after ablation. Recent evidence shows that a combined reverse electrical and structural remodeling occurs after ablation of chronic AF when recurrence is paroxysmal AF. Progressive electrical remodeling without any structural remodeling develops in those with recurrence involving chronic AF. Whether progressive atrial remodeling is the cause or consequence during the recurrence of AF remains obscure and requires further study.

  10. Cryoballoon Catheter Ablation in Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Cevher Ozcan

    2011-01-01

    Full Text Available Pulmonary vein isolation with catheter ablation is an effective treatment in patients with symptomatic atrial fibrillation refractory or intolerant to antiarrhythmic medications. The cryoballoon catheter was recently approved for this procedure. In this paper, the basics of cryothermal energy ablation are reviewed including its ability of creating homogenous lesion formation, minimal destruction to surrounding vasculature, preserved tissue integrity, and lower risk of thrombus formation. Also summarized here are the publications describing the clinical experience with the cryoballoon catheter ablation in both paroxysmal and persistent atrial fibrillation, its safety and efficacy, and discussions on the technical aspect of the cryoballoon ablation procedure.

  11. Aromatic Thermosetting Copolyesters for Ablative TPS Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Better performing ablative thermal protection systems than currently available are needed to satisfy requirements of the most severe crew exploration vehicles, such...

  12. Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Hai-dong [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Cui, Guo-hong; Yang, Jia-jun [Department of Neurology, Shanghai No. 6 People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233 (China); Wang, Cun [Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Zhu, Jing; Zhang, Li-sheng; Jiang, Jun [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Shao, Shui-jin, E-mail: shaoshuijin@163.com [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer The designer peptide LRKKLGKA could self-assemble into nanofibers. Black-Right-Pointing-Pointer Injection of LRKKLGKA peptides could promote the sustained delivery of VEGF. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides lead to sufficient angiogenesis. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides improves heart function. -- Abstract: Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. This designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.

  13. Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction

    International Nuclear Information System (INIS)

    Highlights: ► The designer peptide LRKKLGKA could self-assemble into nanofibers. ► Injection of LRKKLGKA peptides could promote the sustained delivery of VEGF. ► Injection of VEGF with LRKKLGKA peptides lead to sufficient angiogenesis. ► Injection of VEGF with LRKKLGKA peptides improves heart function. -- Abstract: Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. This designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.

  14. Analysis of iodinated contrast delivered during thermal ablation: is material trapped in the ablation zone?

    Science.gov (United States)

    Wu, Po-hung; Brace, Chris L.

    2016-08-01

    Intra-procedural contrast-enhanced CT (CECT) has been proposed to evaluate treatment efficacy of thermal ablation. We hypothesized that contrast material delivered concurrently with thermal ablation may become trapped in the ablation zone, and set out to determine whether such an effect would impact ablation visualization. CECT images were acquired during microwave ablation in normal porcine liver with: (A) normal blood perfusion and no iodinated contrast, (B) normal perfusion and iodinated contrast infusion or (C) no blood perfusion and residual iodinated contrast. Changes in CT attenuation were analyzed from before, during and after ablation to evaluate whether contrast was trapped inside of the ablation zone. Visualization was compared between groups using post-ablation contrast-to-noise ratio (CNR). Attenuation gradients were calculated at the ablation boundary and background to quantitate ablation conspicuity. In Group A, attenuation decreased during ablation due to thermal expansion of tissue water and water vaporization. The ablation zone was difficult to visualize (CNR  =  1.57  ±  0.73, boundary gradient  =  0.7  ±  0.4 HU mm-1), leading to ablation diameter underestimation compared to gross pathology. Group B ablations saw attenuation increase, suggesting that iodine was trapped inside the ablation zone. However, because the normally perfused liver increased even more, Group B ablations were more visible than Group A (CNR  =  2.04  ±  0.84, boundary gradient  =  6.3  ±  1.1 HU mm-1) and allowed accurate estimation of the ablation zone dimensions compared to gross pathology. Substantial water vaporization led to substantial attenuation changes in Group C, though the ablation zone boundary was not highly visible (boundary gradient  =  3.9  ±  1.1 HU mm-1). Our results demonstrate that despite iodinated contrast being trapped in the ablation zone, ablation visibility was

  15. Analysis of iodinated contrast delivered during thermal ablation: is material trapped in the ablation zone?

    Science.gov (United States)

    Wu, Po-hung; Brace, Chris L.

    2016-08-01

    Intra-procedural contrast-enhanced CT (CECT) has been proposed to evaluate treatment efficacy of thermal ablation. We hypothesized that contrast material delivered concurrently with thermal ablation may become trapped in the ablation zone, and set out to determine whether such an effect would impact ablation visualization. CECT images were acquired during microwave ablation in normal porcine liver with: (A) normal blood perfusion and no iodinated contrast, (B) normal perfusion and iodinated contrast infusion or (C) no blood perfusion and residual iodinated contrast. Changes in CT attenuation were analyzed from before, during and after ablation to evaluate whether contrast was trapped inside of the ablation zone. Visualization was compared between groups using post-ablation contrast-to-noise ratio (CNR). Attenuation gradients were calculated at the ablation boundary and background to quantitate ablation conspicuity. In Group A, attenuation decreased during ablation due to thermal expansion of tissue water and water vaporization. The ablation zone was difficult to visualize (CNR  =  1.57  ±  0.73, boundary gradient  =  0.7  ±  0.4 HU mm‑1), leading to ablation diameter underestimation compared to gross pathology. Group B ablations saw attenuation increase, suggesting that iodine was trapped inside the ablation zone. However, because the normally perfused liver increased even more, Group B ablations were more visible than Group A (CNR  =  2.04  ±  0.84, boundary gradient  =  6.3  ±  1.1 HU mm‑1) and allowed accurate estimation of the ablation zone dimensions compared to gross pathology. Substantial water vaporization led to substantial attenuation changes in Group C, though the ablation zone boundary was not highly visible (boundary gradient  =  3.9  ±  1.1 HU mm‑1). Our results demonstrate that despite iodinated contrast being trapped in the ablation zone, ablation visibility

  16. Collagenase IV plays an important role in regulating hair cycle by inducing VEGF, IGF-1, and TGF-β expression

    Directory of Open Access Journals (Sweden)

    Hou C

    2015-09-01

    Full Text Available Chun Hou, Yong Miao, Jin Wang, Xue Wang, Chao-Yue Chen, Zhi-Qi Hu Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China Background: It has been reported that collagenases (matrix metalloproteinase 2 [MMP-2] and matrix metalloproteinase 9 [MMP-9] are associated with hair cycle, whereas the mechanism of the association is largely unknown.Methods: The mice were randomly allocated into four groups: saline, and 5, 10, and 15 nM SB-3CT. Immunohistochemical analysis was employed to examine MMP-2 and MMP-9 protein. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay were performed to determine mRNA and protein levels of VEGF, IGF-1, TGF-β, and GAPDH. Growing hair follicles from anagen phase III–IV were scored based on hematoxylin and eosin staining. Hair regrowth was also evaluated.Results: Results showed that mRNA expressions of enzymes changed with a peak at late anagen and a trough at telogen after depilation. Immunostaining showed that the highest expression of MMP-2 was more than that of MMP-9, and the highest expression of enzymes changed during anagen. The localizations of MMP-2 changed from dermal papilla, keratinocyte strand, out of root sheath, and basal plate at early anagen, to hair bulb, inner root sheath, and outer root sheath at late anagen. The localization of MMP-9 changed from partial keratinocyte to dermal papilla at early anagen and to outer root sheath at late anagen. VEGF, IGF-1, and TGF-β have been shown to regulate hair growth. We found mRNA and protein expressions of VEGF and IGF-1 fluctuated with a peak at anagen and a decrease at catagen to telogen. In contrast, mRNA and protein expressions of TGF-β changed with highest and lowest levels at anagen and telogen, respectively. With selective inhibitor of collagenase IV, SB-3CT, mice showed significant suppressed hair growth and decreased expression of VEGF, IGF-1

  17. Vascular endothelial growth factor B (VEGF-B is up-regulated and exogenous VEGF-B is neuroprotective in a culture model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Zhang Shiling

    2009-12-01

    Full Text Available Abstract Parkinson's disease (PD results from the degeneration of dopaminergic neurons in the substantia nigra and the consequent deficit of dopamine released in the striatum. Current oral dopamine replacement or surgical therapies do not address the underlying issue of neurodegeneration, they neither slow nor halt disease. Neurotrophic factors have shown preclinical promise, but the choice of an appropriate growth factor as well as the delivery has proven difficult. In this study, we used a rotenone rat midbrain culture model to identify genes that are changed after addition of the neurotoxin. (1 We challenged rat midbrain cultures with rotenone (20 nM, a pesticide that has been shown to be toxic for dopaminergic neurons and that has been a well-characterized model of PD. A gene chip array analysis demonstrated that several genes were up-regulated after the rotenone treatment. Interestingly transcriptional activation of vascular endothelial growth factor B (VEGF-B was evident, while vascular endothelial growth factor A (VEGF-A levels remained unaltered. The results from the gene chip array experiment were verified with real time PCR and semi-quantitative western analysis using β-actin as the internal standard. (2 We have also found evidence that exogenously applied VEGF-B performed as a neuroprotective agent facilitating neuron survival in an even more severe rotenone culture model of PD (40 nM rotenone. VEGF-B has very recently been added to the list of trophic factors that reduce effects of neurodegeneration, as was shown in an in vivo model of motor neuron degeneration, while lacking potential adverse angiogenic activity. The data of an in vivo protective effect on motor neurons taken together with the presented results demonstrate that VEGF-B is a new candidate trophic factor distinct from the GDNF family of trophic factors. VEGF-B is activated by neurodegenerative challenges to the midbrain, and exogenous application of VEGF-B has a

  18. Increase in Volume of Ablation Zones during Follow-up Is Highly Suggestive of Ablation Site Recurrence in Colorectal Liver Metastases Treated with Radiofrequency Ablation

    NARCIS (Netherlands)

    Kele, Petra G.; de Jong, Koert P.; van der Jagt, Eric J.

    2012-01-01

    Purpose: To test the hypothesis that volume changes of ablation zones (AZs) on successive computed tomography (CT) scans could predict ablation site recurrences (ASRs) in patients with colorectal liver metastases treated by radiofrequency (RF) ablation. Materials and Methods: RF ablation was perform

  19. Therapeutic efficacy of percutaneous radiofrequency ablation versus microwave ablation for hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    Full Text Available The aim of this study was to investigate the therapeutic efficacy of percutaneous radiofrequency (RF ablation versus microwave (MW ablation for hepatocellular carcinoma (HCC measuring ≤ 5 cm in greatest diameter. From January 2006 to December 2006, 78 patients had undergone RF ablation whereas 77 had undergone MW ablation. Complete ablation (CA, local tumour progression (LTP and distant recurrence (DR were compared. The overall survival curves were calculated with the Kaplan-Meier technique and compared with the log-rank test. The CA rate was 83.4% (78/93 for RF ablation and 86.7%(91/105 for MW ablation. The LTP rate was 11.8% (11/93 for RF ablation and 10.5% (11/105 for MW ablation. DR was found in 51 (65.4% in the RF ablation and 62 (80.5% in the MW ablation. There was no significant difference in the 1-, 3-, and 5-year overall survival rates (P = 0.780 and the 1-, 3-, and 5-year disease-free survival rates (P = 0.123 between RF and MW ablation. At subgroup analyses, for patients with tumors ≤ 3.0 cm, there was no significant difference in the 1-, 3-, and 5-year overall survival rates (P = 0.067 and the corresponding disease-free survival rates(P = 0.849. For patients with tumor diameters of 3.1-5.0 cm, the 1-, 3-, and 5-year overall survival rates were 87.1%, 61.3%, and 40.1% for RF ablation and 85.4%, 36.6%, and 22% for MW ablation, with no significant difference (P = 0.068. The corresponding disease-free survival rates were 74.2%, 54.8%, and 45.2% for the RF ablation group and 53.3%, 26.8%, and 17.1% for the MW ablation group. The disease-free survival curve for the RF ablation group was significantly better than that for the MW ablation group (P = 0.018. RF ablation and MW ablation are both effective methods in treating hepatocellular carcinomas, with no significant differences in CA, LTP, DR, and overall survival.

  20. Possible role for cryoballoon ablation of right atrial appendage tachycardia when conventional ablation fails.

    Science.gov (United States)

    Amasyali, Basri; Kilic, Ayhan

    2015-06-01

    Focal atrial tachycardia arising from the right atrial appendage usually responds well to radiofrequency ablation; however, successful ablation in this anatomic region can be challenging. Surgical excision of the right atrial appendage has sometimes been necessary to eliminate the tachycardia and prevent or reverse the resultant cardiomyopathy. We report the case of a 48-year-old man who had right atrial appendage tachycardia resistant to multiple attempts at ablation with use of conventional radiofrequency energy guided by means of a 3-dimensional mapping system. The condition led to cardiomyopathy in 3 months. The arrhythmia was successfully ablated with use of a 28-mm cryoballoon catheter that had originally been developed for catheter ablation of paroxysmal atrial fibrillation. To our knowledge, this is the first report of cryoballoon ablation without isolation of the right atrial appendage. It might also be an alternative to epicardial ablation or surgery when refractory atrial tachycardia originates from the right atrial appendage.

  1. Attitudes Towards Catheter Ablation for Atrial Fibrillation

    DEFF Research Database (Denmark)

    Vadmann, Henrik; Pedersen, Susanne S; Nielsen, Jens Cosedis;

    2015-01-01

    BACKGROUND: Catheter ablation for atrial fibrillation (AF) is an important but expensive procedure that is the subject of some debate. Physicians´ attitudes towards catheter ablation may influence promotion and patient acceptance. This is the first study to examine the attitudes of Danish...

  2. Hyperkalaemia after radiofrequency ablation of hepatocellular carcinoma

    NARCIS (Netherlands)

    Verhoevena, BH; Haagsma, EB; Appeltans, BMG; Slooff, MJH; de Jong, KP

    2002-01-01

    Radiofrequency ablation of liver tumours is a useful therapy for otherwise unresectable tumours. The complication rate is said to be low. In this case report we describe hyperkalaemia after radiofrequency ablation of a hepatocellular carcinoma in a patient with end-stage renal insufficiency. (C) 200

  3. Cooperation between HMGA1 and HIF-1 Contributes to Hypoxia-Induced VEGF and Visfatin Gene Expression in 3T3-L1 Adipocytes.

    Science.gov (United States)

    Messineo, Sebastiano; Laria, Anna Elisa; Arcidiacono, Biagio; Chiefari, Eusebio; Luque Huertas, Raúl M; Foti, Daniela P; Brunetti, Antonio

    2016-01-01

    The architectural transcription factor high-mobility group AT-hook 1 (HMGA1) is a chromatin regulator with implications in several biological processes, including tumorigenesis, inflammation, and metabolism. Previous studies have indicated a role for this factor in promoting the early stages of adipogenesis, while inhibiting adipocyte terminal differentiation, and decreasing fat mass. It has been demonstrated that hypoxia - through the hypoxia-inducible factor 1 (HIF-1) - plays a major role in triggering changes in the adipose tissue of the obese, leading to inhibition of adipocyte differentiation, adipose cell dysfunction, inflammation, insulin resistance, and type 2 diabetes. To examine the possible cooperation between HMGA1 and HIF-1, herein, we investigated the role of HMGA1 in the regulation of Visfatin and VEGF, two genes normally expressed in adipose cells, which are both responsive to hypoxia. We demonstrated that HMGA1 enhanced Visfatin and VEGF gene expression in human embryonic kidney (HEK) 293 cells in hypoxic conditions, whereas HMGA1 knockdown in differentiated 3T3-L1 adipocytes reduced these effects. Reporter gene analysis showed that Visfatin and VEGF transcriptional activity was increased by the addition of either HMGA1 or HIF-1 and even further by the combination of both factors. As demonstrated by chromatin immunoprecipitation in intact cells, HMGA1 directly interacted with the VEGF gene, and this interaction was enhanced in hypoxic conditions. Furthermore, as indicated by co-immunoprecipitation studies, HMGA1 and HIF-1 physically interacted with each other, supporting the notion that this association may corroborate a functional link between these factors. Therefore, our findings provide evidence for molecular cross-talk between HMGA1 and HIF-1, and this may be important for elucidating protein and gene networks relevant to obesity. PMID:27445976

  4. Vascular endothelial growth factor (VEGF and monocyte chemoattractant protein (MCP-1 levels unaltered in symptomatic atherosclerotic carotid plaque patients from North India

    Directory of Open Access Journals (Sweden)

    Dheeraj eKhurana

    2013-04-01

    Full Text Available We aimed to identify the role of vascular endothelial growth factor(VEGF and monocyte chemoattractant protein(MCP-1 as a serum biomarker of symptomatic carotid atherosclerotic plaque in North Indian population. Individuals with symptomatic carotid atherosclerotic plaque have high risk of ischemic stroke. Previous studies from western countries have shown an association between VEGF and MCP-1 levels and the incidence of ischemic stroke. In this study, venous blood from 110 human subjects was collected, 57 blood samples of which were obtained from patients with carotid plaques, 38 neurological controls without carotid plaques and another 15 healthy controls who had no history of serious illness. Serum VEGF and MCP-1 levels were measured using commercially available enzyme-linked immunosorbent assay(ELISA. We also correlated the data clinically and carried out risk factor analysis based on the detailed questionnaire obtained from each patient. For risk factor analysis, a total of 70 symptomatic carotid plaque cases and equal number of age and sex matched healthy controls were analyzed. We found that serum VEGF levels in carotid plaque patients did not show any significant change when compared to either of the controls. Similarly, there was no significant upregulation of monocyte chemoattractant protein-1 in the serum of these patients. The risk factor analysis revealed that hypertension, diabetes, and physical inactivity were the main correlates of carotid atherosclerosis(p<0.05. Prevalence of patients was higher residing in urban areas as compared to rural region. We also found that patients coming from mountaineer region were relatively less vulnerable to cerebral atherosclerosis as compared to the ones residing at plain region. We conclude that the pathogenesis of carotid plaques may progress independent of these inflammatory molecules. In parallel, risk factor analysis indicates hypertension, diabetes and sedentary lifestyle as the most

  5. VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson's disease.

    Science.gov (United States)

    Xiong, N; Zhang, Z; Huang, J; Chen, C; Zhang, Z; Jia, M; Xiong, J; Liu, X; Wang, F; Cao, X; Liang, Z; Sun, S; Lin, Z; Wang, T

    2011-04-01

    The umbilical cord provides a rich source of primitive mesenchymal stem cells (human umbilical cord mesenchymal stem cells (HUMSCs)), which have the potential for transplantation-based treatments of Parkinson's Disease (PD). Our pervious study indicated that adenovirus-associated virus-mediated intrastriatal delivery of human vascular endothelial growth factor 165 (VEGF 165) conferred molecular protection to the dopaminergic system. As both VEGF and HUMSCs displayed limited neuroprotection, in this study we investigated whether HUMSCs combined with VEGF expression could offer enhanced neuroprotection. HUMSCs were modified by adenovirus-mediated VEGF gene transfer, and subsequently transplanted into rotenone-lesioned striatum of hemiparkinsonian rats. As a result, HUMSCs differentiated into dopaminergic neuron-like cells on the basis of neuron-specific enolase (NSE) (neuronal marker), glial fibrillary acidic protein (GFAP) (astrocyte marker), nestin (neural stem cell marker) and tyrosine hydroxylase (TH) (dopaminergic marker) expression. Further, VEGF expression significantly enhanced the dopaminergic differentiation of HUMSCs in vivo. HUMSC transplantation ameliorated apomorphine-evoked rotations and reduced the loss of dopaminergic neurons in the lesioned substantia nigra (SNc), which was enhanced significantly by VEGF expression in HUMSCs. These findings present the suitability of HUMSC as a vector for gene therapy and suggest that stem cell engineering with VEGF may improve the transplantation strategy for the treatment of PD.

  6. Wnt3a upregulates transforming growth factor-β-stimulated VEGF synthesis in osteoblasts.

    Science.gov (United States)

    Natsume, Hideo; Tokuda, Haruhiko; Matsushima-Nishiwaki, Rie; Kato, Kenji; Yamakawa, Kengo; Otsuka, Takanobu; Kozawa, Osamu

    2011-07-01

    It is recognized that Wnt3a affects bone metabolism via the canonical Wnt/β-catenin signalling pathway. We have previously shown that transforming growth factor-β (TGF-β) stimulates the synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of Wnt3a on TGF-β-stimulated VEGF synthesis in these cells. Wnt3a, which alone had little effect on the VEGF levels, significantly enhanced the TGF-β-stimulated VEGF release. Lithium chloride and SB216763, inhibitors of glycogen synthase kinase 3β, markedly amplified the TGF-β-stimulated VEGF release. Wnt3a failed to affect the TGF-β-induced phosphorylation of Smad2, p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. Wnt3a and lithium chloride strengthened the VEGF mRNA expression induced by TGF-β. These results strongly suggest that Wnt3a upregulates VEGF synthesis stimulated by TGF-β via activation of the canonical pathway in osteoblasts.

  7. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis

    International Nuclear Information System (INIS)

    The VEGF/VPF (vascular endothelial growth factor/vascular permeability factor) ligands and receptors are crucial regulators of vasculogenesis, angiogenesis, lymphangiogenesis and vascular permeability in vertebrates. VEGF-A, the prototype VEGF ligand, binds and activates two tyrosine kinase receptors: VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). VEGFR1, which occurs in transmembrane and soluble forms, negatively regulates vasculogenesis and angiogenesis during early embryogenesis, but it also acts as a positive regulator of angiogenesis and inflammatory responses, playing a role in several human diseases such as rheumatoid arthritis and cancer. The soluble VEGFR1 is overexpressed in placenta in preeclampsia patients. VEGFR2 has critical functions in physiological and pathological angiogenesis through distinct signal transduction pathways regulating proliferation and migration of endothelial cells. VEGFR3, a receptor for the lymphatic growth factors VEGF-C and VEGF-D, but not for VEGF-A, regulates vascular and lymphatic endothelial cell function during embryogenesis. Loss-of-function variants of VEGFR3 have been identified in lymphedema. Formation of tumor lymphatics may be stimulated by tumor-produced VEGF-C, allowing increased spread of tumor metastases through the lymphatics. Mapping the signaling system of these important receptors may provide the knowledge necessary to suppress specific signaling pathways in major human diseases

  8. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jinqiao, E-mail: jinqiao1977@163.com [Institute of Pediatrics, Children' s Hospital of Fudan University (China); Sha, Bin [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Zhou, Wenhao, E-mail: zhou_wenhao@yahoo.com.cn [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Yang, Yi [Institute of Pediatrics, Children' s Hospital of Fudan University (China)

    2010-03-26

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  9. Relationsip between PTEN and VEGF Expression and Clinicopathological Characteristics in HCC

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homlog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC), and to analyze the relationship between their expressions and the tumor's invasion and their pericarcinomatous tissues, the correlation of their expressions with the tumor's clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in pericarcinomatous liver tissues, while the expressions of both VEGF and MVD were higher than that in pericarcinomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively related to the progression of the pathological differentiation and invasion of tumor, whereas the expressions of VEGF and MVD were positively related. Moreover, there was a negative relationship between the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression probably induces abnormal hyperexpression of VEGF may play an important role in the invasion and metastasis of HCC.

  10. Increased Expression of VEGF and CD31 in Postradiation Rectal Tissue: Implications for Radiation Proctitis

    Directory of Open Access Journals (Sweden)

    G. Karamanolis

    2013-01-01

    Full Text Available Background. Inflammation mediators related to radiation proctitis are partially elucidated, and neovascularization is thought to play a key role. Objectives. To investigate the expression of vascular endothelial growth factor (VEGF and CD31 as angiogenetic markers in postradiation rectal tissue. Methods. Rectal mucosa biopsies from 11 patients who underwent irradiation for prostate cancer were examined immunohistochemically for the expression of VEGF and CD31 at three time settings—before, at the completion of, and 6 months after radiotherapy. VEGF expressing vascular endothelial cells and CD31 expressing microvessels were counted separately in 10 high-power fields (HPFs. VEGF vascular index (VEGF-VI and microvascular density (MVD were calculated as the mean number of VEGF positive cells per vessel or the mean number of vessels per HPF, respectively. Histological features were also evaluated. Results. VEGF-VI was significantly higher at the completion of radiotherapy (0.17±0.15 versus 0.41±0.24, P=0.001 declining 6 months after. MVD increased significantly only 6 months after radiotherapy (7.3±3.2 versus 10.5±3.1, P<0.005. The histopathological examination revealed inflammatory changes at the completion of radiotherapy regressing in the majority of cases 6 months after. Conclusions. Our results showed that in postradiation rectal biopsy specimens neoangiogenesis seems to be inflammation-related and constitutes a significant postradiation component of the tissue injury.

  11. Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

    Directory of Open Access Journals (Sweden)

    Dong Hyun Jo

    Full Text Available Anti-vascular endothelial growth factor (VEGF agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.

  12. Expression and significance of HIF-1α and VEGF in rats with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Hong-Tao Yan; Guan-Fang Su

    2014-01-01

    Objective:To investigate the expression of hypoxia inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF) in diabetic retinopathy(DR) rats and its effect on theDR occurrence and development.Methods:A total of120SD rats were randomly divided into trial group and control group with60 in each.STZi.p. was used in the trial group to establish theDM model, citrate buffer salt of same amount was usedi.p. to the control group.1,3 and6 months after injection, respective20 rats were sacrificed in each group to observe expression ofHIF-1α andVEGF in the rat retina tissue at different time points.Results:Expression ofHIF-1α andVEGF were negative in the control group; expression ofHIF-1α andVEGF protein in retinal tissue were weak after1 month ofDR mold formation.It showed progressive enhancement along with the progression in different organizations, differences between groups were significant (P<0.05).Conclusions:Expressions ofHIF-1α andVEGF were correlated with disease progression in early diabetic retinopathy.Retinal oxygen can induce over-expression ofHIF-1α andVEGF.It shows thatHIF-1α andVEGF play an important role in the pathogenesis ofDR.

  13. Association of Chemerin and Vascular Endothelial Growth Factor (VEGF) with Diabetic Nephropathy.

    Science.gov (United States)

    Lin, Shuhua; Teng, Jian; Li, Jixia; Sun, Fang; Yuan, Dong; Chang, Jing

    2016-01-01

    BACKGROUND Diabetic nephropathy (DN) is a common complication of diabetes, caused by diabetic microvascular lesions. The pathogenesis of DN is complicated, involving genetics, physics, chemistry, and environmental factors. Chemerin is a fat cell factor that participates in regulating inflammation. Vascular endothelial growth factor (VEGF) promotes vascular endothelial cell proliferation, differentiation, and angiogenesis. The relationship role of Chemerin and VEGF in DN is not fully understood. MATERIAL AND METHODS SD rats were randomly divided into 2 groups: the control group and the DN group. Streptozotocin was used to construct the DN model. Serum creatinine (Scr), blood urea nitrogen (BUN), and urine microalbumin (UAlb) were detected. Real-time PCR and Western blot were used to test Chemerin and VEGF mRNA and protein expression in kidney tissue. ELISA was performed to test TGF-β1, TNF-α, and INF-γ levels. The correlation of Chemerin and VEGF with renal function and inflammatory factors was analyzed. RESULTS DN group rats showed obviously increased Scr and BUN levels, and elevated TGF-β1, TNF-α, and INF-γ secretion (P<0.05). Compared with controls, Chemerin and VEGF were clearly overexpressed in the DN group (P<0.05). Chemerin and VEGF expression were positively correlated with inflammatory factors and renal function. CONCLUSIONS Chemerin and VEGF play important roles in DN by regulating inflammatory factors and renal function. They may be treated as indicators of DN. PMID:27612613

  14. Role of VEGF in the growth and metastasis of a murine bladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Feng; WU Jihong; TIAN Yuhua; CHEN Xiafang; HU Honghui; WU Wensen; LI Chuanyuan; HUANG Qian

    2003-01-01

    Bladder transitional cell carcinoma is the most common form of carcinoma in the urinary system. Although overexpression of VEGF has been identified in tissue, serum, and urine of patients with bladder cancer, the role of VEGF in transitional cell carcinoma of the bladder has not been clearly elucidated. Here, we dissected the effect of VEGF during bladder tumor growth and progression by modifying a BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine) induced mouse bladder transitional cell carcinoma cell line BTT-T739 by stable transfection of antisense VEGF121 cDNA. The transfection resulted in more than 80% reduction in VEGF production. The growth of the transduced tumor cells in vitro was not affected, however, these cells formed small or no tumors in vivo. Even in the tumors formed, there were mini- mal vascularization, extensive necrosis and longer latency compared to those formed by parental cells. The permeability of tumor vasculature and metastatic tumor growth were also significantly suppressed in antisense VEGF cDNA trans- fected cells. In addition, the transfer of anti-angiogenic gene in a combination of sFlk-1 and ExTek with electroporation can suppress the tumor growth efficiently. Taken together, these results demonstrated that VEGF plays an important role in bladder tumor angiogenesis and angiogenesis plays an important role in bladder tumor growth and metastasis.

  15. Expression of VEGF-C in Rat Cornea after Alkali Injury

    Institute of Scientific and Technical Information of China (English)

    姜冬玲; 胡燕华; 凌士奇

    2004-01-01

    The expression of VEGF-C and molecular mechanisms of lymphangiogenesis in rat cornea after alkali injury was studied. The rat alkali injured corneal models were made. Under electron microscopy, the lymphatic vessels in the rat injured corneas were examined. The expression of VEGF-C proteins was detected by using immunohistochemical assay at day 1, 3, 5, 7, 9 after injury. The expression levels of VEGF-C mRNA were quantified with reverse transcription polymerase chain reaction (RT-PCR). The results showed that the lymphatic vessels were found in the injured rat corneas 14 days after the injury. The VEGF-C protein was detectable 3 days after injury,reached the peak 5 days after injury, and gradually decreased. In the control group, no VEGF-C proteins were detected. The VEGF-C mRNA was minimally detected in the normal rat corneas, but it was highly expressed 5 days after the injury. The difference was statistically significant. It was concluded that VEGF-C might be one of the most important relevant factors in corneal lymphangiogenesis after alkali injury.

  16. Association of Chemerin and Vascular Endothelial Growth Factor (VEGF) with Diabetic Nephropathy

    Science.gov (United States)

    Lin, Shuhua; Teng, Jian; Li, Jixia; Sun, Fang; Yuan, Dong; Chang, Jing

    2016-01-01

    Background Diabetic nephropathy (DN) is a common complication of diabetes, caused by diabetic microvascular lesions. The pathogenesis of DN is complicated, involving genetics, physics, chemistry, and environmental factors. Chemerin is a fat cell factor that participates in regulating inflammation. Vascular endothelial growth factor (VEGF) promotes vascular endothelial cell proliferation, differentiation, and angiogenesis. The relationship role of Chemerin and VEGF in DN is not fully understood. Material/Methods SD rats were randomly divided into 2 groups: the control group and the DN group. Streptozotocin was used to construct the DN model. Serum creatinine (Scr), blood urea nitrogen (BUN), and urine microalbumin (UAlb) were detected. Real-time PCR and Western blot were used to test Chemerin and VEGF mRNA and protein expression in kidney tissue. ELISA was performed to test TGF-β1, TNF-α, and INF-γ levels. The correlation of Chemerin and VEGF with renal function and inflammatory factors was analyzed. Results DN group rats showed obviously increased Scr and BUN levels, and elevated TGF-β1, TNF-α, and INF-γ secretion (P<0.05). Compared with controls, Chemerin and VEGF were clearly overexpressed in the DN group (P<0.05). Chemerin and VEGF expression were positively correlated with inflammatory factors and renal function. Conclusions Chemerin and VEGF play important roles in DN by regulating inflammatory factors and renal function. They may be treated as indicators of DN. PMID:27612613

  17. High Heat Flux Block Ablator-in-Honeycomb Heat Shield Using Ablator/Aerogel-Filled Foam Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Ultramet and ARA Ablatives Laboratory previously developed and demonstrated advanced foam-reinforced carbon/phenolic ablators that offer substantially increased...

  18. Expression of Protein Slit2, VEGF and VEGF -C Correlates with Clinical Study of Colorectal Cancers%Slit2、VEGF和VEGF-C蛋白表达与大肠癌关系的临床研究

    Institute of Scientific and Technical Information of China (English)

    王琴伊; 卢雪峰; 季锐; 杨淑萍

    2010-01-01

    研究神经迁移因子(Slit2)、血管生成因子(VEGF、VEGF-C)在大肠癌中的表达及临床意义.检测60例大肠癌组织和36例癌旁组织中Slit2、VEGF和VEGF-C的表达水平.结果三者在大肠癌和癌旁组织中的表达水平均与肿瘤大小、浸润深度、TNM分期、淋巴结转移相关;VEGF和VEGF-C表达水平还与远处转移相关.结果提示Slit2是调节大肠癌血管生成的重要因子.

  19. Linked Lives

    NARCIS (Netherlands)

    Djundeva, Maja; Wright, James D.

    2015-01-01

    This article refers to the Linked Lives, following the development of the life course theory during the 1980s and the 1990s and the seminal works of Elder and colleagues. In the first part the concepts linked to Linked Lives: timing, living in time and place, human agency are described in detail wit

  20. The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Esther J Kuiper

    Full Text Available BACKGROUND: In proliferative diabetic retinopathy (PDR, vascular endothelial growth factor (VEGF and connective tissue growth factor (CTGF cause blindness by neovascularization and subsequent fibrosis, but their relative contribution to both processes is unknown. We hypothesize that the balance between levels of pro-angiogenic VEGF and pro-fibrotic CTGF regulates angiogenesis, the angio-fibrotic switch, and the resulting fibrosis and scarring. METHODS/PRINCIPAL FINDINGS: VEGF and CTGF were measured by ELISA in 68 vitreous samples of patients with proliferative DR (PDR, N = 32, macular hole (N = 13 or macular pucker (N = 23 and were related to clinical data, including degree of intra-ocular neovascularization and fibrosis. In addition, clinical cases of PDR (n = 4 were studied before and after pan-retinal photocoagulation and intra-vitreal injections with bevacizumab, an antibody against VEGF. Neovascularization and fibrosis in various degrees occurred almost exclusively in PDR patients. In PDR patients, vitreous CTGF levels were significantly associated with degree of fibrosis and with VEGF levels, but not with neovascularization, whereas VEGF levels were associated only with neovascularization. The ratio of CTGF and VEGF was the strongest predictor of degree of fibrosis. As predicted by these findings, patients with PDR demonstrated a temporary increase in intra-ocular fibrosis after anti-VEGF treatment or laser treatment. CONCLUSIONS/SIGNIFICANCE: CTGF is primarily a pro-fibrotic factor in the eye, and a shift in the balance between CTGF and VEGF is associated with the switch from angiogenesis to fibrosis in proliferative retinopathy.

  1. Rho-kinase limits FGF-2-stimulated VEGF release in osteoblasts.

    Science.gov (United States)

    Natsume, Hideo; Tokuda, Haruhiko; Adachi, Seiji; Takai, Shinji; Matsushima-Nishiwaki, Rie; Kato, Kenji; Minamitani, Chiho; Niida, Shunpei; Mizutani, Jun; Kozawa, Osamu; Otsuka, Takanobu

    2010-04-01

    We previously reported that basic fibroblast growth factor (FGF-2) stimulates the release of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates the VEGF release in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether Rho-kinase is involved in FGF-2-stimulated VEGF release in MC3T3-E1 cells. FGF-2 induced the phosphorylation of myosin phosphatase targeting subunit (MYPT-1), a substrate of Rho-kinase. Y27632, a specific inhibitor of Rho-kinase, which attenuated the MYPT-1 phosphorylation, significantly enhanced the FGF-2-stimulated VEGF release. Fasudil, another Rho-kinase inhibitor, also amplified the VEGF release. FGF-2 significantly stimulated VEGF accumulation and fasudil enhanced FGF-2-stimulated VEGF accumulation also in whole cell lysates. Neither Y27632 nor fasudil affected the phosphorylation levels of p44/p42 MAP kinase or p38 MAP kinase. Y27632 and fasudil markedly strengthened the FGF-2-induced phosphorylation of SAPK/JNK. Y27632 as well as fasudil enhanced FGF-2-stimulated VEGF release and Y27632 enhanced the FGF-2-induced phosphorylation levels of SAPK/JNK also in human osteoblasts. These results strongly suggest that Rho-kinase negatively regulates FGF-2-stimulated VEGF release in osteoblasts.

  2. Impaired VEGF Signaling in Lungs with Hypoplastic Esophageal Atresia and Effects on Branching Morphogenesis

    Directory of Open Access Journals (Sweden)

    Xiaomei Liu

    2016-07-01

    Full Text Available Background/Aims: Patients with esophageal atresia (EA and tracheoesophageal fistula (TEF often suffer chronic respiratory tract disease. We previously reported that primary lung maldevelopment caused by deficient branching of embryonal airways in experimental EA-TEF was induced by Adriamycin. In this study, we investigated the Vascular endothelial growth factor (VEGF pathway in the developing lung in an EA-TEF rat model. We further analyzed the effect of recombinant VEGF treatment in vitro on branching morphogenesis of embryo lungs in experimental EA-TEF. Methods: Pregnant rats received either Adriamycin or vehicle on E7, E8 and E9. Lungs were recovered at E15, E18 and E21. Expression of VEGF and receptors (Flk-1 and Flt-1 were assessed by quantitative PCR, immunohistochemistry and immunoblotting. E13 lungs were cultured for 72 hours with 50 ng/mL of recombinant rat VEGF in serum-free medium. The rates of increase in bud count and airway contour were evaluated. Results: Our results showed a significant downregulation of VEGF during pseudoglandular and canalicular stages. In contrast, there were significantly higher levels of the Flt-1 receptor in the canalicular stage, which may represent a compensatory response to decreased VEGF. However, both variables returned to normal levels at the saccular stage. Exogenous VEGF treatment enhanced hypoplastic lung growth, evidenced by the increase in bud count and airway contour. Conclusions: A VEGF signaling defect possibly plays an important role in defective embryonic airway branching. Additionally, VEGF treatment may accelerate lung growth in EA-TEF lungs.

  3. A nanobody directed to a functional epitope on VEGF, as a novel strategy for cancer treatment

    International Nuclear Information System (INIS)

    Highlights: • A novel nanobody directed to antigenic regions on VEGF was identified. • Our nanobody was successfully purified. • Our nanobody significantly inhibited VEGF-induced proliferation of HUVECs in a dose dependent manner. - Abstract: Compelling evidence suggests that vascular endothelial growth factor (VEGF), due to its essential role in angiogenesis, is a critical target for cancer treatment. Neutralizing monoclonal antibodies against VEGF are important class of drugs used in cancer therapy. However, the cost of production, large size, and immunogenicity are main drawbacks of conventional monoclonal therapy. Nanobodies are the smallest antigen-binding antibody fragments, which occur naturally in camelidae. Because of their remarkable features, we decided to use an immune library of nanobody to direct phage display to recognition of novel functional epitopes on VEGF. Four rounds of selection were performed and six phage-displayed nanobodies were obtained from an immune phage library. The most reactive clone in whole-cell ELISA experiments, was purified and assessed in proliferation inhibition assay. Purified ZFR-5 not only blocked interaction of VEGF with its receptor in cell ELISA experiments, but also was able to significantly inhibit proliferation response of human umbilical vein endothelial cells to VEGF in a dose-dependent manner. Taken together, our study demonstrates that by using whole-cell ELISA experiments, nanobodies against antigenic regions included in interaction of VEGF with its receptors can be directed. Because of unique and intrinsic properties of a nanobody and the ability of selected nanobody for blocking the epitope that is important for biological function of VEGF, it represents novel potential drug candidate

  4. VEGF-expressing Bone Marrow Mesenchymal Stem Cells Transplantation Improved Heart Function of Myocardial Infarct Rabbits

    Institute of Scientific and Technical Information of China (English)

    Sheng Xiaogang; Song Hui; Feng Jianzhang; Chen Qiuxiong; Wu Shulin

    2006-01-01

    Objectives To treat myocardial infarction with MSCs transplantation combined with VEGF gene therapy in rabbits and to study its mechanisms. Methods Forty-eight rabbits were randomly divided into MI group (n=12), MSCs group (n=12), VEGF group (n=12), MSCs+VEGF group (M+V group, n=12). Rabbit myocardial infarction models were founded by the ligation of left anterior descending artery. 107 MSCs were injected into the infarct-zone in four sites 2 weeks later in MSCs and M+V group. phVEGF gene were injected in infarct-zone in VEGF group and MSCs transfected with phVEGF gene were injected in M+V group. Heart function including LVEDP, LVSP, LVDP, -dp/dtmax, +dp/dtmax, were measured in vivo. The hearts were harvested at 4 weeks after transplantation and sectioned for HE stain,immunohistochemical stain of BrdU and Ⅷ factor antigen. Results The left ventricular hemodynamics parameters showed that heart function were improved more in M+V group than MSCs group, MI group and VEGF group. The numbers of BrdU positive cells in M+V group(61±8)were more than in MSCs group (44±8,P<0.01). The numbers of vessels in infarcted zone were more in M+V group (49±8) than in MSCs group (33±6, P<0.01)、VEGF group(30±8,P<0.01)and MI group (18±4,P<0.01). Conclusions VEGF-expressing MSCs transplantation could improve heart function after myocardial infarction, and they were more effective than sole MSCs transplantation. Keeping more MSCs survival and ameliorating the blood supply of infarct-zone might be involved in the mechanisms.

  5. A nanobody directed to a functional epitope on VEGF, as a novel strategy for cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Farajpour, Zahra [Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Rahbarizadeh, Fatemeh, E-mail: rahbarif@modares.ac.ir [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Kazemi, Bahram [Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ahmadvand, Davoud [School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2014-03-28

    Highlights: • A novel nanobody directed to antigenic regions on VEGF was identified. • Our nanobody was successfully purified. • Our nanobody significantly inhibited VEGF-induced proliferation of HUVECs in a dose dependent manner. - Abstract: Compelling evidence suggests that vascular endothelial growth factor (VEGF), due to its essential role in angiogenesis, is a critical target for cancer treatment. Neutralizing monoclonal antibodies against VEGF are important class of drugs used in cancer therapy. However, the cost of production, large size, and immunogenicity are main drawbacks of conventional monoclonal therapy. Nanobodies are the smallest antigen-binding antibody fragments, which occur naturally in camelidae. Because of their remarkable features, we decided to use an immune library of nanobody to direct phage display to recognition of novel functional epitopes on VEGF. Four rounds of selection were performed and six phage-displayed nanobodies were obtained from an immune phage library. The most reactive clone in whole-cell ELISA experiments, was purified and assessed in proliferation inhibition assay. Purified ZFR-5 not only blocked interaction of VEGF with its receptor in cell ELISA experiments, but also was able to significantly inhibit proliferation response of human umbilical vein endothelial cells to VEGF in a dose-dependent manner. Taken together, our study demonstrates that by using whole-cell ELISA experiments, nanobodies against antigenic regions included in interaction of VEGF with its receptors can be directed. Because of unique and intrinsic properties of a nanobody and the ability of selected nanobody for blocking the epitope that is important for biological function of VEGF, it represents novel potential drug candidate.

  6. Tumor ablation with irreversible electroporation.

    Directory of Open Access Journals (Sweden)

    Bassim Al-Sakere

    Full Text Available We report the first successful use of irreversible electroporation for the minimally invasive treatment of aggressive cutaneous tumors implanted in mice. Irreversible electroporation is a newly developed non-thermal tissue ablation technique in which certain short duration electrical fields are used to permanently permeabilize the cell membrane, presumably through the formation of nanoscale defects in the cell membrane. Mathematical models of the electrical and thermal fields that develop during the application of the pulses were used to design an efficient treatment protocol with minimal heating of the tissue. Tumor regression was confirmed by histological studies which also revealed that it occurred as a direct result of irreversible cell membrane permeabilization. Parametric studies show that the successful outcome of the procedure is related to the applied electric field strength, the total pulse duration as well as the temporal mode of delivery of the pulses. Our best results were obtained using plate electrodes to deliver across the tumor 80 pulses of 100 micros at 0.3 Hz with an electrical field magnitude of 2500 V/cm. These conditions induced complete regression in 12 out of 13 treated tumors, (92%, in the absence of tissue heating. Irreversible electroporation is thus a new effective modality for non-thermal tumor ablation.

  7. Estimation of Immunohistochemical Expression of VEGF in Ductal Carcinomas of the Breast

    DEFF Research Database (Denmark)

    Maae, Else; Nielsen, Martin; Dahl Steffensen, Karina;

    2011-01-01

    Vascular endothelial growth factor A (VEGF-A) is a very important growth factor in angiogenesis and holds the potential as both a predictive marker for anti-angiogenic cancer treatment and as a prognostic variable. Consequently, reliable estimation of VEGF expression is crucial. We immunostained...... delineation of the tumor area. We found that the AI scores were correlated to the manual scoring of VEGF intensity, but reproducibility of manual IHC scores was rather poor. The AI scores were reproducible and the restricted analysis of 25% of the tumor area at 5x magnifications was the most efficient...

  8. Semaphorin 3A suppresses VEGF-mediated angiogenesis yet acts as a vascular permeability factor

    OpenAIRE

    Acevedo, Lisette M; Barillas, Samuel; Weis, Sara M.; Göthert, Joachim R.; Cheresh, David A.

    2008-01-01

    Semaphorin 3A (Sema3A), a known inhibitor of axonal sprouting, also alters vascular patterning. Here we show that Sema3A selectively interferes with VEGF- but not bFGF-induced angiogenesis in vivo. Consistent with this, Sema3A disrupted VEGF- but not bFGF-mediated endothelial cell signaling to FAK and Src, key mediators of integrin and growth factor signaling; however, signaling to ERK by either growth factor was unperturbed. Since VEGF is also a vascular permeability (VP) factor, we examined...

  9. Insulin directly stimulates VEGF-A production in the glomerular podocyte

    OpenAIRE

    Hale, L. J.; Hurcombe, J.; Lay, A.; Santamaría, B.; Valverde, A M; Saleem, M A; Mathieson, P. W.; Welsh, G. I.; Coward, R. J.

    2013-01-01

    Podocytes are critically important for maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Recently, it has become clear that to achieve this, they need to be insulin sensitive and produce an optimal amount of VEGF-A. In other tissues, insulin has been shown to regulate VEGF-A release, but this has not been previously examined in the podocyte. Using in vitro and in vivo approaches, in the present study, we now show that insulin regulates VEGF-A in the po...

  10. Relationship between the Expression of VEGF, FIk-1 and Fit-1 Proteins and Clinicopcrthology in Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    JihuiHao; HuikaiLi; YuQin; QiangLi; DianchangWang; XishanHao

    2004-01-01

    OBJECTIVE To study the relationship between the expression of VEGF, FIk-1 and Fit-1 proteins and clinical pathology in hepatocellular carcinoma.METHODS The expression of VEGF, FIk-1 and Fit-1 proteins in hepatocellular carcinomas from 60 patients was determined by immunohistochemistry (ABC method) and VEGF expression in relation to the clinicopathology evaluated.RESULTS The positive rates of VEGF, FIk-1 and Fit-1 protein expression were 81.3%, 88.3%, 80.0% in tumor tissues, respectively, rates which were significantly higher than those in normal liver tissue (P<0.05). The expression of VEGF protein was correlated with the histologic grade and metastases of the tumors.CONCLUSION The results showed that, in hepatocellular carcinoma, a higher expression of VEGF protein was associated with a higher degree of malignancy and a greater tendency for metastases. VEGF, FIk-1 and Fit-1 play an important role in tumourgenesis.

  11. Expression of VEGF-c and VEGFR-3 in Breast Cancer%VEGF-C及VEGFR-3在乳腺癌中的表达

    Institute of Scientific and Technical Information of China (English)

    李庆

    2011-01-01

    目的 探讨乳腺癌中血管内皮生长因子-C(VEGF-C)、血管内皮生长因子受体-3(VEGFR-3)的表达及与淋巴管生成的关系.方法 采用免疫组化SP法检测57例乳腺癌组织中VEGF-C及VEGFR-3的表达,并在显微镜下记数VEGFR-3标记的脉管.结果 淋巴结转移组VEGF-C的阳性率(90.48%)显著高于无淋巴结转移组(47.22%)(P<0.05);淋巴结转移组VEGFR-3阳性脉管数(7.62士1.18)显著高于无淋巴结转移组(5.27士0.96)(P<0.05); VEGF-C的阳性表达与VEGFR-3阳性脉管数呈正相关,相关系数为r为0.882 (P<0.05).结论VEGF-C及VEGFR-3与乳腺癌的生长,淋巴管的生长及淋巴结的转移有关.

  12. Identification and function analysis of a novel vascular endothelial growth factor, LvVEGF3, in the Pacific whiteleg shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Wang, Zhiwei; Li, Shihao; Li, Fuhua; Xie, Shijun; Xiang, Jianhai

    2016-10-01

    VEGF signaling pathway is first discovered in mammals and proved to play important roles in the biological processes of angiogenesis, tumor migration, cell differentiation, apoptosis, host-virus interaction etc. Three members in the VEGF signaling pathway, including LvVEGFR, LvVEGF1 and LvVEGF2 in shrimp have been proved to be related with WSSV infection in our previous studies. Currently, another member of VEGF family, LvVEGF3, was isolated and its function during the WSSV infection of shrimp was studied. The deduced amino acid sequence of LvVEGF3 contained a signal peptide, a typical PDGF/VEGF domain and a cysteine-knot motif (CXCXC). Tissue distribution analysis showed that LvVEGF3 was predominantly expressed in hemocytes. The transcriptional level of LvVEGF3 in hemocytes was apparently up-regulated during WSSV infection. Silencing of LvVEGF3 with double-stranded RNA caused a reduction of the cumulative mortality rate of shrimp during WSSV infection. The expression of LvVEGFR was apparently down-regulated after LvVEGF3 silencing and up-regulated after injection of recombinant LvVEGF3 protein, suggesting an interaction between LvVEGF3 and LvVEGFR. Furthermore, the interaction between LvVEGFR and LvVEGF3 was confirmed using the yeast two-hybrid system. The results provided new insights into understanding the role of VEGF signaling pathway during virus infection. PMID:27241034

  13. Vascular Endothelial Growth Factor (VEGF) Bioavailability Regulates Angiogenesis and Intestinal Stem and Progenitor Cell Proliferation during Postnatal Small Intestinal Development

    Science.gov (United States)

    Holoyda, Kathleen A.; Hou, Xiaogang; Fowler, Kathryn L.; Grikscheit, Tracy C.

    2016-01-01

    Background Vascular endothelial growth factor (VEGF) is a highly conserved, master regulatory molecule required for endothelial cell proliferation, organization, migration and branching morphogenesis. Podocoryne carnea and drosophila, which lack endothelial cells and a vascular system, express VEGF homologs, indicating potential roles beyond angiogenesis and vasculogenesis. The role of VEGF in the development and homeostasis of the postnatal small intestine is unknown. We hypothesized regulating VEGF bioavailability in the postnatal small intestine would exhibit effects beyond the vasculature and influence epithelial cell stem/progenitor populations. Methods VEGF mutant mice were created that overexpressed VEGF in the brush border of epithelium via the villin promotor following doxycycline treatment. To decrease VEGF bioavailability, sFlt-1 mutant mice were generated that overexpressed the soluble VEGF receptor sFlt-1 upon doxycycline administration in the intestinal epithelium. Mice were analyzed after 21 days of doxycycline administration. Results Increased VEGF expression was confirmed by RT-qPCR and ELISA in the intestine of the VEGF mutants compared to littermates. The VEGF mutant duodenum demonstrated increased angiogenesis and vascular leak as compared to littermate controls. The VEGF mutant duodenum revealed taller villi and increased Ki-67-positive cells in the transit-amplifying zone with reduced Lgr5 expression. The duodenum of sFlt-1 mutants revealed shorter villi and longer crypts with reduced proliferation in the transit-amplifying zone, reduced expression of Dll1, Bmp4 and VE-cadherin, and increased expression of Sox9 and EphB2. Conclusions Manipulating VEGF bioavailability leads to profound effects on not only the intestinal vasculature, but epithelial stem and progenitor cells in the intestinal crypt. Elucidation of the crosstalk between VEGF signaling in the vasculature, mesenchyme and epithelial stem/progenitor cell populations may direct future

  14. Neural Ablation and Regeneration in Pain Practice.

    Science.gov (United States)

    Choi, Eun Ji; Choi, Yun Mi; Jang, Eun Jung; Kim, Ju Yeon; Kim, Tae Kyun; Kim, Kyung Hoon

    2016-01-01

    A nerve block is an effective tool for diagnostic and therapeutic methods. If a diagnostic nerve block is successful for pain relief and the subsequent therapeutic nerve block is effective for only a limited duration, the next step that should be considered is a nerve ablation or modulation. The nerve ablation causes iatrogenic neural degeneration aiming only for sensory or sympathetic denervation without motor deficits. Nerve ablation produces the interruption of axonal continuity, degeneration of nerve fibers distal to the lesion (Wallerian degeneration), and the eventual death of axotomized neurons. The nerve ablation methods currently available for resection/removal of innervation are performed by either chemical or thermal ablation. Meanwhile, the nerve modulation method for interruption of innervation is performed using an electromagnetic field of pulsed radiofrequency. According to Sunderland's classification, it is first and foremost suggested that current neural ablations produce third degree peripheral nerve injury (PNI) to the myelin, axon, and endoneurium without any disruption of the fascicular arrangement, perineurium, and epineurium. The merit of Sunderland's third degree PNI is to produce a reversible injury. However, its shortcoming is the recurrence of pain and the necessity of repeated ablative procedures. The molecular mechanisms related to axonal regeneration after injury include cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules, and their receptors. It is essential to establish a safe, long-standing denervation method without any complications in future practices based on the mechanisms of nerve degeneration as well as following regeneration. PMID:26839664

  15. 肾细胞癌组织中 VEGF 和 PDGF 的表达%Expressions of VEGF and PDGF in the Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    姜春霞

    2015-01-01

    Objective To investigate the expressions and clinical significance of vascular endothelial growth fac-tor(VEGF)and platelet-derived growth factor(PDGF)in the renal cell carcinoma. Methods Immunohistochemistry S-P method was used to detect the expressions of VEGF and PDGF in the 50 cases of renal cell carcinoma and the 25 cases of paraneoplastic normal renal tissue. The relationship between clinicopathological features and VEGF and PDGF were analyzed. Results The positive rate of VEGF and PDGF were 76. 00% and 78. 00% in the renal cell carcinoma,and were 8. 00% and 4. 00% in the paraneoplastic normal renal tissue(P ﹤ 0. 05). The expressions of VEGF and PDGF in the renal cell carcinoma were related with the lymph node metastasis,pathological cell differen-tiation degree and clinical stage(P ﹤ 0. 05). The expressions of VEGF was positively related with PDGF in the renal cell carcinoma(r = 0. 606,P ﹤ 0. 05). Conclusion The high expressions of VEGF and PDGF are related to the progression of renal cell carcinoma,detection of them can be used to guide the targeted therapy and prognosis of re-nal cell carcinoma.%目的:探讨肾细胞癌组织中血管内皮生长因子( VEGF)和血小板衍生生长因子(PDGF)的表达及临床意义。方法采用免疫组化 S-P 法检测50例肾细胞癌和25例癌旁正常肾脏组织中 VEGF 和 PDGF 的表达,并分析两者与肾细胞癌临床病理参数的关系。结果肾细胞癌组织中 VEGF 和 PDGF 的阳性表达率分别为76.00%、78.00%,均高于癌旁正常膀胱组织的8.00%、4.00%(P 均﹤0.05)。肾细胞癌组织中VEGF 和 PDGF 的表达与其淋巴结转移、病理分化程度和临床分期有关(P 均﹤0.05)。肾细胞癌组织中VEGF 和 PDGF 的表达呈正相关关系(r =0.606,P ﹤0.05)。结论肾细胞癌组织中 VEGF 和 PDGF 存在高表达,对其疾病进展具有促进作用,且两者的检测可用于肾细胞癌的预后评估和靶向治疗药物疗效的监测指标。

  16. Cloning and Prokaryotic Expression of VEGF-SLC Fusion Gene%VEGF-SLC融合基因的克隆与原核表达

    Institute of Scientific and Technical Information of China (English)

    蒋攀; 陈全; 郑毅; 刘革力; 张璐瑜

    2011-01-01

    目的 构建血管内皮生长因子(Vascular endothelial growthfactor,VEGF)-次级淋巴组织趋化因子(Secondary lymphoid-fissue chemokine,SLC)融合基因(VEGF-SLC)的原核表达质粒,表达并纯化重组VEGF-SLC融合蛋白.方法 利用Gene SOEing法扩增VEGF-SLC基因,将融合基因插入载体pQE30,构建重组表达质粒pQE30-VEGF-SLC,转化大肠杆菌M15,IPTG诱导表达.表达产物经SDS-PAGE和Western blot鉴定后,用Ni-Agarose His标签蛋白纯化试剂盒纯化.结果 重组表达质粒经双酶切和测序证明构建正确;表达的重组融合蛋白相对分子质量约28 000,诱导5 h表达量最高,约占菌体总蛋白的19%,主要以包涵体形式存在,可与鼠抗人VEGF单抗特异性结合;纯化的重组融合蛋白纯度可达90%以上.结论 已成功在大肠杆菌中表达并纯化了重组VEGF-SLC融合蛋白,为进一步研究其生物学活性及其靶向抗肿瘤效应以及开发肺癌等肿瘤的靶向生物制剂奠定了基础.%Objective To construct a prokaryotic expression vector for vascular endothelial growth factor (VEGF)-secondary lymphoid-tissue chemokine (SLC) fusion gene and purify the expressed fusion protein. Methods VEGF-SLC gene was amplified by Gene SOEing and inserted into vector pQE30. The constructed recombinant plasmid pQE30-VEGF-SLC was transformed to E. coli M15 for expression under induction of IPTG. The expressed product was identified by SDS-PAGE and Western blot, then purified by Ni-Agarose His-tagged protein purification kit. Results Both restriction analysis and sequencing proved that recombinant plasmid pQE30-VEGF-SLC was constructed correctly. The relative molecular mass of expressed recombinant fusion protein was about 28 000.The expression level reached a peak value 5 h after induction, which accounted for about 19% of total somatic protein. The expressed product mainly existed in a form of inclusion body, showed specific binding to mouse anti-human VEGF monoclonal antibody, and

  17. An experimental study of simultaneous ablation with dual probes in radiofrequency thermal ablation

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Il Soo; Rhim, Hyun Chul; Koh, Byung Hee; Cho, On Koo; Seo, Heung Suk; Kim, Yong Soo; Kim, Young Sun; Heo, Jeong Nam [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2003-02-01

    To determine the differences between sequential ablation with a single probe and simultaneous ablation with dual probes. Using two 14-gauge expandable probes (nine internal prongs with 4-cm deployment), radiofrequency was applied sequentially (n=8) or simultaneously (n=8) to ten ex-vivo cow livers. Before starting ablation, two RF probes with an inter-probe space of 2 cm (n=8) or 3 cm (n=8) were inserted. In the sequential group, switching the connecting cable to an RF generator permitted ablation with the second probe just after ablation with the first probe had finished. In the simultaneous group, single ablation was performed only after connecting the shafts of both RF probes using a connection device. Each ablation lasted 7 minutes at a target temperature of 105-110 .deg. C. The size and shape of the ablated area, and total ablation time were then compared between the two groups. With 2-cm spacing, the group, mean length and overlapping width of ablated lesions were, respectively, 5.20 and 5.05 cm in the sequential group (n=4), and 5.81 and 5.65 cm in the simultaneous group (n=4). With 3-cm spacing, the corresponding figures were 4.99 and 5.60 cm in the sequential group (n=4), and 6.04 and 6.78 cm in the simultaneous group (n=4). With 2-cm spacing, the mean depth of the proximal waist was 0.58 cm in the sequential (group and 0.28 cm in the simultaneous group, while with 3-cm spacing, the corresponding figures were 1.65 and 1.48 cm. In neither group was there a distal waist. Mean total ablation time was 23.4 minutes in the sequential group and 14 minutes in the simultaneous group. In terms of ablation size and ablation time, simultaneous radiofrequency ablation with dual probes is superior to sequential ablation with a single probe. A simultaneous approach will enable an operator to overcome difficulty in probe repositioning during overlapping ablation, resulting in complete ablation with a successful safety margin.

  18. Anti-VEGF agents in the treatment of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Vladimir Iosifovich Konenkov

    2013-12-01

    Full Text Available Diabetic macular edema (DME is a common complication associated with the loss of visual acuity in diabetic patients. Intravitreal injections of vascular endothelium growth factor (VEGF inhibitors (anti-VEGF therapy have been proposed recently as a new treatment option for patients with DME. In this review we summarized results of randomized clinical trials of VEGF inhibitors in DME patients. The results indicate that all studied inhibitors (ranibizumab, bevacizumab, pegaptanib and aflibersept reduce the retinal thickness and improve of visual acuity in DME when are used as a monotherapy or in combination with the laser treatment. Optimal course duration and effectiveness predictors of anti-VEGF therapy in DME should be elucidate in the future studies.

  19. Urethral tissue regeneration using collagen scaffold modified with collagen binding VEGF in a beagle model.

    Science.gov (United States)

    Jia, Weisheng; Tang, He; Wu, Jianjian; Hou, Xianglin; Chen, Bing; Chen, Wei; Zhao, Yannan; Shi, Chunying; Zhou, Feng; Yu, Wei; Huang, Shengquan; Ye, Gang; Dai, Jianwu

    2015-11-01

    Extensive urethral defects have a serious impact on quality of life, and treatment is challenging. A shortage of material for reconstruction is a key limitation. Improving the properties of biomaterials and making them suitable for urethral reconstruction will be helpful. Previously, we constructed a fusion protein, collagen-binding VEGF (CBD-VEGF), which can bind to collagen scaffold, stimulate cell proliferation, and promote angiogenesis and tissue regeneration. We proposed that CBD-VEGF could improve the performance of collagen in reconstruction of extensive urethral defects. Our results showed that collagen scaffolds modified with CBD-VEGF could promote urethral tissue regeneration and improve the function of the neo-urethra in a beagle extensive urethral defect model. Thus, modifying biomaterials with bioactive factors provides an alternative strategy for the production of suitable biomaterials for urethral reconstruction.

  20. VEGF concentrations in tumour arteries and veins from patients with rectal cancer

    DEFF Research Database (Denmark)

    Werther, Kim; Bülow, Steffen; Hesselfeldt, Peter;

    2002-01-01

    , automated complete white cell and platelet counts were performed. In serum and EDTA plasma, no significant differences in VEGF concentrations were observed (p = 0.1 and p = 0.5), respectively) between tumour arteries and tumour veins. However, in supernatants from lysed blood, VEGF concentrations were......This pilot study investigated the hypothesis that the tumour itself is the source of the elevated vascular endothelial growth factor (VEGF) concentrations which are often observed in peripheral blood from patients with rectal cancer. Twenty-four consecutive patients with primary rectal cancer were...... included. Blood samples were drawn preoperatively from peripheral veins (I) and intraoperatively from peripheral veins (II), tumour arteries (III), and tumour veins (IV). In the four compartments, VEGF concentrations were measured in serum, EDTA plasma, and supernatants from lysed whole blood. Additionally...

  1. Tnactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ye-Jiang Zhou; Yu-Xia Xiong; Xiao-Ting Wu; De Shi; Wei Fan; Tong Zhou; Yue-Chun Li; Xiong Huang

    2004-01-01

    AIM: To investigate the expression of PTEN/MMAC1/TEP1and vascular endothelial growth factor (VEGF), their roles in biologic behavior and angiogenesis and their association in gastric cancer.METHODS: Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF and microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial gastritis (CSG). Expression of PTEN, VEGF and MVD were compared with clinicopathological features of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated.RESULTS: PTEN expression significantly decreased (t= 3.98,P<0.01) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P<0.01)in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t = 1.95,P<0.05) whereas VEGF expression (t = 2.37, P<0.05) and MVD (t = 3.28, P<0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t= 3.91, P<0.01),invasion depth (t= 1.95, P<0.05) and age (t= 4.69, P<0.01).MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer (t = 3.69,P<0.01), and there was a negative correlation between PTEN expression and MVD (γ = -0.363, P<0.05). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P<0.01), lymph node metastasis (t= 2.31, P<0.05) and TNM stage (t= 3.04,P<0.01). MVD in VEGF-positive gastric cancer was significantly higher than that in VEGF-negative gastric cancer (t = 4.62,P<0.01), and there was a positive correlation between VEGF expression of and MVD (γ = 0.512, P<0.05). VEGF expression in PTEN

  2. Study on VEGF, bFGF and TGF-β1 in the Endometriumof Norplant Users

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To investigate the relationship between abnormal uterus bleeding and en dometrium vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) as well as transforming growth factor-β1(TGF-β1) expressions among Nor plant users. Materials & Methods Thirty-six endometrium samples from Norplant users with nor mal and abnormal bleeding were studied morphologically and immunohistochemically for VEGF, bFGF and TGF-β1 expression. Six normal samples of proliferate endome tria were studied as control. Results In the Norplant users, the characteristics of endometrium changed and glands decreased in numbers. The VEGF expression in epithelium and vascular en dothelium was lower in those with abnormal uterine bleeding. However, no difference was detected on bFGF and TGF-β1 expression. Conclusion The decline of VEGF expression may relate to the abnormal uterine bleed ing in Norplant users.

  3. Impact of VEGF and VEGF receptor 1 (FLT1) expression on the prognosis of stage III esophageal cancer patients after radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D. [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf (Germany); Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Luebeck (Germany); Golke, H. [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf (Germany); Inst. of Pathology, Univ. Medical Center Hamburg-Eppendorf (Germany); Schild, S.E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Kilic, E. [Inst. of Pathology, Univ. Medical Center Hamburg-Eppendorf (Germany); Inst. of Pathology, Univ. Hospital Basel-Stadt (Switzerland)

    2008-08-15

    Background and purpose: high expression of vascular endothelial growth factor (VEGF) is negatively associated with clinical outcome. The prognostic value of VEGF receptor 1 (FLT1) is unclear. This retrospective study investigated the impact of tumor expression of VEGF and FLT1 on outcome in 68 stage III esophageal cancer patients. Material and methods: the impact of tumor VEGF and FLT expression (< 10% vs. > 10%) and five additional potential prognostic factors on overall survival (OS) and locoregional control (LC) was retrospectively evaluated. These factors included T-stage (T3 vs. T4), N-stage (NO vs. N1), treatment (radiochemotherapy plus resection vs. radiochemotherapy alone), erythropoietin (ERYPO {sup registered} 10000, Janssen-Cilag, Neuss, Germany) administration during radiotherapy, and majority of hemoglobin levels during radiotherapy (< 12 vs. {>=} 12 g/dl). Subgroup analyses were performed for patients receiving resection (R0 vs. R1/2 resection). The factors found to be significant on univariate analyses (Kaplan-Meier method, log-rank test) were included in multivariate analyses performed with the Cox proportional hazard model. Results: on univariate analysis, improved OS was associated with T3 stage (p = 0.011), surgery (p = 0.019), and hemoglobin {>=} 12 g/dl (p < 0.001). Improved LC was associated with T3 stage (p = 0.025), hemoglobin {>=} 12 g/dl (p < 0.001), and VEGF negativity (p = 0.045). On multivariate analyses, only hemoglobin maintained significance. In patients having surgery, R0 resection was significantly better than R1/2 resection for OS (p < 0.001) and LC (p < 0.001). Conclusion: preradiotherapy tumor VEGF expression appears negatively correlated with outcomes, whereas FLT1 expression appears to have no significant impact on OS and LC. (orig.)

  4. Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF gene therapy

    Directory of Open Access Journals (Sweden)

    Haninec Pavel

    2012-06-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF is not only a potent angiogenic factor but it also promotes axonal outgrowth and proliferation of Schwann cells. The aim of the present study was to quantitatively assess reinnervation of musculocutaneous nerve (MCN stumps using motor and primary sensory neurons after plasmid phVEGF transfection and end-to-end (ETE or end-to-side (ETS neurorrhaphy. The distal stump of rat transected MCN, was transfected with plasmid phVEGF, plasmid alone or treated with vehiculum and reinnervated following ETE or ETS neurorrhaphy for 2 months. The number of motor and dorsal root ganglia neurons reinnervating the MCN stump was estimated following their retrograde labeling with Fluoro-Ruby and Fluoro-Emerald. Reinnervation of the MCN stumps was assessed based on density, diameter and myelin sheath thickness of regenerated axons, grooming test and the wet weight index of the biceps brachii muscles. Results Immunohistochemical detection under the same conditions revealed increased VEGF in the Schwann cells of the MCN stumps transfected with the plasmid phVEGF, as opposed to control stumps transfected with only the plasmid or treated with vehiculum. The MCN stumps transfected with the plasmid phVEGF were reinnervated by moderately higher numbers of motor and sensory neurons after ETE neurorrhaphy compared with control stumps. However, morphometric quality of myelinated axons, grooming test and the wet weight index were significantly better in the MCN plasmid phVEGF transfected stumps. The ETS neurorrhaphy of the MCN plasmid phVEGF transfected stumps in comparison with control stumps resulted in significant elevation of motor and sensory neurons that reinnervated the MCN. Especially noteworthy was the increased numbers of neurons that sent out collateral sprouts into the MCN stumps. Similarly to ETE neurorrhaphy, phVEGF transfection resulted in significantly higher morphometric quality of myelinated axons

  5. Establishment of a recombinant adeno-associated virus expressing hVEGF165

    Institute of Scientific and Technical Information of China (English)

    Xianghui Huang; Zhibin Shi; Xiaoqian Dang; Chen Zhang; Pengbo Yu; Kunzheng Wang

    2008-01-01

    BACKGROUND: Because certain gene vectors could have deleterious effects in the central nervous system, the choice of a safe and effective vector system has become more important for gene therapy of nerve regeneration. OBJECTIVE: To construct a non-pathogenic, recombinant adeno-associated virus (AAV) simultaneously expressing human vascular endothelial growth factor 165 (hVEGF165) and green fluorescent protein (GFP). DESIGN, TIME AND SETTING: A randomized controlled experiment was performed at the Virology Laboratory of Shaanxi Provincial Center for Disease Control and Prevention between March and September 2007. MATERIALS: AAV helper-free system, AAV-293 packaging cell line, and AAV HT-1080 cells were purchased from Stratagene, USA. E. Coli DH5α was a stocked strain from Centers for Disease Control and Prevention of Shaanxi, China. Plasmid pUC18-hHVEGF165 was a gift from Zhibin Shi. METHODS: The hVEGF165 gene was amplified by PCR from pUC18-hHVEGF165 and inserted into plasmid pAAV-IRES-hrGFP to construct recombinant plasmid pAAV-hVEGF165-IRES-hrGFP. Subsequently pAAV-hVEGF165-IRES-hrGFP, pAAV-RC (the rep/cap-gene containing plasmid), and pHelper were co-transfected into AAV-293 cells to complete rAAV-hVEGF165-IRES-hrGFP packaging through homologous recombination. The efficiency of AAV packaging was monitored under a fluorescent microscope, and the recombinant viral particles were harvested from infected AAV-293 cells, and further concentrated and purified. AAV HT-1080 cells were infected with the recombinant virus AAV-hVEGF165-IRES-hrGFP. MAIN OUTCOME MEASURES: Recombinant virus titer was measured by fluorescent cell counting, and infection efficiency was detected by Fluorescence Activated Cell Sorter (FACS) upon infecting AAV-HT1080 cells. The recombination with the exogenous gene was verified by PCR. RESULTS: The PCR amplified products were verified as hVEGF165 gene by DNA sequencing, and the recombinant pAAV-hVEGF165-IRES-GFP was confirmed by double digestion

  6. Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF)

    International Nuclear Information System (INIS)

    Background: Tissue hypoxia is a major stimulus for the up-regulation of vascular endothelial growth factor (VEGF). Anemia might theoretically impact on angiogenesis via impairment of tissue oxygenation. We have investigated this hypothesis in patients with solid cancers and benign diseases. Patients and methods: 49 patients with untreated locoregionally confined solid cancers of the head and neck, cervix, rectum and lung and 59 additional patients with non-malignant diseases (36 normemic patients without serious diseases and 23 patients with renal anemia) were enrolled and the impact of anemia on plasma VEGF levels were determined. VEGF was measured with a commercially available sandwich enzyme immunoassay technique. Results: Plasma levels of VEGF were 16.2±12.7 pg/ml in 36 normemic patients without malignant disease, 49,2±34.5 pg/ml in 49 patients with cancers (p<0.001), and 89.9±67.8 pg/ml in 23 patients with renal anemia (p=0.001). VEGF levels in cancer patients were significantly correlated with hemoglobin (hb) levels and platelet counts (each p=0.001), but not with type of tumor, stage, histology or age. Patients with cancers had higher plasma levels of VEGF than patients with non-malignant diseases in case of hb≥12 g/dl (33.1±17.5 vs. 16.6±13.0 pg/ml, p<0.001) and in case of hb between 11.0 and 11.9 g/dl (56.1±26.4 vs 18.5±14.5 pg/ml, p=0.038). In case of a hb<11 g/dl, plasma VEGF levels were significantly elevated in patients with and without cancers (67.0±47.5 vs 88.9±68.8 pg/ml, n.s.). In a multivariate model, a significant association between low hb levels and increased plasma levels of VEGF was confirmed. In 16 patients with renal anemia, changes in hb under erythropoietin treatment were inversely correlated with changes in plasma VEGF levels with decreasing VEGF after increase in hb (p=0.01). Conclusions: Anemic patients have elevated levels of VEGF. The data suggest that anemia might impact on the progression of angiogenesis in malignant and

  7. Laser induced ablation studies from gold target

    International Nuclear Information System (INIS)

    Laser produced gold plasmas show an enhanced mass ablation rate and ablation pressure as compared to theoretical prediction. This is attributed to radiation effect. Experimental results indicate an increase in the C-J point density and an agreement with self-regulating ablation scaling. Using 1.06 μm laser radiation on 12.5 μm thick planar gold targets, at an absorbed laser intensity IA ≤ 2 x 1013 W/cm2, the experimental results are presented. (Author)

  8. Atrioventricular Junction Ablation for Atrial Fibrillation.

    Science.gov (United States)

    Patel, Dilesh; Daoud, Emile G

    2016-04-01

    Atrioventricular junction (AVJ) ablation is an effective therapy in patients with symptomatic atrial fibrillation who are intolerant to or unsuccessfully managed with rhythm control or medical rate control strategies. A drawback is that the procedure mandates a pacing system. Overall, the safety and efficacy of AVJ ablation is high with a majority of the patients reporting significant improvement in symptoms and quality-of-life measures. Risk of sudden cardiac death after device implantation is low, especially with an appropriate postprocedure pacing rate. Mortality benefit with AVJ ablation has been shown in patients with heart failure and cardiac resynchronization therapy devices. PMID:26968669

  9. Ablation response testing of aerospace power supplies

    Science.gov (United States)

    Lutz, S. A.; Chan, C. C.

    1993-01-01

    An experimental program was performed to assess the aerothermal ablation response of aerospace power supplies. Full-scale General Purpose Heat Source (GPHS) test articles, Graphite Impact Shell (GIS) test articles, and Lightweight Radioisotope Heater Unit (LWRHU) test articles were all tested without nuclear fuel in simulated reentry environments at the NASA Ames Research Center. Stagnation heating, stagnation pressure, stagnation surface temperature, stagnation surface recession profile, and weight loss measurements were obtained for diffusion-limited and sublimation ablation conditions. The recession profile and weight loss measurements showed an effect of surface features on the stagnation face. The surface features altered the local heating which in turn affected the local ablation.

  10. How I do it: Radiofrequency ablation

    International Nuclear Information System (INIS)

    Over the past decade, image-guided tumor ablation using thermal energy has emerged as a promising technique for treating focal, primary or secondary, nonoperable tumors. Radiofrequency ablation (RFA) is minimally invasive and requires less resources, time, and recovery period and is, moreover, relatively inexpensive. RFA has been used to treat tumors located in the liver, lung, bone, kidneys, brain, thyroid, breast, and pancreas. This article will describe how to choose an appropriate case; precisely place the needle into the tumor; the precautions to be taken before, during, and after the procedure; probable complications; and the follow-up of patients undergoing ablation

  11. The Atrial Fibrillation Ablation Pilot Study

    DEFF Research Database (Denmark)

    Arbelo, Elena; Brugada, Josep; Hindricks, Gerhard;

    2014-01-01

    was achieved in 40.7% of patients (43.7% in paroxysmal AF; 30.2% in persistent AF; 36.7% in long-lasting persistent AF). A second ablation was required in 18% of the cases and 43.4% were under antiarrhythmic treatment. Thirty-three patients (2.5%) suffered an adverse event, 272 (21%) experienced a left atrial...... tachycardia, and 4 patients died (1 haemorrhagic stroke, 1 ventricular fibrillation in a patient with ischaemic heart disease, 1 cancer, and 1 of unknown cause). CONCLUSION: The AFib Ablation Pilot Study provided crucial information on the epidemiology, management, and outcomes of catheter ablation of AFib...

  12. Elevated SP-1 Transcription Factor Expression and Activity Drives Basal and Hypoxia-induced Vascular Endothelial Growth Factor (VEGF) Expression in Non-Small Cell Lung Cancer

    OpenAIRE

    Deacon, Karl; Onion, David; Kumari, Rajendra; Watson, Susan A.; Knox, Alan J

    2012-01-01

    VEGF plays a central role in angiogenesis in cancer. Non-small cell lung cancer (NSCLC) tumors have increased microvascular density, localized hypoxia, and high VEGF expression levels; however, there is a lack of understanding of how oncogenic and tumor microenvironment changes such as hypoxia lead to greater VEGF expression in lung and other cancers. We show that NSCLC cells secreted higher levels of VEGF than normal airway epithelial cells. Actinomycin D inhibited all NSCLC VEGF secretion, ...

  13. Investigation of different liquid media and ablation times on pulsed laser ablation synthesis of aluminum nanoparticles

    International Nuclear Information System (INIS)

    Aluminum nanoparticles were synthesized by pulsed laser ablation of Al targets in ethanol, acetone, and ethylene glycol. Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM) images, Particle size distribution diagram from Laser Particle Size Analyzer (LPSA), UV-visible absorption spectra, and weight changes of targets were used for the characterization and comparison of products. The experiments demonstrated that ablation efficiency in ethylene glycol is too low, in ethanol is higher, and in acetone is highest. Comparison between ethanol and acetone clarified that acetone medium leads to finer nanoparticles (mean diameter of 30 nm) with narrower size distribution (from 10 to 100 nm). However, thin carbon layer coats some of them, which was not observed in ethanol medium. It was also revealed that higher ablation time resulted in higher ablated mass, but lower ablation rate. Finer nanoparticles, moreover, were synthesized in higher ablation times.

  14. Investigation of different liquid media and ablation times on pulsed laser ablation synthesis of aluminum nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Baladi, Arash [Materials Engineering Department, Tarbiat Modares University, Jalal Al Ahmad, P.O. Box 14115-143, Tehran (Iran, Islamic Republic of); Sarraf Mamoory, Rasoul, E-mail: rsarrafm@modares.ac.ir [Materials Engineering Department, Tarbiat Modares University, Jalal Al Ahmad, P.O. Box 14115-143, Tehran (Iran, Islamic Republic of)

    2010-10-01

    Aluminum nanoparticles were synthesized by pulsed laser ablation of Al targets in ethanol, acetone, and ethylene glycol. Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM) images, Particle size distribution diagram from Laser Particle Size Analyzer (LPSA), UV-visible absorption spectra, and weight changes of targets were used for the characterization and comparison of products. The experiments demonstrated that ablation efficiency in ethylene glycol is too low, in ethanol is higher, and in acetone is highest. Comparison between ethanol and acetone clarified that acetone medium leads to finer nanoparticles (mean diameter of 30 nm) with narrower size distribution (from 10 to 100 nm). However, thin carbon layer coats some of them, which was not observed in ethanol medium. It was also revealed that higher ablation time resulted in higher ablated mass, but lower ablation rate. Finer nanoparticles, moreover, were synthesized in higher ablation times.

  15. Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population

    DEFF Research Database (Denmark)

    Kjaer-Frifeldt, Sanne; Fredslund, Rikke; Lindebjerg, Jan;

    2012-01-01

    To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients.......To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients....

  16. Moderation of calpain activity promotes neovascular integration and lumen formation during VEGF-induced pathological angiogenesis.

    Directory of Open Access Journals (Sweden)

    Mien V Hoang

    Full Text Available BACKGROUND: Successful neovascularization requires that sprouting endothelial cells (ECs integrate to form new vascular networks. However, architecturally defective, poorly integrated vessels with blind ends are typical of pathological angiogenesis induced by vascular endothelial growth factor-A (VEGF, thereby limiting the utility of VEGF for therapeutic angiogenesis and aggravating ischemia-related pathologies. Here we investigated the possibility that over-exuberant calpain activity is responsible for aberrant VEGF neovessel architecture and integration. Calpains are a family of intracellular calcium-dependent, non-lysosomal cysteine proteases that regulate cellular functions through proteolysis of numerous substrates. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse skin model of VEGF-driven angiogenesis, retroviral transduction with dominant-negative (DN calpain-I promoted neovessel integration and lumen formation, reduced blind ends, and improved vascular perfusion. Moderate doses of calpain inhibitor-I improved VEGF-driven angiogenesis similarly to DN calpain-I. Conversely, retroviral transduction with wild-type (WT calpain-I abolished neovessel integration and lumen formation. In vitro, moderate suppression of calpain activity with DN calpain-I or calpain inhibitor-I increased the microtubule-stabilizing protein tau in endothelial cells (ECs, increased the average length of microtubules, increased actin cable length, and increased the interconnectivity of vascular cords. Conversely, WT calpain-I diminished tau, collapsed microtubules, disrupted actin cables, and inhibited integration of cord networks. Consistent with the critical importance of microtubules for vascular network integration, the microtubule-stabilizing agent taxol supported vascular cord integration whereas microtubule dissolution with nocodazole collapsed cord networks. CONCLUSIONS/SIGNIFICANCE: These findings implicate VEGF-induction of calpain activity and impairment of

  17. Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers.

    Directory of Open Access Journals (Sweden)

    Judith Brouwers

    Full Text Available INTRODUCTION: The angiogenic proteins angiopoietin (Ang-1, Ang-2 and vascular endothelial growth factor (VEGF are regulators of endothelial inflammation and integrity. Since platelets store large amounts of Ang-1 and VEGF, measurement of circulation levels of these proteins is sensitive to platelet number, in vivo platelet activation and inadvertent platelet activation during blood processing. We studied plasma Ang-1, Ang-2 and VEGF levels in malaria patients, taking the necessary precautions to avoid ex vivo platelet activation, and related plasma levels to platelet count and the soluble platelet activation markers P-selectin and CXCL7. METHODS: Plasma levels of Ang-1, Ang-2, VEGF, P-selectin and CXCL7 were measured in CTAD plasma, minimizing ex vivo platelet activation, in 27 patients with febrile Plasmodium falciparum malaria at presentation and day 2 and 5 of treatment and in 25 healthy controls. RESULTS: Levels of Ang-1, Ang-2 and VEGF were higher at day 0 in malaria patients compared to healthy controls. Ang-2 levels, which is a marker of endothelial activation, decreased after start of antimalarial treatment. In contrast, Ang-1 and VEGF plasma levels increased and this corresponded with the increase in platelet number. Soluble P-selectin and CXCL7 levels followed the same trend as Ang-1 and VEGF levels. Plasma levels of these four proteins correlated strongly in malaria patients, but only moderately in controls. CONCLUSION: In contrast to previous studies, we found elevated plasma levels of Ang-1 and VEGF in patients with malaria resulting from in vivo platelet activation. Ang-1 release from platelets may be important to dampen the disturbing effects of Ang-2 on the endothelium. Evaluation of plasma levels of these angiogenic proteins requires close adherence to a stringent protocol to minimize ex vivo platelet activation.

  18. Angiomodulin is a specific marker of vasculature and regulates VEGF-A dependent neo-angiogenesis

    OpenAIRE

    Hooper, Andrea T.; Shmelkov, Sergey V.; Gupta, Sunny; Milde, Till; Bambino, Kathryn; Gillen, Kelly; Goetz, Mollie; Chavala, Sai; Baljevic, Muhamed; Murphy, Andrew J.; Valenzuela, David M; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; Vahdat, Linda

    2009-01-01

    Blood vessel formation is controlled by the balance between pro- and anti-angiogenic pathways. Although much is known about the factors that drive sprouting of neovessels, the factors that stabilize and pattern neovessels are undefined. The expression of angiomodulin (AGM), a VEGF-A binding protein, was increased in the vasculature of several human tumors as compared to normal tissue, raising the hypothesis that AGM may modulate VEGF-A-dependent vascular patterning. To elucidate the expressio...

  19. Transcriptional profiling of mouse uterus at pre-implantation stage under VEGF repression.

    Directory of Open Access Journals (Sweden)

    Yan Ji

    Full Text Available Uterus development during pre-implantation stage affects implantation process and embryo growth. Aberrant uterus development is associated with many human reproductive diseases. Among the factors regulating uterus development, vascular remodeling promoters are critical for uterus function and fertility. Vascular endothelial growth factor (VEGF, as one of the major members, has been found to be important in endothelial cell growth and blood vessel development, as well as in non-endothelial cells. VEGF mediation in reproduction has been broadly studied, but VEGF-induced transcriptional machinery during implantation window has not been systematically studied. In this study, a genetically repressed VEGF mouse model was used to analyze uterus transcriptome at gestation 2.5 (G2.5 by Solexa/Illumina's digital gene expression (DGE system. A number of 831 uterus-specific and 2398 VEGF-regulated genes were identified. Gene ontology (GO analysis indicated that genes actively involved in uterus development were members of collagen biosynthesis, cell proliferation and cell apoptosis. Uterus-specific genes were enriched in activities of phosphatidyl inositol phosphate kinase, histone H3-K36 demethylation and protein acetylation. Among VEGF-regulated genes, up-regulated were associated with RNA polymerase III activity while down-regulated were strongly related with muscle development. Comparable numbers of antisense transcripts were identified. Expression levels of the antisense transcripts were found tightly correlated with their sense expression levels, an indication of possibly non-specific transcripts generated around the active promoters and enhancers. The antisense transcripts with exceptionally high or low expression levels and the antisense transcripts under VEGF regulation were also identified. These transcripts may be important candidates in regulation of uterus development. This study provides a global survey on genes and antisense transcripts

  20. Genetic variation in VEGF does not contribute significantly to the risk of congenital cardiovascular malformation.

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    Helen R Griffin

    Full Text Available Several previous studies have investigated the role of common promoter variants in the vascular endothelial growth factor (VEGF gene in causing congenital cardiovascular malformation (CVM. However, results have been discrepant between studies and no study to date has comprehensively characterised variation throughout the gene. We genotyped 771 CVM cases, of whom 595 had the outflow tract malformation Tetralogy of Fallot (TOF, and carried out TDT and case-control analyses using haplotype-tagging SNPs in VEGF. We carried out a meta-analysis of previous case-control or family-based studies that had typed VEGF promoter SNPs, which included an additional 570 CVM cases. To identify rare variants potentially causative of CVM, we carried out mutation screening in all VEGF exons and splice sites in 93 TOF cases. There was no significant effect of any VEGF haplotype-tagging SNP on the risk of CVM in our analyses of 771 probands. When the results of this and all previous studies were combined, there was no significant effect of the VEGF promoter SNPs rs699947 (OR 1.05 [95% CI 0.95-1.17]; rs1570360 (OR 1.17 [95% CI 0.99-1.26]; and rs2010963 (OR 1.04 [95% CI 0.93-1.16] on the risk of CVM in 1341 cases. Mutation screening of 93 TOF cases revealed no VEGF coding sequence variants and no changes at splice consensus sequences. Genetic variation in VEGF appears to play a small role, if any, in outflow tract CVM susceptibility.

  1. Sequestration of Vascular Endothelial Growth Factor (VEGF Induces Late Restrictive Lung Disease.

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    Minna M Wieck

    Full Text Available Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF, which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function.To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function.Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1 were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model.Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes.These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions.

  2. Clinical Significance of Vascular Endothelial Growth Factor (VEGF) in Sera of Patients with Pediatric Malignancies

    International Nuclear Information System (INIS)

    Angiogenesis is essential for solid tumor growth. It is induced by tumor cells through stimulatory angiogenic peptides, one such peptide is vascular endothelial growth factor (VEGF). Purpose: The ultimate aim of the work is to investigate the possible role of VEGF as an early bio molecule involved in the progression of pediatric malignant tumors with high metastatic potential. Patients and Methods: Forty-five pediatric patients were studied. They included four groups with malignant solid tumors suffering from Ewing's sarcoma, osteosarcoma, neuroblastoma, and rhabdomyosarcoma. In addition, a healthy control group including fifteen age and sex matched children was included in the study. Serum VEGF levels were determined by ELISA technique. The level of VEGF was significantly higher in all types of solid tumors compared to normal healthy children. The mean values obtained for patients and controls were 429.44±258.55 pg/ml and 79.36±63.81 pg/ml, respectively. No significant difference was detected in the level of VEGF among males and females. Also, no statistically significant difference was detected among the different types of malignant tumors. However, a marked significant difference was elucidated between metastatic and non-metastatic cancer patients, the values recorded were 753.33±173.64 pg/ml and 267.5±75.54 pg/ml, respectively (p < 0.00 I). Furthermore, the results showed that 207 pg/ml of serum level of VEGF is the optimal cutoff value (mean ± 2 SD of control) with sensitivity of 87% and specificity of 100%. Using the receiver operating characteristic (ROC) curve analysis, the area under the curve (0.917) indicated the validity of using serum VEGF level in the diagnosis of all different types of pediatric malignant solid tumors with high potentiality to metastasis. VEGF is an angiogenic stimulatory peptide. Its serum level colud be a reliable marker in assessing pediatric malignancies with high metastatic potentials

  3. Construction of adeno-associated virus coexpression system for human angiopoietin-1 and VEGF gene

    Institute of Scientific and Technical Information of China (English)

    陈德杰; 谭最; 谢友利; 刘芳

    2004-01-01

    Background Ischemic disease is one of the leading causes of death in the world. In order to further study gene therapy for ischemic disease, we constructed a recombinant plasmid for co-expression of human angiopoietin-1 and vascular endothelial growth factor 165 (VEGF165) gene in adeno-associated virus (AAV) gene delivery system.Methods Human angiopoietin 1 and VEGF165 gene were obtained using PCR. The upstream of angiopoietin 1 contained restriction enzyme site Hind Ⅲ, and the downstream of angiopoietin 1contained restriction enzyme site BamH Ⅰ. The upstream of VEGF165 contained restriction enzyme site Bgl Ⅱ, and the downstream of VEGF165 contained restriction enzyme site BamH Ⅰ . Using the multiple cloning sites (MCS) in plasmid pZero ++ such as BamH Ⅰ , Bgl Ⅱ, Hind Ⅲ, Not Ⅰ , XhoⅠ,Xba Ⅰ , Sal Ⅰ , BspH Ⅰ , Ksp Ⅰ and the corresponding MCS in plasmid pAAV-MCS, angiopoietin 1 and VEGF165 gene were subcloned into pAAV-MCS.Results DNA sequencing revealed that the PCR- amplified angiopoietin 1 and VEGF165 were consistent with NCBI Gene Bank. The recombinant plasmid was identified using PCR and digestion,which proved to be consistent with our hypothesis. In recombinant plasmid, angiopoietin1 and VEGF possessed a CMV promoter and polyA terminator system respectively, thus assuring co-expression of the two genes.Conclusion Successful construction of AAV co-expression system for human angiopoietin 1 and VEGF165 gene will provide the foundation for gene therapy to cure severe ischemic disease.

  4. Local Ablative Strategies for Ductal Pancreatic Cancer (Radiofrequency Ablation, Irreversible Electroporation): A Review

    OpenAIRE

    Salvatore Paiella; Roberto Salvia; Marco Ramera; Roberto Girelli; Isabella Frigerio; Alessandro Giardino; Valentina Allegrini; Claudio Bassi

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. Locally advanced pancreatic cancer (LAPC) accounts for the 40% of the new diagnoses. Current treatment options are based on chemo- and radiotherapy regimens. Local ablative techniques seem to be the future therapeutic option for stage-III patients with PDAC. Radiofrequency Ablation (RFA) and Irreversible Electroporation (IRE) are actually the most emerging local ablative techniques used on LAPC. Initial clinical studies on ...

  5. Typical flutter ablation as an adjunct to catheter ablation of atrial fibrillation

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    Dipen Shah

    2008-12-01

    Full Text Available Typical atrial flutter and atrial fibrillation are frequently observed to coexist(1 .  In the current context of interventional electrophysiology, curative or at least definitive ablation is available for both arrhythmias. Despite their coexistence, it is not clear whether typical flutter ablation is necessary in all patients undergoing catheter ablation of atrial fibrillation. The following review explores the pathophysiology of both arrhythmias, their interrelationships and the available data pertaining to this theme.

  6. Comparative VEGF receptor tyrosine kinase modeling for the development of highly specific inhibitors of tumor angiogenesis.

    Science.gov (United States)

    Schmidt, Ulrike; Ahmed, Jessica; Michalsky, Elke; Hoepfner, Michael; Preissner, Robert

    2008-01-01

    The Vascular Endothelial Growth Factor receptors (VEGF-Rs) play a significant role in tumor development and tumor angiogenesis and are therefore interesting targets in cancer therapy. Targeting the VEGF-R is of special importance as the feed of the tumor has to be reduced. In general, this can be carried out by inhibiting the tyrosine kinase function of the VEGF-R. Nevertheless, there arise some problems with the specificity of known kinase inhibitors: they bind to the ATP-binding site and inhibit a number of kinases, moreover the so far most specific inhibitors act at least on these three major types of VEGF-Rs: Flt-1, Flk-1/KDR, Flt-4. The goal is a selective VEGF-R-2 (Flk-1/KDR) inhibitor, because this receptor triggers rather unspecific signals from VEGF-A, -C, -D and -E. Here, we describe a protocol starting from an established inhibitor (Vatalanib) with 2D-/3D-searching and property filtering of the in silico screening hits and the "negative docking approach". With this approach we were able to identify a compound, which shows a fourfold higher reduction of the proliferation rate of endothelial cells compared to the reduction effect of the lead structure.

  7. Expression of Human Vascular Endothelial Growth Factor (VEGF165) in Pichia pastoris and Its Biological Activity

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To express human vascular endothelial growth factor (hVEGF165) cDNA in Pichia pastroris, purify the expressed product and detect the biological activity of it. Methods  By inserting hVEGF165 cDNA coding 165 amino acid residues into Pichia pastoris expression vector pPIC9K containing AOX1 promoter and the sequences of α secreting signal peptides, a recombinant expression plasmid pPIC9K/hVEGF165 was constructed and transformed to yeast host strain KM71, then multiple-copy insert transformants were screened out and cultured in flasks, and hVEGF165 was expressed under the induction of 1% methanol. Results  SDS-PAGE showed that after being induced with 1% methanol for 4d, the expressed product existed in supernatant in the form of soluble molecule and contained 60% of total protein expressed. Western blot showed good antigenicity and specificity of expressed product. After being purified by Heparin-Sepharose CL6B affinity chromatography, the purity of expressed product reached above 90%. Biological assays proved that the expressed product could stimulate the proliferation of HUVEC. Conclusion  hVEGF165 was successfully expressed. The study opened up a wide prospect for the application of VEGF165 in the prevention and treatment of ischemic heart disease and other tissue ischemic diseases such as secondary arterial occlusion in limbs.

  8. Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity.

    Science.gov (United States)

    Jais, Alexander; Solas, Maite; Backes, Heiko; Chaurasia, Bhagirath; Kleinridders, André; Theurich, Sebastian; Mauer, Jan; Steculorum, Sophie M; Hampel, Brigitte; Goldau, Julia; Alber, Jens; Förster, Carola Y; Eming, Sabine A; Schwaninger, Markus; Ferrara, Napoleone; Karsenty, Gerard; Brüning, Jens C

    2016-05-01

    High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity. PMID:27133169

  9. Inhibition Effect of shRNA on VEGF-C in Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Xi-ling Gu; You-de Cao

    2009-01-01

    Objective: To investigate the effect of RNA interfering on VEGF-C in MDA-MB-231 cells.Methods: Three small interfering RNAs (siRNAa, siRNAb, siRNAc) were prepared. The most efficient one was screened and short hairpin (shRNA) was designed, the recombinant plasmid pGenesil-1/VEGF-C was constructed, and transfected into MDA-MB-231 cells by Lipofectamine TM 2000. RT-PCR, Western-blot an immunohistochemical methods were performed to detect the expression of VEGF-C.Results: RT-PCR results showed that siRNAa, siRNAb, siRNAc could inhibit the growth of MDA-MB-231 cells, among which, siRNAa was the most significant, with an inhibition rate of 72.1%. The recombinant plasmid pGenesil-1/VEGF-C was successfully constructed using shRNA and pGenesil-1. VEGF-C expression was significantly inhibited as determined by RT-PCR,immunocytochemistry staining and Western blot (P<0.05).Conclusion: shRNA RNAi technology could silence the expression of VEGF-C in MDA-MB-231 cells, which suggested that the technology may be one of the effective methods for inhibiting lymphangiogenesis in breast cancer.

  10. Thymosin beta 10 Prompted the VEGF-C Expression in Lung Cancer Cell

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    Zixuan LI

    2014-05-01

    Full Text Available Background and objective Our previous study found that thymosin β10 overexpressed in lung cancer and positively correlated with differentiation, lymph node metastasis and stage of lung cancer. In this reasearch we aim to study the effects and mechanism of exogenous human recombinant Tβ10 on the expression of VEGF-C on non-small cell lung cancer. Methods After SPC, A549 and LK2 cells were treated with 100 ng/mL recombinant human Tβ10, the mRNA level of VEGF-C were detected by RT-PCR. The mean while the protein expression of VEGF-C, P-AKT and AKT were determined by Western blot assay. Results Exogenous recombinant human Tβ10 were significantly promote the expression levels of VEGF-C mRNA and protein while promoting the phosphorylation of AKT. Exogenous Tβ10 can promote the expression of VEGF-C mRNA and protein in lung cancer cell lines A549 and LK2 (P<0.05, and this effect can be inhibited by use AKT inhibitor LY294002 (P<0.05. Conclusion Tβ10 human recombinant proteins can promote the expression of VEGF-C by activating AKT phosphorylation in lung cancer cell lines.

  11. VEGF receptor-2 (Flk-1 overexpression in mice counteracts focal epileptic seizures.

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    Litsa Nikitidou

    Full Text Available Vascular endothelial growth factor (VEGF was first described as an angiogenic agent, but has recently also been shown to exert various neurotrophic and neuroprotective effects in the nervous system. These effects of VEGF are mainly mediated by its receptor, VEGFR-2, which is also referred to as the fetal liver kinase receptor 1 (Flk-1. VEGF is up-regulated in neurons and glial cells after epileptic seizures and counteracts seizure-induced neurodegeneration. In vitro, VEGF administration suppresses ictal and interictal epileptiform activity caused by AP4 and 0 Mg(2+ via Flk-1 receptor. We therefore explored whether increased VEGF signaling through Flk-1 overexpression may regulate epileptogenesis and ictogenesis in vivo. To this extent, we used transgenic mice overexpressing Flk-1 postnatally in neurons. Intriguingly, Flk-1 overexpressing mice were characterized by an elevated threshold for seizure induction and a decreased duration of focal afterdischarges, indicating anti-ictal action. On the other hand, the kindling progression in these mice was similar to wild-type controls. No significant effects on blood vessels or glia cells, as assessed by Glut1 and GFAP immunohistochemistry, were detected. These results suggest that increased VEGF signaling via overexpression of Flk-1 receptors may directly affect seizure activity even without altering angiogenesis. Thus, Flk-1 could be considered as a novel target for developing future gene therapy strategies against ictal epileptic activity.

  12. Enhanced Vascularization in Hybrid PCL/Gelatin Fibrous Scaffolds with Sustained Release of VEGF

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    Kai Wang

    2015-01-01

    Full Text Available Creating a long-lasting and functional vasculature represents one of the most fundamental challenges in tissue engineering. VEGF has been widely accepted as a potent angiogenic factor involved in the early stages of blood vessel formation. In this study, fibrous scaffolds that consist of PCL and gelatin fibers were fabricated. The gelatin fibers were further functionalized by heparin immobilization, which provides binding sites for VEGF and thus enables the sustained release of VEGF. In vitro release test confirms the sustained releasing profile of VEGF, and stable release was observed over a time period of 25 days. In vitro cell assay indicates that VEGF release significantly promoted the proliferation of endothelial cells. More importantly, in vivo subcutaneous implantation reflects that vascularization has been effectively enhanced in the PCL/gelatin scaffolds compared with the PCL counterpart due to the sustained release of VEGF. Therefore, the heparinized PCL/gelatin scaffolds developed in this study may be a promising candidate for regeneration of complex tissues with sufficient vascularization.

  13. Immunohistochemical Expression of VEGF and Podoplanin in Uterine Cervical Squamous Intraepithelial Lesions

    Science.gov (United States)

    Belfort-Mattos, Patrícia Napoli; Focchi, Gustavo Rubino de Azevedo; Ribalta, Julisa Chamorro Lascasas; Megale De Lima, Tatiana; Nogueira Carvalho, Carmen Regina; Kesselring Tso, Fernanda; De Góis Speck, Neila Maria

    2016-01-01

    VEGF and podoplanin (PDPN) have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone) and podoplanin (D2-40 clone). Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (P < 0.001). Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (P = 0.016). We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (P = 0.018). Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression. PMID:27313335

  14. The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel.

    Science.gov (United States)

    Aspelund, Aleksanteri; Tammela, Tuomas; Antila, Salli; Nurmi, Harri; Leppänen, Veli-Matti; Zarkada, Georgia; Stanczuk, Lukas; Francois, Mathias; Mäkinen, Taija; Saharinen, Pipsa; Immonen, Ilkka; Alitalo, Kari

    2014-09-01

    In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment.

  15. Nuclear translocation of phosphorylated STAT3 regulates VEGF-A-induced lymphatic endothelial cell migration and tube formation

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Hideki; Tokumaru, Sho; Hanakawa, Yasushi; Shiraishi, Ken; Shirakata, Yuji; Dai, Xiuju; Yang, Lijun; Tohyama, Mikiko; Hashimoto, Koji [Department of Dermatology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295 (Japan); Sayama, Koji, E-mail: sayama@m.ehime-u.ac.jp [Department of Dermatology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295 (Japan)

    2011-09-02

    Highlights: {yields} VEGF-A enhanced lymphatic endothelial cell migration and increased tube formation. {yields} VEGF-A treated lymphatic endothelial cell showed activation of STAT3. {yields} Dominant-negative STAT3 inhibited VEGF-A-induced lymphatic endothelial cell migration and tube formation. -- Abstract: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific growth factor that regulates endothelial functions, and signal transducers and activators of transcription (STATs) are known to be important during VEGF receptor signaling. The aim of this study was to determine whether STAT3 regulates VEGF-induced lymphatic endothelial cell (LEC) migration and tube formation. VEGF-A (33 ng/ml) enhanced LEC migration by 2-fold and increased tube length by 25% compared with the control, as analyzed using a Boyden chamber and Matrigel assay, respectively. Western blot analysis and immunostaining revealed that VEGF-A induced the nuclear translocation of phosphorylated STAT3 in LECs, and this translocation was blocked by the transfection of LECs with an adenovirus vector expressing a dominant-negative mutant of STAT3 (Ax-STAT3F). Transfection with Ax-STAT3F also almost completely inhibited VEGF-A-induced LEC migration and tube formation. These results indicate that STAT3 is essential for VEGF-A-induced LEC migration and tube formation and that STAT3 regulates LEC functions.

  16. VEGF Silencing Inhibits Human Osteosarcoma Angiogenesis and Promotes Cell Apoptosis via PI3K/AKT Signaling Pathway.

    Science.gov (United States)

    Zhao, Jian; Zhang, Zi-Ru; Zhao, Na; Ma, Bao-An; Fan, Qing-Yu

    2015-11-01

    Vascular endothelial growth factor (VEGF) is one of the most effective angiogenic factors that promote generation of tumor vasculature. VEGF is usually up-regulated in multiple cancers including osteosarcoma and glioma. To further explore the potential molecular mechanism that inhibits tumor growth induced by interference of VEGF expression, we constructed a Lv-shVEGF vector and assessed the efficiency of VEGF silencing and its influence in U2OS cells. The data demonstrate that Lv-shVEGF has high inhibition efficiency on VEGF expression, which inhibits proliferation and promotes apoptosis of U2OS cells in vitro. Our results also indicate that inhibition of VEGF expression suppresses osteosarcoma tumor growth in vivo and reduces osteosarcoma angiogenesis. We also found that the activations of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) were considerably reduced after osteosarcoma cells were treated with Lv-shVEGF. Taken together, our data demonstrate that VEGF silencing suppresses cell proliferation, promotes cell apoptosis, and reduces osteosarcoma angiogenesis through inactivation of PI3K/AKT signaling pathway. PMID:27352347

  17. Hypertonic stress induces VEGF production in human colon cancer cell line Caco-2: inhibitory role of autocrine PGE₂.

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    Luciana B Gentile

    Full Text Available Vascular Endothelial Growth Factor (VEGF is a major regulator of angiogenesis. VEGF expression is up regulated in response to micro-environmental cues related to poor blood supply such as hypoxia. However, regulation of VEGF expression in cancer cells is not limited to the stress response due to increased volume of the tumor mass. Lipid mediators in particular arachidonic acid-derived prostaglandin (PGE₂ are regulators of VEGF expression and angiogenesis in colon cancer. In addition, increased osmolarity that is generated during colonic water absorption and feces consolidation seems to activate colon cancer cells and promote PGE₂ generation. Such physiological stimulation may provide signaling for cancer promotion. Here we investigated the effect of exposure to a hypertonic medium, to emulate colonic environment, on VEGF production by colon cancer cells. The role of concomitant PGE₂ generation and MAPK activation was addressed by specific pharmacological inhibition. Human colon cancer cell line Caco-2 exposed to a hypertonic environment responded with marked VEGF and PGE₂ production. VEGF production was inhibited by selective inhibitors of ERK 1/2 and p38 MAPK pathways. To address the regulatory role of PGE₂ on VEGF production, Caco-2 cells were treated with cPLA₂ (ATK and COX-2 (NS-398 inhibitors, that completely block PGE₂ generation. The Caco-2 cells were also treated with a non selective PGE₂ receptor antagonist. Each treatment significantly increased the hypertonic stress-induced VEGF production. Moreover, addition of PGE₂ or selective EP₂ receptor agonist to activated Caco-2 cells inhibited VEGF production. The autocrine inhibitory role for PGE₂ appears to be selective to hypertonic environment since VEGF production induced by exposure to CoCl₂ was decreased by inhibition of concomitant PGE₂ generation. Our results indicated that hypertonicity stimulates VEGF production in colon cancer cell lines. Also PGE

  18. Atrial Tachycardias Occurring After Atrial Fibrillation Ablation: Strategies for Mapping and Ablation

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    Stavros Mountantonakis, MD

    2010-10-01

    Full Text Available The occurrence of left atrial tachycardias (AT after catheter ablation for atrial fibrillation (AF is common, especially after more extensive ablation of persistent AF. These AT are invariably symptomatic and often do not respond to medical therapy. The initial strategy involves ventricular rate control, cardioversion, and observation as some tachycardias may resolve with time. For persistent ATs, effective management frequently requires catheter intervention. Careful characterization of the tachycardia mechanism is essential in designing an effective ablation strategy that would also avoid further creation of pro-arrhythmic substrate. With this review, we summarize the incidence, mechanism, diagnosis and treatment of ATs occurring after AF ablation.

  19. 重组人VEGF165的表达纯化及单抗的初步筛选%Prokaryotic Expression of VEGF165 and Preliminary Screening of Anti-VEGF Hybridoma Cell Lines

    Institute of Scientific and Technical Information of China (English)

    包欣晨; 李孜; 高向东; 陆小冬; 徐晨

    2011-01-01

    Vascular endothelial growth factor (VEGF) plays a key role in physiological and pathological angiogenesis and is a potent and critical target as blocking tumor growth and metastasis. The process described in this report involves a complex auto-induced expression in Escherichia coli and a downstream purification process consisting of protein refolding and three chromatography steps in order to obtain the functional rhVEGF165. Biological activity of the purified 38kDa homodimer was verified by the induction of the proliferation of human umbilical vein endothelial cells (HUVECs). The EC50 for this effect was 2. 4ng/ml. Finally, three Anti-VEGF hybridoma cell lines were obtained after immunization, fusion and preliminary screening.%血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)是抑制肿瘤生长和转移的重要靶点.为获得抗VEGF单抗细胞株,构建了rhVEGFt165工程菌,并利用复合自动诱导获得高效表达.经纯化获得高纯度rhVEGF165蛋白,经检测具有促人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)增殖活性,其EC50为2.4ng/ml.免疫小鼠,获得了3株能稳定分泌抗VEGF单抗的杂交瘤细胞株,为开发VEGF治疗性单抗提供了重要基础.

  20. EXPRESSION OF VEGF RECEPTOR KDR IN DIFFERENT ORIGINATED CARCINOMAS

    Institute of Scientific and Technical Information of China (English)

    Song Shumei; Wujian; Shou Chengchao

    1998-01-01

    Objective: To detect the expression of KDR in different originated carcinomas and to explore its expressed ways and the relationship with tumor progression. Methods: KDR cDNA (Ⅴ-Ⅶ domains)fragment was cloned from human umbilical vein with RTPCR and was expressed in Ecoli.Jm109. The fusion protein of GST-KDR was used for immunizing Balb/c mice to prepare monoclonal antibodies against KDR.The different tumor tissues and related normal tissues were examined with KDR McAb by S-P immunohistochemistry. Results: the rate and intensification of KDR expression among different originated cancers are very different, bladder cancers from transmigrated epidermis are 100% positive and highest intensification.The expression of KDR in breast cancer and intestinal cancer lie in the second-rate, the weakest expression of KDR is in lung squamous carcinoma. Moreover,expression of KDR in tumor tissues lie both in endothelial cells (EC) of tumor blood vessels and tumor cells.Conclusion: VEGF may be not only the para-secretory factor making EC proliferation but also auto-secretory factor stimulating the proliferation of tumor cells to benefit the growth and metastasis of malignant tumors.The different expression of KDR in different originated carcinomas may relate with malignant degree of tumor.

  1. Nanosecond laser ablation of silver nanoparticle film

    Science.gov (United States)

    Chung, Jaewon; Han, Sewoon; Lee, Daeho; Ahn, Sanghoon; Grigoropoulos, Costas P.; Moon, Jooho; Ko, Seung H.

    2013-02-01

    Nanosecond laser ablation of polyvinylpyrrolidone (PVP) protected silver nanoparticle (20 nm diameter) film is studied using a frequency doubled Nd:YAG nanosecond laser (532 nm wavelength, 6 ns full width half maximum pulse width). In the sintered silver nanoparticle film, absorbed light energy conducts well through the sintered porous structure, resulting in ablation craters of a porous dome shape or crown shape depending on the irradiation fluence due to the sudden vaporization of the PVP. In the unsintered silver nanoparticle film, the ablation crater with a clean edge profile is formed and many coalesced nanoparticles of 50 to 100 nm in size are observed inside the ablation crater. These results and an order of magnitude analysis indicate that the absorbed thermal energy is confined within the nanoparticles, causing melting of nanoparticles and their coalescence to larger agglomerates, which are removed following melting and subsequent partial vaporization.

  2. Nanoscale ablation through optically trapped microspheres

    Science.gov (United States)

    Fardel, Romain; McLeod, Euan; Tsai, Yu-Cheng; Arnold, Craig B.

    2010-10-01

    The ability to directly create patterns with size scales below 100 nm is important for many applications where the production or repair of high resolution and density features is needed. Laser-based direct-write methods have the benefit of being able to quickly and easily modify and create structures on existing devices, but ablation can negatively impact the overall technique. In this paper we show that self-positioning of near-field objectives through the optical trap assisted nanopatterning (OTAN) method allows for ablation without harming the objective elements. Small microbeads are positioned in close proximity to a substrate where ablation is initiated. Upon ablation, these beads are temporarily displaced from the trap but rapidly return to the initial position. We analyze the range of fluence values for which this process occurs and find that there exists a critical threshold beyond which the beads are permanently ejected.

  3. Laser ablation in analytical chemistry - A review

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Richard E.; Mao, Xianglei; Liu, Haichen; Gonzalez, Jhanis; Mao, Samuel S.

    2001-10-10

    Laser ablation is becoming a dominant technology for direct solid sampling in analytical chemistry. Laser ablation refers to the process in which an intense burst of energy delivered by a short laser pulse is used to sample (remove a portion of) a material. The advantages of laser ablation chemical analysis include direct characterization of solids, no chemical procedures for dissolution, reduced risk of contamination or sample loss, analysis of very small samples not separable for solution analysis, and determination of spatial distributions of elemental composition. This review describes recent research to understand and utilize laser ablation for direct solid sampling, with emphasis on sample introduction to an inductively coupled plasma (ICP). Current research related to contemporary experimental systems, calibration and optimization, and fractionation is discussed, with a summary of applications in several areas.

  4. Ablative Ceramic Foam Based TPS Project

    Data.gov (United States)

    National Aeronautics and Space Administration — A novel composite material ablative TPS for planetary vehicles that can survive a dual heating exposure is proposed. NextGen's TPS concept is a bi-layer functional...

  5. Principles of the radiative ablation modeling

    Science.gov (United States)

    Saillard, Yves; Arnault, Philippe; Silvert, Virginie

    2010-12-01

    Indirectly driven inertial confinement fusion (ICF) rests on the setting up of a radiation temperature within a laser cavity and on the optimization of the capsule implosion ablated by this radiation. In both circumstances, the ablation of an optically thick medium is at work. The nonlinear radiation conduction equations that describe this phenomenon admit different kinds of solutions called generically Marshak waves. In this paper, a completely analytic model is proposed to describe the ablation in the subsonic regime relevant to ICF experiments. This model approximates the flow by a deflagrationlike structure where Hugoniot relations are used in the stationary part from the ablation front up to the isothermal sonic Chapman-Jouguet point and where the unstationary expansion from the sonic point up to the external boundary is assumed quasi-isothermal. It uses power law matter properties. It can also accommodate arbitrary boundary conditions provided the ablation wave stays very subsonic and the surface temperature does not vary too quickly. These requirements are often met in realistic situations. Interestingly, the ablated mass rate, the ablation pressure, and the absorbed radiative energy depend on the time history of the surface temperature, not only on the instantaneous temperature values. The results compare very well with self-similar solutions and with numerical simulations obtained by hydrodynamic code. This analytic model gives insight into the physical processes involved in the ablation and is helpful for optimization and sensitivity studies in many situations of interest: radiation temperature within a laser cavity, acceleration of finite size medium, and ICF capsule implosion, for instance.

  6. Retained Foreign Body After Laser Ablation

    OpenAIRE

    Ren, Shiyan; Liu, Peng; Wang, Wei; Yang, Yuguan

    2012-01-01

    Laser ablation for varicose veins is a common practice, and postoperative complications may happen. A retained foreign body could be left accidently in the treated leg. It is rarely reported in literature. We herein describe two cases of retained foreign body during the laser ablation for varicose veins. One patient with varicose veins received laser therapy 5 years earlier, and had experienced discomfort and pain. After investigation, an overlooked sheath fragment was removed surgically from...

  7. Laser Ablation for Small Hepatocellular Carcinoma

    Science.gov (United States)

    Pacella, Claudio Maurizio; Francica, Giampiero; Di Costanzo, Giovanni Giuseppe

    2011-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is increasingly detected at small size (liver transplantation, or percutaneous ablation have been proposed. When surgical options are precluded, image-guided tumor ablation is recommended as the most appropriate therapeutic choice in terms of tumor local control, safety, and improvement in survival. Laser ablation (LA) represents one of currently available loco-ablative techniques: light is delivered via flexible quartz fibers of diameter from 300 to 600 μm inserted into tumor lesion through either fine needles (21g Chiba needles) or large-bore catheters. The thermal destruction of tissue is achieved through conversion of absorbed light (usually infrared) into heat. A range of different imaging modalities have been used to guide percutaneous laser ablation, but ultrasound and magnetic resonance imaging are most widely employed, according to local experience and resource availability. Available clinical data suggest that LA is highly effective in terms of tumoricidal capability with an excellent safety profile; the best results in terms of long-term survival are obtained in early HCC so that LA can be proposed not only in unresectable cases but, not differently from radiofrequency ablation, also as the first-line treatment. PMID:22191028

  8. Optical modeling of laser ablated microstructures

    Science.gov (United States)

    Gower, M. C.; Davies, E.; Holmes, A. S.

    2012-11-01

    From only an a priori knowledge of the optical parameters of a laser beam, the delivery system together with a substrate's material properties, a ray-tracing model capable of predicting the 3-D topology of micro/nanostructures machined by pulsed laser ablation has been developed. The model includes secondary illumination effects produced by the microstructure created by successive pulses (wall reflections, refraction, wave guiding, shadowing, etc.) as well as the complete optical properties of the beam delivery system. We have used material ablation by pulsed excimer lasers and associated beam delivery systems to demonstrate some of the capabilities of the model. Good agreement is obtained between computations and experimental results in terms of the predicted ablation depth per pulse and the wall taper angle of channels and holes. The model can predict ablated profiles of holes and indicate the most efficient drilling strategy in terms of material removal rates. The model also shows diffraction effects are not required to explain the tapering vertical walls observed when ablating microstructures. Finally, the model has been used to demonstrate aberrations in an optical imaging system limiting the creation of submicron features in an ablated microstructure. Provided photons are absorbed linearly in a substrate according to Beer's law with negligible thermal diffusion effects, the model is equally applicable to using other types of pulsed laser sources and systems with imaged or focused beams.

  9. Basic ablation phenomena during laser thrombolysis

    Science.gov (United States)

    Sathyam, Ujwal S.; Shearin, Alan; Prahl, Scott A.

    1997-05-01

    This paper presents studies of microsecond ablation phenomena that take place during laser thrombolysis. The main goals were to optimize laser parameters for efficient ablation, and to investigate the ablation mechanism. Gelatin containing an absorbing dye was used as the clot model. A parametric study was performed to identify the optimal wavelength, spot size, pulse energies, and repetition rate for maximum material removal. The minimum radiant exposures to achieve ablation at any wavelength were measured. The results suggest that most visible wavelengths were equally efficient at removing material at radiant exposures above threshold. Ablation was initiated at surface temperatures just above 100 degrees Celsius. A vapor bubble was formed during ablation. Less than 5% of the total pulse energy is coupled into the bubble energy. A large part of the delivered energy is unaccounted for and is likely released partly as acoustic transients from the vapor expansion and partly wasted as heat. The current laser and delivery systems may not be able to completely remove large clot burden that is sometimes encountered in heart attacks. However, laser thrombolysis may emerge as a favored treatment for strokes where the occlusion is generally smaller and rapid recanalization is of paramount importance. A final hypothesis is that laser thrombolysis should be done at radiant exposures close to threshold to minimize any damaging effects of the bubble dynamics on the vessel wall.

  10. Impact of different termination modes on atrial fibrillation termination in catheter ablation of persistent atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    WANG Ping; MA Chang-sheng; DONG Jian-zeng; LONG De-yong; NING Man; TANG Ri-bo; YU Rong-hui; XUE Zeng-ming; SANG Cai-hua; JIANG Chen-xi

    2012-01-01

    Background The optimal endpoint for catheter ablation of persistent atrial fibrillation (AF) remains ambiguous.This study investigated the impact of AF termination as a procedural endpoint and the termination mode on long-term clinical outcome.Methods Two hundred and ninety-three patients who underwent stepwise ablation for persistent AF were categorized into the AF termination by ablation group and into the electrical cardioversion (CV) group.Subgroups were also analyzed based on different termination modes.Follow-up assessment included early recurrence and sinus rhythm (SR) maintenance.Results During initial ablation,33 patients (11.3%) were directly converted to SR,166 patients (56.7%) were converted to atrial tachycardia (AT) that subsequently restored SR with further ablation in 98 patients (33.4%),and a total of 162 patients (55.3%) underwent cardioversion due to persistent atrial arrhythmias.Comparison between termination by ablation and termination by cardioversion in patients exhibiting AF or AT revealed that no significant difference was observed in early recurrence (38.2% vs.43.8%,P=0.328) and SR maintenance (67.2% vs.59.8%,P=0.198) during the (23±7) months follow-up.Even after repeat ablation,the SR maintenance continued to exhibit no statistical difference in above two groups (72.5% vs.70.4%,P=0.686).Further analysis of subgroups,however,demonstrated that patients with AF terminated directly to SR experienced better clinical outcomes than other subgroups (P <0.05).Furthermore,atrial arrhythmias present during ablation have been implicated in prediction of recurrence mode:AF or AT (P <0.05).Conclusions Termination as a procedural endpoint is not associated with favorable long-term SR maintenance in persistent AF.AF methods that convert arrhythmia directly to SR have,however,been linked with improved clinical outcomes,although conversions to AT may not be correlated.Atrial arrhythmias observed during the ablation may be used to

  11. Concentrations of VEGF and VEGFR1 in paired tumor arteries and veins in patients with rectal cancer

    DEFF Research Database (Denmark)

    Svendsen, Mads N; Lykke, Jakob; Werther, Kim;

    2004-01-01

    platelets were performed in all samples. No significant difference between plasma VEGF levels in the obtained blood samples was found (0.35 < P < 0.86). Plasma sVEGFR1 concentrations were significantly increased in tumor veins compared with tumor arteries. In addition, a significant reduction in plasma s......VEGFR1 concentrations from preoperative to intraoperative samples was observed. There was a significant efflux of neutrophils to the tumor, but none of the observed changes in plasma VEGF or VEGFR1 levels correlated to changes in counts of white blood cells or platelets (sVEGF: 0.33 < P < 0.73 and s......Increased plasma concentrations of vascular endothelial growth factor (sVEGF) are associated with poor prognosis of colorectal cancer patients. The aim was to investigate the contribution of the tumor to plasma concentrations of VEGF and VEGF receptor 1 (VEGFR1). Preoperative blood samples from a...

  12. Placenta growth factor-1 antagonizes VEGF-induced angiogenesis and tumor growth by the formation of functionally inactive PIGF-1/VEGF heterodimers

    DEFF Research Database (Denmark)

    Eriksson, A.; Cao, R.; Pawliuk, R.;

    2002-01-01

    , the biological function of its related homolog, placenta growth factor (PlGF), is poorly understood. Here we demonstrate that PlGF-1, an alternatively spliced isoform of the PlGF gene, antagonizes VEGF-induced angiogenesis when both factors are coexpressed in murine fibrosarcoma cells. Overexpression of PlGF-1...

  13. Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF)

    Energy Technology Data Exchange (ETDEWEB)

    Dunst, J.; Becker, A.; Lautenschlaeger, C.; Markau, S.; Becker, H.; Fischer, K.; Haensgen, G. [Martin-Luther Univ. Halle-Wittenberg (Germany)

    2002-08-01

    Background: Tissue hypoxia is a major stimulus for the up-regulation of vascular endothelial growth factor (VEGF). Anemia might theoretically impact on angiogenesis via impairment of tissue oxygenation. We have investigated this hypothesis in patients with solid cancers and benign diseases. Patients and methods: 49 patients with untreated locoregionally confined solid cancers of the head and neck, cervix, rectum and lung and 59 additional patients with non-malignant diseases (36 normemic patients without serious diseases and 23 patients with renal anemia) were enrolled and the impact of anemia on plasma VEGF levels were determined. VEGF was measured with a commercially available sandwich enzyme immunoassay technique. Results: Plasma levels of VEGF were 16.2{+-}12.7 pg/ml in 36 normemic patients without malignant disease, 49,2{+-}34.5 pg/ml in 49 patients with cancers (p<0.001), and 89.9{+-}67.8 pg/ml in 23 patients with renal anemia (p=0.001). VEGF levels in cancer patients were significantly correlated with hemoglobin (hb) levels and platelet counts (each p=0.001), but not with type of tumor, stage, histology or age. Patients with cancers had higher plasma levels of VEGF than patients with non-malignant diseases in case of hb{>=}12 g/dl (33.1{+-}17.5 vs. 16.6{+-}13.0 pg/ml, p<0.001) and in case of hb between 11.0 and 11.9 g/dl (56.1{+-}26.4 vs 18.5{+-}14.5 pg/ml, p=0.038). In case of a hb<11 g/dl, plasma VEGF levels were significantly elevated in patients with and without cancers (67.0{+-}47.5 vs 88.9{+-}68.8 pg/ml, n.s.). In a multivariate model, a significant association between low hb levels and increased plasma levels of VEGF was confirmed. In 16 patients with renal anemia, changes in hb under erythropoietin treatment were inversely correlated with changes in plasma VEGF levels with decreasing VEGF after increase in hb (p=0.01). Conclusions: Anemic patients have elevated levels of VEGF. The data suggest that anemia might impact on the progression of

  14. Prokaryotic Soluble Overexpression and Purification of Human VEGF165 by Fusion to a Maltose Binding Protein Tag.

    Directory of Open Access Journals (Sweden)

    Minh Tan Nguyen

    Full Text Available Human vascular endothelial growth factor (VEGF is a key regulator of angiogenesis and plays a central role in the process of tumor growth and metastatic dissemination. Escherichia coli is one of the most common expression systems used for the production of recombinant proteins; however, expression of human VEGF in E. coli has proven difficult because the E. coli-expressed VEGF tends to be misfolded and forms inclusion bodies, resulting in poor solubility. In this study, we successfully produced semi-preparative amounts of soluble bioactive human VEGF165 (hVEGF. We created seven N-terminal fusion tag constructs with hexahistidine (His6, thioredoxin (Trx, glutathione S-transferase (GST, maltose-binding protein (MBP, N-utilization substance protein A (NusA, human protein disulfide isomerase (PDI, and the b'a' domain of PDI (PDIb'a', and tested each construct for soluble overexpression in E. coli. We found that at 18°C, 92.8% of the MBP-tagged hVEGF to be soluble and that this tag significantly increased the protein's solubility. We successfully purified 0.8 mg of pure hVEGF per 500 mL cell culture. The purified hVEGF is stable after tag cleavage, contains very low levels of endotoxin, and is 97.6% pure. Using an Flk1+ mesodermal precursor cell (MPC differentiation assay, we show that the purified hVEGF is not only bioactive but has similar bioactivity to hVEGF produced in mammalian cells. Previous reports on producing hVEGF in E. coli have all been based on refolding of the protein from inclusion bodies. To our knowledge, this is the first report on successfully expressing and purifying soluble hVEGF in E. coli.

  15. Prokaryotic Soluble Overexpression and Purification of Human VEGF165 by Fusion to a Maltose Binding Protein Tag.

    Science.gov (United States)

    Nguyen, Minh Tan; Krupa, Martin; Koo, Bon-Kyung; Song, Jung-A; Vu, Thu Trang Thi; Do, Bich Hang; Nguyen, Anh Ngoc; Seo, Taewook; Yoo, Jiwon; Jeong, Boram; Jin, Jonghwa; Lee, Kyung Jin; Oh, Heung-Bum; Choe, Han

    2016-01-01

    Human vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and plays a central role in the process of tumor growth and metastatic dissemination. Escherichia coli is one of the most common expression systems used for the production of recombinant proteins; however, expression of human VEGF in E. coli has proven difficult because the E. coli-expressed VEGF tends to be misfolded and forms inclusion bodies, resulting in poor solubility. In this study, we successfully produced semi-preparative amounts of soluble bioactive human VEGF165 (hVEGF). We created seven N-terminal fusion tag constructs with hexahistidine (His6), thioredoxin (Trx), glutathione S-transferase (GST), maltose-binding protein (MBP), N-utilization substance protein A (NusA), human protein disulfide isomerase (PDI), and the b'a' domain of PDI (PDIb'a'), and tested each construct for soluble overexpression in E. coli. We found that at 18°C, 92.8% of the MBP-tagged hVEGF to be soluble and that this tag significantly increased the protein's solubility. We successfully purified 0.8 mg of pure hVEGF per 500 mL cell culture. The purified hVEGF is stable after tag cleavage, contains very low levels of endotoxin, and is 97.6% pure. Using an Flk1+ mesodermal precursor cell (MPC) differentiation assay, we show that the purified hVEGF is not only bioactive but has similar bioactivity to hVEGF produced in mammalian cells. Previous reports on producing hVEGF in E. coli have all been based on refolding of the protein from inclusion bodies. To our knowledge, this is the first report on successfully expressing and purifying soluble hVEGF in E. coli. PMID:27231876

  16. Elevated VEGF-D Modulates Tumor Inflammation and Reduces the Growth of Carcinogen-Induced Skin Tumors.

    Science.gov (United States)

    Honkanen, Hanne-Kaisa; Izzi, Valerio; Petäistö, Tiina; Holopainen, Tanja; Harjunen, Vanessa; Pihlajaniemi, Taina; Alitalo, Kari; Heljasvaara, Ritva

    2016-07-01

    Vascular endothelial growth factor D (VEGF-D) promotes the lymph node metastasis of cancer by inducing the growth of lymphatic vasculature, but its specific roles in tumorigenesis have not been elucidated. We monitored the effects of VEGF-D in cutaneous squamous cell carcinoma (cSCC) by subjecting transgenic mice overexpressing VEGF-D in the skin (K14-mVEGF-D) and VEGF-D knockout mice to a chemical skin carcinogenesis protocol involving 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate treatments. In K14-mVEGF-D mice, tumor lymphangiogenesis was significantly increased and the frequency of lymph node metastasis was elevated in comparison with controls. Most notably, the papillomas regressed more often in K14-mVEGF-D mice than in littermate controls, resulting in a delay in tumor incidence and a remarkable reduction in the total tumor number. Skin tumor growth and metastasis were not obviously affected in the absence of VEGF-D; however, the knockout mice showed a trend for reduced lymphangiogenesis in skin tumors and in the untreated skin. Interestingly, K14-mVEGF-D mice showed an altered immune response in skin tumors. This consisted of the reduced accumulation of macrophages, mast cells, and CD4(+) T-cells and an increase of cytotoxic CD8(+) T-cells. Cytokine profiling by flow cytometry and quantitative real time PCR revealed that elevated VEGF-D expression results in an attenuated Th2 response and promotes M1/Th1 and Th17 polarization in the early stage of skin carcinogenesis, leading to an anti-tumoral immune environment and the regression of primary tumors. Our data suggest that VEGF-D may be beneficial in early-stage tumors since it suppresses the pro-tumorigenic inflammation, while at later stages VEGF-D-induced tumor lymphatics provide a route for metastasis. PMID:27435926

  17. Paradoxical effects of VEGF on synaptic activity partially involved in notch1 signaling in the mouse hippocampus.

    Science.gov (United States)

    Yang, Jiajia; Yang, Chunxiao; Liu, Chunhua; Zhang, Tao; Yang, Zhuo

    2016-05-01

    It is well known that the neuronal effects of vascular endothelial growth factor (VEGF) include modulating learning and memory, plasticity of mature neurons, and synaptic transmission in addition to neurogenesis. However, there is conflicting evidence particularly of its role in the regulation of excitatory synaptic activity. In this study, application of the patch-clamp technique revealed that lower doses (10 and 50 ng/mL) of VEGF enhanced excitatory neurotransmission in hippocampal slices of mice through both presynaptic and postsynaptic mechanisms. However, the effects were reversed by higher doses of VEGF (>100 ng/mL), which inhibited excitatory neurotransmission via a presynaptic mechanism. These competing, concentration-dependent effects of VEGF suggested that different pathways were involved. The involvement of the Notch1 receptor was tested in the modulation of VEGF on synaptic activity by using heterozygous Notch1(+/-) mice. Notch1 knockdown did not influence the inhibitory effect of high VEGF doses (200 ng/mL) but reduced the enhancement effects of low concentration of VEGF (50 ng/mL) at the postsynaptic level, which might be due to the decreased level of VEGF receptor. The results indicate that the Notch1 receptor plays a role in VEGF-induced modulation of synaptic activity, which provides new insights into a complex VEGF/Notch signaling cross-talk. These findings set the groundwork for understanding new mechanisms of Notch signaling and the neurotrophic effects of VEGF, which is beneficial to develop new therapeutic targets to the VEGF/Notch axis and improve current treatments for neural diseases. PMID:26482652

  18. VEGF induces proliferation of human hair follicle dermal papilla cells through VEGFR-2-mediated activation of ERK

    International Nuclear Information System (INIS)

    Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DP cells was analyzed by MTT assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF165 stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF165-induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF165. Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling. -- Highlights: ► We examine the expression of VEGFR-2 on cultured human dermal papilla (DP) cells. ► VEGF165 stimulated proliferation of human DP cells in a dose-dependent manner. ► This stimulation was through VEGFR-2-mediated activation of ERK.

  19. The growth and aggressive behavior of human osteosarcoma is regulated by a CaMKII-controlled autocrine VEGF signaling mechanism.

    Directory of Open Access Journals (Sweden)

    Paul G Daft

    Full Text Available Osteosarcoma (OS is a hyperproliferative malignant tumor that requires a high vascular density to maintain its large volume. Vascular Endothelial Growth Factor (VEGF plays a crucial role in angiogenesis and acts as a paracrine and autocrine agent affecting both endothelial and tumor cells. The alpha-Ca2+/Calmodulin kinase two (α-CaMKII protein is an important regulator of OS growth. Here, we investigate the role of α-CaMKII-induced VEGF in the growth and tumorigenicity of OS. We show that the pharmacologic and genetic inhibition of α-CaMKII results in decreases in VEGF gene expression (50% and protein secretion (55%, while α- CaMKII overexpression increases VEGF gene expression (250% and protein secretion (1,200%. We show that aggressive OS cells (143B express high levels of VEGF receptor 2 (VEGFR-2 and respond to exogenous VEGF (100nm by increasing intracellular calcium (30%. This response is ameliorated by the VEGFR inhibitor CBO-P11, suggesting that secreted VEGF results in autocrine stimulated α-CaMKII activation. Furthermore, we show that VEGF and α-CaMKII inhibition decreases the transactivation of the HIF-1α and AP-1 reporter constructs. Additionally, chromatin immunoprecipitation assay shows significantly decreased binding of HIF-1α and AP-1 to their responsive elements in the VEGF promoter. These data suggest that α-CaMKII regulates VEGF transcription by controlling HIF-1α and AP-1 transcriptional activities. Finally, CBO-P11, KN-93 (CaMKII inhibitor and combination therapy significantly reduced tumor burden in vivo. Our results suggest that VEGF-induced OS tumor growth is controlled by CaMKII and dual therapy by CaMKII and VEGF inhibitors could be a promising therapy against this devastating adolescent disease.

  20. Clinical significance of co-expression of VEGF-C and VEGFR-3 in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    李庆昌; 董昕; 顾伟; 邱雪杉; 王恩华

    2003-01-01

    Objective To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).Methods Seventy-six NSCLC samples were stained for VEGF-C, VEGFR-3 and CD34 with immunohistochemical methods. Assessment of lymphatic vessel density (LVD) and microvessel density (MVD) was performed. The expressions of VEGF-C in 24 fresh NSCLC samples were determined with Western blot assay.Results Of the 76 NSCLC cases, 55 were VEGF-C positive and 40 were VEGFR-3 positive in cancer cells. A significant positive correlation was found between VEGF-C expression and VEGFR-3 expression in cancer cells (P<0.05). VEGF-C expression was negatively associated with differentiation of tumor cells (P<0.05). VEGF-C expression and VEGFR-3 expression were positively associated with lymph node metastasis and lymphatic invasion (P<0.05). LVD was positively related to VEGF-C expression, lymph node metastasis, lymphatic invasion and clinical stage (P<0.05). There was a significant correlation between LVD and MVD (R=0.732, P<0.05). Patients with positive VEGF-C expression had worse outcomes than those with negative VEGF-C expression (P<0.001).Conclusions In NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.

  1. Binding of VEGF-A to canine cancer cells with preferential expression of VEGFR1

    Directory of Open Access Journals (Sweden)

    Antonella Borgatti,

    2014-01-01

    Full Text Available Aim: Despite encouraging results in syngeneic and xenografts cancer models with various inhibitors of vascular endothelial growth factor (VEGF or its receptors (VEGFRs, beneficial effects have not been consistently translated to the clinic, underscoring the need to develop strategies that go beyond the inhibition of these targets. The purpose of this study was to generate data to support the hypothesis that VEGF may be used as “bait” to selectively deliver therapeutics to VEGFR-expressing cancer cells. Materials and Methods: VEGFR1 and VEGFR2 expression was characterized using real time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR in canine hemangiosarcoma (Grace-HSA, Emma-HSA, melanoma (TLM-1, and thyroid adenocarcinoma (CTAC cell lines. TLM-1 and Grace-HSA were identified as representative cell lines that selectively expressed high levels of VEGFR1. Flow cytometry was performed to examine binding of a single VEGF molecule (biotinylated VEGFA and avidin conjugated to fluorescein isothiocyanate (FITC by these chemoresistant cell lines. Results: RT-qPCR showed that canine tumor cells can preferentially express VEGFR1 over VEGFR2. Both TLM-1 and Grace-HSA cell lines, which represent VEGFR1-expressing tumors, showed specific binding to VEGF-A and this binding was competitively inhibited by anti-VEGF antibody. Conclusions: Cells preferentially expressing VEGFR1 can be targeted with a single VEGF molecule and these ligand-receptor pairs are well suited for targeting cytotoxic molecules in various canine tumor cells. Further studies are needed to develop strategies to selectively deliver therapeutics through VEGF-VEGFRs binding into VEGFR-expressing tumors.

  2. Critical requirement of VEGF-C in transition to fetal erythropoiesis.

    Science.gov (United States)

    Fang, Shentong; Nurmi, Harri; Heinolainen, Krista; Chen, Shuo; Salminen, Essi; Saharinen, Pipsa; Mikkola, Hanna K A; Alitalo, Kari

    2016-08-01

    Vascular endothelial growth factor C (VEGF-C) is a major driver of lymphangiogenesis in embryos and adults. Vegfc gene deletion in mouse embryos results in failure of lymphangiogenesis, fluid accumulation in tissues, and lethality. The VEGF-C receptors VEGFR3 and VEGFR2 are required for embryonic blood vessel formation. The related VEGF is essential for both blood vessel formation and embryonic hematopoiesis, whereas the possible involvement of VEGF-C in hematopoiesis is unknown. Here we unveil a novel hematopoietic function of VEGF-C in fetal erythropoiesis. Deletion of Vegfc in embryonic day 7.5 (E7.5) embryos in the C57BL6 mouse genetic background led to defective fetal erythropoiesis, characterized by anemia and lack of enucleated red blood cells in blood circulation. Macrophages and erythroid cells in the fetal liver (FL) were also decreased after midgestation because of decreased cell proliferation and increased apoptosis. However, the Lin(-)Sca-1(+)c-Kit(+) stem cell compartment in E14.5 FL was not affected by Vegfc deletion. VEGF-C loss did not disrupt the generation of primitive erythroid cells or erythro-myeloid progenitors (EMPs) in the yolk sac, but it decreased the expression of α4-integrin on EMPs and compromised EMP colonization of the FL. The distribution, maturation, and enucleation of primitive erythroblasts were also impaired by Vegfc deletion. In contrast, Vegfc deletion from E10.5 onward did not compromise definitive hematopoiesis in the liver, and Vegfc deletion in adult mice did not cause anemia. These results reveal an unexpected role for VEGF-C, a major lymphangiogenic growth factor, in the transition to FL erythropoiesis. PMID:27343251

  3. Percutaneous Microwave Ablation of Renal Angiomyolipomas

    Energy Technology Data Exchange (ETDEWEB)

    Cristescu, Mircea, E-mail: mcristescu@uwhealth.org [University of Wisconsin, Department of Radiology (United States); Abel, E. Jason, E-mail: abel@urology.wisc.edu [University of Wisconsin, Department of Urology (United States); Wells, Shane, E-mail: swells@uwhealth.org; Ziemlewicz, Timothy J., E-mail: tziemlewicz@uwhealth.org [University of Wisconsin, Department of Radiology (United States); Hedican, Sean P., E-mail: hedican@surgery.wisc.edu [University of Wisconsin, Department of Urology (United States); Lubner, Megan G., E-mail: mlubner@uwhealth.org; Hinshaw, J. Louis, E-mail: jhinshaw@uwhealth.org; Brace, Christopher L., E-mail: cbrace@uwhealth.org; Lee, Fred T., E-mail: flee@uwhealth.org [University of Wisconsin, Department of Radiology (United States)

    2016-03-15

    PurposeTo evaluate the safety and efficacy of US-guided percutaneous microwave (MW) ablation in the treatment of renal angiomyolipoma (AML).Materials and MethodsFrom January 2011 to April 2014, seven patients (5 females and 2 males; mean age 51.4) with 11 renal AMLs (9 sporadic type and 2 tuberous sclerosis associated) with a mean size of 3.4 ± 0.7 cm (range 2.4–4.9 cm) were treated with high-powered, gas-cooled percutaneous MW ablation under US guidance. Tumoral diameter, volume, and CT/MR enhancement were measured on pre-treatment, immediate post-ablation, and delayed post-ablation imaging. Clinical symptoms and creatinine were assessed on follow-up visits.ResultsAll ablations were technically successful and no major complications were encountered. Mean ablation parameters were ablation power of 65 W (range 60–70 W), using 456 mL of hydrodissection fluid per patient, over 4.7 min (range 3–8 min). Immediate post-ablation imaging demonstrated mean tumor diameter and volume decreases of 1.8 % (3.4–3.3 cm) and 1.7 % (27.5–26.3 cm{sup 3}), respectively. Delayed imaging follow-up obtained at a mean interval of 23.1 months (median 17.6; range 9–47) demonstrated mean tumor diameter and volume decreases of 29 % (3.4–2.4 cm) and 47 % (27.5–12.1 cm{sup 3}), respectively. Tumoral enhancement decreased on immediate post-procedure and delayed imaging by CT/MR parameters, indicating decreased tumor vascularity. No patients required additional intervention and no patients experienced spontaneous bleeding post-ablation.ConclusionOur early experience with high-powered, gas-cooled percutaneous MW ablation demonstrates it to be a safe and effective modality to devascularize and decrease the size of renal AMLs.

  4. Dust ablation in Pluto's atmosphere

    Science.gov (United States)

    Horanyi, Mihaly; Poppe, Andrew; Sternovsky, Zoltan

    2016-04-01

    Based on measurements by dust detectors onboard the Pioneer 10/11 and New Horizons spacecraft the total production rate of dust particles born in the Edgeworth Kuiper Belt (EKB) has been be estimated to be on the order of 5 ṡ 103 kg/s in the approximate size range of 1 - 10 μm. Dust particles are produced by collisions between EKB objects and their bombardment by both interplanetary and interstellar dust particles. Dust particles of EKB origin, in general, migrate towards the Sun due to Poynting-Robertson drag but their distributions are further sculpted by mean-motion resonances as they first approach the orbit of Neptune and later the other planets, as well as mutual collisions. Subsequently, Jupiter will eject the vast majority of them before they reach the inner solar system. The expected mass influx into Pluto atmosphere is on the order of 200 kg/day, and the arrival speed of the incoming particles is on the order of 3 - 4 km/s. We have followed the ablation history as function of speed and size of dust particles in Pluto's atmosphere, and found that volatile rich particles can fully sublimate due to drag heating and deposit their mass in narrow layers. This deposition might promote the formation of the haze layers observed by the New Horizons spacecraft. This talk will explore the constraints on the composition of the dust particles by comparing the altitude of the deposition layers to the observed haze layers.

  5. Fractional ablative erbium YAG laser

    DEFF Research Database (Denmark)

    Taudorf, Elisabeth H; Haak, Christina S; Erlendsson, Andrés M;

    2014-01-01

    BACKGROUND AND OBJECTIVES: Treatment of a variety of skin disorders with ablative fractional lasers (AFXL) is driving the development of portable AFXLs. This study measures micropore dimensions produced by a small 2,940 nm AFXL using a variety of stacked pulses, and determines a model correlating...... laser parameters with tissue effects. MATERIALS AND METHODS: Ex vivo pig skin was exposed to a miniaturized 2,940 nm AFXL, spot size 225 µm, density 5%, power levels 1.15-2.22 W, pulse durations 50-225 microseconds, pulse repetition rates 100-500 Hz, and 2, 20, or 50 stacked pulses, resulting in pulse...... 190 to 347 µm. CONCLUSIONS: Pulse stacking with a small, low power 2,940 nm AFXL created reproducible shallow to deep micropores, and influenced micropore configuration. Mathematical modeling established relations between laser settings and micropore dimensions, which assists in choosing laser...

  6. Link Analysis

    Science.gov (United States)

    Donoho, Steve

    Link analysis is a collection of techniques that operate on data that can be represented as nodes and links. This chapter surveys a variety of techniques including subgraph matching, finding cliques and K-plexes, maximizing spread of influence, visualization, finding hubs and authorities, and combining with traditional techniques (classification, clustering, etc). It also surveys applications including social network analysis, viral marketing, Internet search, fraud detection, and crime prevention.

  7. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    educational approaches. Methods: Mixed qualitative design: survey based on telephone interviews with health managers (n=72), personal and focus group interviews with health professionals (n=84) and pupils (n=108) from 18 school classes, and comparative case studies in five selected municipalities of various......, health professionalism, and management strategies pose the foremost challenge. Operational links indicates cooperative levels that facilitate a creative and innovative effort across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  8. Femtosecond ultraviolet laser ablation of silver and comparison with nanosecond ablation

    DEFF Research Database (Denmark)

    Christensen, Bo Toftmann; Doggett, B.; Budtz-Jørgensen, C.;

    2013-01-01

    The ablation plume dynamics arising from ablation of silver with a 500 fs, 248 nm laser at ~2 J cm-2 has been studied using angle-resolved Langmuir ion probe and thin film deposition techniques. For the same laser fluence, the time-of-flight ion signals from femtosecond and nanosecond laser...

  9. An increase in vascular endothelial growth factor (VEGF and VEGF soluble receptor-1 (sFlt-1 are associated with early recurrent spontaneous abortion.

    Directory of Open Access Journals (Sweden)

    Lihong Pang

    Full Text Available Recurrent spontaneous abortion (RSA is a health problem that affects approximately 1% to 5% reproductive age woman. Yet, in around half of these patients, the mechanism for RSA is unexplained. Recent studies have indicated that placental ischemia/hypoxia and endothelial dysfunction are important factors in miscarriage. Other studies have indicated that the level and expression of soluble FMS-like tyrosine kinase-1 (sFlt1 is increased under a hypoxic environment. However, decreased sFlt-1 in the maternal circulation during the first trimester has recently been proposed as a potential marker for identifying risk of pregnancy loss. In this prospective study clinical samples were obtained within a short time after the fetal death, protein expression and maternal serum levels of sFlt1 were assessed and compared to samples taken from those with normal pregnancies. Our results indicate that levels of VEGF and sFlt-1 are both increased in women during early pregnancy compared women that are not pregnant (p<0.05 indicating that VEGF and sFlt-1 are both associated with pregnancy. More importantly, we detected a significant (p<0.05 increase in sFlt1 and VEGF levels and expression in the RSA patients who suffered subsequent miscarriages compare to controls. These results demonstrate that there is likely a relationship between VEGF, sFlt-1 and RSA suggesting that the high levels and over expression of sFlt-1 and VEGF might be associated with the pathogenesis of RSA.

  10. Ionic Effects on VEGF G-Quadruplex Stability.

    Science.gov (United States)

    Kim, Byul G; Long, Ji; Dubins, David N; Chalikian, Tigran V

    2016-06-01

    In a potassium solution, a modified 22-meric DNA sequence Pu22-T12T13 from a region proximal to the transcription initiation site of the human VEGF gene adopts a single parallel-stranded G-quadruplex conformation with a 1:4:1 loop-size arrangement. We measured the thermal stability, TM, of the K(+)-stabilized Pu22-T12T13 G-quadruplex as a function of stabilizing K(+) ions and nonstabilizing Cs(+) and TMA(+) ions. The thermal stability, TM, of the Pu22-T12T13 G-quadruplex increases with the concentration of the stabilizing potassium ions, while it sharply decreases upon the addition of the nonstabilizing cations. We interpret these results as underscoring the opposing effects of internal binding and counterion condensation on the stability of the Pu22-T12T13 G-quadruplex. While centrally bound ions stabilize the G-quadruplex conformation, counterion condensation destabilizes it, favoring the coil conformation. From the initial slopes of the dependences of TM on the concentration of Cs(+) and TMA(+) cations, we estimate that the deleterious effect of counterion condensation stems from roughly one extra counterion associated with the coil relative to the G-quadruplex state of Pu22-T12T13. The reduced accumulation of counterions around the G-quadruplex state of Pu22-T12T13 relative to its coil state is due to the low surface charge density of the G-quadruplex reflecting its structural characteristics. On the basis of the analysis of our data along with the results of a previous study, we propose that the differential effect of internally (stabilizing) and externally (destabilizing) bound cations may be a general feature of parallel intramolecular G-quadruplexes. PMID:27196695

  11. Radiofrequency thermal ablation of malignant hepatic tumors: post-ablation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jung Bin; Rhim, Hyunchul; Kim, Yongsoo; Koh, Byung Hee; Cho, On Koo; Seo, Heung Suk; Lee, Seung Ro [College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    2000-07-01

    To evaluate post-ablation syndrome after radiofrequency thermal ablation of malignant hepatic tumors. Forty-two patients with primary (n=3D29) or secondary (n=3D13) hepatic tumors underwent radiofrequency thermal ablation. A total of 65 nodules ranging in size from 1.1 to 5.0 (mean, 3.1) cm were treated percutaneously using a 50W RF generator with 15G expandable needle electrodes. We retrospectively evaluated the spectrum of post-ablation syndrome including pain, fever ({>=}3D 38 deg C), nausea, vomiting, right shoulder pain, and chest discomfort according to frequency, intensity and duration, and the findings were correlated with tumor location and number of ablations. We also evaluated changes in pre-/post-ablation serum aminotransferase (ALT/AST) and prothrombin time, and correlated these findings with the number of ablations. Post-ablation syndrome was noted in 29 of 42 patients (69.0%), and most symptoms improved with conservative treatment. The most important of these were abdominal plan (n=3D20, 47.6%), fever (n=3D8, 19.0%), and nausea (n=3D7, 16.7%), and four of 42 (9.5%) patients complained of severe pain. The abdominal pain lasted from 3 hours to 5.5 days (mean; 20.4 hours), the fever from 6 hours to 5 days (mean; 63.0 hours). And the nausea from 1 hours to 4 days (mean; 21.0 hours). Other symptoms were right shoulder pain (n=3D6, 14.3%), chest discomfort (n=3D3, 7.1%), and headache (n=3D3, 7.1%). Seventeen of 20 patients (85%) with abdominal pain had subcapsular tumor of the liver. There was significant correlation between pain, location of the tumor, and a number of ablations. After ablation, ALT/AST was elevated more than two-fold in 52.6%/73.7% of patients, respectively but there was no significant correlation with the number of ablation. Post-ablation syndrome is a frequent and tolerable post-procedural process after radiofrequency thermal ablation. The spectrum of this syndrome provides a useful guideline for the post-ablation management. (author)

  12. Radiofrequency thermal ablation of malignant hepatic tumors: post-ablation syndrome

    International Nuclear Information System (INIS)

    To evaluate post-ablation syndrome after radiofrequency thermal ablation of malignant hepatic tumors. Forty-two patients with primary (n=3D29) or secondary (n=3D13) hepatic tumors underwent radiofrequency thermal ablation. A total of 65 nodules ranging in size from 1.1 to 5.0 (mean, 3.1) cm were treated percutaneously using a 50W RF generator with 15G expandable needle electrodes. We retrospectively evaluated the spectrum of post-ablation syndrome including pain, fever (≥3D 38 deg C), nausea, vomiting, right shoulder pain, and chest discomfort according to frequency, intensity and duration, and the findings were correlated with tumor location and number of ablations. We also evaluated changes in pre-/post-ablation serum aminotransferase (ALT/AST) and prothrombin time, and correlated these findings with the number of ablations. Post-ablation syndrome was noted in 29 of 42 patients (69.0%), and most symptoms improved with conservative treatment. The most important of these were abdominal plan (n=3D20, 47.6%), fever (n=3D8, 19.0%), and nausea (n=3D7, 16.7%), and four of 42 (9.5%) patients complained of severe pain. The abdominal pain lasted from 3 hours to 5.5 days (mean; 20.4 hours), the fever from 6 hours to 5 days (mean; 63.0 hours). And the nausea from 1 hours to 4 days (mean; 21.0 hours). Other symptoms were right shoulder pain (n=3D6, 14.3%), chest discomfort (n=3D3, 7.1%), and headache (n=3D3, 7.1%). Seventeen of 20 patients (85%) with abdominal pain had subcapsular tumor of the liver. There was significant correlation between pain, location of the tumor, and a number of ablations. After ablation, ALT/AST was elevated more than two-fold in 52.6%/73.7% of patients, respectively but there was no significant correlation with the number of ablation. Post-ablation syndrome is a frequent and tolerable post-procedural process after radiofrequency thermal ablation. The spectrum of this syndrome provides a useful guideline for the post-ablation management. (author)

  13. VEGF dose regulates vascular stabilization through Semaphorin3A and the Neuropilin-1+ monocyte/TGF-β1 paracrine axis.

    Science.gov (United States)

    Groppa, Elena; Brkic, Sime; Bovo, Emmanuela; Reginato, Silvia; Sacchi, Veronica; Di Maggio, Nunzia; Muraro, Manuele G; Calabrese, Diego; Heberer, Michael; Gianni-Barrera, Roberto; Banfi, Andrea

    2015-10-01

    VEGF is widely investigated for therapeutic angiogenesis, but while short-term delivery is desirable for safety, it is insufficient for new vessel persistence, jeopardizing efficacy. Here, we investigated whether and how VEGF dose regulates nascent vessel stabilization, to identify novel therapeutic targets. Monoclonal populations of transduced myoblasts were used to homogeneously express specific VEGF doses in SCID mouse muscles. VEGF was abrogated after 10 and 17 days by Aflibercept treatment. Vascular stabilization was fastest with low VEGF, but delayed or prevented by higher doses, without affecting pericyte coverage. Rather, VEGF dose-dependently inhibited endothelial Semaphorin3A expression, thereby impairing recruitment of Neuropilin-1-expressing monocytes (NEM), TGF-β1 production and endothelial SMAD2/3 activation. TGF-β1 further initiated a feedback loop stimulating endothelial Semaphorin3A expression, thereby amplifying the stabilizing signals. Blocking experiments showed that NEM recruitment required endogenous Semaphorin3A and that TGF-β1 was necessary to start the Semaphorin3A/NEM axis. Conversely, Semaphorin3A treatment promoted NEM recruitment and vessel stabilization despite high VEGF doses or transient adenoviral delivery. Therefore, VEGF inhibits the endothelial Semaphorin3A/NEM/TGF-β1 paracrine axis and Semaphorin3A treatment accelerates stabilization of VEGF-induced angiogenesis. PMID:26323572

  14. Bacterial antigen induced release of soluble vascular endothelial growth factor (VEGF) and VEGFR1 before and after surgery

    DEFF Research Database (Denmark)

    Svendsen, Mads N; Lykke, J; Werther, Kim;

    2005-01-01

    OBJECTIVE: The influence of surgery on release of soluble vascular endothelial growth factor (sVEGF) and the soluble inhibitory receptor (sVEGFR1) is unknown. The effect of major and minor surgery on variations in sVEGF and sVEGFR1 concentrations in vivo was studied, and on bacterial antigen...... concentrations in plasma changed during surgery. In vitro stimulation of blood samples with bacteria-derived antigens resulted in a significant increase in sVEGF (p ... significantly with neutrophil cell counts (0.53 surgery. In vitro bacterial stimulation led to increased release of sVEGF, which...

  15. SLT-VEGF Reduces Lung Metastases, Decreases Tumor Recurrence, and Improves Survival in an Orthotopic Melanoma Model

    Directory of Open Access Journals (Sweden)

    Sini Skariah

    2010-08-01

    Full Text Available SLT-VEGF is a recombinant cytotoxin comprised of Shiga-like toxin (SLT subunit A fused to human vascular endothelial growth factor (VEGF. It is highly cytotoxic to tumor endothelial cells overexpressing VEGF receptor-2 (VEGFR-2/KDR/Flk1 and inhibits the growth of primary tumors in subcutaneous models of breast and prostate cancer and inhibits metastatic dissemination in orthotopic models of pancreatic cancer. We examined the efficacy of SLT-VEGF in limiting tumor growth and metastasis in an orthotopic melanoma model, using NCR athymic nude mice inoculated with highly metastatic Line IV Cl 1 cultured human melanoma cells. Twice weekly injections of SLT-VEGF were started when tumors became palpable at one week after intradermal injection of 1 × 106 cells/mouse. Despite selective depletion of VEGFR-2 overexpressing endothelial cells from the tumor vasculature, SLT-VEGF treatment did not affect tumor growth. However, after primary tumors were removed, continued SLT-VEGF treatment led to fewer tumor recurrences (p = 0.007, reduced the incidence of lung metastasis (p = 0.038, and improved survival (p = 0.002. These results suggest that SLT-VEGF is effective at the very early stages of tumor development, when selective killing of VEGFR-2 overexpressing endothelial cells can still prevent further progression. We hypothesize that SLT-VEGF could be a promising adjuvant therapy to inhibit or prevent outgrowth of metastatic foci after excision of aggressive primary melanoma lesions.

  16. Aflibercept exhibits VEGF binding stoichiometry distinct from bevacizumab and does not support formation of immune-like complexes.

    Science.gov (United States)

    MacDonald, Douglas A; Martin, Joel; Muthusamy, Kathir K; Luo, Jiann-Kae; Pyles, Erica; Rafique, Ashique; Huang, Tammy; Potocky, Terra; Liu, Yang; Cao, Jingtai; Bono, Françoise; Delesque, Nathalie; Savi, Pierre; Francis, John; Amirkhosravi, Ali; Meyer, Todd; Romano, Carmelo; Glinka, Meredith; Yancopoulos, George D; Stahl, Neil; Wiegand, Stanley J; Papadopoulos, Nicholas

    2016-07-01

    Anti-vascular endothelial growth factor (VEGF) therapies have improved clinical outcomes for patients with cancers and retinal vascular diseases. Three anti-VEGF agents, pegaptanib, ranibizumab, and aflibercept, are approved for ophthalmic indications, while bevacizumab is approved to treat colorectal, lung, and renal cancers, but is also used off-label to treat ocular vascular diseases. The efficacy of bevacizumab relative to ranibizumab in treating neovascular age-related macular degeneration has been assessed in several trials. However, questions persist regarding its safety, as bevacizumab can form large complexes with dimeric VEGF165, resulting in multimerization of the Fc domain and platelet activation. Here, we compare binding stoichiometry, Fcγ receptor affinity, platelet activation, and binding to epithelial and endothelial cells in vitro for bevacizumab and aflibercept, in the absence or presence of VEGF. In contrast to bevacizumab, aflibercept forms a homogenous 1:1 complex with each VEGF dimer. Unlike multimeric bevacizumab:VEGF complexes, the monomeric aflibercept:VEGF complex does not exhibit increased affinity for low-affinity Fcγ receptors, does not activate platelets, nor does it bind to the surface of epithelial or endothelial cells to a greater degree than unbound aflibercept or control Fc. The latter finding reflects the fact that aflibercept binds VEGF in a unique manner, distinct from antibodies not only blocking the amino acids necessary for VEGFR1/R2 binding but also occluding the heparin-binding site on VEGF165. PMID:27234973

  17. VEGF-A isoform-specific regulation of calcium ion flux, transcriptional activation and endothelial cell migration

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2015-07-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A regulates many aspects of vascular physiology such as cell migration, proliferation, tubulogenesis and cell-cell interactions. Numerous isoforms of VEGF-A exist but their physiological significance is unclear. Here we evaluated two different VEGF-A isoforms and discovered differential regulation of cytosolic calcium ion flux, transcription factor localisation and endothelial cell response. Analysis of VEGF-A isoform-specific stimulation of VEGFR2-dependent signal transduction revealed differential capabilities for isoform activation of multiple signal transduction pathways. VEGF-A165 treatment promoted increased phospholipase Cγ1 phosphorylation, which was proportional to the subsequent rise in cytosolic calcium ions, in comparison to cells treated with VEGF-A121. A major consequence of this VEGF-A isoform-specific calcium ion flux in endothelial cells is differential dephosphorylation and subsequent nuclear translocation of the transcription factor NFATc2. Using reverse genetics, we discovered that NFATc2 is functionally required for VEGF-A-stimulated endothelial cell migration but not tubulogenesis. This work presents a new mechanism for understanding how VEGF-A isoforms program complex cellular outputs by converting signal transduction pathways into transcription factor redistribution to the nucleus, as well as defining a novel role for NFATc2 in regulating the endothelial cell response.

  18. Ablation enhancement of silicon by ultrashort double-pulse laser ablation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xin; Shin, Yung C. [Center for Laser-Based Manufacturing, School of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47907 (United States)

    2014-09-15

    In this study, the ultrashort double-pulse ablation of silicon is investigated. An atomistic simulation model is developed to analyze the underlying physics. It is revealed that the double-pulse ablation could significantly increase the ablation rate of silicon, compared with the single pulse ablation with the same total pulse energy, which is totally different from the case of metals. In the long pulse delay range (over 1 ps), the enhancement is caused by the metallic transition of melted silicon with the corresponding absorption efficiency. At ultrashort pulse delay (below 1 ps), the enhancement is due to the electron excitation by the first pulse. The enhancement only occurs at low and moderate laser fluence. The ablation is suppressed at high fluence due to the strong plasma shielding effect.

  19. Effects of Serum Containing Clastrus orbiculatus Extracts on Proliferation and VEGF-c Expression in Hepatoma Cells of Mice%南蛇藤提取物含药血清对小鼠肝癌Hepal-6细胞的增殖能力和VEGF-c表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    员林; 张华; 钱亚云; 侯莹; 朱耀东; 马慧; 郭试瑜; 久光正; 刘延庆

    2011-01-01

    Objective:Preparing rabbit serum containing Clastrus orbiculatus extracts (COE) ,to investigate preliminarily the effects on proliferation and vascular endothelial growth factor-c (VEGF-c) expression in hepatoma cells of mice (Hepa1-6).Method: The New Zealand white rabbits received COE with dose of 20 mg.kg-1 ·d-1 by gavage.The medicated rabbit serum was obtained using serum phamacological approach.Hepal-6 cells were cultured in media with different dosages of COE-containing serum (the low, medium, high dose groups containing 10%,20% ,30% medicated serum respectively).At the same time,the negative control group and 5-fluorouracil (5-Fu) positive control group were set up.The proliferation inhibition effect of medieated serum containing COE on Hepa1-6 cells was detected by microculture tetrazolium (MTT) assay and the expression level of VEGF-c of Hepal-6 cells was tested by enzyme linked immunosorbent (ELISA).Result: The typical morphological changes of apoptosis were observed after incubation with COE-containing serum of each dose.The medium and high dose COE-containing serum could significantly inhibit the proliferation of Hepal-6 cells time-dependently.The VEGF-c expression level of Hepa1-6 cells treating with medium and high dose COE-containing serum for 24 hours were significantly decreased compared with that of the negative control group (P <0.05).Conclusion: COE-containing serum can significantly inhibit proliferation and VEGF-c expression of Hepa1-6 cells in vitro.%目的:制备南蛇藤提取物(Celastrus orbiculatus extracts,COE)兔含药血清,初步研究其对小鼠肝癌Hepal-6细胞株的增殖能力及血管内皮生长因子-c(VEGF-c)表达水平的影响.方法:取新西兰白兔,以20 mg·kg-1·d-1南蛇藤提取物ig,按通法制备含药血清.设立低、中、高剂量组(分别含有10%,20%,30%的南蛇藤提取物含药血清),作用小鼠肝癌Hepal-6细胞,同时设阴性对照组及5-氟尿嘧啶(5-fluorouracil,5-Fu)阳性对照

  20. MR Guided RF Ablation and Thermometery

    Directory of Open Access Journals (Sweden)

    Sara Eskandari

    2009-01-01

    Full Text Available "nIntroduction: Liver metastasis is detected in more than one million people in each year. Only 10% of them are eligible for surgery. Radiofrequency ablation is the most popular local ablation technique for the management of the other 90% of the metastases. Complete ablation of the lesion with a safe margin is the goal of such a local ablative method. There is no routine available technique for monitoring the treatment process. MRI is the only method which can monitor tissue ablation in real time however interaction of radiofrequency energy by MRI acquisition makes it impossible for clinical use. "nMaterials and Methods: In our in-vitro study, the effect of bipolar needles were evaluated on the signal intensity of theliver parenchyma. This evaluation was repeated 15 times. A calibration curve was also calculated from the in-vitro measurement of tissue temperature with an interstitial NTC sensor with dedicated data collecting software written by our team. Finally the correlation between temperature and signal intensity was prepared and during the RF ablation, the temperature map could be created in an almost real time manner. "nResults: Our results show an exponential calibration curve for sensors and a linear reduction of the signal intensities during the RF procedure. "nConclusion: We introduce a method for calibration of the MRI signal intensity with tissue temperature between alternative RF pulses. This method brings MR monitoring as the practical method in clinical use. By this innovative technique it is possible for all the hospitals and clinics to use their routine MR scanner for monitoring this ablative technique without any additional hardware.  

  1. Photoacoustic characterization of radiofrequency ablation lesions

    Science.gov (United States)

    Bouchard, Richard; Dana, Nicholas; Di Biase, Luigi; Natale, Andrea; Emelianov, Stanislav

    2012-02-01

    Radiofrequency ablation (RFA) procedures are used to destroy abnormal electrical pathways in the heart that can cause cardiac arrhythmias. Current methods relying on fluoroscopy, echocardiography and electrical conduction mapping are unable to accurately assess ablation lesion size. In an effort to better visualize RFA lesions, photoacoustic (PA) and ultrasonic (US) imaging were utilized to obtain co-registered images of ablated porcine cardiac tissue. The left ventricular free wall of fresh (i.e., never frozen) porcine hearts was harvested within 24 hours of the animals' sacrifice. A THERMOCOOLR Ablation System (Biosense Webster, Inc.) operating at 40 W for 30-60 s was used to induce lesions through the endocardial and epicardial walls of the cardiac samples. Following lesion creation, the ablated tissue samples were placed in 25 °C saline to allow for multi-wavelength PA imaging. Samples were imaged with a VevoR 2100 ultrasound system (VisualSonics, Inc.) using a modified 20-MHz array that could provide laser irradiation to the sample from a pulsed tunable laser (Newport Corp.) to allow for co-registered photoacoustic-ultrasound (PAUS) imaging. PA imaging was conducted from 750-1064 nm, with a surface fluence of approximately 15 mJ/cm2 maintained during imaging. In this preliminary study with PA imaging, the ablated region could be well visualized on the surface of the sample, with contrasts of 6-10 dB achieved at 750 nm. Although imaging penetration depth is a concern, PA imaging shows promise in being able to reliably visualize RF ablation lesions.

  2. Mechanism of Spatiotemporal Distribution of Laser Ablated Materials

    Institute of Scientific and Technical Information of China (English)

    XU Rong-Qing; CUI Yi-Ping; LU Jian; NI Xiao-Wu

    2009-01-01

    Interaction between subsequent laser and ablated materials in laser processing changes the laser spatiotemporal distribution and has influences on the efficiency and quality of laser processing. The theoretical and experimental researches on transportation behayiour of ablated materials are provided. It is shown that the velocity distribution of ablated materials is determined by ablation mechanism. The transportation behaviour of ablated materials is controlled by diffusion mechanism and light field force during laser pulse duration while it is only determined by diffusion mechanism when the laser pulse terminates. In addition, the spatiotemporal distribution of ablated materials is presented.

  3. Laser ablation of hepatocellular carcinoma-A review

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A wide range of local thermal ablative therapies have been developed in the treatment of non resectable hepatocellular carcinoma (HCC) in the last decade. Laser ablation (LA) and radiofrequency ablation (RFA) are the two most widely used of these. This article provides an up to date overview of the role of laser ablation in the local treatment of HCC. General principles, technique, image guidance and patient selection are discussed. A review of published data on treatment efficacy, long term outcome and complication rates of laser ablation is included and comparison with RFA made. The role of laser ablation in combination with transcatheter arterial chemoembolisation is also discussed.

  4. Ablation threshold and ablation mechanism transition of polyoxymethylene irradiated by CO2 laser.

    Science.gov (United States)

    Li, Gan; Cheng, Mousen; Li, Xiaokang

    2016-09-01

    Polyoxymethylene (POM) decomposes gradually as it is heated up by the irradiation of CO2 laser; the long-chain molecules of POM are broken into short chains, which leads to the lowering of the melting point and the critical temperature of the ablation products. When the product temperature is above the melting point, ablation comes up in the way of vaporization; when the product temperature is higher than the critical temperature, all liquid products are transformed into gas instantly and the ablation mechanism is changed. The laser fluence at which significant ablation is observed is defined as the ablation threshold, and the fluence corresponding to the ablation mechanism changing is denoted as the flyover threshold. In this paper, random pyrolysis is adopted to describe the pyrolytic decomposition of POM, and consequently, the components of the pyrolysis products under different pyrolysis rates are acquired. The Group Contribution method is used to count the thermodynamic properties of the pyrolysis products, and the melting point and the critical temperature of the product mixture are obtained by the Mixing Law. The Knudsen layer relationship is employed to evaluate the ablation mass removal when the product temperature is below the critical temperature. The gas dynamics conservation laws associated with the Jouguet condition are used to calculate the mass removal when the product temperature is higher than the critical temperature. Based on the model, a set of simulations for various laser intensities and lengths are carried out to generalize the relationships between the thresholds and the laser parameters. Besides the ablated mass areal density, which fits the experimental data quite well, the ablation temperature, pyrolysis rate, and product components are also discussed for a better understanding of the ablation mechanism of POM. PMID:27607281

  5. VEGF Mediates ApoE4-Induced Neovascularization and Synaptic Pathology in the Choroid and Retina.

    Science.gov (United States)

    Antes, Ran; Salomon-Zimri, Shiran; Beck, Susanne C; Garcia Garrido, Marina; Livnat, Tami; Maharshak, Idit; Kadar, Tamar; Seeliger, Mathias; Weinberger, Dov; Michaelson, Daniel M

    2015-01-01

    Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. Recent findings suggest that retina of apoE4 mice have synaptic and functional impairments. We presently investigated the effects of apoE4 on retinal and choroidal vasculature and the possible role of VEGF in these effects. There were no histological differences between the retinal and choroidal vasculatures of naïve apoE3 and apoE4 mice. In contrast, laserdriven choroidal injury induced higher levels of choroidal neovascularization (CNV) in apoE4 than in apoE3 mice. These effects were associated with an inflammatory response and with activation of the Muller cells and asrocytic markers gluthatione synthetase and GFAP, all of which were more pronounced in the apoE4 mice. CNV also induced a transient increase in the levels of the synaptic markers synaptophysin and PSD95 which were however similar in the apoE4 and apoE3 naive mice. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation and the associated surge in VEGF following injury. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation

  6. Expression of VEGF and semaphorin genes define subgroups of triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    R Joseph Bender

    Full Text Available Triple negative breast cancers (TNBC are difficult to treat due to a lack of targets and heterogeneity. Inhibition of angiogenesis is a promising therapeutic strategy, but has had limited effectiveness so far in breast cancer. To quantify heterogeneity in angiogenesis-related gene expression in breast cancer, we focused on two families--VEGFs and semaphorins--that compete for neuropilin co-receptors on endothelial cells. We compiled microarray data for over 2,600 patient tumor samples and analyzed the expression of VEGF- and semaphorin-related ligands and receptors. We used principal component analysis to identify patterns of gene expression, and clustering to group samples according to these patterns. We used available survival data to determine whether these clusters had prognostic as well as therapeutic relevance. TNBC was highly associated with dysregulation of VEGF- and semaphorin-related genes; in particular, it appeared that expression of both VEGF and semaphorin genes were altered in a pro-angiogenesis direction. A pattern of high VEGFA expression with low expression of secreted semaphorins was associated with 60% of triple-negative breast tumors. While all TNBC groups demonstrated poor prognosis, this signature also correlated with lower 5-year survival rates in non-TNBC samples. A second TNBC pattern, including high VEGFC expression, was also identified. These pro-angiogenesis signatures may identify cancers that are more susceptible to VEGF inhibition.

  7. A peptide fusion protein in hibits angiogenesis and tumorgrowth by blocking VEGF binding to KDR

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Vascular endothelial growth factor (VEGF) binding to its tyrosine kinase receptors (KDR/FLK1, Flt-1) induces angiogenesis. In search of the peptides blocking VEGF binding to its receptor KDR/FLK1 to inhibit tumor- angiogenesis and growth, we screened a phage display peptide library with KDR as target protein, and some candidate peptides were isolated. In this study, we cloned the DNA fragment coding the peptide K237 from the library, into a vector pQE42 to express fusion protein DHFR-K237 in E. coli M15. The affection of fusion protein DHFR-K237 on endothelial cell proliferation and angiogenesis was investigated. In vitro, DHFR-K237 could completely block VEGF binding to KDR and significantly inhibit the VEGF-medi- ated proliferation of the human vascular endothelial cells. In vivo, DHFR-K237 inhibited angiogenesis in chick embryo chorioa- llantoric membrane and tumor growth in nude mice. These results suggest that K237 is an effective antagonist of VEGF binding to KDR, and could be a potential agent for cancer biotherapy.

  8. Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF expression of K562 cells

    Institute of Scientific and Technical Information of China (English)

    叶琇锦; 林茂芳

    2004-01-01

    Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. However, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry, The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner, Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.

  9. VEGF EXPRESSION IS INHIBITED BY APIGENIN IN HUMAN BREAST CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    JIN Xue-ying; REN Chang-shan

    2006-01-01

    Objective: To study the effects of apigenin on vascular endothelial growth factor (VEGF) in human breast cancer cells(MDA-MB-231. Methods: MTT assay was used to detect the cell proliferation inhibitory effect of apigenin on MDA-MB-231 cell. ELISA was used to determine the protein level of VEGF secreted by MDA-MB-231 cells. RT-PCR was used to detect mRNA levels of VEGF in MDA-MB-231 cells. The protein levels of HIF-1α,p-AKT,p-ERK1/2,and p53 were detected by Western Blotting. Results: Apigenin did not inhibit the cell viability of MDA-MB-231 cell. Apigenin reduced the secretion and mRNA levels of VEGF in MDA-MB-231 cells. Additionally, apigenin decreased the expressions of HIF-1α,p-AKT and p-ERK1/2, but induced the expression of p53. Conclusion: Apigenin can inhibit VEGF expression in human breast cancer cells, and this may be achieved through decreasing HIF-1α.

  10. Development of PLGA-coated β-TCP scaffolds containing VEGF for bone tissue engineering.

    Science.gov (United States)

    Khojasteh, Arash; Fahimipour, Farahnaz; Eslaminejad, Mohamadreza Baghaban; Jafarian, Mohammad; Jahangir, Shahrbanoo; Bastami, Farshid; Tahriri, Mohammadreza; Karkhaneh, Akbar; Tayebi, Lobat

    2016-12-01

    Bone tissue engineering is sought to apply strategies for bone defects healing without limitations and short-comings of using either bone autografts or allografts and xenografts. The aim of this study was to fabricate a thin layer poly(lactic-co-glycolic) acid (PLGA) coated beta-tricalcium phosphate (β-TCP) scaffold with sustained release of vascular endothelial growth factor (VEGF). PLGA coating increased compressive strength of the β-TCP scaffolds significantly. For in vitro evaluations, canine mesenchymal stem cells (cMSCs) and canine endothelial progenitor cells (cEPCs) were isolated and characterized. Cell proliferation and attachment were demonstrated and the rate of cells proliferation on the VEGF released scaffold was significantly more than compared to the scaffolds with no VEGF loading. A significant increase in expression of COL1 and RUNX2 was indicated in the scaffolds loaded with VEGF and MSCs compared to the other groups. Consequently, PLGA coated β-TCP scaffold with sustained and localized release of VEGF showed favourable results for bone regeneration in vitro, and this scaffold has the potential to use as a drug delivery device in the future. PMID:27612772

  11. Role of vascular endothelial growth factor (VEGF) in the neurological manifestations of dengue: a preliminary study.

    Science.gov (United States)

    Misra, Usha Kant; Kalita, Jayantee; Singh, Avadhesh Pratap

    2014-04-01

    This study reports on vascular endothelial growth factor (VEGF) in dengue patients with neurological manifestations. Their bleeding diathesis, hypotension, edema, flushing, and hepatosplenomegaly were noted. Complete blood counts, serum chemistry, coagulation profile, liver and kidney function tests, creatine kinase (CK), and MRI in encephalopathic patients were carried out. Serum VEGF was estimated by ELISA in 21 dengue patients and 14 controls. Twelve patients had dengue fever (DF), eight dengue hemorrhagic fever (DHF), and one dengue shock syndrome (DSS). Fifteen patients had neurological manifestation, 12 had muscle involvement (raised CK with or without weakness), and 3 had encephalopathy. The VEGF level in dengue patients was 50.0 ± 56.1 pg/mL and in the controls, 60.6 ± 20.3 pg/mL. The VEGF level neither correlated with the severity nor with the neurological involvement. Thrombocytopenia, however, correlated with the severity of dengue and neurological manifestations. The VEGF level is not related to the severity of dengue and neurological syndrome. PMID:24292799

  12. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

    Science.gov (United States)

    Fey, Theres; Schubert, Kai Michael; Schneider, Holger; Fein, Evelyn; Kleinert, Eike; Pohl, Ulrich; Dendorfer, Andreas

    2016-08-01

    Podosomes are dynamic cytoskeletal membrane structures with local adhesive and proteolytic activity. They are critically involved in angiogenesis and vascular adaptive growth. Here, we studied in HUVECs and murine small vessels whether shear stress controls podosome assembly and local proteolytic activity. Podosomes were characterized by immunohistochemistry, and their proteolytic activity was assessed as degradation imprints in fluorescent gelatin that was used as growth substrate. Compared with controls (10 dyn/cm(2)), the number of podosomes formed per time was doubled when cells were exposed to low shear stress (0.3 dyn/cm(2)) or even increased 5-fold under static conditions. This was a result of an enhanced expression of VEGF after reduction of shear stress. Consequently, enhanced podosome formation could be prevented by a VEGF receptor antagonist as well by interruption of VEGF signaling via inhibition of PI3K, Src, or p38. Increase of podosome assembly went along with significantly augmented cell motility. In vivo experiments in mouse arteries confirmed increased endothelial podosome numbers when shear stress was abolished by vessel occlusion. We conclude that shear stress, by reducing VEGF release, inhibits podosome assembly. Hence, endothelial cell-mediated matrix proteolysis and migratory activity are inhibited, thereby stabilizing the structure of the vessel wall.-Fey, T., Schubert, K. M., Schneider, H., Fein, E., Kleinert, E., Pohl, U., Dendorfer, A. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

  13. Angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium

    Institute of Scientific and Technical Information of China (English)

    DONG Shu-qiang; ZHANG Bao-ren; MEI Ju; XU Zhi-yun; ZOU Liang-jian; HUANG Sheng-dong

    2002-01-01

    Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the circumflex coronary artery. Four weeks later, Ad. VEGF-B, Ad. LacZ or PBS were administrated directly into the myocardium at 10 sites in the circumflex distribution (109 PFU or 100 μl) according to groups. Echocardiography and ex vivo coronary angiography were performed. The injection sites around myocardium were harvested and subjected to histological analysis and immunochemical staining. Results: Echocardiography assessment 4 weeks after vector administration demonstrated significant improvement of regional wall systolic function. Collateral vesseldevelopment assessed by angiography was also significantly greater in Ad. VEGF-B animals than that in control animals. Vascular density analysis revealed a mean of 43±5 neovessels per high-power field in Ad.VEGF-B group versus 19±4 and 17±6 in Ad.LacZ and PBS group. Conclusion:Direct intramyocardial administration of Ad.VEGF-B can induce focal angiogenesis and result in improvement in regional myocardial function, which may be useful in patients with ischemic heart disease who are not eligible for conventional therapies.

  14. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Yi-Yong; Lee, Dong-Keon [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); So, Ju-Hoon; Kim, Cheol-Hee [Department of Biology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Jeoung, Dooil [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Lee, Hansoo [Department of Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Choe, Jongseon [Department of Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Won, Moo-Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Ha, Kwon-Soo [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Kwon, Young-Guen [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-752 (Korea, Republic of); Kim, Young-Myeong, E-mail: ymkim@kangwon.ac.kr [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of)

    2015-08-07

    Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC{sub 50} of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases.

  15. Imaging in percutaneous ablation for atrial fibrillation

    Energy Technology Data Exchange (ETDEWEB)

    Maksimovic, Ruzica [Erasmus Medical Center, Department of Radiology, GD Rotterdam (Netherlands); Institute for Cardiovascular Diseases of the University Medical Center, Belgrade (Czechoslovakia); Dill, Thorsten [Kerckhoff-Heart Center, Department of Cardiology, Bad Nauheim (Germany); Ristic, Arsen D.; Seferovic, Petar M. [Institute for Cardiovascular Diseases of the University Medical Center, Belgrade (Czechoslovakia)

    2006-11-15

    Percutaneous ablation for electrical disconnection of the arrhythmogenic foci using various forms of energy has become a well-established technique for treating atrial fibrillation (AF). Success rate in preventing recurrence of AF episodes is high although associated with a significant incidence of pulmonary vein (PV) stenosis and other rare complications. Clinical workup of AF patients includes imaging before and after ablative treatment using different noninvasive and invasive techniques such as conventional angiography, transoesophageal and intracardiac echocardiography, computed tomography (CT) and magnetic resonance imaging (MRI), which offer different information with variable diagnostic accuracy. Evaluation before percutaneous ablation involves assessment of PVs (PV pattern, branching pattern, orientation and ostial size) to facilitate position and size of catheters and reduce procedure time as well as examining the left atrium (presence of thrombi, dimensions and volumes). Imaging after the percutaneous ablation is important for assessment of overall success of the procedure and revealing potential complications. Therefore, imaging methods enable depiction of PVs and the anatomy of surrounding structures essential for preprocedural management and early detection of PV stenosis and other ablation-related procedures, as well as long-term follow-up of these patients. (orig.)

  16. Imaging in percutaneous ablation for atrial fibrillation

    International Nuclear Information System (INIS)

    Percutaneous ablation for electrical disconnection of the arrhythmogenic foci using various forms of energy has become a well-established technique for treating atrial fibrillation (AF). Success rate in preventing recurrence of AF episodes is high although associated with a significant incidence of pulmonary vein (PV) stenosis and other rare complications. Clinical workup of AF patients includes imaging before and after ablative treatment using different noninvasive and invasive techniques such as conventional angiography, transoesophageal and intracardiac echocardiography, computed tomography (CT) and magnetic resonance imaging (MRI), which offer different information with variable diagnostic accuracy. Evaluation before percutaneous ablation involves assessment of PVs (PV pattern, branching pattern, orientation and ostial size) to facilitate position and size of catheters and reduce procedure time as well as examining the left atrium (presence of thrombi, dimensions and volumes). Imaging after the percutaneous ablation is important for assessment of overall success of the procedure and revealing potential complications. Therefore, imaging methods enable depiction of PVs and the anatomy of surrounding structures essential for preprocedural management and early detection of PV stenosis and other ablation-related procedures, as well as long-term follow-up of these patients. (orig.)

  17. Fundamental studies of pulsed laser ablation

    CERN Document Server

    Claeyssens, F

    2001-01-01

    dopant) have resulted in a coherent view of the resulting plume, which exhibits a multi-component structure correlated with different regimes of ablation, which are attributed to ejection from ZnO and ablation from a Zn melt. OES measurements show that the emitting Zn component within the plume accelerates during expansion in vacuum - an observation attributable to the presence of hot, fast electrons in the plume. The same acceleration behaviour is observed in the case of Al atomic emissions resulting from ablation of an Al target in vacuum. Deposition conditions, substrate temperature and background gas pressure were all varied in a quest for optimally aligned, high quality ZnO thin films. Initial ab initio calculations were performed also, to aid in understanding the stability of these c-axis aligned films. The pulsed ultraviolet (lambda = 193, 248 nm) laser ablation of graphite, polycrystalline diamond and ZnO targets has been investigated. Characteristics of the resulting plumes of ablated material have b...

  18. Percutaneous tumor ablation in medical radiology

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J.; Mack, M.G. [University Hospital Frankfurt Univ. (Germany). Inst. for Diagnostic and Interventional Radiology; Helmberger, T.K. [Klinikum Bogenhausen, Academic Teaching Hospital of the Technical Univ. Munich (Germany). Dept. for Diagnostic and Interventional Radiology and Nuclear Medicine; Reiser, M.F. (eds.) [University Hospitals - Grosshadern and Innenstadt Munich Univ. (Germany). Dept. of Clinical Radiology

    2008-07-01

    Thermal ablation has become an integral part of oncology, especially in the field of interventional oncology. This very comprehensive book encompasses the different technologies employed in thermal ablation, its indications and the results achieved in various clinical conditions. The first part of the book clearly explains the basics of thermal ablative techniques such as laser-induced thermotherapy, radiofrequency ablation, microwave ablation, cryotherapy, and localized tumor therapy. The latest developments in the application of minimally invasive therapies in localized neoplastic disease are demonstrated. In the main part of the book, techniques of guiding the applicators to the target structures by use of different imaging tools such as ultrasound, computed tomography and magnetic resonance imaging are discussed. The results are presented for a variety of clinical indications, including liver and lung tumors and metastases and some rather rare conditions involving the kidney, the head and neck, the prostate, and soft tissue structures. A large number of acknowledged experts have contributed to the book, which benefits from a lucid structure and excellent images. (orig.)

  19. Upregulation of CREM/ICER suppresses wound endothelial CRE-HIF-1α-VEGF-dependent signaling and impairs angiogenesis in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Milad S. Bitar

    2015-01-01

    Full Text Available Impaired angiogenesis and endothelial dysfunction in type 2 diabetes constitute dominant risk factors for non-healing wounds and most forms of cardiovascular disease. We propose that diabetes shifts the ‘angiogenic balance’ in favor of an excessive anti-angiogenic phenotype. Herein, we report that diabetes impairs in vivo sponge angiogenic capacity by decreasing VEGF expression and fibrovascular invasion, and reciprocally enhances the formation of angiostatic molecules, such as thrombospondins, NFκB and FasL. Defective in vivo angiogenesis prompted cellular studies in cultured endothelial cells derived from subcutaneous sponge implants (SIECs of control and Goto-Kakizaki rats. Ensuing data from diabetic SIECs demonstrated a marked upregulation in cAMP-PKA-CREB signaling, possibly stemming from increased expression of adenylyl cyclase isoforms 3 and 8, and decreased expression of PDE3. Mechanistically, we found that oxidative stress and PKA activation in diabetes enhanced CREM/ICER expression. This reduces IRS2 cellular content by inhibiting cAMP response element (CRE transcriptional activity. Consequently, a decrease in the activity of Akt-mTOR ensued with a concomitant reduction in the total and nuclear protein levels of HIF-1α. Limiting HIF-1α availability for the specific hypoxia response elements in diabetic SIECs elicited a marked reduction in VEGF expression, both at the mRNA and protein levels. These molecular abnormalities were illustrated functionally by a defect in various pro-angiogenic properties, including cell proliferation, migration and tube formation. A genetic-based strategy in diabetic SIECs using siRNAs against CREM/ICER significantly augmented the PKA-dependent VEGF expression. To this end, the current data identify the importance of CREM/ICER as a negative regulator of endothelial function and establish a link between CREM/ICER overexpression and impaired angiogenesis during the course of diabetes. Moreover, it could

  20. Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice.

    Science.gov (United States)

    Turunen, Mikko P; Husso, Tiia; Musthafa, Haja; Laidinen, Svetlana; Dragneva, Galina; Laham-Karam, Nihay; Honkanen, Sanna; Paakinaho, Anne; Laakkonen, Johanna P; Gao, Erhe; Vihinen-Ranta, Maija; Liimatainen, Timo; Ylä-Herttuala, Seppo

    2014-01-01

    "Epigenetherapy" alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model. shRNA complementary to the promoter of vascular endothelial growth factor (VEGF-A) was able to upregulate endogenous VEGF-A expression. Histological and multiphoton microscope analysis confirmed the therapeutic effect in the transduced hearts. Magnetic resonance imaging (MRI) showed in vivo that the infarct size was significantly reduced in the treatment group 14 days after the epigenetherapy. Importantly, we show that promoter-targeted shRNA upregulates all isoforms of endogenous VEGF-A and that an intact hairpin structure is required for the shRNA activity. In conclusion, regulation of gene expression at the promoter level is a promising new treatment strategy for myocardial infarction and also potentially useful for the upregulation of other endogenous genes. PMID:24587164

  1. The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    M Franklin; E Navarro; Y Wang; S Patel; P Singh; Y Zhang; K Persaud; A Bari; H Griffith; et al.

    2011-12-31

    The anti-VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer. We have determined the structure of the 1121B Fab fragment in complex with domain 3 of VEGFR2, as well as the structure of a different neutralizing anti-VEGFR2 antibody, 6.64, also in complex with VEGFR2 domain 3. The two Fab fragments bind at opposite ends of VEGFR2 domain 3; 1121B directly blocks VEGF binding, whereas 6.64 may prevent receptor dimerization by perturbing the domain 3:domain 4 interface. Mutagenesis reveals that residues essential for VEGF, 1121B, and 6.64 binding are nonoverlapping among the three contact patches.

  2. The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Franklin, Matthew C.; Navarro, Elizabeth C.; Wang, Yujie; Patel, Sheetal; Singh, Pinki; Zhang, Yi; Persaud, Kris; Bari, Amtul; Griffith, Heather; Shen, Leyi; Balderes, Paul; Kussie, Paul (ImClone)

    2011-10-28

    The anti-VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer. We have determined the structure of the 1121B Fab fragment in complex with domain 3 of VEGFR2, as well as the structure of a different neutralizing anti-VEGFR2 antibody, 6.64, also in complex with VEGFR2 domain 3. The two Fab fragments bind at opposite ends of VEGFR2 domain 3; 1121B directly blocks VEGF binding, whereas 6.64 may prevent receptor dimerization by perturbing the domain 3:domain 4 interface. Mutagenesis reveals that residues essential for VEGF, 1121B, and 6.64 binding are nonoverlapping among the three contact patches.

  3. VEGF pathway inhibition by anticancer agent sunitinib and susceptibility to atherosclerosis plaque disruption.

    Science.gov (United States)

    Ropert, Stanislas; Vignaux, Olivier; Mir, Olivier; Goldwasser, François

    2011-12-01

    Patients treated with anti-VEGF agents are at increased risk for arterial thrombo-embolic events (ATEs). However, the pathophysiology of such acute vascular complications remains unclear. We report on a case of bowel infarction in a renal cancer patient treated with the anti-VEGF agent sunitinib. An abdominal CT-scan evidenced the rupture of an atherosclerotic plaque located at the emergence of the superior mesenteric artery. In view of this report, we suggest that evaluation of the risk of ATE in patients receiving anti-VEGF agents should include not only age and past history of ATE as suggested by previous studies, but also assessment of atherosclerotic lesions on CT-scan.

  4. Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Demontis, Ditte; Ollendorff, Mathias Kaas;

    2015-01-01

    measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum...... sortilin levels in depressed individuals compared with controls (P = 0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level...... was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate...

  5. Alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy

    DEFF Research Database (Denmark)

    Jensen, Morten K; Prinz, Christian; Horstkotte, Dieter;

    2013-01-01

    The infarction induced by alcohol septal ablation (ASA) may predispose to arrhythmia and sudden cardiac death (SCD).......The infarction induced by alcohol septal ablation (ASA) may predispose to arrhythmia and sudden cardiac death (SCD)....

  6. Advances in Imaging for Atrial Fibrillation Ablation

    International Nuclear Information System (INIS)

    Over the last fifteen years, our understanding of the pathophysiology of atrial fibrillation (AF) has paved the way for ablation to be utilized as an effective treatment option. With the aim of gaining more detailed anatomical representation, advances have been made using various imaging modalities, both before and during the ablation procedure, in planning and execution. Options have flourished from procedural fluoroscopy, electro anatomic mapping systems, pre procedural computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and combinations of these technologies. Exciting work is underway in an effort to allow the electro physiologist to assess scar formation in real time. One advantage would be to lessen the learning curve for what are very complex procedures. The hope of these developments is to improve the likelihood of a successful ablation procedure and to allow more patients access to this treatment

  7. Deep Dive Topic: Choosing between ablators

    Energy Technology Data Exchange (ETDEWEB)

    Hurricane, O. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Thomas, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Olson, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-07-14

    Recent data on implosions using identical hohlraums and very similar laser drives underscores the conundrum of making a clear choice of one ablator over another. Table I shows a comparison of Be and CH in a nominal length, gold, 575 μm-diameter, 1.6 mg/cc He gas-fill hohlraum while Table II shows a comparison of undoped HDC and CH in a +700 length, gold, 575 μm diameter, 1.6 mg/cc He gas fill hohlraum. As can be seen in the tables, the net integrated fusion performance of these ablators is the same to within error bars. In the case of the undoped HDC and CH ablators, the hot spot shapes of the implosions were nearly indistinguishable for the experiments listed in Table II.

  8. Image-Guided Spinal Ablation: A Review.

    Science.gov (United States)

    Tsoumakidou, Georgia; Koch, Guillaume; Caudrelier, Jean; Garnon, Julien; Cazzato, Roberto Luigi; Edalat, Faramarz; Gangi, Afshin

    2016-09-01

    The image-guided thermal ablation procedures can be used to treat a variety of benign and malignant spinal tumours. Small size osteoid osteoma can be treated with laser or radiofrequency. Larger tumours (osteoblastoma, aneurysmal bone cyst and metastasis) can be addressed with radiofrequency or cryoablation. Results on the literature of spinal microwave ablation are scarce, and thus it should be used with caution. A distinct advantage of cryoablation is the ability to monitor the ice-ball by intermittent CT or MRI. The different thermal insulation, temperature and electrophysiological monitoring techniques should be applied. Cautious pre-procedural planning and intermittent intra-procedural monitoring of the ablation zone can help reduce neural complications. Tumour histology, patient clinical-functional status and life-expectancy should define the most efficient and least disabling treatment option. PMID:27329231

  9. Unexplained liver laceration after metastasis radiofrequency ablation

    Institute of Scientific and Technical Information of China (English)

    Esther U(n)a; Javier Trueba; Jose Manuel Montes

    2009-01-01

    Many studies have established the role of radiofrequency (RF) ablation as a minimally invasive treatment for liver metastases. Although relatively safe, several complications have been reported with the increased use of RF ablation. We describe here a case of unexplained liver laceration after a RF procedure. A woman who presented a solitary metachronous liver metastasis underwent RF ablation treatment for this lesion. Six hours later the patient displayed fatigue and pallor.Emergency blood tests showed a haemoglobin level of < 7 g/dL and markedly elevated transaminase levels.A computed tomography examination revealed two areas of liver laceration with haematoma, one of them following the path of the needle and the other leading away from the first. Following a blood transfusion, the patient was haemodynamically stable and completely recovered 24 h later. The patient remained in bed for 1 wk. No surgical intervention was required, and she was discharged 1 wk later.

  10. Thermal Ablation Modeling for Silicate Materials

    Science.gov (United States)

    Chen, Yih-Kanq

    2016-01-01

    A thermal ablation model for silicates is proposed. The model includes the mass losses through the balance between evaporation and condensation, and through the moving molten layer driven by surface shear force and pressure gradient. This model can be applied in ablation simulations of the meteoroid or glassy Thermal Protection Systems for spacecraft. Time-dependent axi-symmetric computations are performed by coupling the fluid dynamics code, Data-Parallel Line Relaxation program, with the material response code, Two-dimensional Implicit Thermal Ablation simulation program, to predict the mass lost rates and shape change. For model validation, the surface recession of fused amorphous quartz rod is computed, and the recession predictions reasonably agree with available data. The present parametric studies for two groups of meteoroid earth entry conditions indicate that the mass loss through moving molten layer is negligibly small for heat-flux conditions at around 1 MW/cm(exp. 2).

  11. Ablation therapy for left atrial autonomic modification.

    Science.gov (United States)

    Malcolme-Lawes, Louisa; Sandler, Belinda C; Sikkel, Markus B; Lim, Phang Boon; Kanagaratnam, Prapa

    2016-08-01

    The autonomic nervous system is implicated in the multifactorial pathogenesis of atrial fibrillation (AF) but few studies have attempted neural targeting for therapeutic intervention. We have demonstrated that short bursts of stimulation, at specific sites of left atrial ganglionated plexi (GPs), trigger fibrillation-inducing atrial ectopy and importantly continuous stimulation of these sites may not induce AV block, the 'conventional' marker used to locate GPs. We have shown that these ectopy-triggering GP (ET-GP) sites are anatomically stable and can be rendered inactive by either ablation at the site or by ablation between the site and the adjacent pulmonary vein (PV). This may have important implications for planning patient specific strategies for ablation of paroxysmal AF in the future. PMID:27595199

  12. Interactive Volumetry Of Liver Ablation Zones

    CERN Document Server

    Egger, Jan; Brandmaier, Philipp; Seider, Daniel; Gawlitza, Matthias; Strocka, Steffen; Voglreiter, Philip; Dokter, Mark; Hofmann, Michael; Kainz, Bernhard; Hann, Alexander; Chen, Xiaojun; Alhonnoro, Tuomas; Pollari, Mika; Schmalstieg, Dieter; Moche, Michael

    2015-01-01

    Percutaneous radiofrequency ablation (RFA) is a minimally invasive technique that destroys cancer cells by heat. The heat results from focusing energy in the radiofrequency spectrum through a needle. Amongst others, this can enable the treatment of patients who are not eligible for an open surgery. However, the possibility of recurrent liver cancer due to incomplete ablation of the tumor makes post-interventional monitoring via regular follow-up scans mandatory. These scans have to be carefully inspected for any conspicuousness. Within this study, the RF ablation zones from twelve post-interventional CT acquisitions have been segmented semi-automatically to support the visual inspection. An interactive, graph-based contouring approach, which prefers spherically shaped regions, has been applied. For the quantitative and qualitative analysis of the algorithm's results, manual slice-by-slice segmentations produced by clinical experts have been used as the gold standard (which have also been compared among each o...

  13. P70S6K 1 regulation of angiogenesis through VEGF and HIF-1{alpha} expression

    Energy Technology Data Exchange (ETDEWEB)

    Bian, Chuan-Xiu; Shi, Zhumei [Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing 210029 (China); Meng, Qiao; Jiang, Yue; Liu, Ling-Zhi [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jiang, Bing-Hua, E-mail: binghjiang@yahoo.com [Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing 210029 (China); Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States)

    2010-07-30

    Research highlights: {yields} P70S6K1 regulates VEGF expression; {yields} P70S6K1 induces transcriptional activation through HIF-1{alpha} binding site; {yields} P70S6K1 regulates HIF-1{alpha}, but not HIF-1{beta} protein expression; {yields} P70S6K1 mediates tumor growth and angiogenesis through HIF-1{alpha} and VEGF expression. -- Abstract: The 70 kDa ribosomal S6 kinase 1 (p70S6K1), a downstream target of phosphoinositide 3-kinase (PI3K) and ERK mitogen-activated protein kinase (MAPK), is an important regulator of cell cycle progression, and cell proliferation. Recent studies indicated an important role of p70S6K1 in PTEN-negative and AKT-overexpressing tumors. However, the mechanism of p70S6K1 in tumor angiogenesis remains to be elucidated. In this study, we specifically inhibited p70S6K1 activity in ovarian cancer cells using vector-based small interfering RNA (siRNA) against p70S6K1. We found that knockdown of p70S6K1 significantly decreased VEGF protein expression and VEGF transcriptional activation through the HIF-1{alpha} binding site at its enhancer region. The expression of p70S6K1 siRNA specifically inhibited HIF-1{alpha}, but not HIF-1{beta} protein expression. We also found that p70S6K1 down-regulation inhibited ovarian tumor growth and angiogenesis, and decreased cell proliferation and levels of VEGF and HIF-1{alpha} expression in tumor tissues. Our results suggest that p70S6K1 is required for tumor growth and angiogenesis through HIF-1{alpha} and VEGF expression, providing a molecular mechanism of human ovarian cancer mediated by p70S6K1 signaling.

  14. Extracellular matrix stiffness modulates VEGF calcium signaling in endothelial cells: individual cell and population analysis.

    Science.gov (United States)

    Derricks, Kelsey E; Trinkaus-Randall, Vickery; Nugent, Matthew A

    2015-09-01

    Vascular disease and its associated complications are the number one cause of death in the Western world. Both extracellular matrix stiffening and dysfunctional endothelial cells contribute to vascular disease. We examined endothelial cell calcium signaling in response to VEGF as a function of extracellular matrix stiffness. We developed a new analytical tool to analyze both population based and individual cell responses. Endothelial cells on soft substrates, 4 kPa, were the most responsive to VEGF, whereas cells on the 125 kPa substrates exhibited an attenuated response. Magnitude of activation, not the quantity of cells responding or the number of local maximums each cell experienced distinguished the responses. Individual cell analysis, across all treatments, identified two unique cell clusters. One cluster, containing most of the cells, exhibited minimal or slow calcium release. The remaining cell cluster had a rapid, high magnitude VEGF activation that ultimately defined the population based average calcium response. Interestingly, at low doses of VEGF, the high responding cell cluster contained smaller cells on average, suggesting that cell shape and size may be indicative of VEGF-sensitive endothelial cells. This study provides a new analytical tool to quantitatively analyze individual cell signaling response kinetics, that we have used to help uncover outcomes that are hidden within the average. The ability to selectively identify highly VEGF responsive cells within a population may lead to a better understanding of the specific phenotypic characteristics that define cell responsiveness, which could provide new insight for the development of targeted anti- and pro-angiogenic therapies.

  15. Circulating TGF-β1 and VEGF and risk of cancer among liver transplant recipients.

    Science.gov (United States)

    Engels, Eric A; Jennings, Linda; Kemp, Troy J; Chaturvedi, Anil K; Pinto, Ligia A; Pfeiffer, Ruth M; Trotter, James F; Acker, Michelle; Onaca, Nicholas; Klintmalm, Goran B

    2015-08-01

    Transplant recipients have elevated cancer risk, perhaps partly due to direct carcinogenic effects of immunosuppressive medications. Experimental evidence indicates that calcineurin inhibitors given to transplant recipients increase cellular expression of transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF), which could promote cancer. To assess the potential role of these pathways in the transplantation setting, we conducted a case-control study nested in a cohort of liver recipients. Cases had nonmelanoma skin cancer (N = 84), cancer of the lung (N = 29), kidney (N = 20), or colorectum (N = 17), or melanoma (N = 3). We selected N = 463 recipients without cancer as controls. TGF-β1 and VEGF levels were measured in sera obtained, on average, approximately 3 years before case diagnosis/control selection. We also measured platelet factor 4 (PF4), a marker of ex vivo platelet degranulation, because TGF-β1 and VEGF can be released from platelets, and we developed a statistical model to isolate the platelet-derived fraction from the remaining circulating component. Compared with controls, lung cancer cases had higher levels of TGF-β1 (median 22.8 vs. 19.4 ng/mL, P = 0.02) and VEGF (277 vs. 186 pg/mL, P = 0.02). However, lung cancer cases also had higher platelet counts (P = 0.08) and PF4 levels (P = 0.02), while residual serum levels of TGF-β1 and VEGF, after accounting for PF4, were unassociated with lung cancer (P = 0.40 and P = 0.15, respectively). Associations were not seen for other cancers. In conclusion, TGF-β1 and VEGF levels were increased in association with lung cancer among transplant recipients, which may be explained by increased platelet counts and platelet degranulation in lung cancer cases. PMID:25919050

  16. Association of mast cell-derived VEGF and proteases in Dengue shock syndrome.

    Directory of Open Access Journals (Sweden)

    Takahisa Furuta

    Full Text Available BACKGROUND: Recent in-vitro studies have suggested that mast cells are involved in Dengue virus infection. To clarify the role of mast cells in the development of clinical Dengue fever, we compared the plasma levels of several mast cell-derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF receptors [sVEGFRs], tryptase, and chymase and -related cytokines (IL-4, -9, and -17 between patients with differing severity of Dengue fever and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: The study was performed at Children's Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from 2002 to 2005. Study patients included 103 with Dengue fever (DF, Dengue hemorrhagic fever (DHF, and Dengue shock syndrome (DSS, as diagnosed by the World Health Organization criteria. There were 189 healthy subjects, and 19 febrile illness patients of the same Kinh ethnicity. The levels of mast cell-derived mediators and -related cytokines in plasma were measured by ELISA. VEGF and sVEGFR-1 levels were significantly increased in DHF and DSS compared with those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in DHF and DSS. Significant increases in tryptase and chymase levels, which were accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned to similar levels as DF and controls. In-vitro VEGF production by mast cells was examined in KU812 and HMC-1 cells, and was found to be highest when the cells were inoculated with Dengue virus and human Dengue virus-immune serum in the presence of IL-9. CONCLUSIONS: As mast cells are an important source of VEGF, tryptase, and chymase, our findings suggest that mast cell activation and mast cell-derived mediators participate in the development of DHF. The two proteases, particularly chymase, might serve as good predictive markers of Dengue disease severity.

  17. Subcellular analysis by laser ablation electrospray ionization mass spectrometry

    Science.gov (United States)

    Vertes, Akos; Stolee, Jessica A; Shrestha, Bindesh

    2014-12-02

    In various embodiments, a method of laser ablation electrospray ionization mass spectrometry (LAESI-MS) may generally comprise micro-dissecting a cell comprising at least one of a cell wall and a cell membrane to expose at least one subcellular component therein, ablating the at least one subcellular component by an infrared laser pulse to form an ablation plume, intercepting the ablation plume by an electrospray plume to form ions, and detecting the ions by mass spectrometry.

  18. Ablation driven by hot electrons in shock ignition

    Science.gov (United States)

    Piriz, A. R.; Rodriguez Prieto, G.; Tahir, N. A.; Zhao, Y. T.

    2016-03-01

    An analytical model for the ablation driven by hot electrons is developed. The hot electrons are assumed to carry on the totality of the absorbed laser energy. Efficient energy coupling requires to keep the critical surface sufficiently close to the ablation front. To achieve this goal for high laser intensities a short enough laser wavelength is required. Scaling laws for the ablation pressure and the other relevant magnitudes of the ablation cloud are found in terms of the laser and target parameters.

  19. Quantifying Local Stiffness Variations in Radiofrequency Ablations with Dynamic Indentation

    OpenAIRE

    DeWall, Ryan J.; Varghese, Tomy; Brace, Christopher L.

    2011-01-01

    Elastographic imaging can be used to monitor ablation procedures, however confident and clear determination of the ablation boundary is essential to ensure complete treatment of the pathological target. To investigate the potential for ablation boundary representation on elastographic images, local variations in the viscoelastic properties in radiofrequency ablated regions that were formed in vivo in porcine liver tissue were quantified using dynamic indentation. Spatial stiffness maps were t...

  20. Thermal Ablation for Benign Thyroid Nodules: Radiofrequency and Laser

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Jung Hwan; Lee, Jeong Hyun [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Valcavi, Roberto [Endocrinology Division and Thyroid Disease Center, Arcispedale Santa Maria Nuova, Reggio Emilia (Italy); Pacella, Claudio M. [Diagnostic Imaging and Interventional Radiology Department, Ospedale Regina Apostolorum, Albano Laziale-Rome (IT); Rhim, Hyun Chul [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Na, Dong Kyu [Human Medical Imaging and Intervention Center, Seoul (Korea, Republic of)

    2011-10-15

    Although ethanol ablation has been successfully used to treat cystic thyroid nodules, this procedure is less effective when the thyroid nodules are solid. Radiofrequency (RF) ablation, a newer procedure used to treat malignant liver tumors, has been valuable in the treatment of benign thyroid nodules regardless of the extent of the solid component. This article reviews the basic physics, techniques, applications, results, and complications of thyroid RF ablation, in comparison to laser ablation.

  1. Stereotactic Body Radiotherapy and Ablative Therapies for Lung Cancer.

    Science.gov (United States)

    Abbas, Ghulam; Danish, Adnan; Krasna, Mark J

    2016-07-01

    The treatment paradigm for early stage lung cancer and oligometastatic disease to the lung is rapidly changing. Ablative therapies, especially stereotactic body radiation therapy, are challenging the surgical gold standard and have the potential to be the standard for operable patients with early stage lung cancer who are high risk due to co- morbidities. The most commonly used ablative modalities include stereotactic body radiation therapy, microwave ablation, and radiofrequency ablation.

  2. Thermal Ablation for Benign Thyroid Nodules: Radiofrequency and Laser

    OpenAIRE

    Baek, Jung Hwan; Lee, Jeong Hyun; Valcavi, Roberto; Pacella, Claudio M.; Rhim, Hyunchul; Na, Dong Gyu

    2011-01-01

    Although ethanol ablation has been successfully used to treat cystic thyroid nodules, this procedure is less effective when the thyroid nodules are solid. Radiofrequency (RF) ablation, a newer procedure used to treat malignant liver tumors, has been valuable in the treatment of benign thyroid nodules regardless of the extent of the solid component. This article reviews the basic physics, techniques, applications, results, and complications of thyroid RF ablation, in comparison to laser ablation.

  3. Kilohertz laser ablation for doping helium nanodroplets

    CERN Document Server

    Mudrich, M; Müller, S; Dvorak, M; Buenermann, O; Stienkemeier, F

    2007-01-01

    A new setup for doping helium nanodroplets by means of laser ablation at kilohertz repetition rate is presented. The doping process is characterized and two distinct regimes of laser ablation are identified. The setup is shown to be efficient and stable enough to be used for spectroscopy, as demonstrated on beam-depletion spectra of lithium atoms attached to helium nanodroplets. For the first time, helium droplets are doped with high temperature refractory materials such as titanium and tantalum. Doping with the non-volatile DNA basis Guanine is found to be efficient and a number of oligomers are detected.

  4. Estimation of Immunohistochemical Expression of VEGF in Ductal Carcinomas of the Breast

    DEFF Research Database (Denmark)

    Maae, Else; Nielsen, Martin; Dahl Steffensen, Karina;

    2012-01-01

    Introduction: Vascular endothelial growth factor A (VEGF-A) is a very important growth factor in angiogenesis and holds the potential as both a predictive marker for anti-angiogenic cancer treatment and as a prognostic variable. Consequently, reliable estimation of VEGF expression is crucial...... at 5x magnifications was the most efficient considering data load and time consumption. Discussion and conclusion: The need for biomarkers is obvious and reliable measurements are crucial to enable application in clinical trials and routine settings. We described a method to gain reproducible...

  5. mRNA EXPRESSION OF PTEN AND VEGF GENES IN EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    陈颖; 赵雨杰; 郑华川; 杨雪飞; 汪桂兰; 辛彦

    2003-01-01

    Objective: To investigate the mRNA expression of PTEN and vascular endothelial growth factor (VEGF) genes in ovarian cancer. Methods:We examined mRNA expression of PTEN and VEGF165 in normal ovary (n=5), ovarian cyst (n=5), ovarian borderline tumor (n=9), epithelial ovarian cancer (n=60) and ovarian cancer cell line (CAOV-3) by RT-PCR. Their expressions were compared with clinicopathological features of ovarian cancer. The relationship between their expressions was concerned in all ovarian samples as well. Results:mRNA expression level of PTEN gene was significantly lower in ovarian borderline tumor or ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was negatively correlated with clinicopathological staging(P<0.05),whereas positively with histological differentiation (P<0.05). mRNA expression level of PTEN gene was significantly lower in ovarian endometrioid cancer than ovarian serous or mucinous cancer(P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was positively correlated with clinicopathological staging(P<0.05), whereas negatively with histological differentiation (P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian serous cancer than in other ovarian epithelial cancers (P<0.05). mRNA expression of VEGF165 gene was inversely correlated with mRNA expression level of PTEN gene. Conclusion:Down-regulated expression of PTEN and up-regulated expression of VEGF were considered as two important events in tumorigenesis of ovarian cancer and could be used as molecular markers to indicate the pathobiological behaviors of ovarian cancer. Decreased PTEN expression and increased VEGF expression were closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid and serous cancer respectively. Reduced expression of PTEN gene might be involved in carcinogenesis and progression of ovarian cancer by

  6. Peri- and Postnatal Effects of Prenatal Adenoviral VEGF Gene Therapy in Growth-Restricted Sheep

    OpenAIRE

    Carr, D. J.; J. M. Wallace; Aitken, R. P.; Milne, J. S.; Martin, J. F.; Zachary, I. C.; Peebles, D. M.; David, A. L.

    2016-01-01

    Uterine artery (UtA) adenovirus vector (Ad)-mediated over-expression of vascular endothelial growth factor (VEGF) enhances uterine blood flow in normal sheep pregnancy and increases fetal growth in the overnourished adolescent sheep model of fetal growth restriction (FGR). Herein we examined its impact on gestation length, neonatal survival, early postnatal growth and metabolism. Singleton-bearing ewes were evenly allocated to receive Ad.VEGF-A165(5 x 10(10)particles/ml, 10 ml, n =17) or Sali...

  7. Vascular endothelial growth factor (VEGF) is increased in serum, but not in cerebrospinal fluid in HIV associated CNS diseases.

    Science.gov (United States)

    Sporer, B; Koedel, U; Paul, R; Eberle, J; Arendt, G; Pfister, H-W

    2004-02-01

    Vascular endothelial growth factor (VEGF) is a potent angiogenic and mitogenic peptide, which also induces several mediators that may play a role in HIV induced CNS damage. VEGF levels were determined in cerebrospinal fluid (CSF) and serum samples from patients with (n = 8) and without (n = 19) directly HIV associated CNS disorders and HIV negative control patients (n = 18). VEGF serum but not CSF levels were significantly increased in HIV infected patients with (381.1 (78.9) pg/ml) HIV associated CNS diseases compared with those without (120.8 (13.1) pg/ml) and HIV negative control patients (133.1(14.8) pg/ml). Serum samples from patients with untreated HIV associated encephalopathy (HIVE, n = 3) contained the highest VEGF levels (583.9 (71.5) pg/ml). In two patients VEGF serum levels were reduced during antiretroviral therapy. However, regardless of effective viral suppression, patients with HIVE still had higher levels compared with HIV infected patients without HIVE. A relevant increase of serum VEGF was not observed in patients without HIVE though high HI viral load. We conclude that HIVE is associated with increased serum VEGF levels. Further studies are warranted to elucidate the role of VEGF in HIVE. PMID:14742610

  8. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Caiwen; Zhou Huifang; Fu Yao; Gu Ping; Fan Xianqun [Department of Ophthalmology, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Liu Guangpeng [Key Laboratory of Tissue Engineering, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Zhang Peng [Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science (China); Hou Hongliang; Tang Tingting, E-mail: drfanxianqun@126.com [Department of Orthopedics, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China)

    2011-02-15

    Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

  9. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    International Nuclear Information System (INIS)

    Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

  10. Efficacy and satisfaction rate comparing endometrial ablation by rollerball electrocoagulation to uterine balloon thermal ablation in a randomised controlled trial.

    NARCIS (Netherlands)

    Zon-Rabelink, I.A.A. van; Vleugels, M.P.; Merkus, J.M.W.M.; Graaf, R.M. de

    2004-01-01

    OBJECTIVE: To compare two methods of endometrial ablation, hysteroscopic rollerball electrocoagulation (RBE) and non-hysteroscopic uterine balloon thermal ablation (Thermachoice trade mark ), regarding efficacy for reducing dysfunctional uterine bleeding and patients satisfaction rate. METHODS: A ra

  11. Ablation techniques for primary and metastatic liver tumors.

    Science.gov (United States)

    Ryan, Michael J; Willatt, Jonathon; Majdalany, Bill S; Kielar, Ania Z; Chong, Suzanne; Ruma, Julie A; Pandya, Amit

    2016-01-28

    Ablative treatment methods have emerged as safe and effective therapies for patients with primary and secondary liver tumors who are not surgical candidates at the time of diagnosis. This article reviews the current literature and describes the techniques, complications and results for radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. PMID:26839642

  12. Treatment of colorectal metastases: surgery, cryotherapy, or radiofrequency ablation

    OpenAIRE

    Primrose, J N

    2002-01-01

    The liver is the most common site of metastases from colorectal cancer. There has therefore been growing interest in how liver metastases may be ablated. The most common techniques for ablation of liver metastases are surgical resection, cryotherapy, and increasingly in recent years, radiofrequency ablation.

  13. Cardiac ablation by transesophageal high intensity focused ultrasound

    Institute of Scientific and Technical Information of China (English)

    JIANG Chen-xi; YU Rong-hui; MA Chang-sheng

    2010-01-01

    @@ Cardiac ablation is an important modality of invasive therapy in modern cardiology, especially in the treatment of arrhythmias, as well as other diseases such as hypertrophic obstructive cardiomyopathy (HOCM). Since Huang et al1 used radiofrequency (RF) to ablate canine atrial ventricular junction, RF has developed into the leading energy source in catheter ablation of arrhythmias.

  14. Monitoring of tumor radio frequency ablation using derivative spectroscopy

    NARCIS (Netherlands)

    Spliethoff, J.W.; Tanis, E.; Evers, Daniel James; Hendriks, B.H.; Prevoo, W.; Ruers, T.J.M.

    2014-01-01

    Despite the widespread use of radio frequency (RF) ablation, an effective way to assess thermal tissue damage during and after the procedure is still lacking. We present a method for monitoring RF ablation efficacy based on thermally induced methemoglobin as a marker for full tissue ablation. Diffus

  15. Experimental measurement of ablation effects in plasma armature railguns

    Energy Technology Data Exchange (ETDEWEB)

    Parker, J.V.; Parsons, W.M.

    1986-01-01

    Experimental evidence supporting the importance of ablation in plasma armature railguns is presented. Experiments conducted using the HYVAX and MIDI-2 railguns are described. Several indirect effects of ablation are identified from the experimental results. An improved ablation model of plasma armature dynamics is proposed which incorporates the restrike process.

  16. Vascular endothelial growth factor C (VEGF-C in esophageal cancer correlates with lymph node metastasis and poor patient prognosis

    Directory of Open Access Journals (Sweden)

    Naganawa Yasuhiro

    2010-06-01

    Full Text Available Abstract Background The diagnosis of lymph node metastasis in esophageal cancer by the presence and number of metastatic lymph nodes is an extremely important prognostic factor. In addition, the indication of non-surgical therapy is gaining more attention. Vascular endothelial growth factor C (VEGF-C is potentially lymphangiogenic and selectively induces hyperplasia of the lymphatic vasculature. In this study, we investigated the expression of VEGF-C and whether it correlated with various clinico-pathologic findings. Methods KYSE series of esophageal cancer cell lines and 106 patients with primary esophageal squamous cell carcinomas who had undergone radical esophagectomy were analyzed. VEGF-C mRNA expression was determined by quantitative RT-PCR. Results High expression of VEGF-C was detected in most of the KYSE cell lines, especially KYSE410, yet, in an esophageal normal epithelium cell line, Het-1A, VEGF-C was not detected. In the clinical specimen, the expression of VEGF-C in the cancerous tissue was higher than in the corresponding noncancerous esophageal mucosa (p = 0.026. The expression of VEGF-C was found to be higher in Stage2B-4A tumors than in Stage0-2A tumors (p = 0.049. When the patients were divided into two groups according to their expression levels of VEGF-C (a group of 53 cases with high expression and a group of 53 cases with low expression, the patients with high VEGF-C expression had significantly shorter survival after surgery than the patients with low expression (p = 0.0065. Although univariate analysis showed that high expression of VEGF-C was a statistically significant prognostic factor, this was not shown in multivariate analysis. In the subgroup of patients with Tis and T1 tumors, the expression of VEGF-C was higher in N1 tumors than in N0 tumors (p = 0.029. The survival rate of patients from the high expression group (n = 10 was lower than that in the low expression group (n = 11, and all the patients in the low

  17. The Evolution of Tissue Stiffness at Radiofrequency Ablation Sites During Lesion Formation and in the Peri‐Ablation Period

    OpenAIRE

    Eyerly, Stephanie A.; VEJDANI‐JAHROMI, MARYAM; Dumont, Douglas M.; Trahey, Gregg E.; Wolf, Patrick D.

    2015-01-01

    Peri‐Ablation Monitoring of RFA Lesion Stiffness Introduction Elastography imaging can provide radiofrequency ablation (RFA) lesion assessment due to tissue stiffening at the ablation site. An important aspect of assessment is the spatial and temporal stability of the region of stiffness increase in the peri‐ablation period. The aim of this study was to use 2 ultrasound‐based elastography techniques, shear wave elasticity imaging (SWEI) and acoustic radiation force impulse (ARFI) imaging, to ...

  18. Inhibitory effect of extracts of Ginkgo biloba leaves on VEGF-induced hyperpermeability of bovine coronary endothelial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Yan QIU; Yao-cheng RUI; Tie-jun LI; Li ZHANG; Peng-yuan YANG

    2004-01-01

    AIM: To study whether extract of Ginkgo biloba (EGb) can protect against atherosclerosis. METHODS: Confluent monolayers of bovine coronary endothelial cells (BCECs), bovine coronary smooth muscle cells (BCSMCs), and cocultures of the two were incubated with medium containing VEGF and/or EGb, and flux of 125Ⅰ-labeled oxidized low density lipoprotein (ox-LDL) across the monolayers was measured. RESULTS: Incubation with VEGF significantly increased the permeability of BCEC monolayers to 125Ⅰ-ox-LDL in a time- and concentration-dependent manner, but had no effect on permeability of BCSMCs or endothelial cells-smooth muscle cells cocultures. EGb significantly inhibited the VEGF-induced hyperpermeability of BCECs. CONCLUSION: VEGF was important in the formation and development of atherosclerosis. The inhibition of VEGF-induced permeability by EGb suggests that extracts of Ginkgo biloba leaves may have important clinical applications in the treatment of cardiovascular diseases.

  19. What is the contribution of two genetic variants regulating VEGF levels to type 2 diabetes risk and to microvascular complications?

    DEFF Research Database (Denmark)

    Bonnefond, Amélie; Saulnier, Pierre-Jean; Stathopoulou, Maria G;

    2013-01-01

    Vascular endothelial growth factor (VEGF) is a key chemokine involved in tissue growth and organ repair processes, particularly angiogenesis. Elevated circulating VEGF levels are believed to play a role in type 2 diabetes (T2D) microvascular complications, especially diabetic retinopathy. Recently......6921438 or rs10738760 on diabetic microvascular complications or the variation in related traits in T2D patients.In spite of their impact on the variance in circulating VEGF, we did not find any association between SNPs rs6921438 and rs10738760, and the risk of T2D, diabetic nephropathy or retinopathy......, a genome-wide association study identified two common single nucleotide polymorphisms (SNPs; rs6921438 and rs10738760) explaining nearly half of the variance in circulating VEGF levels. Considering the putative contribution of VEGF to T2D and its complications, we aimed to assess the effect of these...

  20. Quantitative assessment of first-pass perfusion using a low-dose method at multidetector CT in oesophageal squamous cell carcinoma: Correlation with VEGF expression

    Energy Technology Data Exchange (ETDEWEB)

    Chen, T.-W. [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China) and Sichuan Province Key Laboratory of Medical Imaging and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 63 Wen Hua Lu, Nanchong, Sichuan 637000 (China); Yang, Z.-G., E-mail: yangzg1117@yahoo.com.cn [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Chen, H.-J. [Department of Pathology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Li, Y.; Tang, S.-S.; Yao, J.; Dong, Z.-H. [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); He, D. [Department of Pathology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China)

    2012-08-15

    Aim: To investigate the correlation between vascular endothelial cell growth factor (VEGF) expression and first-pass perfusion parameters at multidetector computed tomography (MDCT) using a low-dose technique, and to determine how to discriminate VEGF positivity from VEGF negativity by perfusion CT in oesophageal squamous cell carcinomas. Materials and methods: Thirty-two patients with oesophageal squamous cell carcinomas underwent first-pass perfusion with 64-section MDCT at 50 mAs. Perfusion parameters, including perfusion, peak enhanced density (PED), time to peak (TTP), and blood volume (BV), were measured. Postoperative specimens were assessed for VEGF expression. Correlation tests were performed to determine the associations between each CT perfusion parameter and VEGF expression. The cut-off values of perfusion parameters were obtained statistically to discriminate VEGF positivity from VEGF negativity. Results: Mean perfusion, PED, TTP, and BV were 38.47 {+-} 30.26 ml/min/ml, 24.68 {+-} 9.65 HU, 28.35 {+-} 9.03 s, and 11.82 {+-} 6.06 ml/100 g, respectively. PED or BV were significantly higher in the VEGF-positive group than in the VEGF-negative group (all p < 0.05), but no significant difference in perfusion or TTP was found between the VEGF-positive and VEGF-negative groups (all p > 0.05). In VEGF positivity, PED and BV were correlated with VEGF expression (r = 0.576 and 0.765, respectively; all p < 0.05), whereas perfusion and TTP were not (r = 0.361 and 0.239, respectively; all p > 0.05). A threshold of BV (10.23 ml/100 g) achieved a sensitivity of 94.4%, and a specificity of 92.9% for discriminating VEGF positivity from VEGF negativity. Conclusion: BV could reflect tumour VEGF expression, and could be an indicator for evaluating angiogenesis in oesophageal tumours.

  1. VEGF reverts the cognitive impairment induced by a focal traumatic brain injury during the development of rats raised under environmental enrichment

    OpenAIRE

    Rico-Barrio, Irantzu; Bengoetxea, Harkaitz; Argandoña, Enrike G.; Lafuente, Jose V.

    2013-01-01

    The role of VEGF in the nervous system is extensive; apart from its angiogenic effect, VEGF has been described as a neuroprotective, neurotrophic and neurogenic molecule. Similar effects have been described for enriched environment (EE). Moreover, both VEGF and EE have been related to improved spatial memory. Our aim was to investigate the neurovascular and cognitive effects of intracerebrally-administered VEGF and enriched environment during the critical period of the rat visual cortex devel...

  2. Efficient downregulation of VEGF in retinal pigment epithelial cells by integrin ligand-labeled liposome-mediated siRNA delivery

    Directory of Open Access Journals (Sweden)

    Chen C

    2013-07-01

    Full Text Available Cheng-Wei Chen,1 Ming-Kung Yeh,2 Chia-Yang Shiau,3 Chiao-Hsi Chiang,4,* Da-Wen Lu5,*1Chengwei Biotechnology Co, Ltd, 2Bureau of Pharmaceutical Affairs, Military of National Defense Medical Affairs Bureau, 3Graduate Institute of Medical Sciences, 4School of Pharmacy, National Defense Medical Center, 5Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan *These authors contributed equally to this workBackground: The purpose of this study was to demonstrate the effectiveness of an integrin peptide ligand-labeled liposomal delivery system loaded with vascular endothelial growth factor (VEGF-siRNA in a model study of gene therapy for retinopathy using human retinal pigment epithelial cells.Methods: Arg(R-Gly(G-Asp(D motif peptide conjugating polyethylene glycol modified (RGD-PEGylated liposomes were prepared using a thin-film hydration method and optimized for surface charge, particle size, small interfering RNA (siRNA load, and entrapment efficiency. Reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine VEGF levels in retinal pigment epithelial cells. Cytotoxicity was determined using the 3-[4, 5-dimethylthiazol-2-yl]-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS assay and flow cytometry.Results: Physicochemical properties, including particle size, zeta potential, and siRNA load, of the prepared RGD-PEGylated liposomes and their entrapment efficiency were determined to be within the following ranges: 123.8–234.1 nm, 17.31–40.09 mV, 5.27%–6.33%, and >97%, respectively. RGD-PEGylated liposome-mediated fluorescent-labeled siRNA delivery demonstrated significantly enhanced cellular uptake, and 3 mol% RGD-PEGylated liposomes (having 3β-[N-(N´, N´-dimethylaminoethane carbamoyl] cholesterol (DC-cholesterol DSPE and DSPE-PEG(2000-RGD with molar ratio of 50/47/3 were shown to have better efficacy with regard to specificity for retinal pigment epithelial

  3. Experimental Study of Adenovirus Vector Mediated-hVEGF165 Gene on Prevention of Restenosis after Angioplasty

    Institute of Scientific and Technical Information of China (English)

    刘启功; 陆再英; 岳远坤; 林立; 张卫东; 颜进

    2004-01-01

    This study evaluated the effects of adenovirus vector mediated human vascular endothelial growth factor-165 (hVEGF165) gene on prevention of restenosis after angioplasty. Rabbit models of bilateral carotid artery injury were established by balloon denudation. The recombinant adenoviruses containing hVEGF165 cDNA was directly injected into left side of the injured carotid arteries.On day 3 and week 3 after transfection the expression of VEGF was observed by RT-PCR and immunohistochemistry. The thrombokinesis, reendothelialization (rET) and intimal hyperplasia in carotid arteries were evaluated by computerized image analysis system 3 weeks after gene transfer.The changes in the VEGF gene-treated side were compared with the control side. Our results showed that 3 days and 3 weeks after hVEGF165 gene transfer the VEGF mRNA and antigen expression were detected in vivo. 3 weeks after the transfer, the carotid artery rET was markedly better in the VEGF gene-treated group compared with the control. The thrombokinesis, intima area/media area (I/M), maximal intimal and medial thicknesses (ITmax and MTmax) demonstrated a statistically significant decrease in arteries treated with VEGF gene as compared with the control group. It is concluded that VEGF gene transfer could be achieved by intra-arterial injection of recombinant adenoviruses. It might accelerate the restoration of endothelial integrity, inhibit thrombokinesis and attenuate intimal hyperplasia in the injured arteries after VEGF gene transfer. This procedure could be useful in preventing restenosis after angioplasty.

  4. A review of the safety aspects of radio frequency ablation

    Directory of Open Access Journals (Sweden)

    Abhishek Bhaskaran

    2015-09-01

    Full Text Available In light of recent reports showing high incidence of silent cerebral infarcts and organized atrial arrhythmias following radiofrequency (RF atrial fibrillation (AF ablation, a review of its safety aspects is timely. Serious complications do occur during supraventricular tachycardia (SVT ablations and knowledge of their incidence is important when deciding whether to proceed with ablation. Evidence is emerging for the probable role of prophylactic ischemic scar ablation to prevent VT. This might increase the number of procedures performed. Here we look at the various complications of RF ablation and also the methods to minimize them. Electronic database was searched for relevant articles from 1990 to 2015. With better awareness and technological advancements in RF ablation the incidence of complications has improved considerably. In AF ablation it has decreased from 6% to less than 4% comprising of vascular complications, cardiac tamponade, stroke, phrenic nerve injury, pulmonary vein stenosis, atrio-esophageal fistula (AEF and death. Safety of SVT ablation has also improved with less than 1% incidence of AV node injury in AVNRT ablation. In VT ablation the incidence of major complications was 5–11%, up to 3.4%, up to 1.8% and 4.1–8.8% in patients with structural heart disease, without structural heart disease, prophylactic ablations and epicardial ablations respectively. Vascular and pericardial complications dominated endocardial and epicardial VT ablations respectively. Up to 3% mortality and similar rates of tamponade were reported in endocardial VT ablation. Recent reports about the high incidence of asymptomatic cerebral embolism during AF ablation are concerning, warranting more research into its etiology and prevention.

  5. Ultrasound-guided percutaneous thermal ablation of hepatocellular carcinoma using microwave and radiofrequency ablation

    Energy Technology Data Exchange (ETDEWEB)

    Xu, H.-X.; Xie, X.-Y.; Lu, M.-D. E-mail: lumd@21cn.com; Chen, J.-W.; Yin, X.-Y.; Xu, Z.-F.; Liu, G.-J

    2004-01-01

    AIM: To investigate the therapeutic efficacy of thermal ablation for treatment of hepatocellular carcinoma (HCC) using microwave and radiofrequency (RF) energy application. MATERIALS AND METHODS: A total of 190 nodules in 97 patients (84 male, 13 female; mean age 53.4 years, range 24-74 years) with HCC were treated with microwave or RF ablation in the last 4 years. The applicators were introduced into the tumours under conscious analgesic sedation by intravenous administration of fentanyl citrate and droperidol and local anaesthesia in both thermal ablation procedures. The patients were then followed up with contrast-enhanced computed tomography (CT) to evaluate treatment response. Survival was analysed using the Kaplan-Meier method. RESULTS: Complete ablation was obtained in 92.6% (176/190) nodules. The complete ablation rates were 94.6% (106/112) in microwave ablation and 89.7% (70/78) in RF ablation. The complete ablation rates in tumours{<=}2.0, 2.1-3.9 and {>=}4.0 cm were 93.1, 93.8 and 86.4%, respectively. Local recurrence was found in 9.5% nodules and the rates in tumours{<=}2.0, 2.1-3.9 and {>=}4.0 cm in diameter were 3.4, 9.9 and 31.8%, respectively. In the follow-up period, 7.1% nodules ablated by microwave and 12.8% by RF presented local recurrence. The 1, 2 and 3-year distant recurrence-free survivals were 47.2, 34.9 and 31.0%, respectively. Estimated mean survival was 32 months, and 1, 2 and 3-year cumulative survivals were 75.6, 58.5, and 50.0%, respectively. One and 2 years survivals of Child-Pugh class A, B and C patients were 83.8 and 70.4%, 78.2 and 53.2%, 36.3 and 27.3%, respectively. CONCLUSION: Thermal ablation therapy by means of microwave and RF energy application is an effective and safe therapeutic technique for hepatocellular carcinoma. Large tumours can be completely ablated, but have a significantly higher risk of local recurrence at follow-up.

  6. Monitoring Atrial Fibrillation After Catheter Ablation

    Directory of Open Access Journals (Sweden)

    Giovanni B Forleo, MD PhD; MAssimo Moltrasio, MD; Michela Casella MD, PhD; Antonio Dello Russo MD, PhD; Getano Fassini, MD; Manfredi Tesauro, MD, PhD; Claudio Tondo, MD, PhD.

    2014-04-01

    Full Text Available Although catheter ablation is an effective treatment for recurrent atrial fibrillation (AF, there is no consensus on the definition of success or follow-up strategies. Symptoms are the major motivation for undergoing catheter ablation in patients with AF, however it is well known that reliance on perception of AF by patients after AF ablation results in an underestimation of recurrence of the arrhythmia. Because symptoms of AF occurrence may be misleading, a reliable assessment of rhythm outcome is essential for the definition of success in both clinical care and research trials. Continuous rhythm monitoring over long periods of time is superior to intermittent recording using external monitors to detect the presence of AF episodes and to quantify the AF burden. Today, new devices implanted subcutaneously using a minimally invasive technique have been developed for continuous AF monitoring. Implantable devices keep detailed information about arrhythmia recurrences and might allow identification of very brief episodes of AF, the significance of which is still uncertain. In particular, it is not known whether there is any critical value of daily AF burden that has a prognostic significance. This issue remains an area of active discussion, debate and investigation. Further investigation is required to determine if continuous AF monitoring with implantable devices is effective in reducing stroke risk and facilitating maintenance of sinus rhythm after AF ablation.

  7. Bending diamonds by femtosecond laser ablation

    DEFF Research Database (Denmark)

    Balling, Peter; Esberg, Jakob; Kirsebom, Kim;

    2009-01-01

    We present a new method based on femtosecond laser ablation for the fabrication of statically bent diamond crystals. Using this method, curvature radii of 1 m can easily be achieved, and the curvature obtained is very uniform. Since diamond is extremely tolerant to high radiation doses, partly due...

  8. Diagnostics of laser ablated plasma plumes

    DEFF Research Database (Denmark)

    Amoruso, S.; Toftmann, B.; Schou, Jørgen;

    2004-01-01

    The effect of an ambient gas on the expansion dynamics of laser ablated plasmas has been studied for two systems by exploiting different diagnostic techniques. First, the dynamics of a MgB2 laser produced plasma plume in an Ar atmosphere has been investigated by space-and time-resolved optical...

  9. Combining Electrolysis and Electroporation for Tissue Ablation.

    Science.gov (United States)

    Phillips, Mary; Rubinsky, Liel; Meir, Arie; Raju, Narayan; Rubinsky, Boris

    2015-08-01

    Electrolytic ablation is a method that operates by delivering low magnitude direct current to the target region over long periods of time, generating electrolytic products that destroy cells. This study was designed to explore the hypothesis stating that electrolytic ablation can be made more effective when the electrolysis-producing electric charges are delivered using electric pulses with field strength typical in reversible electroporation protocols. (For brevity we will refer to tissue ablation protocols that combine electroporation and electrolysis as E(2).) The mechanistic explanation of this hypothesis is related to the idea that products of electrolysis generated by E(2) protocols can gain access to the interior of the cell through the electroporation permeabilized cell membrane and therefore cause more effective cell death than from the exterior of an intact cell. The goal of this study is to provide a first-order examination of this hypothesis by comparing the charge dosage required to cause a comparable level of damage to a rat liver, in vivo, when using either conventional electrolysis or E(2) approaches. Our results show that E(2) protocols produce tissue damage that is consistent with electrolytic ablation. Furthermore, E(2) protocols cause damage comparable to that produced by conventional electrolytic protocols while delivering orders of magnitude less charge to the target tissue over much shorter periods of time.

  10. Atmospheric Profile Imprint in Firewall Ablation Coefficient

    Science.gov (United States)

    Ceplecha, Z.; Pecina, P.

    1984-01-01

    A general formula which expresses the distance along the meteoric fireball trajectory 1 as a function of t is discussed. Differential equations which include the motion and ablation of a single nonfragmenting meteor body are presented. The importance of the atmospheric density profile in the meteor formula is emphasized.

  11. K20E, an oxidative-coupling compound of methyl caffeate, exhibits anti-angiogenic activities through down-regulations of VEGF and VEGF receptor-2

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Chun-Hsu [Department of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan (China); Lin, Wen-Hsin; Chien, Yi-Chung; Liu, Fon-Chang; Sheu, Ming-Jyh [School of Pharmacy, China Medical University, Taichung 40402, Taiwan (China); Kuo, Yueh-Hsiung, E-mail: kuoyh@mail.cmu.edu.tw [Tsuzuki Institute for Traditional Medicine, China Medical University, Taichung 40402, Taiwan (China); Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan (China); Department of Biotechnology, Asia University, Taichung 41354, Taiwan (China); Wu, Chieh-Hsi, E-mail: chhswu@tmu.edu.tw [Department of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan (China); School of Pharmacy, China Medical University, Taichung 40402, Taiwan (China); Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan (China)

    2015-01-15

    Anti-angiogenesis is one of the most popular clinical interventions for cancer chemotherapy. A series of synthesized derivative of methyl caffeate were used to evaluate the anti-angiogenic activity and to investigate possible pharmacological mechanisms in the present study. The most potent anti-angiogenic compound was evaluated in the experiments of murine allograft tumor model and Matrigel plug assay as well as cell models in the human umbilical vascular endothelial cells (HUVECs) and the LLC1 lung cancer cells. Our results suggested that K20E suppressed the tumor growth in the allograft tumor model and exhibited anti-angiogenic activity in Matrigel plug assay. Besides, HUVEC viability was found to be significantly reduced by arresting cell cycle at G{sub 2}/M phase and apoptosis. Cell migration, invasion, and tube formation of the HUVECs were also markedly suppressed by K20E treatment. K20E largely down-regulated the intracellular and secreted vascular endothelial growth factor (VEGF) in the LLC1 cancer cells. Besides, VEGF receptor-2 (VEGFR-2) and its downstream signaling cascades (AKT-mTOR and MEK1/2-ERK1/2) as well as gelatinases were all evidently reduced in the HUVECs treated with K20E. Inversely, K20E can up-regulate the expression levels of p53 and p21 proteins in the HUVECs. Based on these results, our study suggested that K20E possessed inhibiting angiogenesis through regulation of VEGF/VEGFR-2 and its downstream signaling cascades in the vascular endothelial cells (VECs). - Highlights: • K20E is an oxidative-coupling compound of methyl caffeate. • K20E exhibits anti-tumor and anti-angiogenesis effects. • K20E suppresses the expressions of VEGF and VEGF receptor-2 (VEGFR-2) proteins. • K20E deactivates VEGFR-2-mediated downstream signaling pathways to inhibit angiogenesis. • K20E up-regulates p53-p21 pathway to induce apoptosis and cell arrest at G2/M phase.

  12. Plume collimation for laser ablation electrospray ionization mass spectrometry

    Science.gov (United States)

    Vertes, Akos; Stolee, Jessica A.

    2014-09-09

    In various embodiments, a device may generally comprise a capillary having a first end and a second end; a laser to emit energy at a sample in the capillary to ablate the sample and generate an ablation plume in the capillary; an electrospray apparatus to generate an electrospray plume to intercept the ablation plume to produce ions; and a mass spectrometer having an ion transfer inlet to capture the ions. The ablation plume may comprise a collimated ablation plume. The device may comprise a flow cytometer. Methods of making and using the same are also described.

  13. Plume collimation for laser ablation electrospray ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Vertes, Akos; Stolee, Jessica A.

    2016-06-07

    In various embodiments, a device may generally comprise a capillary having a first end and a second end; a laser to emit energy at a sample in the capillary to ablate the sample and generate an ablation plume in the capillary; an electrospray apparatus to generate an electrospray plume to intercept the ablation plume to produce ions; and a mass spectrometer having an ion transfer inlet to capture the ions. The ablation plume may comprise a collimated ablation plume. The device may comprise a flow cytometer. Methods of making and using the same are also described.

  14. A chemical model of meteoric ablation

    Directory of Open Access Journals (Sweden)

    T. Vondrak

    2008-12-01

    Full Text Available Most of the extraterrestrial dust entering the Earth's atmosphere ablates to produce metal vapours, which have significant effects on the aeronomy of the upper mesosphere and lower thermosphere. A new Chemical Ablation Model (CAMOD is described which treats the physics and chemistry of ablation, by including the following processes: sputtering by inelastic collisions with air molecules before the meteoroid melts; evaporation of atoms and oxides from the molten particle; diffusion-controlled migration of the volatile constituents (Na and K through the molten particle; and impact ionization of the ablated fragments by hyperthermal collisions with air molecules. Evaporation is based on thermodynamic equilibrium in the molten meteoroid (treated as a melt of metal oxides, and between the particle and surrounding vapour phase. The loss rate of each element is then determined assuming Langmuir evaporation. CAMOD successfully predicts the meteor head echo appearance heights, observed from incoherent scatter radars, over a wide range of meteoroid velocities. The model also confirms that differential ablation explains common-volume lidar observations of K, Ca and Ca+ in fresh meteor trails. CAMOD is then used to calculate the injection rates into the atmosphere of a variety of elements as a function of altitude, integrated over the meteoroid mass and velocity distributions. The most abundant elements (Fe, Mg and Si have peak injection rates around 85 km, with Na and K about 8 km higher. The more refractory element Ca ablates around 82 km with a Na:Ca ratio of 4:1, which does therefore not explain the depletion of atomic Ca to Na, by more than 2 orders of magnitude, in the upper mesosphere. Diffusion of the most volatile elements (Na and K does not appear to be rate-limiting except in the fastest meteoroids. Non-thermal sputtering causes ~35% mass loss from the fastest (~60–70 km s−1 and smallest (10−17–10

  15. A chemical model of meteoric ablation

    Directory of Open Access Journals (Sweden)

    T. Vondrak

    2008-07-01

    Full Text Available Most of the extraterrestrial dust entering the Earth's atmosphere ablates to produce metal vapours, which have significant effects on the aeronomy of the upper mesosphere and lower thermosphere. A new Chemical Ablation Model (CAMOD is described which treats the physics and chemistry of ablation, by including the following processes: sputtering by inelastic collisions with air molecules before the meteoroid melts; evaporation of atoms and oxides from the molten particle; diffusion-controlled migration of the volatile constituents (Na and K through the molten particle; and impact ionization of the ablated fragments by hyperthermal collisions with air molecules. Evaporation is based on thermodynamic equilibrium in the molten meteoroid (treated as a melt of metal oxides, and between the particle and surrounding vapour phase. The loss rate of each element is then determined assuming Langmuir evaporation. CAMOD successfully predicts the meteor head echo appearance heights, observed from incoherent scatter radars, over a wide range of meteoroid velocities. The model also confirms that differential ablation explains common-volume lidar observations of K, Ca and Ca+ in fresh meteor trails. CAMOD is then used to calculate the injection rates into the atmosphere of a variety of elements as a function of altitude, integrated over the meteoroid mass and velocity distributions. The most abundant elements (Fe, Mg and Si have peak injection rates around 85 km, with Na and K about 8 km higher. The more refractory element Ca ablates around 82 km with a Na:Ca ratio of 4:1, which does therefore not explain the depletion of atomic Ca to Na, by more than 2 orders of magnitude, in the upper mesosphere. Diffusion of the most volatile elements (Na and K does not appear to be rate-limiting except in the fastest meteoroids. Non-thermal sputtering causes ~35% mass loss from the fastest (~60–70 km s−1 and smallest (10−17–10

  16. Nd:YAG laser cleaning of ablation debris from excimer-laser-ablated polyimide

    Science.gov (United States)

    Gu, Jianhui; Low, Jason; Lim, Puay K.; Lim, Pean

    2001-10-01

    In the processing of excimer laser ablation of nozzles on polyimide in air, both gases like CO2, CO and HCN and solid debris including C2 approximately C12 are produced in laser ablation area. In this paper, we reported for the first time a Nd:YAG laser cleaning of ablation debris generated in excimer laser ablation of polyimide. It demonstrated effective cleaning with the advantages of shortening cleaning cycle time and simplifying cleaning process. The laser used for the cleaning was a Q-switched and frequency doubled Nd:YAG laser with wavelength of 532 nm and repetition rate of 10 Hz. The laser cleaning effect was compared with conventional plasma ashing. AFM measurement showed that the Nd:YAG laser cleaning had no damage to the substrate. XPS results indicated that the polyimide surface cleaned with laser beam had a lower oxygen/carbon ratio than that of plasma ashing. The study shows that frequency doubled Nd:YAG laser cleaning is effective in ablation debris removal from excimer laser ablated polyimide.

  17. Ablation of Atrial Fibrillation: Patient Selection, Periprocedural Anticoagulation, Techniques, and Preventive Measures After Ablation.

    Science.gov (United States)

    Link, Mark S; Haïssaguerre, Michel; Natale, Andrea

    2016-07-26

    Atrial fibrillation (AF) is the most common arrhythmia encountered by cardiologists and is a major cause of morbidity and mortality. Risk factors for AF include age, male sex, genetic predisposition, hypertension, diabetes mellitus, sleep apnea, obesity, excessive alcohol, smoking, hyperthyroidism, pulmonary disease, air pollution, heart failure, and possibly excessive exercise. The management of AF involves decisions about rate versus rhythm control. Asymptomatic patients are generally managed with rate control and anticoagulation. Symptomatic patients will desire rhythm control. Rhythm control options are either antiarrhythmic agents or ablation, with each having its own risks and benefits. Ablation of AF has evolved from a rare and complex procedure to a common electrophysiological technique. Selection of patients to undergo ablation is an important aspect of AF care. Patients with the highest success rates of ablation are those with normal structural hearts and paroxysmal AF, although those with congestive heart failure have the greatest potential benefit of the procedure. Although pulmonary vein isolation of any means/energy source is the approach generally agreed on for those with paroxysmal AF, optimal techniques for the ablation of nonparoxysmal AF are not yet clear. Anticoagulation reduces thromboembolic complications; the newer anticoagulants have eased management for both the patient and the cardiologist. Aggressive management of modifiable risk factors (hypertension, diabetes mellitus, sleep apnea, obesity, excessive alcohol, smoking, hyperthyroidism, pulmonary disease, air pollution, and possibly excessive exercise) after ablation reduces the odds of recurrent AF and is an important element of care. PMID:27462054

  18. Burn, freeze, or photo-ablate?: comparative symptom profile in Barrett's dysplasia patients undergoing endoscopic ablation

    Science.gov (United States)

    Gill, Kanwar Rupinder S.; Gross, Seth A.; Greenwald, Bruce D.; Hemminger, Lois L.; Wolfsen, Herbert C.

    2009-06-01

    Background: There are few data available comparing endoscopic ablation methods for Barrett's esophagus with high-grade dysplasia (BE-HGD). Objective: To determine differences in symptoms and complications associated with endoscopic ablation. Design: Prospective observational study. Setting: Two tertiary care centers in USA. Patients: Consecutive patients with BE-HGD Interventions: In this pilot study, symptoms profile data were collected for BE-HGD patients among 3 endoscopic ablation methods: porfimer sodium photodynamic therapy, radiofrequency ablation and low-pressure liquid nitrogen spray cryotherapy. Main Outcome Measurements: Symptom profiles and complications from the procedures were assessed 1-8 weeks after treatment. Results: Ten BE-HGD patients were treated with each ablation modality (30 patients total; 25 men, median age: 69 years (range 53-81). All procedures were performed in the clinic setting and none required subsequent hospitalization. The most common symptoms among all therapies were chest pain, dysphagia and odynophagia. More patients (n=8) in the porfimer sodium photodynamic therapy group reported weight loss compared to radio-frequency ablactation (n=2) and cryotherapy (n=0). Four patients in the porfimer sodium photodynamic therapy group developed phototoxicity requiring medical treatment. Strictures, each requiring a single dilation, were found in radiofrequency ablactation (n=1) and porfimer sodium photodynamic therapy (n=2) patients. Limitations: Small sample size, non-randomized study. Conclusions: These three endoscopic therapies are associated with different types and severity of post-ablation symptoms and complications.

  19. 10-20-30 training increases performance and lowers blood pressure and VEGF in runners

    DEFF Research Database (Denmark)

    Gliemann, Lasse; Gunnarsson, Thomas Gunnar Petursson; Hellsten, Ylva;

    2015-01-01

    -20-30 increased VO2max but did not influence muscle fiber area, distribution or capillarization, whereas the expression of the pro-angiogenic vascular endothelial growth factor (VEGF) was lowered by 22%. No changes were observed in CON. These results suggest that 10-20-30 training is an effective and easily...

  20. VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model.

    Science.gov (United States)

    Azzouz, Mimoun; Ralph, G Scott; Storkebaum, Erik; Walmsley, Lucy E; Mitrophanous, Kyriacos A; Kingsman, Susan M; Carmeliet, Peter; Mazarakis, Nicholas D

    2004-05-27

    Amyotrophic lateral sclerosis (ALS) causes adult-onset, progressive motor neuron degeneration in the brain and spinal cord, resulting in paralysis and death three to five years after onset in most patients. ALS is still incurable, in part because its complex aetiology remains insufficiently understood. Recent reports have indicated that reduced levels of vascular endothelial growth factor (VEGF), which is essential in angiogenesis and has also been implicated in neuroprotection, predispose mice and humans to ALS. However, the therapeutic potential of VEGF for the treatment of ALS has not previously been assessed. Here we report that a single injection of a VEGF-expressing lentiviral vector into various muscles delayed onset and slowed progression of ALS in mice engineered to overexpress the gene coding for the mutated G93A form of the superoxide dismutase-1 (SOD1(G93A)) (refs 7-10), even when treatment was only initiated at the onset of paralysis. VEGF treatment increased the life expectancy of ALS mice by 30 per cent without causing toxic side effects, thereby achieving one of the most effective therapies reported in the field so far. PMID:15164063

  1. Reducible poly(amido ethylenediamine) for hypoxia-inducible VEGF delivery

    NARCIS (Netherlands)

    Christensen, Lane V.; Chang, Chien-Wen; Yockman, James W.; Conners, Rafe; Jackson, Heidi; Zhong, Zhiyuan; Feijen, Jan; Bull, David A.; Kim, Sung Wan

    2007-01-01

    Delivery of the hypoxia-inducible vascular endothelial growth factor (RTP-VEGF) plasmid using a novel reducible disulfide poly(amido ethylenediamine) (SS-PAED) polymer carrier was studied in vitro and in vivo. In vitro transfection of primary rat cardiomyoblasts (H9C2) showed SS-PAED at a weighted r

  2. Tumour control by whole brain irradiation of anti-VEGF-treated mice bearing intracerebral glioma

    NARCIS (Netherlands)

    J.J.C. Verhoeff; L.J.A. Stalpers; A. Claes; K.E. Hovinga; G.D. Musters; W. Vandertop; D.J. Richel; W.P.J. Leenders; W.R. van Furth

    2009-01-01

    Aim of the study: Tumour angiogenesis and invasion are key features of glioblastoma multiforme (GBM). Angiogenesis inhibitors increase progression-free survival (PFS) of recurrent GBM patients. VEGF inhibition controls the bulk tumour growth by inhibition of angiogenesis, but does not inhibit the in

  3. Tumour control by whole brain irradiation of anti-VEGF-treated mice bearing intracerebral glioma.

    NARCIS (Netherlands)

    Verhoeff, J.J.; Stalpers, L.J.; Claes, A.; Hovinga, K.E.; Musters, G.D.; Top, W.P. van der; Richel, D.J.; Leenders, W.P.J.; Furth, W.R. van

    2009-01-01

    AIM OF THE STUDY: Tumour angiogenesis and invasion are key features of glioblastoma multiforme (GBM). Angiogenesis inhibitors increase progression-free survival (PFS) of recurrent GBM patients. VEGF inhibition controls the bulk tumour growth by inhibition of angiogenesis, but does not inhibit the in

  4. Primary breast cancer induces pulmonary vascular hyperpermeability and promotes metastasis via the VEGF-PKC pathway.

    Science.gov (United States)

    Jiang, Man; Qin, Chengyong; Han, Mingyong

    2016-06-01

    The lung is one of the most frequent target organs for breast cancer metastasis. When breast cancer cells from a primary tumor do not colonize the lung, which we named the premetastatic phase, the microenvironment of the lung has already been influenced by the primary tumor. However, little is known about the exact premetastatic alteration and regulatory mechanisms of the lung. Here, we used 4T1 cells (a mouse breast cancer cell line which can specifically metastasize to the lung) to build a mouse breast cancer model. We found that primary breast tumor induced increased pulmonary vascular permeability in the premetastatic phase, which facilitated the leakage of rhodamine-dextran and the extravasation of intravenous therapy injected cancer cells. Furthermore, tight junctions (TJs) were disrupted, and the expression of zonula occludens-1(ZO-1), one of the most important components of tight junctions, was decreased in the premetastatic lung. In addition, elevated serum vascular endothelial growth factor (VEGF) was involved in the destabilization of tight junctions and the VEGF antagonist bevacizumab reversed the primary tumor-induced vascular hyperpermeability. Moreover, activation of the protein kinase C (PKC) pathway disrupted the integrity of TJs and accordingly, the disruption could be alleviated by blocking VEGF. Taken together, these data demonstrate that primary breast cancer may induce tight junction disruptions in the premetastatic lung via the VEGF-PKC pathway and promote pulmonary vascular hyperpermeability before metastasis. © 2015 Wiley Periodicals, Inc. PMID:26152457

  5. Mapping of Fab-1:VEGF Interface Using Carboxyl Group Footprinting Mass Spectrometry

    Science.gov (United States)

    Wecksler, Aaron T.; Kalo, Matt S.; Deperalta, Galahad

    2015-12-01

    A proof-of-concept study was performed to demonstrate that carboxyl group footprinting, a relatively simple, bench-top method, has utility for first-pass analysis to determine epitope regions of therapeutic mAb:antigen complexes. The binding interface of vascular endothelial growth factor (VEGF) and the Fab portion of a neutralizing antibody (Fab-1) was analyzed using carboxyl group footprinting with glycine ethyl ester (GEE) labeling. Tryptic peptides involved in the binding interface between VEGF and Fab-1 were identified by determining the specific GEE-labeled residues that exhibited a reduction in the rate of labeling after complex formation. A significant reduction in the rate of GEE labeling was observed for E93 in the VEGF tryptic peptide V5, and D28 and E57 in the Fab-1 tryptic peptides HC2 and HC4, respectively. Results from the carboxyl group footprinting were compared with the binding interface identified from a previously characterized crystal structure (PDB: 1BJ1). All of these residues are located at the Fab-1:VEGF interface according to the crystal structure, demonstrating the potential utility of carboxyl group footprinting with GEE labeling for mapping epitopes.

  6. Soluble forms of VEGF receptor-1 and -2 promote vascular maturation via mural cell recruitment.

    Science.gov (United States)

    Lorquet, Sophie; Berndt, Sarah; Blacher, Silvia; Gengoux, Emily; Peulen, Olivier; Maquoi, Erik; Noël, Agnès; Foidart, Jean-Michel; Munaut, Carine; Péqueux, Christel

    2010-10-01

    Two soluble forms of vascular endothelial growth factor (VEGF) receptors, sVEGFR-1 and sVEGFR-2, are physiologically released and overproduced in some pathologies. They are known to act as anti-VEGF agents. Here we report that these soluble receptors contribute to vessel maturation by mediating a dialogue between endothelial cells (ECs) and mural cells that leads to blood vessel stabilization. Through a multidisciplinary approach, we provide evidence that these soluble VEGF receptors promote mural cell migration through a paracrine mechanism involving interplay in ECs between VEGF/VEGFR-2 and sphingosine-1-phosphate type-1 (S1P)/S1P1 pathways that leads to endothelial nitric oxyde synthase (eNOS) activation. This new paradigm is supported by the finding that sVEGFR-1 and -2 perform the following actions: 1) induce an eNOS-dependent outgrowth of a mural cell network in an ex vivo model of angiogenesis, 2) increase the mural cell coverage of neovessels in vitro and in vivo, 3) promote mural cell migration toward ECs, and 4) stimulate endothelial S1P1 overproduction and eNOS activation that promote the migration and the recruitment of neighboring mural cells. These findings provide new insights into mechanisms regulating physiological and pathological angiogenesis and vessel stabilization.

  7. Single-step nanoplasmonic VEGF165 aptasensor for early cancer diagnosis.

    Science.gov (United States)

    Cho, Hansang; Yeh, Erh-Chia; Sinha, Raghu; Laurence, Ted A; Bearinger, Jane P; Lee, Luke P

    2012-09-25

    Early cancer diagnosis is very important for the prevention or mitigation of metastasis. However, effective and efficient methods are needed to improve the diagnosis and assessment of cancer. Here, we report a single-step detection method using a nanoplasmonic aptamer sensor (aptasensor), targeting a vascular endothelial growth factor-165 (VEGF(165)), a predominant biomarker of cancer angiogenesis. Our single-step detection is accomplished by (1) specific target recognition by an aptamer-target molecule interaction and (2) direct readouts of the target recognition. The readout is achieved by inactivation of surface plasmon enhancement of fluorescent probes preattached to the aptamers. Our aptasensor provides the appropriate sensitivity for clinical diagnostics with a wide range of linear detection from 25 pg/mL to 25 μg/mL (=from 1.25 pM to 1.25 μM), high specificity for VEGF(165) against PDGF-BB, osteopontin (OPN), VEGF(121), NaCl, and temporal/thermal/biological stability. In experiments with 100% serum and saliva from clinical samples, readouts of the aptasensor and an ELISA for VEGF(165) show good agreement within the limit of the ELISA kit. We envision that our developed aptasensor holds utilities for point-of-care cancer prognostics by incorporating simplicity in detection, low-cost for test, and required small sample volumes. PMID:22880609

  8. Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    McLeod DS

    2016-05-01

    Full Text Available D Scott McLeod, Gerard A Lutty Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD, USA Abstract: Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF. Keywords: angioblasts, blood vessels, endothelial cells, oxygen, retinopathy, retina, vascular endothelial cell growth factor

  9. Contact Force and Atrial Fibrillation Ablation

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    Waqas Ullah; Richard Schilling; Tom Wong

    2016-02-01

    Full Text Available Catheters able to measure the force and vector of contact between the catheter tip and myocardium are now available. Pre-clinical work has established that the degree of contact between the radiofrequency ablation catheter and myocardium correlates with the size of the delivered lesion. Excess contact is associated with steam pops and perforation. Catheter contact varies within the left atrium secondary to factors including respiration, location, atrial rhythm and the trans-septal catheter delivery technology used. Compared with procedures performed without contact force (CF-sensing, the use of this technology has, in some studies, been found to improve complication rates, procedure and fluoroscopy times, and success rates. However, for each of these parameters there are also studies suggesting a lack of difference from the availability of CF data. Nevertheless, CF-sensing technology has been adopted as a standard of care in many institutions. It is likely that use of CF-sensing technology will allow for the optimization of each individual radiofrequency application to maximize efficacy and procedural safety. Recent work has attempted to define what these optimal targets should be, and approaches to do this include assessing for sites of pulmonary vein reconnection after ablation, or comparing the impedance response to ablation. Based on such work, it is apparent that factors including mean CF, force time integral (the area under the force-time curve and contact stability are important determinants of ablation efficacy. Multicenter prospective randomized data are lacking in this field and required to define the CF parameters required to produce optimal ablation.

  10. Silicon-Class Ablators for NIC Ignition Capsules

    Science.gov (United States)

    Ho, Darwin; Salmonson, Jay; Haan, Steve

    2012-10-01

    We present design studies using silicon-class ablators (i.e., Si, SiC, SiB6, and SiB14) for NIC ignition capsules. These types of ablators have several advantages in that they: (a) require no internal dopant layers and are robust to M-band radiation; (b) have smooth outer surfaces; (c) have stable fuel-ablator interface; and (d) have good 1-D performance. The major disadvantage for some of the ablators in this class is the relatively smaller ablation stabilization. Consequently, the ablator is more susceptible to breakup caused by RT instabilities. However, smoother outer surfaces on this class of ablators can reduce the effect of RT instabilities. 2-D simulations of SiC ablators show ignition failure despite smooth surfaces and good 1-D performance. But SiB6 and SiB14 ablators exhibit promising behaviors. SiB6 (SiB14) ablators have high 1-D ignition margin and high peak core hydrodynamic pressure 880 (900) Gbar. The ablation scale length for SiB6 is longer than that for SiC and for SiB14 is comparable to that of plastic. Therefore, we expect acceptable performance for SiB6 and less RT growth for SiB14. 2-D simulations are now in progress.

  11. Wavelength dependence of soft tissue ablation by using pulsed lasers

    Institute of Scientific and Technical Information of China (English)

    Xianzeng Zhang; Shusen Xie; Qing Ye; Zhenlin Zhan

    2007-01-01

    Pulsed laser ablation of soft biological tissue was studied at 10.6-, 2.94-, and 2.08-μm wavelengths. The ablation effects were assessed by means of optical microscope, the ablation crater depths were measured with reading microscope. It was shown that Er:YAG laser produced the highest quality ablation with clear,sharp cuts following closely the patial contour of the incident beam and the lowest fluence threshold. The pulsed CO2 laser presented the moderate quality ablation with the highest ablation efficiency. The craters drilled with Ho:YAG laser were generally larger than the incident laser beam spot, irregular in shape, and clearly dependent on the local morphology of biotissue. The blation characteristics, including fluence threshold and ablation efficiency, varied substantially with wavelength. It is not evident that water is the only dominant chromophore in tissue.

  12. Tissue temperatures and lesion size during irrigated tip catheter radiofrequency ablation: an in vitro comparison of temperature-controlled irrigated tip ablation, power-controlled irrigated tip ablation, and standard temperature-controlled ablation

    DEFF Research Database (Denmark)

    Petersen, H H; Chen, X; Pietersen, A;

    2000-01-01

    The limited success rate of radiofrequency catheter ablation in patients with ventricular tachycardias related to structural heart disease may be increased by enlarging the lesion size. Irrigated tip catheter ablation is a new method for enlarging the size of the lesion. It was introduced...... in the power-controlled mode with high power and high infusion rate, and is associated with an increased risk of crater formation, which is related to high tissue temperatures. The present study explored the tissue temperatures during temperature-controlled irrigated tip ablation, comparing it with standard...... temperature-controlled ablation and power-controlled irrigated tip ablation. In vitro strips of porcine left ventricular myocardium were ablated. Temperature-controlled irrigated tip ablation at target temperatures 60 degrees C, 70 degrees C, and 80 degrees C with infusion of 1 mL saline/min were compared...

  13. MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.

    Directory of Open Access Journals (Sweden)

    Zhong Hua

    Full Text Available MicroRNAs (miRNAs are a class of 20-24 nt non-coding RNAs that regulate gene expression primarily through post-transcriptional repression or mRNA degradation in a sequence-specific manner. The roles of miRNAs are just beginning to be understood, but the study of miRNA function has been limited by poor understanding of the general principles of gene regulation by miRNAs. Here we used CNE cells from a human nasopharyngeal carcinoma cell line as a cellular system to investigate miRNA-directed regulation of VEGF and other angiogenic factors under hypoxia, and to explore the principles of gene regulation by miRNAs. Through computational analysis, 96 miRNAs were predicted as putative regulators of VEGF. But when we analyzed the miRNA expression profile of CNE and four other VEGF-expressing cell lines, we found that only some of these miRNAs could be involved in VEGF regulation, and that VEGF may be regulated by different miRNAs that were differentially chosen from 96 putative regulatory miRNAs of VEGF in different cells. Some of these miRNAs also co-regulate other angiogenic factors (differential regulation and co-regulation principle. We also found that VEGF was regulated by multiple miRNAs using different combinations, including both coordinate and competitive interactions. The coordinate principle states that miRNAs with independent binding sites in a gene can produce coordinate action to increase the repressive effect of miRNAs on this gene. By contrast, the competitive principle states when multiple miRNAs compete with each other for a common binding site, or when a functional miRNA competes with a false positive miRNA for the same binding site, the repressive effects of miRNAs may be decreased. Through the competitive principle, false positive miRNAs, which cannot directly repress gene expression, can sometimes play a role in miRNA-mediated gene regulation. The competitive principle, differential regulation, multi-miRNA binding sites, and false

  14. Glucagon like peptide-2 induces intestinal restitution through VEGF release from subepithelial myofibroblasts.

    Science.gov (United States)

    Bulut, Kerem; Pennartz, Christian; Felderbauer, Peter; Meier, Juris J; Banasch, Matthias; Bulut, Daniel; Schmitz, Frank; Schmidt, Wolfgang E; Hoffmann, Peter

    2008-01-14

    Glucagon like peptide-2 (GLP-2) exerts intestinotrophic actions, but the underlying mechanisms are still a matter of debate. Recent studies demonstrated the expression of the GLP-2 receptor on fibroblasts located in the subepithelial tissue, where it might induce the release of growth factors such as keratinocyte growth factor (KGF) or vascular endothelial growth factor (VEGF). Therefore, in the present studies we sought to elucidate the downstream mechanisms involved in improved intestinal adaptation by GLP-2. Human colonic fibroblasts (CCD-18Co), human colonic cancer cells (Caco-2 cells) and rat ileum IEC-18 cells were used. GLP-2 receptor mRNA expression was determined using real time RT-PCR. Conditioned media from CCD-18Co cells were obtained following incubation with GLP-2 (50-250 nM) for 24 h. Cell viability was assessed by a 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT)-assay, and wound healing was determined with an established migration-assay. Transforming Growth Factor beta (TGF-beta), VEGF and KGF mRNA levels were determined by RT-PCR. Protein levels of VEGF and TGF-beta in CCD-18Co cells following GLP-2 stimulation were determined using ELISA. Neutralizing TGF-beta and VEGF-A antibodies were utilized to assess the role of TGF-beta and VEGF-A in the process of wound healing. GLP-2 receptor expression was detected in CCD-18Co cells. Conditioned media from CCD-18Co cells dose-dependently induced proliferation in Caco-2 cells, but not in IEC-18 cells. Conditioned media also enhanced cell migration in IEC-18 cells (PCCD-18Co. The migratory effects of GLP-2 were completely abolished in the presence of TGF-beta and VEGF-A antibodies. GLP-2 exerts differential effects on the epithelium of the small intestine and the colon. Thus, in small intestinal cells GLP-2 stimulates wound repair, whereas no such effects were observed in colonic cells. The mechanisms underlying GLP-2 induced intestinal wound repair seem to involve the secretion of

  15. Peri- and Postnatal Effects of Prenatal Adenoviral VEGF Gene Therapy in Growth-Restricted Sheep.

    Science.gov (United States)

    Carr, David J; Wallace, Jacqueline M; Aitken, Raymond P; Milne, John S; Martin, John F; Zachary, Ian C; Peebles, Donald M; David, Anna L

    2016-06-01

    Uterine artery (UtA) adenovirus (Ad) vector-mediated overexpression of vascular endothelial growth factor (VEGF) enhances uterine blood flow in normal sheep pregnancy and increases fetal growth in the overnourished adolescent sheep model of fetal growth restriction (FGR). Herein, we examined its impact on gestation length, neonatal survival, early postnatal growth and metabolism. Singleton-bearing ewes were evenly allocated to receive Ad.VEGF-A165 (5 × 10(10) particles/ml, 10 ml, n = 17) or saline (10 ml, n = 16) injected into each UtA at laparotomy (0.6 gestation). Fetal growth was serially monitored (blind) by ultrasound until delivery. Lambs were weighed and blood was sampled weekly and a glucose tolerance test performed (68-day postnatal age). Hepatic DNA/RNA was extracted at necropsy (83-day postnatal age) to examine methylation status of eight somatotropic axis genes. IGF1 mRNA and protein expression were measured by RT-PCR and radioimmunoassay, respectively. All pregnancies remained viable following Ad.VEGF-A165 treatment. Fetal abdominal circumference and renal volume were greater in the Ad.VEGF-A165 group compared with the saline group at 21/28 days (P ≤ 0.04) postinjection. At delivery, gestation length (P = 0.07), lamb birthweight (P = 0.08), umbilical girth (P = 0.06), and plasma glucose (P = 0.09) tended to be greater in Ad.VEGF-A165-treated lambs. Levels of neonatal intervention required to ensure survival was equivalent between groups. Absolute postnatal growth rate (P = 0.02), insulin area under the curve (P = 0.04) and carcass weight at necropsy (P = 0.04) were increased by Ad.VEGF-A165 treatment. There was no impact on markers of insulin sensitivity or methylation/expression of key genes involved in somatic growth. Ad.VEGF-A165 gene therapy increased fetal growth in a sheep FGR model, and lambs continued to thrive during the neonatal and early postnatal period. PMID:27103444

  16. Elevated SP-1 transcription factor expression and activity drives basal and hypoxia-induced vascular endothelial growth factor (VEGF) expression in non-small cell lung cancer.

    Science.gov (United States)

    Deacon, Karl; Onion, David; Kumari, Rajendra; Watson, Susan A; Knox, Alan J

    2012-11-16

    VEGF plays a central role in angiogenesis in cancer. Non-small cell lung cancer (NSCLC) tumors have increased microvascular density, localized hypoxia, and high VEGF expression levels; however, there is a lack of understanding of how oncogenic and tumor microenvironment changes such as hypoxia lead to greater VEGF expression in lung and other cancers. We show that NSCLC cells secreted higher levels of VEGF than normal airway epithelial cells. Actinomycin D inhibited all NSCLC VEGF secretion, and VEGF minimal promoter-luciferase reporter constructs were constitutively active until the last 85 base pairs before the transcription start site containing three SP-1 transcription factor-binding sites; mutation of these VEGF promoter SP-1-binding sites eliminated VEGF promoter activity. Furthermore, dominant negative SP-1, mithramycin A, and SP-1 shRNA decreased VEGF promoter activity, whereas overexpression of SP-1 increased VEGF promoter activity. Chromatin immunoprecipitation assays demonstrated SP-1, p300, and PCA/F histone acetyltransferase binding and histone H4 hyperacetylation at the VEGF promoter in NSCLC cells. Cultured NSCLC cells expressed higher levels of SP-1 protein than normal airway epithelial cells, and double-fluorescence immunohistochemistry showed a strong correlation between SP-1 and VEGF in human NSCLC tumors. In addition, hypoxia-driven VEGF expression in NSCLC cells was SP-1-dependent, with hypoxia increasing SP-1 activity and binding to the VEGF promoter. These studies are the first to demonstrate that overexpression of SP-1 plays a central role in hypoxia-induced VEGF secretion. PMID:22992725

  17. Low-power Helium-Neon laser irradiation enhances the expression of VEGF in murine myocardium

    Institute of Scientific and Technical Information of China (English)

    张卫光; 吴长燕; 潘文潇; 田珑; 夏家骝

    2004-01-01

    Background Low-power helium-neon (He-Ne) lasers have been increasingly widely applied in the treatment of cardiovascular diseases, and its vasodilation effect has been proven. The aim of this study was to determine the effects of low-power He-Ne laser irradiation directed at the precardial region of Wistar rats on capillary permeability in the myocardium and the expression of myocardial vascular endothelial growth factor (VEGF). Methods Sixteen rats were divided randomly into control and irradiated groups (n=8, each). A He-Ne laser (632.8 nm) was applied to the irradiated group with a dose of 60.5 J/cm2. Ferritin was perfused into the left femoral vein and capillary permeability was examined under an electron microscope. VEGF expression in the myocardium was investigated by immunohistochemical methods, RT-PCR, and image analysis. Results The ultrastructures of the myocardial capillaries were examined. Compared to the control group, more high-density granules (ferritin), which were present within the capillary endothelium and the mitochondrions of myocardial cells in the internal layer of the myocardium, were observed in the irradiated group. VEGF staining of the myocardium was stronger in the irradiated group than that in the control group. The optic density of the irradiated group (0.246±0.015) was significantly higher than that of the control group (0.218±0.012, P<0.05). Finally, the levels of RT-PCR products of VEGF165 mRNA were 2.79 times higher in irradiated rats than in the control rats.Conclusions Our study demonstrates that He-Ne laser irradiation (in doses of 60.5 J/cm2) increases myocardial capillary permeability and the production of VEGF in myocardial microvessels and in myocardium. Our study provides experimental morphological evidence that myocardial microcirculation can be improved using He-Ne laser irradiation.

  18. Serum 25(OHD and VEGF in diabetes mellitus type 2: gender-specific associations '

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    Nikolaos Tentolouris

    2011-10-01

    Full Text Available Background: Vitamin D insufficiency has been defined as serum 25-hydroxyvitamin D (25(OHD levels below 30 ng/mL and is common among patients with diabetes mellitus (DM type 2 and the elderly.Aim & Objectives: Our aim was to investigate clinically meaningful associations implicating low serum levels of 25(OHD and vascular endothelial growth factor (VEGF levels in DM type 2.Methods: Serum 25(OHD and VEGF levels were determined in 40 patients with DM type 2 and vitamin D insufficiency. Their correlation with markers of advanced diabetic disease (amputation, diabetic foot, proliferative diabetic retinopathy, insulin dependence as well as with serum biochemical parameters was examined. Subanalyses were performed on men and women.Results: Compared with males, female patients exhibited lower 25(OHD levels (p<0.0001 but higher serum VEGF (p=0.018. There was a trend towards an inverse vitamin D - VEGF association. Subanalysis on women showed low serum 25(OHD levels strongly associated with amputation (p=0.003. High serum VEGF levels were associated with amputation (p=0.038, and marginally with diabetic foot (p=0.058, insulin dependence (p=0.084 and proliferative diabetic retinopathy (p=0.086. Higher serum 25(OHD levels were associated with serum uric acid (p=0.007, calcium (p=0.042 and albumin levels (p=0.033. Subanalysis on men demonstrated positive correlation between 25(OHD levels, albumin (p=0.004 and calcium levels (p=0.060, borderline association.Conclusion: The association between low serum 25(OHD levels and amputation in women may be inscribed into the wider context portraying vitamin D insufficiency as a poor prognostic factor. Vitamin D insufficiency may exert gender-specific effects in the context of DM type 2.

  19. Endostatin inhibits VEGF-A induced osteoclastic bone resorption in vitro

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    Ilvesaro Joanna

    2006-07-01

    Full Text Available Abstract Background Endostatin is a C-terminal fragment of collagen XVIII which is a component of basement membranes with the structural properties of both collagens and proteoglycans. Endostatin has a major role in angiogenesis which is intimately associated with bone development and remodeling. Signaling between the endothelial cells and the bone cells, for example, may have a role in recruitment of osteoclastic precursor cells. Our study aims at exploring a possibility that endostatin, either as a part of basement membrane or as a soluble molecule, may control osteoclastogenesis and osteoclastic bone resorption in vitro. Methods Rat pit formation assay was employed in order to examine the effect of endostatin alone or in combination with vascular endothelial growth factor-A (VEGF-A on bone resorption in vitro. Effect of these agents on osteoclast differentiation in vitro was also tested. Osteoclastogenesis and the number of osteoclasts were followed by tartrate resistant acid phosphatase (TRACP staining and resorption was evaluated by measuring the area of excavated pits. Results Endostatin inhibited the VEGF-A stimulated osteoclastic bone resorption, whereas endostatin alone had no effect on the basal resorption level in the absence of VEGF-A. In addition, endostatin could inhibit osteoclast differentiation in vitro independent of VEGF-A. Conclusion Our in vitro data indicate that collagen XVIII/endostatin can suppress VEGF-A induced osteoclastic bone resorption to the basal level. Osteoclastogenesis is also inhibited by endostatin. The regulatory effect of endostatin, however, is not critical since endostatin alone does not modify the basal bone resorption.

  20. Anti-VEGF treatment for myopic choroid neovascularization: from molecular characterization to update on clinical application

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-07-01

    Full Text Available Yan Zhang,1 Qian Han,2 Yusha Ru,1 Qiyu Bo,1 Rui Hua Wei1 1Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 2Tangshan Eye Hospital, Tangshan, Hebei Province, People’s Republic of China Abstract: Choroidal neovascularization (CNV secondary to pathologic myopia has a very high incidence in global, especially in Asian, populations. It is a common cause of irreversible central vision loss, and severely affects the quality of life in the patients with pathologic myopia. The traditional therapeutic modalities for CNV secondary to pathologic myopia include thermal laser photocoagulation, surgical management, transpupillary thermotherapy, and photodynamic therapy with verteporfin. However, the long-term outcomes of these modalities are disappointing. Recently, intravitreal administration of anti-VEGF biological agents, including bevacizumab, ranibizumab, pegaptanib, aflibercept, and conbercept, has demonstrated promising outcomes for this ocular disease. The anti-VEGF regimens are more effective on improving visual acuity, reducing central fundus thickness and central retina thickness than the traditional modalities. These anti-VEGF agents thus hold the potential to become the first-line medicine for treatment of CNV secondary to pathologic myopia. This review follows the trend of “from bench to bedside”, initially discussing the pathogenesis of myopic CNV, delineating the molecular structures and mechanisms of action of the currently available anti-VEGF drugs, and then systematically comparing the up to date clinical applications as well as the efficacy and safety of the anti-VEGF drugs to the CNV secondary to pathologic myopia. Keywords: formation of new vessels, choroid membrane, pathologic myopia, vascular endothelial growth factor, molecular mechanisms, clinical trials

  1. Multi-modal albedo distributions in the ablation area of the southwestern Greenland Ice Sheet

    Science.gov (United States)

    Moustafa, S. E.; Rennermalm, A. K.; Smith, L. C.; Miller, M. A.; Mioduszewski, J. R.; Koenig, L. S.; Hom, M. G.; Shuman, C. A.

    2015-05-01

    Surface albedo is a key variable controlling solar radiation absorbed at the Greenland Ice Sheet (GrIS) surface and, thus, meltwater production. Recent decline in surface albedo over the GrIS has been linked to enhanced snow grain metamorphic rates, earlier snowmelt, and amplified melt-albedo feedback from atmospheric warming. However, the importance of distinct surface types on ablation area albedo and meltwater production is still relatively unknown. In this study, we analyze albedo and ablation rates using in situ and remotely sensed data. Observations include (1) a new high-quality in situ spectral albedo data set collected with an Analytical Spectral Devices Inc. spectroradiometer measuring at 325-1075 nm along a 1.25 km transect during 3 days in June 2013; (2) broadband albedo at two automatic weather stations; and (3) daily MODerate Resolution Imaging Spectroradiometer (MODIS) albedo (MOD10A1) between 31 May and 30 August 2012 and 2013. We find that seasonal ablation area albedos in 2013 have a bimodal distribution, with snow and ice facies characterizing the two peaks. Our results show that a shift from a distribution dominated by high to low albedos corresponds to an observed melt rate increase of 51.5% (between 10-14 July and 20-24 July 2013). In contrast, melt rate variability caused by albedo changes before and after this shift was much lower and varied between ~10 and 30% in the melting season. Ablation area albedos in 2012 exhibited a more complex multimodal distribution, reflecting a transition from light to dark-dominated surface, as well as sensitivity to the so called "dark-band" region in southwest Greenland. In addition to a darkening surface from ice crystal growth, our findings demonstrate that seasonal changes in GrIS ablation area albedos are controlled by changes in the fractional coverage of snow, bare ice, and impurity-rich surface types. Thus, seasonal variability in ablation area albedos appears to be regulated primarily as a function

  2. Expression level, tissue distribution pattern, and prognostic impact of vascular endothelial growth factors VEGF and VEGF-C and their receptors Flt-1, KDR, and Flt-4 in different subtypes of non-Hodgkin lymphomas

    DEFF Research Database (Denmark)

    Jørgensen, Judit M; Sørensen, Flemming B; Bendix, Knud;

    2009-01-01

    The aim of the study was to investigate the expression of angio- and lymphangiogenic molecules (vascular endothelial growth factors VEGF and VEGF-C and their receptors Flt-1, KDR, and Flt-4) in non-Hodgkin lymphomas (NHL) treated in the pre-rituximab era. Pre-therapeutic lymph-node biopsies from...... analyzed biopsies. In FL, diffuse intratumoral VEGF staining correlated with shorter overall survival (OS) (p = 0.008) and diffuse KDR staining was associated with a higher risk of histologic transformation (p = 0.05). In DLBCL, high KDR expression predicted poor treatment response (p = 0.03) and had a...

  3. Effect of HIF-1α on VEGF-C Induced Lymphangiogenesis and Lymph Nodes Metastases of Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    TAO Jing; LI Tao; LI Kai; XIONG Jiongxin; YANG Zhiyong; WU Heshui; WANG Chunyou

    2006-01-01

    The effect of hypoxia inducible factor-1 α (HIF-1α) on vascular endothelial growth factor C (VEGF-C) and the correlation between HIF-1α and lymphangiogenesis and lymph nodes metastases (LNM) in pancreatic cancer were investigated. Immunohistochemical SP method was used to detect the protein expression of HIF-1α and VEGF-C, and Lymphatic vessel density (LVD) was determined by stain of VEGFR-3, collagen type Ⅳ in 75 pancreatic head cancers from regional pancreatectomy (RP) during Dec. 2001 to Dec. 2003. The relationship between HIF-1α and VEGF-C, lymphangiogenesis, LNM was analyzed statistically. The results showed that the positive expression rate of HIF-1α and VEGF-C in pancreatic cancer tissues was 48.00 % (36/75) and 65.33 % (49/75) respectively. In positive group of HIF-1α, the positive rate of VEGF-C and LVD, and LVD rate was 80.56 % (29/36), 13.22±3.76 and 88.89 % (32/36) respectively, and in negative group of HIF-1α,positive rate of VEGF-C and LVD was 51.28 % (20/39), 5.98±2.17 and 66.67 % (26/39) respectively (P<0.01 or P<0.05). It was suggested that HIF-1α could promote the expression of VEGF-C, lymphangiogenesis and LNM in pancreatic cancer.

  4. Vascular endothelial growth factor (VEGF-C - a potent risk factor in children diagnosed with stadium 4 neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Bogdan Miskowiak

    2009-01-01

    Full Text Available To evaluate the immunohistochemical expression of VEGF-C, CD34 and VEGFR-2 in cancer tissue of children diagnosed with stadium 4 neuroblastoma (NB and correlate their presence with the survival rate of children diagnosed with that stage of the disease. Eighteen children assigned to stadium 4 composed the study group. Fourteen patients (allocated to stadium 3 formed a control group. VEGF-C, CD34 and VEGFR-2 expressions were evaluated by immunohistochemical assay. Consecutive slides incubated with anti-CD34 and anti-VEGFR-2 antibodies revealed that the two markers were colocalized within endothelial layer of the blood vessels. On the other hand, VEGF-C was expressed exclusively in tumour cells. As demonstrated by Fisher's exact test, the risk of NB treatment failure (progression or relapse as well as tumour related death, when all the patients were considered, was found to be significant in VEGF-C positive patients. VEGF-C expression in NB constitutes a potent risk factor and may direct future anti-angiogenic treatment strategy. The proximity of VEGF-C and CD34/VEGFR-2 of NB could be the equivalent of a potentially interesting VEGF-C fashion involving a tumour cell invasion into the blood vessels in an early phase of metastases promoting.

  5. VEGF and eNOS Expression in Umbilical Cord from Pregnancy Complicated by Hypertensive Disorder with Different Severity

    Directory of Open Access Journals (Sweden)

    K. Bhavina

    2014-01-01

    Full Text Available Background. Reduced blood flow in hypertensive pregnancy may influence the production vasoconstrictors; subsequently the vessel remains in highly contracted state. NO is a vasodilator; VEGF influences its synthesis by regulating eNOS production. Aim of our study was to evaluate the expression of VEGF and eNOS in different severity of hypertensive pregnancy. Methods. Study was conducted in 4 groups with 40 members: group 1—control, group 2—gestational hypertension, group 3—mild preeclampsia, and group 4—severe preeclampsia. Fetal end of umbilical cord was taken and follows IHC staining protocol for VEGF and eNOS antibody. Staining intensity were measured by semiquantitative scoring method. Mann Whitney U test was used to compare each group. Results. Decreased expression of both VEGF and eNOS was found in hypertensive condition than in normal condition. Among hypertensive group, severe preeclamptic group showed more intensity in staining than gestational hypertension and mild preeclampsia. Conclusion. Reduction of VEGF and eNOS in gestational hypertension may lead to hypoperfusion and subsequent hypoxia of fetus in hypertensive pregnancy. The developed hypoxic state may upregulate the synthesis of VEGF and thereby eNOS. Increased expression of VEGF and eNOS in severe group may be a compensatory mechanism to dilate the blood vessels and to improve blood flow of fetus.

  6. R-Ras Inhibits VEGF-Induced p38MAPK Activation and HSP27 Phosphorylation in Endothelial Cells.

    Science.gov (United States)

    Sawada, Junko; Li, Fangfei; Komatsu, Masanobu

    2015-01-01

    R-Ras is a Ras family small GTPase that is highly expressed in mature functional blood vessels in normal tissues. It inhibits pathological angiogenesis and promotes vessel maturation and stabilization. Previous studies suggest that R-Ras affects cellular signaling in endothelial cells, pericytes and smooth-muscle cells to regulate vessel formation and remodeling in adult tissues. R-Ras suppresses VEGF-induced endothelial permeability and vessel sprouting while promoting normalization of pathologically developing vessels in mice. It attenuates VEGF receptor-2 (VEGFR2) activation by inhibiting internalization of the receptor upon VEGF ligand binding, leading to significant reduction of VEGFR2 autophosphorylation. Here, we show that R-Ras strongly suppresses the VEGF-dependent activation of stress-activated protein kinase-2/p38 mitogen-activated protein kinase (SAPK2/p38MAPK) and the phosphorylation of downstream heat-shock protein 27 (HSP27), a regulator of actin cytoskeleton organization, in endothelial cells. The suppression of p38MAPK activation and HSP27 phosphorylation by R-Ras concurred with altered actin cytoskeleton architecture, reduced membrane protrusion and inhibition of endothelial cell migration toward VEGF. Silencing of endogenous R-Ras by RNA interference increased membrane protrusion and cell migration stimulated by VEGF, and these effects were offset by p38MAPK inhibitor SB203580. These results suggest that R-Ras regulates angiogenic activities of endothelial cells in part via inhibition of the p38MAPK-HSP27 axis of VEGF signaling. PMID:27029009

  7. Cytokine levels correlate with immune cell infiltration after anti-VEGF therapy in preclinical mouse models of breast cancer.

    Directory of Open Access Journals (Sweden)

    Christina L Roland

    Full Text Available The effect of blocking VEGF activity in solid tumors extends beyond inhibition of angiogenesis. However, no studies have compared the effectiveness of mechanistically different anti-VEGF inhibitors with respect to changes in tumor growth and alterations in the tumor microenvironment. In this study we use three distinct breast cancer models, a MDA-MB-231 xenograft model, a 4T1 syngenic model, and a transgenic model using MMTV-PyMT mice, to explore the effects of various anti-VEGF therapies on tumor vasculature, immune cell infiltration, and cytokine levels. Tumor vasculature and immune cell infiltration were evaluated using immunohistochemistry. Cytokine levels were evaluated using ELISA and electrochemiluminescence. We found that blocking the activation of VEGF receptor resulted in changes in intra-tumoral cytokine levels, specifically IL-1beta, IL-6 and CXCL1. Modulation of the level these cytokines is important for controlling immune cell infiltration and ultimately tumor growth. Furthermore, we demonstrate that selective inhibition of VEGF binding to VEGFR2 with r84 is more effective at controlling tumor growth and inhibiting the infiltration of suppressive immune cells (MDSC, Treg, macrophages while increasing the mature dendritic cell fraction than other anti-VEGF strategies. In addition, we found that changes in serum IL-1beta and IL-6 levels correlated with response to therapy, identifying two possible biomarkers for assessing the effectiveness of anti-VEGF therapy in breast cancer patients.

  8. Structural basis for the selective vascular endothelial growth factor-A (VEGF-A) binding to neuropilin-1

    Energy Technology Data Exchange (ETDEWEB)

    Parker, Matthew W.; Xu, Ping; Li, Xiaobo; Vander Kooi, Craig W. (Kentucky)

    2012-07-25

    Neuropilin-1 (Nrp1) is an essential receptor for angiogenesis that binds to VEGF-A. Nrp1 binds directly to VEGF-A with high affinity, but the nature of their selective binding has remained unclear. Nrp1 was initially reported to bind to the exon 7-encoded region of VEGF-A and function as an isoform-specific receptor for VEGF-A164/165. Recent data have implicated exon 8-encoded residues, which are found in all proangiogenic VEGF-A isoforms, in Nrp binding. We have determined the crystal structure of the exon 7/8-encoded VEGF-A heparin binding domain in complex with the Nrp1-b1 domain. This structure clearly demonstrates that residues from both exons 7 and 8 physically contribute to Nrp1 binding. Using an in vitro binding assay, we have determined the relative contributions of exon 7- and 8-encoded residues. We demonstrate that the exon 8-encoded C-terminal arginine is essential for the interaction of VEGF-A with Nrp1 and mediates high affinity Nrp binding. Exon 7-encoded electronegative residues make additional interactions with the L1 loop of Nrp1. Although otherwise conserved, the primary sequences of Nrp1 and Nrp2 differ significantly in this region. We further show that VEGF-A{sub 164} binds 50-fold more strongly to Nrp1 than Nrp2. Direct repulsion between the electronegative exon 7-encoded residues of the heparin binding domain and the electronegative L1 loop found only in Nrp2 is found to significantly contribute to the observed selectivity. The results reveal the basis for the potent and selective binding of VEGF-A{sub 164} to Nrp1.

  9. Influence of hepatic arterial blockage on blood perfusion and VEGF, MMP-1 expression of implanted Iiver cancer rats

    Institute of Scientific and Technical Information of China (English)

    Wei-Jian Guo; Jie Li; Wan-Long Ling; Yong-Rui Bai; Wen-Zhu Zhang; Yu-Fan Cheng; Wen-Hua Gu; Jun-Yan Zhuang

    2002-01-01

    AIM: To investigate the influence of hepatic arterial blockageon blood perfusion of transplanted cancer in rat liver and theexpression of vascular endothelial growth factor (VEGF)and matrix metalloproteinase-1 (MMP-1), and to explore themechanisms involved in transarterial embolization (TAE)-induced metastasis of liver cancer preliminarily.METHODS: Wallker 256 carcinosarcoma was transplanted intorat liver to establish the liver cancer model. Hepatic arterialligation (HAL) was used to block the hepatic arterial bloodsupply and simulate TAE. Blood perfusion of tumor incontrol, laparotomy control, and HAL group was anslyzedby Hoechst 33 342 labeling assay, the serum VEGF level wasassayed by ELISA, the expression of VEGF and MMP-1mRNA was detected by in situ hybridization.RESULTS: Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion oftumor directly and hypoxia of tumor indirectly in HAL groupdecreased significantly compared with that in control group(329+29 vs 384+ 19, P<0.01). The serum VEGF level inthe HAL group increased significantly as against that of thecontrol group (93 ng@ L-1 + 44 ng@ L-1 vs 55 ng@ L-1 + 19 ng@ L-1,P< 0.05). The expression of VEGF and MMP-1 mRNA in thetumor tissue of the HAL group increased significantlycompared with that of the control and the laparotomy controlgroups ( P < 0. 05). The blood perfusion data of the tumor,represented by the number of Hoechst 33 342 labeled calls,showed a good linear inverse correlation with the serumVEGF level ( r = -0.606, P < 0. 05 ) and the expression ofVEGF mRNA in the tumor tissue ( r= -0.338, P< 0.01).CONCLUSION: Blockage of hepatic arterial blood supplyresults in decreased blood perfusion and increasedexpression of metastasis-associated genes VEGF and MMP-1of transplanted liver cancer in rats. Decreased bloodperfusion and hypoxia may be the major cause of up-regulated expression of VEGF.

  10. Regional differences in expression of VEGF mRNA in rat gastrocnemius following 1 hr exercise or electrical stimulation

    Directory of Open Access Journals (Sweden)

    Tang Kechun

    2002-06-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF mRNA levels increase in rat skeletal muscle after a single bout of acute exercise. We assessed regional differences in VEGF165 mRNA levels in rat gastrocnemius muscle using in situ hybridization after inducing upregulation of VEGF by treadmill running (1 hr or electrical stimulation (1 hr. Muscle functional regions were defined as oxidative (primarily oxidative fibers, I and IIa, or glycolytic (entirely IIb or IId/x fibers. Functional regions were visualized on muscle cross sections that were matched in series to slides processed through in situ hybridization with a VEGF165 probe. A greater upregulation in oxidative regions was hypothesized. Results Total muscle VEGF mRNA (via Northern blot was upregulated 3.5-fold with both exercise and with electrical stimulation (P = 0.015. Quantitative densitometry of the VEGF mRNA signal via in situ hybridization reveals significant regional differences (P ≤ 0.01 and protocol differences (treadmill, electrical stimulation, and control, P ≤ 0.05. Mean VEGF mRNA signal was higher in the oxidative region in both treadmill run (~7%, N = 4 muscles, P ≤ 0.05 and electrically stimulated muscles (~60%, N = 4, P ≤ 0.05. These regional differences were not significantly different from control muscle (non-exercised, non-stimulated, N = 2 muscles, although nearly so for electrically stimulated muscle (P = 0.056. Conclusions Moderately higher VEGF mRNA signal in oxidative muscle regions is consistent with regional differences in capillary density. However, it is not possible to determine if the VEGF mRNA signal difference is important in either the maintenance of regional capillarity differences or exercise induced angiogenesis.

  11. Expression ofVEGF,IL-6,IL-8 in serum and peritoneal fluid of patients with endometriosis

    Institute of Scientific and Technical Information of China (English)

    Yu-Xiang Fan

    2015-01-01

    Objective:To explore the expression of VEGF, IL-6, and IL-8 in serum and peritoneal fluid of patients with endometriosis (EMT) and their clinical significances.Methods:EMT patients who were pathologically diagnosed after laparoscopy from February, 2014 to February, 2015 were included in the study and served as the observation group. Moreover, patients with benign ovarian tumor and healthy women who came for physical examination at the same period were selected and served as the disease control group and normal control group, respectively for correlation analysis. The levels of VEGF, IL-6, and IL-8 in serum and peritoneal fluid of subjects in the three groups were compared.Results:The levels of serum VEGF, IL-6, and IL-8 in the observation group were significantly higher than those in the disease control group and the normal control group (P0.05). The levels of VEGF, IL-6, and IL-8 in peritoneal fluid in the observation group were significantly higher than those in the disease control group (P<0.05). With the increasing of EMT staging, the levels of VEGF, IL-6, and IL-8 in serum and peritoneal fluid were correspondingly elevated. The levels of VEGF, IL-6, and IL-8 in serum and peritoneal fluid at stageⅢ-Ⅳ were significantly higher than those at stageⅠ-Ⅱ(P<0.05).Conclusions:VEGF, IL-6 and IL-8 are highly expressed in serum and peritoneal fluid of patients with EMT. With the progression of the disease, the expression of VEGF, IL-6 and IL-8 shows an increasing trend. Clinical detection of the changes of VEGF, IL-6, and IL-8 levels in serum and peritoneal fluid can monitor the progression of EMT condition.

  12. The mRNA expression of hTERT in human breast carcinomas correlates with VEGF expression

    Directory of Open Access Journals (Sweden)

    Kirkpatrick Katharine L

    2004-01-01

    Full Text Available Abstract Background Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase is the rate-limiting determinant of telomerase reactivation. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any correlation between hTERT and the negative prognostic indicators VEGF and PCNA by quantitatively measuring the mRNA expression of these genes in human breast cancer and in adjacent non-cancerous tissue (ANCT. Materials and methods RNA was extracted from 38 breast carcinomas and 40 ANCT. hTERT and VEGF165, VEGF189 and PCNA mRNA expressions were estimated by reverse transcriptase-PCR (RT-PCR and Taqman methodology. Results The level of expression of VEGF-165 and PCNA was significantly higher in carcinoma tissue than ANCT (p = 0.02. The ratio of VEGF165/189 expression was significantly higher in breast carcinoma than ANCT (p = 0.025. hTERT mRNA expression correlated with VEGF-189 mRNA (p = 0.008 and VEGF165 (p = 0.07. Conclusions hTERT mRNA expression is associated with the expression of the VEGF189 and 165 isoforms. This could explain the poorer prognosis reported in breast tumours expressing high levels of hTERT. The relative expression of the VEGF isoforms is significantly different in breast tumour to ANCT, and this may be important in breast carcinogenesis.

  13. Vascular endothelial growth factor (VEGF) expression in locally advanced prostate cancer: secondary analysis of radiation therapy oncology group (RTOG) 8610

    International Nuclear Information System (INIS)

    Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer. The analysis was performed using patients enrolled on RTOG 8610, a phase III randomized control trial of radiation therapy alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and radiation therapy (Arm 2) in men with locally advanced prostate carcinoma. Tissue samples were obtained from the RTOG tissue repository. Hematoxylin and eosin slides were reviewed, and paraffin blocks were immunohistochemically stained for VEGF expression and graded by Intensity score (0–3). Cox or Fine and Gray’s proportional hazards models were used. Sufficient pathologic material was available from 103 (23%) of the 456 analyzable patients enrolled in the RTOG 8610 study. There were no statistically significant differences in the pre-treatment characteristics between the patient groups with and without VEGF intensity data. Median follow-up for all surviving patients with VEGF intensity data is 12.2 years. Univariate and multivariate analyses demonstrated no statistically significant correlation between the intensity of VEGF expression and overall survival, distant metastasis, local progression, disease-free survival, or biochemical failure. VEGF expression was also not statistically significantly associated with any of the endpoints when analyzed by treatment arm. This study revealed no statistically significant prognostic or predictive value of VEGF expression for locally advanced prostate cancer. This analysis is among one of the largest sample bases with long-term follow-up in a well-characterized patient population. There is an urgent need to establish multidisciplinary initiatives for coordinating further research in the area of

  14. Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx

    Directory of Open Access Journals (Sweden)

    Karagoz Filiz

    2010-06-01

    Full Text Available Abstract Background The aim of this study was to assess the relationship between expression of vascular endothelial growth factor (VEGF and phosphatase and tensin homolog deleted in chromosome ten (PTEN, angiogenesis and clinicopathological parameters of squamous cell carcinoma of the larynx. Methods We examined immunohistochemical expression of VEGF and PTEN and CD34 for microvessel density (MVD in sections of formalin-fixed, paraffin embedded tissue blocks of 140 patients with squamous cell carcinoma of the larynx. The intensity of VEGF and PTEN staining and the proportion of cells staining were scored. Results The tumor grade was not significantly related to PTEN expression, but it was to VEGF expression (p = 0.400; p = 0.015, respectively. While there was no significant relationship between PTEN expression and tumor size and cartilage invasion (p = 0.311, p = 0.128, there was a significant relationship between the severity of VEGF expression and tumor size (p = 0.006 and lymph node metastasis (p = 0.048 but not cartilage invasion (p = 0.129. MVD was significantly higher in high-grade tumors (p = 0.003 but had no significant relationship between MVD, lymph node metastasis, and cartilage invasion (p = 0.815, p = 0.204. There was also no significant relationship between PTEN and VEGF expression (p = 0.161 and between PTEN and VEGF expression and the MVD (p = 0.120 and p = 0.175, respectively. Conclusions Increased VEGF expression may play an important role in the outcome of squamous cell carcinoma of the larynx. PTEN expression was not related to VEGF expression and clinicopathological features of squamous cell carcinoma of the larynx.

  15. The effect of ethanol infusion on the size of the ablated lesion in radiofrequency thermal ablation: A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Sun; Rhim, Hyun Chul; Koh, Byung Hee; Cho, On Koo; Seo, Heung Suk; Kim, Yong Soo; Joo, Kyoung Bin [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2001-09-15

    To assess the effect of ethanol infusion on the size of ablated lesion during radiofrequency (RF) thermal ablation. We performed an ex vivo experimental study using a total of 15 pig livers. Three groups were designed: 1)normal control (n=10), 2) saline infusion (n=10) 3) ethanol infusion (n=10). Two radiofrequency ablations were done using a 50 watt RF generator and a 15 guage expandable elections with four prongs in each liver. During ablation for 8 minutes, continuous infusion of fluid at a rate of 0.5 ml/min through the side arm of electrode was performed. We checked the frequency of the 'impeded-out' phenomenon due to abrupt increase of impedance during ablation. Size of ablated lesion was measured according to length, width, height, and subsequently volume after the ablations. The sizes of the ablated lesions were compared between the three groups. 'Impeded-out' phenomenon during ablation was noted 4 times in control group, although that never happened in saline or ethanol infusion groups. There were significant differences in the volumes of ablated lesions between control group (10.62 +- 1.45 cm{sup 3}) and saline infusion group (15.33 +- 2.47 cm{sup 3}), and saline infusion group and ethanol infusion group (18.78 +- 3.58 cm{sup 3}) (p<0.05). Fluid infusion during radiofrequency thermal ablation decrease a chance of charming and increase the volume of the ablated lesion. Ethanol infusion during ablation may induce larger volume of ablated lesion than saline infusion.

  16. Fixation stability and implication for multifocal electroretinography in patients with neovascular age-related macular degeneration after anti-VEGF treatment

    DEFF Research Database (Denmark)

    Pedersen, K B; Sjølie, A K; Vestergaard, A H;

    2016-01-01

    electroretinography (mfERG) measurements. Methods: Fifty eyes of 50 nAMD patients receiving intravitreal anti-VEGF treatment with either bevacizumab or ranibizumab and eight eyes of eight control subjects were included. Fixation stability measurements were performed with the Eye-Link eyetracking system and the...... retinal area in degrees2 (deg2) containing the 68 % most frequently used fixation points (RAF68) was calculated. MfERG P1 amplitude and implicit time were analyzed in six concentric rings and as a summed response. Patients were examined at baseline, 3 and 6 months. Four different mfERG recordings were...... performed for the control subjects to mimic an involuntary unstable fixation: normal central fixation, 2.4°, 4.8°, and 7.1° fixation instability. Results: For control subjects, a fixation instability of 2.4° (corresponding to the central hexagon) did not reduce mfERG ring amplitudes significantly, whereas 4...

  17. Platelet number and interleukin-6 correlate with VEGF but not with bFGF serum levels of advanced cancer patients

    OpenAIRE

    Salgado, R.; Vermeulen, P B; Benoy, I; Weytjens, R; Huget, P; Van Marck, E; Dirix, L Y

    1999-01-01

    We have compared the platelet number and the serum concentration of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and interleukin-6 (IL-6) in 80 blood samples of 50 patients with advanced cancer. We have also measured the mitogenic effect of patient sera on endothelial cells in vitro in order to estimate the biological activity of serum VEGF. Serum VEGF concentration correlated with platelet number (r = 0.61; P < 10−4). Serum IL-6 levels correlated with plat...

  18. Estimating binding free energy of a putative growth factors EGF-VEGF complex - a computational bioanalytical study.

    Science.gov (United States)

    Lin, Meng-Han; Chang, C Allen; Fischer, Wolfgang B

    2016-08-01

    Epidermal growth factor (EGF) and homodimeric vascular endothelial growth factor (VEGF) bind to cell surface receptors. They are responsible for cell growth and angiogenesis, respectively. Docking of the individual proteins as monomeric units using ZDOCK 2.3.2 reveals a partial blocking of the receptor binding site of VEGF by EGF. The receptor binding site of EGF is not affected by VEGF. The calculated binding energy is found to be intermediate between the binding energies calculated for Alzheimer's Aß42 and the barnase/barstar complex. PMID:26338536

  19. Transfection of bone marrow mesenchymal stem cells using green fluorescence protein labeled hVEGF165 recombinant plasmid mediated by liposome

    Institute of Scientific and Technical Information of China (English)

    Tao Wang; Tian-An Liao; Shao-Bo Zhong

    2013-01-01

    Objective:To study the role of bone marrow mesenchymal stem cells (BMSCs) in construction of vascularized engineered tissue. Methods: hVEGF165 was amplified via RT-PCR before recombinant with pShuttle-green fluorescence protein;green fluorescent protein (GFP)-CMV. Then the recombinant shuttle plasmid was transfected into BMSCs with LipofectamineTM 2000 for packaging and amplifying. hVEGF165 mRNA expression in BMSCs cells was tested. Results:The sequence of hVEGF165 in pShuttle-GFP-hVEGF165 plasmid was confirmed by double-enzyme cleavage method and sequencing. hVEGF165 was highly expressed in BMSCs. Conclusions:The GFP/hVEGF165 recombinant plasmid vector was constructed successfully and expressed effectively in host cells, which may be helpful for discussing the possibility of the application of VEGF165-BMSCs in tissue engineering and ischemic disease cure.

  20. Automated planning of ablation targets in atrial fibrillation treatment

    Science.gov (United States)

    Keustermans, Johannes; De Buck, Stijn; Heidbüchel, Hein; Suetens, Paul

    2011-03-01

    Catheter based radio-frequency ablation is used as an invasive treatment of atrial fibrillation. This procedure is often guided by the use of 3D anatomical models obtained from CT, MRI or rotational angiography. During the intervention the operator accurately guides the catheter to prespecified target ablation lines. The planning stage, however, can be time consuming and operator dependent which is suboptimal both from a cost and health perspective. Therefore, we present a novel statistical model-based algorithm for locating ablation targets from 3D rotational angiography images. Based on a training data set of 20 patients, consisting of 3D rotational angiography images with 30 manually indicated ablation points, a statistical local appearance and shape model is built. The local appearance model is based on local image descriptors to capture the intensity patterns around each ablation point. The local shape model is constructed by embedding the ablation points in an undirected graph and imposing that each ablation point only interacts with its neighbors. Identifying the ablation points on a new 3D rotational angiography image is performed by proposing a set of possible candidate locations for each ablation point, as such, converting the problem into a labeling problem. The algorithm is validated using a leave-one-out-approach on the training data set, by computing the distance between the ablation lines obtained by the algorithm and the manually identified ablation points. The distance error is equal to 3.8+/-2.9 mm. As ablation lesion size is around 5-7 mm, automated planning of ablation targets by the presented approach is sufficiently accurate.

  1. Percutaneous thermal ablation of renal neoplasms; Perkutane Thermoablation von Nierentumoren

    Energy Technology Data Exchange (ETDEWEB)

    Tacke, J. [Inst. fuer Diagnostische und Interventionelle Radiologie/Neuroradiologie, Klinikum Passau (Germany); Mahnken, A.H.; Guenther, R.W. [Klinik fuer Radiologische Diagnostik, Universitaetsklinikum Aachen (Germany)

    2005-12-15

    Due to modern examination techniques such as multidetector computed tomography and high-field magnetic resonance imaging, the detection rate of renal neoplasms is continually increasing. Even though tumors exceeding 4 cm in diameter rarely metastasize, all renal lesions that are possible neoplasms should be treated. Traditional treatment techniques include radical nephrectomy or nephron-sparing resection, which are increasingly performed laparoscopically. Modern thermal ablation techniques such as hyperthermal techniques like radiofrequency ablation RFA, laser induced thermal ablation LITT, focused ultrasound FUS and microwave therapy MW, as well as hypothermal techniques (cryotherapy) may be a useful treatment option for patients who are unfit for or refuse surgical resection. Cryotherapy is the oldest and best known thermal ablation technique and can be performed laparoscopically or percutaneously. Since subzero temperatures have no antistyptic effect, additional maneuvers must be performed to control bleeding. Percutaneous cryotherapy of renal tumors is a new and interesting method, but experience with it is still limited. Radiofrequency ablation is the most frequently used method. Modern probe design allows volumes between 2 and 5 cm in diameter to be ablated. Due to hyperthermal tract ablation, the procedure is deemed to be safe and has a low complication rate. Although there are no randomized comparative studies to open resection, the preliminary results for renal RFA are promising and show RFA to be superior to other thermal ablation techniques. Clinical success rates are over 90% for both, cryo- and radiofrequency ablation. Whereas laser induced thermal therapy is established in hepatic ablation, experience is minimal with respect to renal application. For lesions of more than 2 cm in diameter, additional cooling catheters are required. MR thermometry offers temperature control during ablation. Microwave ablation is characterized by small ablation volumes

  2. Laser ablation of multilayer polymer films

    International Nuclear Information System (INIS)

    We study the efficiency of using multilayer structures as an etch-stop mechanism in the ablation of polyimide films by ultraviolet lasers. The study is done using a photothermal model that includes the light absorption by the decomposed fragments, which shield the polymer from the laser beam, an intermediate zone in which the polymer is suffering a phase transition and the underlying unburned material. The layers are differentiated from each other through their optical properties. Variation in the optical properties of polyimide has been achieved by a proper selection of impurities. From our modeling work, we conclude that optically thin foils may be used as etch stop in the ablation process when the penetration depth of the middle layer is around three times larger than the penetration depth of the surrounding layers, this for fluences below 200 mJ/cm2. We also present some experimental results

  3. Monopole antennas for microwave catheter ablation

    Energy Technology Data Exchange (ETDEWEB)

    Labonte, S.; Blais, A.; Legault, S.R.; Ali, H.O.; Roy, L. [Univ. of Ottawa, Ontario (Canada). Dept. of Electrical Engineering

    1996-10-01

    The authors study the characteristics of various monopole antennas for microwave catheter ablation of the endocardium. The investigation is done with a computer model based on the finite-element method in the frequency domain. Three monopole geometries are considered: open-tip, dielectric-tip, and metal-tip. Calculations are made for the magnetic field, the reflection coefficient and the power deposition pattern of the antennas immersed in normal saline. The theoretical results are compared with measurements performed on prototypes and good agreement is obtained. The antenna characteristics suggest that the metal-tip monopole best fulfills the requirements of catheter ablation. The computer model is then used to compare metal-tip monopoles of different dimensions and to determine design trade-offs.

  4. Electrolytic Effects During Tissue Ablation by Electroporation.

    OpenAIRE

    Rubinsky, L; Guenther, E.; Mikus, P; Stehling, M; Rubinsky, B

    2015-01-01

    Nonthermal irreversible electroporation is a new tissue ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible electroporation is of interest because it allows treatment near sensitive tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with electroporation pulses to augment and o...

  5. Radioiodine Remnant Ablation: A Critical Review

    OpenAIRE

    Bal, Chandra Sekhar; Padhy, Ajit Kumar

    2015-01-01

    Radioiodine remnant ablation (RRA) is considered a safe and effective method for eliminating residual thyroid tissue, as well as microscopic disease if at all present in thyroid bed following thyroidectomy. The rationale of RRA is that in the absence of thyroid tissue, serum thyroglobulin (Tg) measurement can be used as an excellent tumor marker. Other considerations are like the presence of significant remnant thyroid tissue makes detection and treatment of nodal or distant metastases diffic...

  6. Design calculations for NIF convergent ablator experiments

    Directory of Open Access Journals (Sweden)

    Olson R.E.

    2013-11-01

    Full Text Available The NIF convergent ablation tuning effort is underway. In the early experiments, we have discovered that the design code simulations over-predict the capsule implosion velocity and shock flash ρr, but under-predict the hohlraum x-ray flux measurements. The apparent inconsistency between the x-ray flux and radiography data implies that there are important unexplained aspects of the hohlraum and/or capsule behavior.

  7. Design calculations for NIF convergent ablator experiments

    OpenAIRE

    Olson R.E.; Hicks D.G.; Meezan N.B.; Callahan D.A.; Landen O.L.; Jones O.S.; Langer S.H.; Kline J.L.; Wilson D.C.; Rinderknecht H.; Zylstra A.; Petrasso R.D.

    2013-01-01

    The NIF convergent ablation tuning effort is underway. In the early experiments, we have discovered that the design code simulations over-predict the capsule implosion velocity and shock flash ρr, but under-predict the hohlraum x-ray flux measurements. The apparent inconsistency between the x-ray flux and radiography data implies that there are important unexplained aspects of the hohlraum and/or capsule behavior.

  8. Radiofrequency ablation of two femoral head chondroblastomas

    Energy Technology Data Exchange (ETDEWEB)

    Petsas, Theodore [Department of Radiology, University of Patras (Greece); Megas, Panagiotis [Department of Orthopaedic Surgery, University of Patras (Greece)]. E-mail: panmegas@med.upatras.gr; Papathanassiou, Zafiria [Department of Radiology, University of Patras (Greece)

    2007-07-15

    Chondroblastoma is a rare benign cartilaginous bone tumor. Surgical resection is the treatment of choice for pain relief and prevention of further growth. Open surgical techniques are associated with complications, particularly when the tumors are located in deep anatomical sites. The authors performed RF ablation in two cases of subarticular femoral head chondroblastomas and emphasize its positive impact. The clinical course, the radiological findings and the post treatment results are discussed.

  9. Resolving Bias in Laser Ablation Geochronology

    Science.gov (United States)

    Bowring, James; Horstwood, Matthew; Gehrels, George

    2013-06-01

    Increasingly, scientific investigations requiring geochronology utilize laser ablation (LA)-inductively coupled plasma mass spectrometry (ICPMS), taking advantage of the efficiency and throughput possible for uranium-thorium-lead (U-Th-Pb) dating. A number of biases exist when comparing data among laboratories and an ongoing community-based effort is working to resolve and eliminate these biases to improve the accuracy of scientific interpretation based on these data.

  10. Insight into 144 patients with ocular vascular events during VEGF antagonist injections

    Directory of Open Access Journals (Sweden)

    Shami M

    2012-03-01

    Full Text Available Ahmad M Mansour1, Maha Shahin2, Peter K Kofoed3, Maurizio B Parodi4, Michel Shami5, Stephen G Schwartz6, Collaborative Anti-VEGF Ocular Vascular Complications GroupDepartment of Ophthalmology, 1American University of Beirut, Beirut, Lebanon, Rafic Hariri University Hospital, Beirut, Lebanon; 2Mansoura University, Mansoura City, Egypt; 3Glostrup Hospital, University of Copenhagen, Denmark, National Eye Clinic, Kennedy Center, Glostrup, Denmark; 4University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy; 5Texas Tech University Health Sciences Center, Lubbock, TX, USA; 6Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples and Miami, FL, USAAim: To record ocular vascular events following injections of vascular endothelium growth factor (VEGF antagonists.Methods: Collaborative multicenter case series (48 cases, literature reviews (32 cases, and reports to the FDA (64 cases of patients that had vascular occlusions during anti-VEGF therapy were collected and analyzed.Results: A total of 144 cases of ocular vascular events were identified, with these diagnosed a median of 15 days after anti-VEGF injection. The majority of patients had pre-existing risk factors for cardiovascular events and nine patients had a prior history of glaucoma. Mean visual acuity dropped by 6.4 lines with severe visual loss after injection to NLP (five eyes, LP (six eyes, and HM (two eyes. The overall risk of ocular vascular events following a VEGF antagonist injection was 0.108% in the general population and 2.61% in the diabetic population. Mean retinal arterial constriction after intravitreal bevacizumab in 13 eyes was 21% (standard deviation = 27%, and mean retinal venous constriction was 8% (standard deviation = 30%.Conclusion: Ocular vascular events are rare during anti-VEGF therapy, but can lead to severe visual loss and may be caused by a number of factors including the vasoconstrictor effect of the drug, a post-injection rise

  11. Radiative Ablation of Disks Around Massive Stars

    CERN Document Server

    Kee, N D

    2015-01-01

    Hot, massive stars (spectral types O and B) have extreme luminosities ($10^4 -10^6 L_\\odot$) that drive strong stellar winds through UV line-scattering. Some massive stars also have disks, formed by either decretion from the star (as in the rapidly rotating "Classical Be stars"), or accretion during the star's formation. This dissertation examines the role of stellar radiation in driving (ablating) material away from these circumstellar disks. A key result is that the observed month to year decay of Classical Be disks can be explained by line-driven ablation without, as previously done, appealing to anomalously strong viscous diffusion. Moreover, the higher luminosity of O stars leads to ablation of optically thin disks on dynamical timescales of order a day, providing a natural explanation for the lack of observed Oe stars. In addition to the destruction of Be disks, this dissertation also introduces a model for their formation by coupling observationally inferred non-radial pulsation modes and rapid stellar...

  12. Osteoid Osteoma Treated with Radiofrequency Ablation

    Directory of Open Access Journals (Sweden)

    Murat Çakar

    2015-01-01

    Full Text Available Purpose. Our aim is to evaluate the results of treatment with computed tomography (CT guided percutaneous radiofrequency ablation for osteoid osteomas which were localized in a difficult area for operation. Materials and Methods. Glenoid, distal tibia, humerus shaft, proximal humerus, and in third finger of the hand proximal phalanx were involved in one patient. Proximal femur was involved in three patients, distal femur was involved in three patients, and proximal tibia was involved in two patients. 9 males and 4 females were aged 4 to 34 years (mean age: 18.5