scholarly journals Combined Anti-PLGF and Anti-Endostatin Treatments Inhibit Ocular Hemangiomas

2015 ◽  
Vol 36 (3) ◽  
pp. 930-936 ◽  
Author(s):  
Hua Jiang ◽  
Xinyi Wu ◽  
Hong Wang ◽  
Chao Huang ◽  
Linna Zhang
Keyword(s):  
Growth Factor ◽  
Normal Tissue ◽  
Bioluminescence Imaging ◽  
Placental Growth Factor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Combined Treatments ◽  
Paired Normal Tissue ◽  
Endothelial Growth Factor ◽  
Cd31 Expression

Background/Aims: The degree of neovascularization determines the aggressiveness of ocular hemangiomas (OH). So far, the anti-angiogenic treatments using either antagonists against vascular endothelial growth factor A (VEGF-A), or endostatin, do not always lead to satisfactory therapeutic outcome. Methods: We examined the VEGF receptor 1 (VEGFR1) levels in the OH specimen. We compared the effects of anti-PLGF, endostatin, as well as their combined treatments on the growth of OH in a mouse model, using bioluminescence imaging in living animals. We also examined vascularization by CD31 expression. Results: We detected higher VEGFR1 levels in the OH, compared to paired normal tissue. Thus, we hypothesize that as a major ligand for VEGFR1, placental growth factor (PLGF) may also play a role in the neovascularization and tumorigenesis of OH. In an implanted OH model in mice, we found that both anti-PLGF and endostatin significantly decreased OH growth as well as vascularization, while combined treatments had a significantly more pronounced effect. Conclusion: Our data suggest that combined anti-PLGF and endostatin may be a more effective therapy for inhibition of ocular vascularization and the tumor growth in OH.

scholarly journals An unexpected tail of VEGF and PlGF in pre-eclampsia

2011 ◽  
Vol 39 (6) ◽  
pp. 1576-1582 ◽  
Author(s):  
David O. Bates
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Endothelial Activation ◽  
Placental Growth Factor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Physiological Changes ◽  
Vegf Family Members ◽  
Endothelial Growth Factor ◽  
Vegf Isoforms

PET (pre-eclamptic toxaemia), characterized by pregnancy-related hypertension and proteinuria, due to widespread endothelial dysfunction, is a primary cause of maternal morbidity. Altered circulating factors, particularly the VEGF (vascular endothelial growth factor) family of proteins and their receptors, are thought to be key contributors to this disease. Plasma from patients with PET induces numerous cellular and physiological changes in endothelial cells, indicating the presence of a circulating imbalance of the normal plasma constituents. These have been narrowed down to macromolecules of the VEGF family of proteins and receptors. It has been shown that responses of endothelial cells in intact vessels to plasma from patients with pre-eclampsia is VEGF-dependent. It has recently been shown that this may be specific to the VEGF165b isoform, and blocked by addition of recombinant human PlGF (placental growth factor). Taken together with results that show that sVEGFR1 (soluble VEGF receptor 1) levels are insufficient to bind VEGF-A in human plasma from patients with pre-eclampsia, and that other circulating macromolecules bind, but do not inactivate, VEGF-A, this suggests that novel hypotheses involving altered bioavailability of VEGF isoforms resulting from reduced or bound PlGF, or increased sVEGFR1 increasing biological activity of circulating plasma, could be tested. This suggests that knowing how to alter the balance of VEGF family members could prevent endothelial activation, and potentially some symptoms, of pre-eclampsia.

scholarly journals Vascular Pool of Releasable Soluble VEGF Receptor-1 (sFLT1) in Women With Previous Preeclampsia and Uncomplicated Pregnancy

2014 ◽  
Vol 99 (3) ◽  
pp. 978-987 ◽  
Author(s):  
Tracey L. Weissgerber ◽  
Augustine Rajakumar ◽  
Ashley C. Myerski ◽  
Lia R. Edmunds ◽  
Robert W. Powers ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Whole Blood ◽  
Placental Growth Factor ◽  
Potential Contribution ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Uncomplicated Pregnancy ◽  
Heparin Plasma ◽  
Endothelial Growth Factor

Context: Research examining the source of excess soluble fms-like tyrosine kinase 1 (sFLT1) in preeclampsia has focused on the placenta. The potential contribution of the releasable store of sFLT1 in the systemic vasculature is unknown. Objective: We asked whether the nonplacental releasable store of sFLT1 is larger in women with previous preeclampsia than in women with a previous uncomplicated pregnancy. Design: We administered heparin to nulligravid women and to women with previous preeclampsia or a previous uncomplicated pregnancy. We compared post-heparin sFLT1 concentrations with those observed in uncomplicated pregnancy and preeclampsia. Setting: The study was performed at Magee-Womens Hospital. Patients: Participants included nulligravidas (n = 8), women 6–24 months postpartum (previous uncomplicated pregnancy, n = 16; previous preeclampsia, n = 15), and pregnant women (uncomplicated pregnancy, n = 30; preeclampsia, n = 25). Intervention: Nonpregnant women received an unfractionated heparin bolus. Main Outcome Measures: Pre- and post-heparin plasma sFLT1, placental growth factor, and vascular endothelial growth factor were measured. Results: In nonpregnant women, heparin increased plasma sFLT1 by 250-fold (P < .01), increased placental growth factor by 7-fold (P < .01), and decreased free vascular endothelial growth factor (P < .01). These changes did not differ between nulligravidas, women with previous preeclampsia, and women with a previous uncomplicated pregnancy. Post-heparin sFLT1 in nonpregnant women was higher than sFLT1 in uncomplicated pregnancy, but lower than sFLT1 in preeclampsia. Baseline and post-heparin sFLT1 were positively correlated (r2 = 0.19; P < .01). Heparin increased the concentration of the 100-kDa sFLT1 isoform. Adding heparin to whole blood or plasma did not increase sFLT1. Conclusions: Nonpregnant women have a significant vascular store of releasable sFLT1. The size of this store does not differ between women with previous preeclampsia vs women with previous uncomplicated pregnancy.

Model of competitive binding of vascular endothelial growth factor and placental growth factor to VEGF receptors on endothelial cells

2004 ◽  
Vol 286 (1) ◽  
pp. H153-H164 ◽  
Author(s):  
Feilim Mac Gabhann ◽  
Aleksander S. Popel
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Synergistic Effects ◽  
Placental Growth Factor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Relative Contribution ◽  
Endothelial Growth Factor

Placental growth factor (PlGF) competes with vascular endothelial growth factor (VEGF) for binding to VEGF receptor (VEGFR)-1 but does not bind VEGFR2. Experiments show that PlGF can augment the response to VEGF in pathological angiogenesis and in models of endothelial cell survival, migration, and proliferation. This synergy has been hypothesized to be due to a combination of the following: signaling by PlGF through VEGFR1 and displacement of VEGF from VEGFR1 to VEGFR2 by PlGF, causing increased signaling through VEGFR2. In this study, the relative contribution of PlGF-induced VEGF displacement to the synergy is quantified using a mathematical model of ligand-receptor binding to examine the effect on ligand-receptor complex formation of VEGF and PlGF acting together. Parameters specific to the VEGF-PlGF system are used based on existing data. The model is used to simulate in silico a specific in vitro experiment in which VEGF-PlGF synergy is observed. We show that, whereas a significant change in the formation of endothelial surface growth factor-VEGFR1 complexes is predicted in the presence of PlGF, the increase in the number of VEGFR2-containing signaling complexes is less significant; these results were shown to be robust to significant variation in the kinetic parameters of the model. Synergistic effects observed in that experiment thus appear unlikely to be due to VEGF displacement but to a shift from VEGF-VEGFR1 to PlGF-VEGFR1 complexes and an increase in total VEGFR1 complexes. These results suggest that VEGFR1 signaling can be functional in adult-derived endothelial cells.

Early predictors of placental dysfunction

2016 ◽  
pp. 25-28
Author(s):  
J.M. Melnik ◽  
◽  
A.A. Shlyahtina ◽  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pregnant Women ◽  
Umbilical Artery ◽  
Placental Growth Factor ◽  
Vascular Endothelial ◽  
Endothelin 1 ◽  
Placental Dysfunction ◽  
Early Predictors ◽  
Endothelial Growth Factor

The article presents the predictors of placental dysfunction on the early stage of pregnancy. The objective: the search for prognostic markers and criteria for the occurrence of placental insufficiency in the early stages of the gestational process to optimize the pregnancy and labor with improved perinatal outcomes. Patients and methods. To solve this goal in the period from 2013 to 2015 were conducted a comprehensive survey of 334 pregnant women, which depending on the peculiarities of pregnancy and childbirth were divided into groups. The control group consisted of 236 pregnant women with uncomplicated gestational period, no morphological signs of placental dysfunction. The study group included 98 patients with a complicated pregnancy who had revealed violations of the fetal-placental relations, which was confirmed by morphological examination of the placenta in the postpartum period. Results. It was found that pregnant women with placental insufficiency in the first trimester of pregnancy have higher levels of interleukin-1B (IL-1v) and interleukin-3 (IL-3) in comparison with physiological pregnancy, as well as there is a direct significant correlation between IL-1v and pulsative index (PI) in the spiral (r=0.84) and uterine artery (r=0.77), and the inverse correlation between the level of IL-3 and PI in the terminal branches of the umbilical artery (r=-0.69). Verified an inverse relationship between the concentration of endothelin-1, the level of vascular endothelial growth factor (r=-0.87) and placental growth factor (r=-0.73), and also a direct link between the content of endothelin-1 and PI in spiral arteries (r=0.89), uterine artery (r=0.83) and the terminal branches of the umbilical artery (r=0.79). Conclusion. Thus, it is proven that early predictors of placental dysfunction can be considered the concentration of endothelin-1, vascular endothelial growth factor, placental growth factor, interleukin-1, interleukin-3, and the indices of pulsative index. Key words: placental dysfunction, predictors, endothelin-1, vascular endothelial growth factor, placental growth factor, interleukin, pulsative index.

scholarly journals Perforation of the Small Intestine after Introduction of Lenvatinib in a Patient with Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 14 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Naomi Suzuki ◽  
Kazuto Tajiri ◽  
Yuka Futsukaichi ◽  
Shinichi Tanaka ◽  
Aiko Murayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Small Intestine ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vegf Receptor ◽  
Advanced Hepatocellular Carcinoma ◽  
Vascular Endothelial ◽  
First Line ◽  
Endothelial Growth Factor ◽  
Line Standard

Lenvatinib is a first-line standard treatment for advanced hepatocellular carcinoma (HCC) with better anti-tumor effects than sorafenib, as shown by greater inhibition of the kinases of fibroblast growth factor receptor and vascular endothelial growth factor (VEGF) receptor. This report describes a patient with advanced HCC who experienced perforation of the small intestine 1 month after starting the treatment with lenvatinib. This patient likely had partial necrosis of a metastasis to the small intestine before starting lenvatinib treatment, with subsequent ischemic changes leading to perforation of the small intestine. Although metastasis of HCC to the small intestine is rare, patients with these metastases should be regarded as being at risk for perforation during lenvatinib treatment.

scholarly journals Adverse Adipose Phenotype and Hyperinsulinemia in Gravid Mice Deficient in Placental Growth Factor

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2176-2183 ◽  
Author(s):  
Bianca Hemmeryckx ◽  
Rita van Bree ◽  
Berthe Van Hoef ◽  
Lisbeth Vercruysse ◽  
H. Roger Lijnen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Adrenergic Receptors ◽  
Growth Factor Receptor ◽  
Placental Growth Factor ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adipocyte Hypertrophy ◽  
Endothelial Growth Factor

Pregnancy-induced metabolic changes are regulated by signals from an expanded adipose organ. Placental growth factor (PlGF), acting through vascular endothelial growth factor receptor-1, may be among those signals. There is a steep rise in circulating PlGF during normal pregnancy, which is repressed in gravidas who develop preeclampsia. PlGF-deficiency in mice impairs adipose vascularization and development. Here we studied young-adult PlGF-deficient (PlGF−/−) and wild-type mice on a high-fat diet in the nongravid state and at embryonic day (E) 13.5 or E18.5 of gestation. Litter size and weight were normal, but E18.5 placentas were smaller in PlGF−/− pregnancies. PlGF−/− mice showed altered intraadipose dynamics, with the following: 1) less blood vessels and fewer brown, uncoupling protein (UCP)-1-positive, adipocytes in white sc and perigonadal fat compartments and 2) white adipocyte hypertrophy. The mRNA expression of β3-adrenergic receptors, peroxisome proliferator-activated receptor-γ coactivator-1α, and UCP-1 was decreased accordingly. Moreover, PlGF−/− mice showed hyperinsulinemia. Pregnancy-associated changes were largely comparable in PlGF−/− and wild-type dams. They included expanded sc fat compartments and adipocyte hypertrophy, whereas adipose expression of key angiogenesis/adipogenesis (vascular endothelial growth factor receptor-1, peroxisome proliferator-activated receptor-γ2) and thermogenesis (β3-adrenergic receptors, peroxisome proliferator-activated receptor-γ coactivator-1α, and UCP-1) genes was down-regulated; circulating insulin levels gradually increased during pregnancy. In conclusion, reduced adipose vascularization in PlGF−/− mice impairs adaptive thermogenesis in favor of energy storage, thereby promoting insulin resistance and hyperinsulinemia. Pregnancy adds to these changes by PlGF-independent mechanisms. Disturbed intraadipose dynamics is a novel mechanism to explain metabolic changes in late pregnancy in general and preeclamptic pregnancy in particular.

Sign in / Sign up

Export Citation Format

Share Document