The ICAM-1-positive vessels in the hippocampal CA1 in the control, 2VO, HL and HL + 2VO groups at 1, 2 and 4 months post-surgery. Scale bar: 20 µm.Values are e

TY - GEN. T1 - Role of Vascular Endothelial Growth Factor-D (VEGF-D) on IL-6 expression in cerulein-stimulated pancreatic acinar cells. AU - Lee, Jangwon. AU - Kyung, Hwan Kim. AU - Kim, Hyeyoung. PY - 2007/1. Y1 - 2007/1. N2 - Cerulein pancreatitis is similar to human edematous pancreatitis with dysregulation of the digestive enzyme production and cytoplasmic vacuolization, the death of acinar cells, edema formation, and an infiltration of inflammatory cells into the pancreas. Our preliminary proteomic analysis showed increased expression of vascular endothelial growth factor-D (VEGF-D) in cerulein (10 -8M)-treated pancreatic acinar cells. We hypothesized that VEGF-D may have a role in cerulein-induced cytokine expression in pancreatic acinar cells. This article was designed to elucidate whether cerulein induces VEGF-D expression in pancreatic AR42J cells, and whether VEGF-D expression is related to interleukin-6 (IL-6) expression by transfecting antisense oligonucleotide (AS ODN) for VEGF-D ...

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Green tea epigallocatechin-3-gallate inhibits angiogenesis and suppresses vascular endothelial growth factor C/vascular endothelial growth factor receptor 2 expression and signaling in experimental endometriosis in vivo. Fertil Steril. 2011 Oct; 96(4):1021-8 ...

When DArcy Wentworth Thompsons On Growth and Form was published 100 years ago, it raised the question of how biological forms arise during development and across evolution. In light of the advances in molecular and cellular biology since then, a succinct modern view of the question states: how do genes encode geometry? Our new special issue is packed with articles that use mathematical and physical approaches to gain insights into cell and tissue patterning, morphogenesis and dynamics, and that provide a physical framework to capture these processes operating across scales.. Read the Editorial by guest editors Thomas Lecuit and L. Mahadevan, as they provide a perspective on the influence of DArcy Thompsons work and an overview of the articles in this issue.. ...

Vegfc - Vegfc (untagged ORF) - Rat vascular endothelial growth factor C (Vegfc), (10 ug) available for purchase from OriGene - Your Gene Company.

VEGFC antibody (vascular endothelial growth factor C) for WB. Anti-VEGFC pAb (GTX59914) is tested in Human samples. 100% Ab-Assurance.

Vascular Endothelial Growth Factor C (Flt4 Ligand or Vascular Endothelial Growth Factor Related Protein or VEGFC) - Drugs in Development, 2021 provides in depth analysis on Vascular Endothelial Growth Factor C (Flt4 Ligand or Vascular Endothelial Growth Factor Related Protein or VEGFC) targeted pipeline therapeutics. The report provides comprehensive information complete with Analysis by Indications, Stage of Development, Mechanism of Action (MoA), Route of Administration (RoA) and Molecule Type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Additionally, the report provides an overview of key players involved in Vascular Endothelial Growth Factor C (Flt4 Ligand or Vascular Endothelial Growth Factor Related Protein or VEGFC) targeted therapeutics development and features dormant and discontinued projects. The report analyses the pipeline products across relevant therapy areas ...

The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family. The encoded protein promotes angiogenesis and endothelial cell growth, and can also affect the permeability of blood vessels. The proprotein is further cleaved into a fully processed form that can bind and activate VEGFR-2 and VEGFR-3 receptors. [provided by RefSeq, Apr 2014 ...

In melanoma, vascular endothelial growth factor-C (VEGF-C) expression and consequent lymphangiogenesis correlate with metastasis and poor prognosis. VEGF-C also promotes tumor immunosuppression, suggesting that lymphangiogenesis inhibitors may be clinically useful in combination with immunotherapy. We addressed this concept in mouse melanoma models with VEGF receptor-3 (VEGFR-3)-blocking antibodies and unexpectedly found that VEGF-C signaling enhanced rather than suppressed the response to immunotherapy. We further found that this effect was mediated by VEGF-C-induced CCL21 and tumor infiltration of naïve T cells before immunotherapy because CCR7 blockade reversed the potentiating effects of VEGF-C. In human metastatic melanoma, gene expression of VEGF-C strongly correlated with CCL21 and T cell inflammation, and serum VEGF-C concentrations associated with both T cell activation and expansion after peptide vaccination and clinical response to checkpoint blockade. We propose that VEGF-C ...

TY - JOUR. T1 - Radiation-induced VEGF-C expression and endothelial cell proliferation in lung cancer. AU - Chen, Yu Hsuan. AU - Pan, Shiow Lin. AU - Wang, Jing Chi. AU - Kuo, Sung Hsin. AU - Cheng, Jason Chia Hsien. AU - Teng, Che Ming. PY - 2014/11/22. Y1 - 2014/11/22. N2 - Background: 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.Materials and methods: 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 ...

VEGFC - VEGFC (Myc-DDK-tagged)-Human vascular endothelial growth factor C (VEGFC) available for purchase from OriGene - Your Gene Company.

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Migration of LECs has previously been shown to be dependent on VEGF-C/Vegfr-3 signaling.12 We analyzed LECs for Vegfr-3 tyrosine phosphorylation (pTYR/Vegfr-3) in situ, using a proximity ligation assay.13 We quantified both the number of Lyve-1+ cells and the number of pTYR/Vegfr-3 sites per Lyve-1+ cell at E10.5 and E12.5 and confirmed a reduction in the number of Lyve-1+ cells in Ccbe1−/− embryos (Online Figure II). However, at critical stages of LEC migration, levels of phosphorylated Vegfr-3 per Lyve-1+ cell were unaltered, indicating that Vegfr-3 activation is not affected by the absence of CCBE1 and suggesting that CCBE1 may function independently of Vegfr-3 phosphorylation (Online Figure II).. Because Vegfr-3 phosphorylation appeared normal in Ccbe1−/− LECs and as suggested by the CCBE1 domain structure, we considered whether CCBE1 might be part of the extracellular matrix (ECM). Because we were unable to produce full-length CCBE1, and because previous6,7,14 and new genetic ...

肿瘤侵袭周边原有淋巴管以及诱导组织内新生淋巴管的形成，是肿瘤淋巴道转移的必要条件。VEGF-C和VEGF-D是特异性淋巴管生长调节因子，与淋巴管的增生和分化密切相关。二者的比值升高可能是肿瘤淋巴道转移的早期事件和潜在评估指标。本文介绍VEGF-C和VEGF-D的结构、功能、比值变化以及二者与肿瘤淋巴道转移关系的研究进展。

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Background: Vascular endothelial growth factor-C (VEGF-C), a homologue of VEGF family, plays a key role in lymphangiogenesis. Recently, we demonstrated that VEGF-C is closely associated with dyslipidemia and atherosclerosis. However, the relationship between serum VEGF-C levels and cardiovascular events in patients with atherosclerotic disease is unknown.. Methods and Results: We performed a prospective cohort study involving a total of 209 patients with arteriosclerotic obliterans (ASO) (age, 73±8 y [SD]; male, 75%; hypertension, 88%; diabetes, 69%; dyslipidemia, 72%; history of smoking, 76%; Fontaine class, 2.1±0.8). Serum levels of VEGF-C, VEGF-A and high-sensitivity C-reactive protein (hsCRP) were determined employing specific enzyme-linked immunosorbent assays. The primary outcome was major adverse cardiac events (MACEs) defined as all-cause mortality, hospitalization due to acute coronary syndrome, stroke, congestive heart failure, aortic disease, and coronary/peripheral ...

Phage-Derived Fully Human Monoclonal Antibody Fragments to Human Vascular Endothelial Growth Factor-C Block Its Interaction with VEGF Receptor-2 and ...

How tumors access and spread via the lymphatics is not understood. Although it is clear that dissemination via the blood system involves hemangiogenesis, it is uncertain whether tumors also induce lymphangiogenesis or simply invade existing peritumoral vessels. To address the issue we quantitated tumor lymph vessels in archival specimens of head and neck cancer by immunostaining for the recently described lymphatic endothelial marker LYVE-1, the vascular endothelial marker CD34, and the pKi67 proliferation marker, correlating lymph vessel density and proliferation index with clinical and pathological variables. Discrete hotspots of intratumoral small proliferating lymphatics were observed in all carcinomas, and a high intratumoral lymph vessel density was associated with neck node metastases (n = 23; P = 0.027) and an infiltrating margin of tumor invasion (P = 0.046) in the oropharyngeal subgroup. Quantitation of the lymphangiogenic growth factor vascular endothelial growth factor C by real-time PCR

OBJECTIVE: To investigate the antiangiogenesis mechanism of epigallocatechin-3-gallate (EGCG) in an endometriosis model in vivo. DESIGN: Animal studies. SETTING: University laboratory. ANIMAL(S): Human endometrium from women with endometriosis (n = 10) was transplanted into immunocompromised mice. INTERVENTION(S): Mice (n = 30) were randomly treated with EGCG, vitamin E (antioxidant control), or vehicle (negative control) for microvessel imaging. MAIN OUTCOME MEASURE(S): Endometriotic implants were collected for angiogenesis microarray and pathway analysis. Differentially expressed angiogenesis molecules were confirmed by quantitative polymerase chain reaction, Western blot, and immunohistochemistry. Effects of EGCG on angiogenesis signal transduction were further characterized in a human endothelial cell line. Microvessel parameters and the angiogenesis signaling pathway in endometriotic implants and endothelial cells were studied. RESULT(S): EGCG, but not vitamin E, inhibited microvessels in

In glaucoma, aqueous outflow into the Schlemms 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 ...

A systematic yet unbiased screening approach in the context of activated Wnt signaling in human cells has enabled the discovery of novel candidate kinase regulators of the Wnt/β-cat pathway. Whereas the Wnt pathway has been extensively pursued with the use of model organism-based genetic screens, recent observations have found newer positive functions of two classic negative regulators of the Wnt pathway, APC (28) and GSK3β (29), highlighting the inherent epistatic bias of conventional assays (30). By interrogating Wnt signaling at the level of transcriptional activation in human STF293 cells with the use of targeted RNA interference, we hoped to identify novel candidate repressors as well as activators of the Wnt/β-cat pathway, which could be further investigated in cell-specific contexts. Additionally, when establishing a screening strategy, there may be concern that the multitude of altered functional pathways and additional dysregulated kinases in colon cancer cell lines could confound ...

Studies of the last decades have revealed the importance of angiogenesis for normal growth and for the pathogenesis of numerous diseases. Much less studied is lymphangiogenesis, the growth of lymphatic vessels, which drain extravasated fluid, proteins, and cells and transport them back to the venous …

CHO-Anti-Human VEGFC MAb stable cell line is clonally-derived from a CHO cell line, which has been transfected with an Anti-human VEGFC MAb gene to allow expression of the MAb. It is an example of a cell line transfected using our proprietary CBTGS gene screening and amplification system.

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The formation of lymphatic vessels from pre-existing lymphatic vessels, in a method believed to be similar to blood vessel development or angiogenesis. See also: * Lymphedema * Pathophysiology of Lymphedema Lymphedema Genetics Genetics, Research, Lymphangiogenesis, Angiogenesis The Formation of Lymphatic Vessels and Its Importance in the Setting of Malignancy Lymphangiogenesis Breast Cancer the VEGF-C Lymphangiogenesis and Gastric Cancer Lymphangiogenesis in Head and Neck Cancer Lymphangiogenesis and Kaposis Sarcoma VEGF-C Lymphangiogenesis and Melanoma Lymphangiogenesis in Wound Healing A model for gene therapy of human hereditary lymphedema VEGFR-3 Ligands and Lymphangiogenesis (1) VEGFR-3 Ligands and Lymphangiogenesis (2) VEGFR-3 Ligands and Lymphangiogenesis (3) Vascular Endothelial Growth Factor; VEGF VEGF-D is the strongest angiogenic and lymphangiogenic effector Inhibition of Lymphatic Regeneration by VEGFR3 VEGFR3 and Metastasis in Prostate Cancer Radiogeneic Lymphangiogenesis in the ...

same day of injury or on day 7 after injury. Injured corneas were imaged using an Axiozoom V16 stereomicroscope and analyzed with Zeiss Zen imaging programs at day 1, 4, 7, 10 and 14. The areas of induced corneal blood and lymphatic vessels were calculated using Adobe Photoshop. Results : In the control group, without tamoxifen treatment, total corneal epithelial debridement resulted in enhanced corneal angiogenesis and lymphangiogenesis in all three mouse strains. In contrast, deletion of lymphatic endothelial VEGFR2 and/or VEGFR3 in the progression assay abolished the injury-induced corneal lymphangiogenesis in all three mouse strains. In the regression assay with tamoxifen treatment 7 days after corneal injury, no injury-induced corneal lymphangiogenesis was observed in mice with conditional deletion of VEGFR3 and those with conditional deletion of both receptors. However, injury-induced corneal lymphangiogenesis was observed in the mice with VEGFR2 deletion. Conclusions : Lymphatic ...

Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of lymphatic vessels (lymphangiogenesis) and the presence of intratumoral lymphatic vessels have been controversial. Using a novel marker for lymphatic endothelium, LYVE-1, we demonstrate here the occurrence of intratumoral lymphangiogenesis within human breast cancers after orthotopic transplantation onto nude mice. Vascular endothelial growth factor (VEGF)-C overexpression in breast cancer cells potently increased intratumoral lymphangiogenesis, resulting in significantly enhanced metastasis to regional lymph nodes and to lungs. The degree of tumor lymphangiogenesis was highly correlated with the extent of lymph node and lung metastases. These results establish the occurrence and biological significance of

In this review, the role of angiogenic and lymphangiogenic growth factors in hematological malignancies is summarized, alongside with possible therapeutic applications. Recent data demonstrate the importance of angiogenesis in hematologic malignancies including leukemia, lymphoma, and multiple myeloma. Expression of angiogenic polypeptides vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) associate with clinical characteristics in human leukemia and lymphoma, and their serum concentrations serve as predictors of poor prognosis. VEGF and VEGF-C also act as survival factors on leukemia. Furthermore, certain hematological malignancies both produce angiogenic or lymphangiogenic growth factors including VEGF and VEGF-C, and also express their receptors, resulting in the generation of autocrine loops that may support cancer cell survival and proliferation. Inhibition of the action of key regulators of endothelial cell growth, alone or in combination with other antiangiogenic

The formation of new lymphatic vessels, or lymphangiogenesis, is a natural process involved in tissue repair and in the resolution of inflammatory reactions. In some cancers, this process is exploited by the tumor to promote its growth and its metastatic dissemination. Our group recently identified a role for the CD73-adenosine pathway in tumor angiogenesis. As angiogenesis and lymphangiogenesis are similar processes, often occurring in parallel, we suspect that the CD73-adenosine pathway could have a role in the regulation of lymphangiogenesis during inflammatory reactions and in the tumor microenvironment.. To confirm this hypothesis, we used in vivo models of inflammatory lymphangiogenesis induced by the administration of lipopolysaccharide (LPS) or Incomplete Freunds Adjuvant (IFA) in the peritoneal cavity of mice. These two models of peritonitis trigger the formation of new lymphatics in the diaphragm that can be analyzed by flow cytometry. To study tumor lymphangiogenesis, we used a ...

TY - JOUR. T1 - VEGFR-3 neutralization inhibits ovarian lymphangiogenesis, follicle maturation, and murine pregnancy. AU - Rutkowski, Joseph M.. AU - Ihm, Jong Eun. AU - Lee, Seung Tae. AU - Kilarski, Witold W.. AU - Greenwood, Veronique I.. AU - Pasquier, Miriella C.. AU - Quazzola, Alexandra. AU - Trono, Didier. AU - Hubbell, Jeffrey A.. AU - Swartz, Melody A.. PY - 2013/11/1. Y1 - 2013/11/1. N2 - Lymphatic vessels surround follicles within the ovary, but their roles in folliculogenesis and pregnancy, as well as the necessity of lymphangiogenesis in follicle maturation and health, are undefined. We used systemic delivery of mF4-31C1, a specific antagonist vascular endothelial growth factor receptor 3 (VEGFR-3) antibody to block lymphangiogenesis in mice. VEGFR-3 neutralization for 2 weeks before mating blocked ovarian lymphangiogenesis at all stages of follicle maturation, most notably around corpora lutea, without significantly affecting follicular blood angiogenesis. The numbers of oocytes ...

To determine the effect of celecoxib on lymphangiogenesis in Nasopharyngeal carcinoma Lymphangiogenesis and factors modulating lymphangiogenesis are associated with clinico-pathological outcome in Nasopharyngeal carcinoma and colorectal cancer. Celecoxib down-regulates lymphangiogenesis Archival colorectal cancer and Nasopharyngeal carcinoma tumor specimens will be obtained from the Department of Pathology. To determine the effect of celecoxib on lymphangiogenesis in Nasopharyngeal carcinoma, the investigators intend to analyze archived specimens collected in a previously conducted study. Colorectal tumor and nodal specimens and Nasopharyngeal carcinoma primary will be examined for MVD, LVD and growth factor expression using established haematoxylin and eosin and immunohistochemical techniques. Quantification of LVD and MVD shall be performed by two pathologists blinded to clinico-pathological variables using standardised methods ...

Although the ability of a high-salt diet (HSD) to promote hypertension in some people has been recognized for decades, the underlying mechanisms remain incompletely understood (see Marvar et al.). Machnik et al. found that rats fed a HSD developed hyperplasia of the lymph capillary network, accompanied by increased numbers of interstitial mononuclear phagocyte system (MPS) cells in skin and changes in skin water and electrolyte content consistent with interstitial Na+ accumulation. Most of the infiltrating MPS cells were immunoreactive for vascular endothelial growth factor-C (VEGF-C, which stimulates lymphangiogenesis), and their depletion inhibited HSD-induced lymph capillary network hyperplasia, as well as HSD-mediated increases in skin abundance of VEGF-C and of the transcription factor TonEBP (tonicity-responsive enhancer binding protein). Moreover, MPS cell depletion exacerbated the HSD-induced increase in mean arterial blood pressure, as well as an HSD-induced increase in skin ...

The physiological functions of LVs and their contributions to pathological mechanisms during chronic disease conditions have not been extensively investigated. We have addressed this gap in the context of CKD by comprehensively investigating the role of lymphangiogenesis in kidneys and RDLNs. We describe a previously unrecognized function of lymphangiogenesis as a key process in the kidney and RDLNs mediating intrarenal inflammation and progressive fibrosis. Although it has been previously reported that lymphangiogenesis is a common feature in the progression of renal fibrosis (19), the origin and function of intrarenal LVs in CKD remained undefined. Here, we observed extensive LEC proliferation in a cohort of 289 CKD patients that was not evident in healthy controls. CKD patients with higher density intrarenal LVs presented with more severe proteinuria and renal fibrosis and decreased eGFR. Our mouse model experiments revealed localized LEC proliferation as the cellular origin of ...

Lymphatic vessels stem from preexisting blood vessels. Elegant lineage tracing by Srinivasan et al. (2007) demonstrated the venous origin of the mammalian lymphatic vasculature as previously proposed (Sabin, 1902; Kaipainen et al., 1995). The venous origin of LECs has been confirmed in Xenopus laevis and zebrafish as shown by real-time imaging in the latter and, therefore, appears to be evolutionary conserved (Ny et al., 2005; Yaniv et al., 2006; Hogan et al., 2009a).. In mice, LECs are first specified in the anterior cardinal vein around embryonic day 9.5 (E9.5) when a subset of venous endothelial cells expresses the transcription factor Prox1 and the lymphatic vessel hyaluronan receptor-1 (LYVE-1) in a polar manner (Fig. 2 B). Prox1−/− mice do not develop any lymphatic structures because of failed budding and sprouting of LECs (Wigle and Oliver, 1999). The transcription factor Sox18 induces Prox1 expression, and Sox18−/− mice develop edema caused by blockage of LEC development in the ...

Garonna, E and Botham, K M and Birdsey, G M and Randi, A M and Gonzalez-Perez, R R and Wheeler-Jones, C P D (2011) Vascular Endothelial Growth Factor Receptor-2 Couples Cyclo-Oxygenase-2 with Pro-Angiogenic Actions of Leptin on Human Endothelial Cells. PLoS One, 6 (4). e18823. ...

Krebs R, Tikkanen JM, Ropponen JO, Jeltsch M, Jokinen JJ, Ylä-Herttuala S, et al.. VEGF-C/VEGFR-3 Signaling Regulates Inflammatory Response in Development of Obliterative Airway Disease. Journal of Heart and Lung Transplantation. 2011;30:S118 - S118. ...

In squamous cell carcinoma of the pores and skin, Hirakawa et al. showed that VEGF-C overexpressing tumors managed their lymphangiogenic profile right after

Our mission is to build healthier lives, free of cardiovascular diseases and stroke. That single purpose drives all we do. The need for our work is beyond question. Find Out More about the American Heart Association. ...

Immunohistochemical staining of the VEGFR-1 ligands and pVEGFR-1 in the vasculature of CC tissue. (A) Characteristic endothelial VEGF expression. VEGF positive

so recently, have so far not been subject to any request. In April 2014, for the first time, the Deontology committee had a discussion as to whether the CCBE should issue interpretations of the CCBE Code... ...

Rationale: Lymphatic vessels in the respiratory tract normally mature into a functional network during the neonatal period, but under some pathological conditions they can grow as enlarged, dilated sacs that result in the potentially lethal condition of pulmonary lymphangiectasia. Objective: We sought to determine whether overexpression of the lymphangiogenic growth factor (vascular endothelial growth factor-C [VEGF-C]) can promote lymphatic growth and maturation in the respiratory tract. Unexpectedly, perinatal overexpression of VEGF-C in the respiratory epithelium led to a condition resembling human pulmonary lymphangiectasia, a life-threatening disorder of the newborn characterized by respiratory distress and the presence of widely dilated lymphatics. Methods and Results: Administration of doxycycline to Clara cell secretory protein-reverse tetracycline-controlled transactivator/tetracycline operator-VEGF-C double-transgenic mice during a critical period from embryonic day 15.5 to postnatal ...

In healthy adults the lymphatic system is stable when homeostasis is maintained and lymphangiogenesis, or expansion of the lymphatic network occurs in response to a variety of circumstances including acute inflammation, tissue repair, and around some tumors [10,15].. Several signaling pathways have prolymphangiogenic effects. However, the vast majority of studies aiming to treat lymphedema in preclinical models have focused on the VEGF-C/VEGFR-3 signaling pathway. VEGF-C stimulation regulates lymphatic endothelial cell proliferation, differentiation, tubule formation, and migration [1,10]. Over-expression of VEGF-C in transgenic mice results in lymphangiogenesis and expansion of the superficial lymphatic system. These lymphatic vessels are functional and can induce physiologic changes such as decreasing the severity of acute skin inflammation and edema in response to inflammatory stimuli [16,17], suggesting that VEGF-C probably can be exploited as an ideal therapeutic target for lymphedema. ...

Purpose.: To analyze whether insulin receptor substrate (IRS-1) is involved in lymphatic vessel development and whether IRS-1 blockade can inhibit lymphangiogenesis in vivo. Methods.: The impact of IRS-1 blockade by GS-101 (Aganirsen), an antisense oligonucleotide against IRS-1, on lymphatic endothelial cell (LEC) proliferation was assessed by ELISA. Furthermore, the effect of IRS-1 blockade on prolymphangiogenic growth factor expression by LECs and macrophages (peritoneal exudate cells) was tested by real-time PCR. The mouse model of inflammatory corneal neovascularization was used to analyze the effect of IRS-1 blockade in vivo: after corneal suture placement, mice were treated with GS-101 eye drops (twice daily afterwards for 1 week, 5 μL per drop; 50, 100, or 200 μM). Afterward, corneal wholemounts were prepared and stained for blood and lymphatic vessels. Results.: Blockade of IRS-1 by GS-101 inhibited LEC proliferation dose dependently. GS-101 led to decreased VEGF-A expression levels in ...

Since formation of the tumor vascular network plays a critical role in tumor growth and metastasis, many angiogenic inhibitors have been developed and clinically used for treating solid tumors (Kamba and McDonald, 2007; Verheul and Pinedo, 2007; Cook and Figg, 2010; Taugourdeau-Raymond et al., 2012; McIntyre and Harris, 2015). The tumor vasculature created by tumor-derived VEGF exhibits a spectrum of morphologic and functional abnormalities characterized by loss of vessel hierarchy, increased tortuosity, poor perfusion, instability, and increased vascular leakage (McDonald and Baluk, 2005). Thus, antiangiogenic agents not only inhibit tumor angiogenesis but also normalize the tumor vasculature, resulting in improved chemotherapeutic efficacy by enhancing the delivery of anticancer drugs to tumors.. We previously demonstrated that the tetrapeptide RLYE effectively suppressed tumor neovascularization by blocking the interaction between VEGF-A and VEGFR-2, resulting in inhibition of tumor growth ...

platelet-derived growth factor C: member of PDGF/VEGF family of growth factors; ligand for PDGF-alpha receptor; amino acid sequence in first source; RefSeq NM_016205 (human), NM_019971 (mouse), NM_031317 (rat)

Rationale: The emergence of lymphatic endothelial cells (LECs) appears to be highly regulated during development. While several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown. Objective: To delineate the role of BMP2 signaling on lymphatic development. Methods and Results: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2 signaling in zebrafish embryos and mouse embryonic stem (ES) cell-derived embryoid bodies (EBs) substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn, result attenuated expression of PROX1 during development. Conclusions: Our data identify BMP2 as a key negative regulator for the emergence of the lymphatic lineage during vertebrate ...

TY - JOUR. T1 - Blood endothelial cells. T2 - Utility from ambiguity. AU - Hebbel, Robert P.. N1 - Funding Information: The work mentioned herein was funded by: the National Institutes of Health (HL55174, HL62931, DK56326, HL70460, HL71269, HL076540, and HL55552); by Octagen Corporation, COR Therapeutics and Millennium Pharmaceuticals; and by the National Hemophilia Foundation. PY - 2017/5/1. Y1 - 2017/5/1. N2 - In the mid-1990s, my research group began to devise a method to establish endothelial cell cultures from human peripheral blood, with an ultimate goal of examining interindividual heterogeneity of endothelial biology. The initial work, published in the JCI in 2000, described the method enabling successful attainment of blood outgrowth endothelial cells (BOEC). Truly endothelial, BOEC are progeny of a transplantable cell that originates in bone marrow, a putative endothelial progenitor. Our subsequent experimental work focused upon practical applications of BOEC: their use for gene ...

Several antigens specific to lymphatic endothelium have been studied, including LYVE-1, podoplanin, and Prox-1. However, antibodies against these antigens cross-react with other tissues, especially vascular endothelium. The LEC26 antibody is generated using a rapid differential immunization technique. It is specific to lymphatic vessels but does not react with vascular endothelium.. ...

Several antigens specific to lymphatic endothelium have been studied, including LYVE-1, podoplanin, and Prox-1. However, antibodies against these antigens cross-react with other tissues, especially vascular endothelium. The LEC26 antibody is generated using a rapid differential immunization technique. It is specific to lymphatic vessels but does not react with vascular endothelium.. ...

My goals are to understand the molecular mechanisms regulating lymphatic and valvular endothelial cell development and maintenance.. The mammalian lymphatic vasculature is important for returning the extravasated plasma fluids in tissue space back to blood circulation, absorption of digested lipids from the intestine and in immune surveillance. Lymphedema is a disfiguring and mobility restricting disease that results due to the abnormal functioning of the lymphatic vasculature. Lymphedema is a common disorder that results either due to mutations in genes that regulate lymphatic vascular development or more often due to infection or surgical damage to the lymphatic vessels. Lymphatic vasculature is also considered as a major route for tumor metastasis especially melanoma and breast cancer. Despite its importance, diagnosis of lymphatic disorders and the identification of new targets to treat those ailments are limited.. Valves regulate the unidirectional flow of fluids (blood or lymph) in the ...

A large number of pseudogenes have been found to be transcribed in human cancers. However, only a few pseudogenes are functionally characterized. Here, we identified a transcribed pseudogene of vascular endothelial growth factor receptor-1 (VEGFR1), or fmsrelated tyrosine kinase 1 (FLT1), in human colorectal cancer (CRC) cells. Interestingly, this pseudogene (designated as FLT1P1) was found to be transcribed bidirectionally and functionally modulated cognate VEGFR1 protein expression in the cells. Mechanistically, expression of FLT1P1 antisense transcript not only inhibited the VEGFR1 expression, but also inhibited non-cognate VEGF-A expression through interaction with miR-520a. Perturbation of FLT1P1 expression by RNA interference (RNAi) markedly inhibited tumor cell proliferation and xenograft tumor growth. This study identifies FLT1P1 antisense as a critical regulator of VEGFR1 and VEGF-A expression in CRC cells, and highlights its role in regulation of the pathogenesis of CRC. Implications: ...

RESULTS: No significant differences were found in the expression of VEGF-C and -D or VEGFR-3 between those patients with VIN and those with invasive vulvar cancers. Weak expression of VEGF-C was confirmed only in two cases of the analyzed series; in all cases, expression of VEGF-D and VEGFR-3 was observed. The strongest expression of VEGF-D and VEGFR-3 was observed in the group of invasive cancers. The highest density of lymphatic vessels per 2 mm was observed in VIN. In the cancer group, small lymphatic vessels with a narrow oval lumen were observed. Moreover, in two cases of vulvar cancer, the presence of intratumoral lymphatic vessels was observed ...

Lymphatic vessels filter and transport fluid away from tissues before returning it to the blood. This helps to maintain normal blood volume and pressure.

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Research into the molecular basis of lymphangiogenesis in embryonic development and pathological processes has led to a rapid increase of our knowledge (Krebs and Jeltsch 2013A, 2013B). The molecular biology era of lymphatic research began with the discovery of the VEGF growth factors and their receptors 25 years ago, and these molecules are the focus of this overview.. ...