A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth

2002 ◽  
Vol 8 (12) ◽  
pp. 1369-1375 ◽  
Author(s):  
Andreas G. Niethammer ◽  
Rong Xiang ◽  
Jürgen C. Becker ◽  
Harald Wodrich ◽  
Ursula Pertl ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Dna Vaccine ◽  
Vegf Receptor

scholarly journals miR-23a-3p is a Key Regulator of IL-17C-Induced Tumor Angiogenesis in Colorectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1363 ◽  
Author(s):  
Yunna Lee ◽  
Su Jin Kim ◽  
Jieun Choo ◽  
Gwangbeom Heo ◽  
Jin-Wook Yoo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Ex Vivo ◽  
Underlying Mechanism ◽  
Vegf Receptor ◽  
Invasion And Migration ◽  
Novel Target ◽  
And Migration

MicroRNAs (miRNAs) have emerged as key players in tumor angiogenesis. Interleukin-17C (IL-17C) was identified to promote colorectal cancer (CRC) progression. Therefore, we aimed to investigate the effect of IL-17C on tumor angiogenesis, the involvement of miR-23a-3p in IL-17C signaling, and the direct target gene of miR-23a-3p in CRC. In vitro and ex vivo angiogenesis, a mouse xenograft experiment, and immunostaining were performed to test the effect of IL-17C on tumor angiogenesis. ELISA, quantitative real time PCR, and gene silencing were used to uncover the underlying mechanism. IL-17C induced angiogenesis of intestinal endothelial cells, subsequently enhancing cell invasion and migration of DLD-1 cells. IL-17C-stimulated DLD-1 cells produced vascular endothelial growth factor (VEGF) to enhance angiogenesis. Moreover, IL-17C markedly accelerated xenograft tumor growth, which was manifested by substantially reduced tumor growth when treated with the VEGF receptor 2 inhibitor Ki8751. Accordingly, Ki8751 suppressed the expression of IL-17C-stimulated PECAM and VE-cadherin in xenografts. Furthermore, IL-17C activated STAT3 to increase the expression of miR-23a-3p that suppressed semaphorin 6D (SEMA6D) expression, thereby permitting VEGF production. Taken together, our study demonstrates that IL-17C promotes tumor angiogenesis through VEGF production via a STAT3/miR-23a-3p/SEMA6D axis, suggesting its potential as a novel target for anti-CRC therapy.

Construction of a DNA vaccine encoding Flk-1 extracellular domain and C3d fusion gene and investigation of its suppressing effect on tumor growth

2009 ◽  
Vol 59 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Pei-he Liang ◽  
Ke-qin Zhang ◽  
Gui-lian Xu ◽  
Yan-feng Li ◽  
Luo-fu Wang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Dna Vaccine ◽  
Fusion Gene ◽  
Extracellular Domain

A novel low molecular weight VEGF receptor-binding antagonist, VGA1102, inhibits the function of VEGF and in vivo tumor growth

2004 ◽  
Vol 54 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Yasuji Ueda ◽  
Takehiro Yamagishi ◽  
Kazunori Samata ◽  
Hisao Ikeya ◽  
Noriko Hirayama ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Tumor Growth ◽  
Receptor Binding ◽  
Low Molecular Weight ◽  
Vegf Receptor

scholarly journals Synchronous inhibition of mTOR and VEGF/NRP1 axis impedes tumor growth and metastasis in renal cancer

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Krishnendu Pal ◽  
Vijay Sagar Madamsetty ◽  
Shamit Kumar Dutta ◽  
Enfeng Wang ◽  
Ramcharan Singh Angom ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Small Molecule ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Vegf Receptor ◽  
Vascular Permeability Factor ◽  
Cell Renal Cell Carcinoma ◽  
Antiangiogenic Therapies

AbstractClear cell renal cell carcinoma (ccRCC) is known for its highly vascular phenotype which is associated with elevated expression of vascular endothelial growth factor A (VEGF), also known as vascular permeability factor (VPF). Accordingly, VEGF has been an attractive target for antiangiogenic therapies in ccRCC. Two major strategies have hitherto been utilized for VEGF-targeted antiangiogenic therapies: targeting VEGF by antibodies, ligand traps or aptamers, and targeting the VEGF receptor signaling via antibodies or small-molecule tyrosine-kinase inhibitors (TKIs). In the present article we utilized two entirely different approaches: targeting mammalian target of rapamycin (mTOR) pathway that is known to be involved in VEGF synthesis, and disruption of VEGF/Neuroplin-1 (NRP1) axis that is known to activate proangiogenic and pro-tumorigenic signaling in endothelial and tumor cells, respectively. Everolimus (E) and a small-molecule inhibitor EG00229 (G) were used for the inhibition of mTOR and the disruption of VEGF/NRP1 axis, respectively. We also exploited a liposomal formulation decorated with a proprietary tumor-targeting-peptide (TTP) to simultaneously deliver these two agents in a tumor-targeted manner. The TTP-liposomes encapsulating both Everolimus and EG00229 (EG-L) demonstrated higher in vitro and in vivo growth retardation than the single drug-loaded liposomes (E-L and G-L) in two different ccRCC models and led to a noticeable reduction in lung metastasis in vivo. In addition, EG-L displayed remarkable inhibition of tumor growth in a highly aggressive syngeneic immune-competent mouse model of ccRCC developed in Balb/c mice. Taken together, this study demonstrates an effective approach to achieve improved therapeutic outcome in ccRCC.

Abstract A020: A novel synthetic CD40L plasmid adjuvant generates unique anti-HPV DNA vaccine induced responses that impact tumor growth

2016 ◽  
Author(s):  
Megan C. Wise ◽  
Elizabeth K. Duperret ◽  
Daniel O. Villarreal ◽  
Lumena Louis ◽  
Jian Yan ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Dna Vaccine ◽  
Induced Responses ◽  
Hpv Dna

μ Opioid Receptor Stimulates a Growth Promoting and Pro-Angiogenic Tumor Microenvironment by Transactivating VEGF Receptor-2/Flk-1.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3687-3687
Author(s):  
Elliot J. Stephenson ◽  
Humberto J. Martinez-Suarez ◽  
Mariya Farooqui ◽  
Debabrata Mukhopadhyay ◽  
Deborah A. Hughes ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Opioid Receptor ◽  
Calcium Release ◽  
Small Gtpase ◽  
Endothelial Cell Proliferation ◽  
Vegf Receptor ◽  
Growth Promoting ◽  
Stimulation Of

Abstract Like VEGF, morphine stimulates MAPK/ERK and Akt, leading to the promotion of angiogenesis via NO dependent signaling (Cancer Res62: 4491, 2002). Morphine acts via pertussis toxin (PT)-dependent G-protein coupled receptors (GPCRS), while VEGF acts via receptor tyrosine kinases (RTKs). We showed that PT-dependent GPCRs transactivate VEGF receptor-2/Flk1 via small GTPase RhoA (JBC277: 4679, 2002; JBC278:20738, 2003). Therefore, we hypothesized that morphine via the mu opioid receptor (MOR) transactivates Flk1 and promotes a pro-angiogenic microenvironment. Morphine-induced proliferation of human umbilical vein endothelial cells (HUVEC) was completely abrogated by Y-27632 (100 μM), a highly selective and potent inhibitor of Rho-associated protein kinases, suggesting the activation of Rho signaling by morphine. Addition of 1 μM morphine potentiated VEGF-induced (10 ng/ml) proliferation of HUVEC by 25%. We observed a 30% increase in intracellular calcium release after VEGF stimulation of HUVEC pre-incubated with morphine as compared to HUVEC pre-incubated with PBS, detected by a change in the fluorescence ratio of the Fura-2 AM dye. These findings show that morphine, via MOR and Rho signaling, transactivates Flk1 leading to the stimulation of calcium signaling and endothelial cell proliferation. To functionally corroborate our hypothesis, we used MOR knockout (MOR-KO) mice and injected them with MOR-replete T241 fibrosarcoma cells. T241 fibrosarcoma tumor growth in vivo showed appearance of palpable and measurable tumors 2 days earlier in wild type (wt) as compared to MOR-KO mice. Tumor growth and angiogenesis were decreased by 20–35% in MOR-KO mice as compared to wt littermates during 3 weeks of tumor growth. None of the MOR-KO showed signs of lung metastasis versus 40% wt mice with metastasis. Morphine (1.42 for the first 2 wks and 2.14 mg/Kg/day later, respectively) stimulated 20–35% tumor growth in wt, but not in MOR-KO mice. Western immunoblotting showed a 10-fold increase in the expression of phospho-Flk1 in morphine treated wt tumors as compared to PBS-treated wt mice. Morphine did not stimulate phospho-Flk1 expression in MOR-KO mice. Western analysis of immunoprecipitates obtained with α-MOR antibody showed the expression of Flk1 and phospho-Flk1 in wt, but were not expressed in MOR-KO tumors. Thus, MOR stimulates the transactivation of Flk1 in wt mice but not in MOR-KO. These in vitro and in vivo data using MOR-KO mice and the MOR agonist, morphine, show that MOR stimulates endothelial proliferation, angiogenesis and promotes tumor growth and metastasis directly as well as by transactivating Flk1 phosphorylation. We speculate that MOR is a critical component of the ‘angiogenic switch’, which regulates the pro-angiogenic and growth promoting tumor microenvironment. Thus, MOR provides a novel target for developing anti-angiogenic therapies.

Realgar transforming solution suppresses angiogenesis and tumor growth by inhibiting VEGF receptor 2 signaling in vein endothelial cells

2018 ◽  
Vol 41 (4) ◽  
pp. 467-480 ◽  
Author(s):  
Peng Song ◽  
Yang Hai ◽  
Xin Wang ◽  
Longhe Zhao ◽  
Baoqiang Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Growth ◽  
Vegf Receptor

VEGF and VEGF Receptor-1 Concentration in Vestibular Schwannoma Homogenates Correlates to Tumor Growth Rate

2005 ◽  
Vol 26 (1) ◽  
pp. 98-101 ◽  
Author(s):  
Per Cay??-Thomasen ◽  
Kim Werther ◽  
Amarnadh Nalla ◽  
Thorkild C. B??g-Hansen ◽  
Hans J??rgen Nielsen ◽  
...  
Keyword(s):  
Growth Rate ◽  
Tumor Growth ◽  
Vestibular Schwannoma ◽  
Tumor Growth Rate ◽  
Vegf Receptor
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