In ovo leptin administration inhibits chorioallantoic membrane angiogenesis in female chicken embryos through the STAT3-mediated vascular endothelial growth factor (VEGF) pathway

2012 ◽  
Vol 43 (1) ◽  
pp. 26-36 ◽  
Author(s):  
L. Su ◽  
K. Rao ◽  
F. Guo ◽  
X. Li ◽  
A.A. Ahmed ◽  
...  
2012 ◽  
Vol 30 (10) ◽  
pp. 1129-1136 ◽  
Author(s):  
María J. Pajares ◽  
Jackeline Agorreta ◽  
Marta Larrayoz ◽  
Aurélien Vesin ◽  
Teresa Ezponda ◽  
...  

PurposeAntiangiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway have yielded more modest clinical benefit to patients with non–small-cell lung cancer (NSCLC) than initially expected. Clinical data suggest a distinct biologic role of the VEGF pathway in the different histologic subtypes of lung cancer. To clarify the influence of histologic differentiation in the prognostic relevance of VEGF-mediated signaling in NSCLC, we performed a concomitant analysis of the expression of three key elements of the VEGF pathway in the earliest stages of the following two principal histologic subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (ADC).Patients and MethodsWe evaluated tumor cell expression of VEGF, VEGF receptor (VEGFR) 1, and VEGFR2 using automatic immunostaining in a series of 298 patients with early-stage NSCLC recruited as part of the multicenter European Early Lung Cancer Detection Group project. A score measuring the VEGF signaling pathway was calculated by adding the tumor cell expression value of VEGF and its two receptors. The results were validated in two additional independent cohorts of patients with NSCLC.ResultsThe combination of high VEGF, VEGFR1, and VEGFR2 protein expression was associated with lower risk of disease progression in early SCC (univariate analysis, P = .008; multivariate analysis, hazard ratio, 0.62; 95% CI, 0.42 to 0.92; P = .02). The results were validated in two independent patient cohorts, confirming the favorable prognostic value of high VEGF signaling score in early lung SCC.ConclusionOur results clearly indicate that the combination of high expression of the three key elements in the VEGF pathway is associated with a good prognosis in patients with early SCC but not in patients with ADC.


2019 ◽  
Author(s):  
Miri Morgulis ◽  
Tsvia Gildor ◽  
Modi Roopin ◽  
Noa Sher ◽  
Assaf Malik ◽  
...  

AbstractBiomineralization is the process in which living organisms use minerals to form hard structures that protect and support them. Biomineralization is believed to have evolved rapidly and independently in different phyla utilizing existing components used for other purposes. The mechanistic understanding of the regulatory networks that drive biomineralization and their evolution is far from clear. The sea urchin skeletogenesis is an excellent model system for studying both gene regulation and mineral uptake and deposition. The sea urchin calcite spicules are formed within a tubular cavity generated by the skeletogenic cells under the control the vascular endothelial growth factor (VEGF) signaling. The VEGF pathway controls tubulogenesis and vascularization across metazoans while its regulation of biomineralization was only observed in echinoderms. Despite the critical role of VEGF signaling in sea urchin spiculogenesis, the downstream program it activates was largely unknown. Here we study the cellular and molecular machinery activated by the VEGF pathway during sea urchin spiculogenesis and reveal multiple parallels to the regulation of tubulogenesis during vertebrate vascularization. Human VEGF rescues sea urchin VEGF knock-down; VEGF-dependent vesicle deposition plays a significant role in both systems and sea urchin VEGF signaling activates hundreds of genes including biomineralization and vascularization genes. Five upstream transcription factors and three signaling genes active in spiculogenesis are homologous to vertebrate factors that regulate vascularization. Overall, our findings suggest that sea urchin spiculogenesis and vertebrate vascularization diverged from a common ancestral tubulogenesis program, broadly adapted for vascularization and specifically co-opted for biomineralization in the echinoderm phylum.Significance statementThe sea urchin calcite spicules and vertebrate blood vessels are quite distinct in their function, yet both have a tubular structure and are controlled by the vascular endothelial growth factor (VEGF) pathway. Here we study the downstream program by which VEGF pathway drives sea urchin spiculogenesis and find remarkable similarities to the control of vertebrate vascularization. The similarities are observed both in the upstream gene regulatory network, in the downstream effector genes and the cellular processes that VEGF signaling controls at the site of the calcite spicule formation. We speculate that sea urchin spiculogenesis and vertebrate vascularization diverged from a common ancestral tubulogenesis program that was co-opted for biomineralization in the echinoderm phylum.


RSC Advances ◽  
2015 ◽  
Vol 5 (89) ◽  
pp. 72515-72528 ◽  
Author(s):  
B. Anu Priya ◽  
K. Senthilguru ◽  
T. Agarwal ◽  
S. N. Gautham Hari Narayana ◽  
S. Giri ◽  
...  

Biomaterial induced activation of vascular endothelial growth factor (VEGF) pathway for angiogenesis is now gaining recognition as an effective option for tissue engineering.


2004 ◽  
Vol 89 (3) ◽  
pp. 1415-1422 ◽  
Author(s):  
Olin D. Liang ◽  
Thomas Korff ◽  
Jessica Eckhardt ◽  
Jasmin Rifaat ◽  
Nelli Baal ◽  
...  

Abstract The molecular coordination between angiogenesis and vascular remodeling is a critical step for the development of a functional vasculature in the placenta and the uterus during pregnancy. The oncodevelopmental albumin homolog α-fetoprotein (AFP) is mainly synthesized in the developing fetus, and its expression has been found to be associated with highly vascularized tumors in the adult. In this study, we investigated the angiogenic activity of AFP and its possible role in the fetomaternal unit. Immunohistochemical studies revealed that the AFP-binding protein(s) is expressed in blood vessels of chorionic villi from placentae of the second and the third but not of the first trimester during pregnancy. At low concentrations, AFP directly stimulates or enhances, respectively, vascular endothelial growth factor-induced proliferation and sprout formation of endothelial cells isolated from the placenta and the uterus possibly by a MAPK-dependent pathway. Furthermore, AFP enhances blood vessel formation in a chick chorioallantoic membrane assay in vivo. Interestingly, AFP has no proliferative or migratory effects on endothelial cells isolated from the umbilical vein in the absence of vascular endothelial growth factor. These data indicate that AFP may act as a specific proangiogenic factor of endothelial cells within the fetomaternal unit during advanced stages in pregnancy.


Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 358 ◽  
Author(s):  
Jun Yeon Park ◽  
Young Seok Ji ◽  
Hucheng Zhu ◽  
Yonghui Zhang ◽  
Do Hwi Park ◽  
...  

Cytochalasans are a group of structurally diverse fungal polyketide-amino acid hybrid metabolites that exhibit diverse biological functions. Asperchalasine A was identified and isolated from an extract of the marine-derived fungus, Aspergillus. Asperchalasine A is a cytochalasan dimer which consists of two cytochalasan molecules connected by an epicoccine. This study investigated the potential antiangiogenic effects of Aspergillus extract and asperchalasine A, which significantly inhibited cell adhesion and tube formation in human umbilical vein endothelial cells (HUVECs). Aspergillus extract and asperchalasine A decreased the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)-2 mRNA expression in a concentration-dependent manner. In addition, Aspergillus extract and asperchalasine A inhibited angiogenesis via downregulation of VEGF, p-p38, p-extracellular signal-regulated protein kinase (ERK), p-VEGFR-2, and p-Akt signaling pathways. Moreover, Aspergillus extract and asperchalasine A significantly inhibited the amount of blood vessel formation in fertilized chicken eggs using a chorioallantoic membrane assay. Our results provide experimental evidence of this novel biological activity of the potential antiangiogenic substances, Aspergillus extract, and asperchalasine A. This study also suggests that Aspergillus extract and its active component asperchalasine A are excellent candidates as adjuvant therapeutic substances for cancer prevention and treatment.


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