angiogenic activity
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Author(s):  
Francesca Moret ◽  
Claudia Conte ◽  
Diletta Esposito ◽  
Giovanni Dal Poggetto ◽  
Concetta Avitabile ◽  
...  

AbstractA biodegradable engineered nanoplatform combining anti-angiogenic activity and targeting of cancer cells to improve the anticancer activity of docetaxel (DTX) is here proposed. Indeed, we have developed biodegradable nanoparticles (NPs) of poly(ethylene glycol)-poly(ε-caprolactone), exposing on the surface both folate motifs (Fol) for recognition in cells overexpressing Folate receptor-α (FRα) and the anti-angiogenic hexapeptide aFLT1. NPs showed a size around 100 nm, the exposure of 60% of Fol moieties on the surface, and the ability to entrap DTX and sustain its release with time. NPs were stable in simulated biological fluids and slightly interacted with Fetal Bovine serum, especially in the formulation decorated with Fol and aFLT1. The presence of Fol on NPs did not impair the anti-angiogenic activity of aFLT1, as assessed by in vitro tube formation assay in HUVEC endothelial cells. In both 2D and 3D KB cell cultures in vitro, the cytotoxicity of DTX loaded in NPs was not significantly affected by Fol/aFLT1 double decoration compared to free DTX. Remarkably, NPs distributed differently in 3D multicellular spheroids of FRα-positive KB cancer cells depending on the type of ligand displayed on the surface. In particular, NPs unmodified on the surface were randomly distributed in the spheroid, whereas the presence of Fol promoted the accumulation in the outer rims of the spheroid. Finally, NPs with Fol and aFLT1 gave a uniform distribution throughout the spheroid structure. When tested in zebrafish embryos xenografted with KB cells, NPs displaying Fol/aFLT1 reduced DTX systemic toxicity and inhibited the growth of the tumor mass and associated vasculature synergistically. Overall, nanotechnology offers excellent ground for combining therapeutic concepts in cancer, paving the way to novel multifunctional nanopharmaceuticals decorated with bioactive elements that can significantly improve therapeutic outcomes. Graphical abstract


Coatings ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1549
Author(s):  
Lixia Wen ◽  
Peng Liu ◽  
Qi Chen ◽  
Jiayuan Ge ◽  
Bo Jia ◽  
...  

Background: To characterize the impaired of proliferation, apoptosis, and angiogenic activity in ASCs isolated at different stages of the disease course from rats with type 1 diabetes mellitus (T1DM) rats induced by streptozotocin (STZ). Methods: Adipose tissues of the epididymis were harvested at 0, 4, 8, 12, and 16 weeks after the induction of T1DM in rats and from normal rats at the same time points and the morphological variations were detected by Oil red O staining. ASCs were collected from adipose tissues. Cell proliferation, apoptosis, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) expression were assessed. Results: With the prolongation of the disease course, the size and the morphology of adipocytes were distorted, and intracellular lipid droplets became smaller. After 4 weeks, the proliferation of ASCs was decreased, while apoptosis in ASCs was increased. Furthermore, as the disease proceeded, proliferation decreased and apoptosis increased. VEGF and bFGF expression in ASCs from diabetic rats was downregulated at 8 weeks. Conclusion: At 4 weeks after T1DM induction, the proliferation of ASCs decreased and apoptosis increased. The expression of angiogenic factors in ASCs declined at 8 weeks after T1DM induction. The changes in the proliferation, apoptosis, and angiogenic activity are related to the prolongation of disease course.


2021 ◽  
Vol 144 ◽  
pp. 112263
Author(s):  
Casimiro Cárdenas ◽  
José Antonio Torres-Vargas ◽  
Abel Cárdenas-Valdivia ◽  
Nuria Jurado ◽  
Ana R. Quesada ◽  
...  

2021 ◽  
pp. 100196
Author(s):  
Özlem Şen ◽  
Attilio Marino ◽  
Carlotta Pucci ◽  
Gianni Ciofani
Keyword(s):  

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Tetsuya Ikawa ◽  
Takuya Miyagawa ◽  
Yuki Fukui ◽  
Satoshi Toyama ◽  
Jun Omatsu ◽  
...  

Abstract Background We have recently demonstrated that serum CCL20 levels positively correlate with mean pulmonary arterial pressure in patients with systemic sclerosis (SSc). Considering a proangiogenic effect of CCL20 on endothelial cells via CCR6, the CCL20/CCR6 axis may contribute to the development of SSc vasculopathy. Therefore, we explored this hypothesis using clinical samples, cultured cells, and murine SSc models. Methods The expression levels of CCL20 and CCR6 in the skin, mRNA levels of target genes, and the binding of transcription factor FLI1 to the target gene promoter were evaluated by immunostaining, quantitative reverse transcription PCR, and chromatin immunoprecipitation, respectively. Vascular permeability was evaluated by Evans blue dye injection in bleomycin-treated mice. Angiogenic activity of endothelial cells was assessed by in vitro angiogenesis assay. Results CCL20 expression was significantly elevated in dermal fibroblasts of patients with early diffuse cutaneous SSc, while CCR6 was significantly up-regulated in dermal small vessels of SSc patients irrespective of disease subtypes and disease duration. In human dermal microvascular endothelial cells, FLI1 siRNA induced the expression of CCR6, but not CCL20, and FLI1 bound to the CCR6 promoter. Importantly, vascular permeability, a representative SSc-like vascular feature of bleomycin-treated mice, was attenuated by Ccr6 siRNA treatment, and CCR6 siRNA suppressed the angiogenic activity of human dermal microvascular endothelial cells assayed by in vitro tube formation. Conclusions The increased expression of endothelial CCR6 due to FLI1 deficiency may contribute to the development of SSc vasculopathy.


Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5090
Author(s):  
Alexandra De Zutter ◽  
Helena Crijns ◽  
Nele Berghmans ◽  
Melissa García-Caballero ◽  
Lotte Vanbrabant ◽  
...  

Growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and epidermal growth factor (EGF) are important angiogenesis-mediating factors. They exert their effects not only through their respective receptor tyrosine kinases (RTKs), but they also require molecular pairing with heparan sulfate proteoglycans (HSPGs). Angiogenic growth factors and their signaling pathways are commonly targeted in current anti-angiogenic cancer therapies but have unfortunately insufficient impact on patient survival. Considering their obvious role in pathological angiogenesis, HS-targeting drugs have become an appealing new strategy. Therefore, we aimed to reduce angiogenesis through interference with growth factor-HS binding and downstream signaling using a CXCL9-derived peptide with a high affinity for glycosaminoglycans (GAGs), CXCL9(74-103). We showed that CXCL9(74-103) reduced EGF-, VEGF165- and FGF-2-mediated angiogenic processes in vitro, such as endothelial cell proliferation, chemotaxis, adhesion and sprouting, without exerting cell toxicity. CXCL9(74-103) interfered with growth factor signaling in diverse ways, e.g., by diminishing VEGF165 binding to HS and by direct association with FGF-2. The dependency of CXCL9(74-103) on HS for binding to HMVECs and for exerting its anti-angiogenic activity was also demonstrated. In vivo, CXCL9(74-103) attenuated neovascularization in the Matrigel plug assay, the corneal cauterization assay and in MDA-MB-231 breast cancer xenografts. Additionally, CXCL9(74-103) reduced vascular leakage in the retina of diabetic rats. In contrast, CXCL9(86-103), a peptide with low GAG affinity, showed no overall anti-angiogenic activity. Altogether, our results indicate that CXCL9(74-103) reduces angiogenesis by interfering with multiple HS-dependent growth factor signaling pathways.


Author(s):  
Ana K. Herrera-Vargas ◽  
Eduardo García-Rodríguez ◽  
Monserrat Olea-Flores ◽  
Miguel A. Mendoza-Catalán ◽  
Eugenia Flores-Alfaro ◽  
...  

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