Antiangiogenesis: Vessel Regression, Vessel Normalization, or Both?

2022 ◽  
Vol 82 (1) ◽  
pp. 15-17
Author(s):  
Hellmut G. Augustin ◽  
Gou Young Koh
Keyword(s):  
Vessel Normalization ◽  
Vessel Regression

scholarly journals Phosphorylation of pericyte FAK-Y861 affects tumour cell apoptosis and tumour blood vessel regression

Angiogenesis ◽  
2021 ◽  
Author(s):  
Delphine M. Lees ◽  
Louise E. Reynolds ◽  
Ana Rita Pedrosa ◽  
Marina Roy-Luzarraga ◽  
Kairbaan M. Hodivala-Dilke
Keyword(s):  
Blood Vessel ◽  
Tumour Growth ◽  
Vascular Endothelial Cell ◽  
Vessel Density ◽  
In Vivo Studies ◽  
Blood Vessel Density ◽  
Tumour Vessel ◽  
Vessel Regression ◽  
Tumour Blood

AbstractFocal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed in many cancer types and in vivo studies have shown that vascular endothelial cell FAK expression and FAK-phosphorylation at tyrosine (Y) 397, and subsequently FAK-Y861, are important in tumour angiogenesis. Pericytes also play a vital role in regulating tumour blood vessel stabilisation, but the specific involvement of pericyte FAK-Y397 and FAK-Y861 phosphorylation in tumour blood vessels is unknown. Using PdgfrβCre + ;FAKWT/WT, PdgfrβCre + ;FAKY397F/Y397F and PdgfrβCre + ;FAKY861F/Y861F mice, our data demonstrate that tumour growth, tumour blood vessel density, blood vessel perfusion and pericyte coverage were affected only in late stage tumours in PdgfrβCre + ;FAKY861F/Y861F but not PdgfrβCre + ;FAKY397F/Y397F mice. Further examination indicates a dual role for pericyte FAK-Y861 phosphorylation in the regulation of tumour vessel regression and also in the control of pericyte derived signals that influence apoptosis in cancer cells. Overall this study identifies the role of pericyte FAK-Y861 in the regulation of tumour vessel regression and tumour growth control and that non-phosphorylatable FAK-Y861F in pericytes reduces tumour growth and blood vessel density.

scholarly journals The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2

2021 ◽  
Vol 22 (14) ◽  
pp. 7511
Author(s):  
Albina Fejza ◽  
Maurizio Polano ◽  
Lucrezia Camicia ◽  
Evelina Poletto ◽  
Greta Carobolante ◽  
...  
Keyword(s):  
Gene Expression ◽  
Effective Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tumor Hypoxia ◽  
Melanoma Cells ◽  
Vessel Normalization ◽  
Melanoma Patients

The use of immune checkpoint inhibitors has revolutionized the treatment of melanoma patients, leading to remarkable improvements in the cure. However, to ensure a safe and effective treatment, there is the need to develop markers to identify the patients that would most likely respond to the therapies. The microenvironment is gaining attention in this context, since it can regulate both the immunotherapy efficacyand angiogenesis, which is known to be affected by treatment. Here, we investigated the putative role of the ECM molecule EMILIN-2, a tumor suppressive and pro-angiogenic molecule. We verified that the EMILIN2 expression is variable among melanoma patients and is associated with the response to PD-L1 inhibitors. Consistently, in preclinical settings,the absence of EMILIN-2 is associated with higher PD-L1 expression and increased immunotherapy efficacy. We verified that EMILIN-2 modulates PD-L1 expression in melanoma cells through indirect immune-dependent mechanisms. Notably, upon PD-L1 blockage, Emilin2−/− mice displayed improved intra-tumoral vessel normalization and decreased tumor hypoxia. Finally, we provide evidence indicating that the inclusion of EMILIN2 in a number of gene expression signatures improves their predictive potential, a further indication that the analysis of this molecule may be key for the development of new markers to predict immunotherapy efficacy.

Recent advances in anti-angiogenic nanomedicines for cancer therapy

Nanoscale ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 5393-5423 ◽  
Author(s):  
Pravin Bhattarai ◽  
Sadaf Hameed ◽  
Zhifei Dai
Keyword(s):  
Cancer Therapy ◽  
Controlled Delivery ◽  
Therapeutic Success ◽  
Vessel Normalization ◽  
Recent Advances

The controlled delivery of nanomedicine-based antiangiogenic inhibitors or chemotherapeutics can revitalize therapeutic success by vessel normalization.

scholarly journals Stable tumor vessel normalization with pO2 increase and endothelial PTEN activation by inositol trispyrophosphate brings novel tumor treatment

2013 ◽  
Vol 91 (7) ◽  
pp. 883-899 ◽  
Author(s):  
Claudine Kieda ◽  
Bouchra El Hafny-Rahbi ◽  
Guillaume Collet ◽  
Nathalie Lamerant-Fayel ◽  
Catherine Grillon ◽  
...  
Keyword(s):  
Tumor Treatment ◽  
Tumor Vessel ◽  
Vessel Normalization
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