Successful management of lung adenocarcinoma with ALK/EGFR co-alterations and PD-L1 over-expression by bevacizumab combined with chemotherapy
We describe a case of advanced lung adenocarcinoma, harboring concurrent ALK/EGFR mutations and extremely high PD-L1 expression, that achieved sustained remission by the first-line treatment strategy of antiangiogenic therapy combined with chemotherapy. It is our firm conviction that the use anti-angiogenics should not have fallen out of favor in this era of targeted therapy and checkpoint inhibitors. (Source: Angiogenesis)
Source: Angiogenesis - August 3, 2021 Category: Molecular Biology Source Type: research
Linalool inhibits the angiogenic activity of endothelial cells by downregulating intracellular ATP levels and activating TRPM8
AbstractAngiogenesis crucially contributes to various diseases, such as cancer and diabetic retinopathy. Hence, anti-angiogenic therapy is considered as a powerful strategy against these diseases. Previous studies reported that the acyclic monoterpene linalool exhibits anticancer, anti-inflammatory and anti-oxidative activity. However, the effects of linalool on angiogenesis still remain elusive. Therefore, we investigated the action of (3R)-( −)-linalool, a main enantiomer of linalool, on the angiogenic activity of human dermal microvascular endothelial cells (HDMECs) by a panel of angiogenesis assays. Non-cytotoxic do...
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
Von Willebrand factor collagen-binding capacity predicts in-hospital mortality in COVID-19 patients: insight from VWF/ADAMTS13 ratio imbalance
ConclusionVWF:CB levels could summarize both VWF increased levels and hyper-reactivity subsequent to ADAMTS13 overflow and, therefore, be a valuable and easy to perform clinical biomarker of microthrombosis and COVID-19 severity. (Source: Angiogenesis)
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
Atorvastatin pleiotropically decreases intraplaque angiogenesis and intraplaque haemorrhage by inhibiting ANGPT2 release and VE-Cadherin internalization
ConclusionsAtorvastatin has beneficial effects on vessel remodeling due to its lipid-lowering capacity. Atorvastatin has strong pleiotropic effects on IPA by decreasing the number of neovessels and on IPH by increasing vessel maturation. Atorvastatin improves vessel maturation by inhibiting ANGPT2 release and phospho(Y658)-mediated VE-Cadherin internalization. (Source: Angiogenesis)
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
Depletion of Arg/Abl2 improves endothelial cell adhesion and prevents vascular leak during inflammation
AbstractEndothelial barrier disruption and vascular leak importantly contribute to organ dysfunction and mortality during inflammatory conditions like sepsis and acute respiratory distress syndrome. We identified the kinase Arg/Abl2 as a mediator of endothelial barrier disruption, but the role of Arg in endothelial monolayer regulation and its relevance in vivo remain poorly understood. Here we show that depletion of Arg in endothelial cells results in the activation of both RhoA and Rac1, increased cell spreading and elongation, redistribution of integrin-dependent cell-matrix adhesions to the cell periphery, and improved...
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
The role of redox system in metastasis formation
AbstractThe metastatic cancer disease represents the real and urgent clinical need in oncology. Therefore, an understanding of the complex molecular mechanisms sustaining the metastatic cascade is critical to advance cancer therapies. Recent studies highlight how redox signaling influences the behavior of metastatic cancer cells, contributes to their travel in bloodstream from the primary tumor to the distant organs and conditions the progression of the micrometastases or their dormant state. Radical oxygen species not only regulate intracellular processes but participate to paracrine circuits by diffusion to nearby cells,...
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
RSF1 requires CEBP/ β and hSNF2H to promote IL-1β-mediated angiogenesis: the clinical and therapeutic relevance of RSF1 overexpression and amplification in myxofibrosarcomas
In conclusion, RSF1 overexpression, partly attributable toRSF1 amplification, contributes a novel proangiogenic function by partnering with CEBP/ β to cotransactivateIL1B, highlighting its prognostic, pathogenetic, and therapeutic relevance in myxofibrosarcomas. (Source: Angiogenesis)
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
Phosphorylation of pericyte FAK-Y861 affects tumour cell apoptosis and tumour blood vessel regression
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. UsingPdgfr βCre + ;FAKWT/WT,Pdgfr βCre + ;FAKY397F/Y397F andPdgfr βCre + ;FAKY861F/Y861F mice, our data demonstrate th...
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
Dysbiotic stress increases the sensitivity of the tumor vasculature to radiotherapy and c-Met inhibitors
AbstractAntibiotic-induced microbial imbalance, or dysbiosis, has systemic and long-lasting effects on the host and response to cancer therapies. However, the effects on tumor endothelial cells are largely unknown. Therefore, the goal of the current study was to generate matched B16-F10 melanoma associated endothelial cell lines isolated from mice with and without antibiotic-induced dysbiosis. After validating endothelial cell markers on a genomic and proteomic level, functional angiogenesis assays (i.e., migration and tube formation) also confirmed their vasculature origin. Subsequently, we found that tumor endothelial ce...
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
The endosomal RIN2/Rab5C machinery prevents VEGFR2 degradation to control gene expression and tip cell identity during angiogenesis
AbstractSprouting angiogenesis is key to many pathophysiological conditions, and is strongly regulated by vascular endothelial growth factor (VEGF) signaling through VEGF receptor 2 (VEGFR2). Here we report that the early endosomal GTPase Rab5C and its activator RIN2 prevent lysosomal routing and degradation of VEGF-bound, internalized VEGFR2 in human endothelial cells. Stabilization of endosomal VEGFR2 levels by RIN2/Rab5C is crucial for VEGF signaling through the ERK and PI3-K pathways, the expression of immediate VEGF target genes, as well as specification of angiogenic ‘tip’ and ‘stalk’ cell phenotypes and cell...
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner
We describe these aggregates as LVEM (LVs encapsulated by TAMs) considering their advantageous metastatic capacity and active involvement in early lymph node metastasis (LNM). Mechanistic investigations revealed that interleukin-10 (IL-10) derived from hypoxic TAMs adjacent to LVs was a prerequisite for lymphangiogenesis and LVEM formation through its induction of Sp1 upregulation in lymphatic endothelial cells (LECs). Interestingly, Sp1high LECs promoted the transactivation of C –C motif chemokine ligand 1 (CCL1) to facilitate TAM and tumour cell recruitment, thereby forming a positive feedback loop to strengthen the LV...
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
Hydrogel-mediated delivery of microRNA-92a inhibitor polyplex nanoparticles induces localized angiogenesis
AbstractLocalized stimulation of angiogenesis is an attractive strategy to improve the repair of ischemic or injured tissues. Several microRNAs (miRNAs) such as miRNA-92a (miR-92a) have been reported to negatively regulate angiogenesis in ischemic disease. To exploit the clinical potential of miR-92a inhibitors, safe and efficient delivery needs to be established. Here, we used deoxycholic acid-modified polyethylenimine polymeric conjugates (PEI-DA) to deliver a locked nucleic acid (LNA)-based miR-92a inhibitor (LNA-92a) in vitro and in vivo. The positively charged PEI-DA conjugates condense the negatively charged inhibito...
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
RIPK3 modulates growth factor receptor expression in endothelial cells to support angiogenesis
AbstractReceptor-interacting protein kinase 3 (RIPK3) is a multifunctional intracellular protein that was first recognized as an important component of the necroptosis programmed cell death pathway. RIPK3 is also highly expressed in non-necroptotic murine embryonic endothelial cells (ECs) during vascular development, indicating its potential contribution to angiogenesis. To test this hypothesis, we generated mice lacking endothelial RIPK3 and found non-lethal embryonic and perinatal angiogenesis defects in multiple vascular beds. Our in vitro data indicate that RIPK3 supports angiogenesis by regulating growth factor recept...
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
Loss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/ β-catenin pathway
ConclusionsLack of endothelial GR triggers autophagy flux, leads to activation of Wnt/ β-catenin signaling and promotes angiogenesis. There may also be a synergistic interaction between autophagy and Wnt/β-catenin signaling. (Source: Angiogenesis)
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
Correction to: Phosphorylation of pericyte FAK ‑Y861 affects tumour cell apoptosis and tumour blood vessel regression
A correction to this paper has been published: https://doi.org/10.1007/s10456-021-09802-9 (Source: Angiogenesis)
Source: Angiogenesis - August 1, 2021 Category: Molecular Biology Source Type: research
