ArticlePloS one2011
Gamma-secretase inhibitor treatment promotes VEGF-A-driven blood vessel growth and vascular leakage but disrupts neovascular perfusion.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- ProNotch converts extracellular protease activity into programmable transcriptional outputs.bioRxiv : the preprint server for biology · 2026Article
- Tumor-associated endothelial cells in tumor immune escape and immunotherapy: multifaceted roles and treatment approaches.Biomarker research · 2025Review
- Molecular docking analysis of phytocompounds from Andrographis paniculata binding with proteins in the notch-signaling pathway.Bioinformation · 2020Article
- Activation of Notch signaling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway.American journal of physiology. Heart and circulatory physiology · 2019Article
- Notch Signaling Pathway Is Involved in bFGF-Induced Corneal Lymphangiogenesis and Hemangiogenesis.Journal of ophthalmology · 2019Article
- Rethinking Gamma-secretase Inhibitors for Treatment of Non-small-Cell Lung Cancer: Is Notch the Target?Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Review
- Ultrasound Molecular Imaging of VEGFR-2 in Clear-Cell Renal Cell Carcinoma Tracks Disease Response to Antiangiogenic and Notch-Inhibition Therapy.Theranostics · 2018Article
- The role of Notch signaling in gastric carcinoma: molecular pathogenesis and novel therapeutic targets.Oncotarget · 2017Review
- Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo.BMC cancer · 2017Article
- Incomplete Dll4/Notch signaling inhibition promotes functional angiogenesis supporting the growth of skin papillomas.BMC cancer · 2015Article
- Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch.Nature communications · 2015Article
- NOTCH decoys that selectively block DLL/NOTCH or JAG/NOTCH disrupt angiogenesis by unique mechanisms to inhibit tumor growth.Cancer discovery · 2015Article
- Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program.Pediatric blood & cancer · 2014Article
- Prolonged inhibition of glioblastoma xenograft initiation and clonogenic growth following in vivo Notch blockade.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Endothelial tip cells in ocular angiogenesis: potential target for anti-angiogenesis therapy.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2013Review
- Sarcoma spreads primarily through the vascular system: are there biomarkers associated with vascular spread?Clinical & experimental metastasis · 2012Article
- Notch signaling in ocular vasculature development and diseases.Molecular medicine (Cambridge, Mass.) · 2012Review
- γ-Secretase inhibition of murine choroidal neovascularization is associated with reduction of superoxide and proinflammatory cytokines.Investigative ophthalmology & visual science · 2012Article
- Notch signaling in developmental and tumor angiogenesis.Genes & cancer · 2011Article
- Investigational Notch and Hedgehog inhibitors--therapies for cardiovascular disease.Expert opinion on investigational drugs · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Notch signaling pathway is essential for normal development due to its role in control of cell differentiation, proliferation and survival. It is also critically involved in tumorigenesis and cancer progression. A key enzyme in the activation of Notch signaling is the gamma-secretase protein complex and therefore, gamma-secretase inhibitors (GSIs)--originally developed for Alzheimer's disease--are now being evaluated in clinical trials for human malignancies. It is also clear that Notch plays an important role in angiogenesis driven by Vascular Endothelial Growth Factor A (VEGF-A)--a process instrumental for tumor growth and metastasis. The effect of GSIs on tumor vasculature has not been conclusively determined. Here we report that Compound X (CX), a GSI previously reported to potently inhibit Notch signaling in vitro and in vivo, promotes angiogenic sprouting in vitro and during developmental angiogenesis in mice. Furthermore, CX treatment suppresses tumor growth in a mouse model of renal carcinoma, leads to the formation of abnormal vessels and an increased tumor vascular density. Using a rabbit model of VEGF-A-driven angiogenesis in skeletal muscle, we demonstrate that CX treatment promotes abnormal blood vessel growth characterized by vessel occlusion, disrupted blood flow, and increased vascular leakage. Based on these findings, we propose a model for how GSIs and other Notch inhibitors disrupt tumor blood vessel perfusion, which might be useful for understanding this new class of anti-cancer agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.