PUBLICATION

Zebrafish functional xenograft vasculature platform identifies PF-502 as a durable vasculature normalization drug

Authors
Zhong, J., Xiao, C., Chen, Q., Pan, X., Xu, T., Wang, Y., Hou, W., Liu, L., Cao, F., Wang, Y., Li, X., Zhou, L., Yang, H., Yang, Y., Zhao, C.
ID
ZDB-PUB-230908-66
Date
2023
Source
iScience   26: 107734107734 (Journal)
Registered Authors
Keywords
Biological sciences, Cell biology, Molecular biology
MeSH Terms
none
PubMed
37680473 Full text @ iScience
Abstract
Tumor vasculature often exhibits disorder and inefficiency. Vascular normalization offers potential for alleviating hypoxia and optimizing drug delivery in tumors. However, identifying effective agents is hindered by a lack of robust screening. We aimed to establish a comprehensive method using the zebrafish functional xenograft vasculature platform (zFXVP) to visualize and quantify tumor vasculature changes. Employing zFXVP, we systematically screened compounds, identifying PF-502 as a robust vascular normalization agent. Mechanistic studies showed PF-502 induces endothelial cell-cycle arrest, streamlines vasculature, and activates Notch1 signaling, enhancing stability and hemodynamics. In murine models, PF-502 exhibited pronounced vascular normalization and improved drug delivery at a sub-maximum tolerated dose. These findings highlight zFXVP's utility and suggest PF-502 as a promising adjunctive for vascular normalization in clinical settings.
Genes / Markers
Figures
Figure Gallery (8 images)
Show all Figures
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s843TgTransgenic Insertion
    sd2TgTransgenic Insertion
      y7TgTransgenic Insertion
        zf527TgTransgenic Insertion
          zf4088
            		Small Deletion
            zf4089
              		Small Deletion
              zf4090
                		Small Deletion
                zf4091
                  		Small Deletion
                  zf4092
                    		Small Deletion
                    1 - 9 of 9
                    Show
                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Target Reagent Reagent Type
                    notch1aCRISPR11-notch1aCRISPR
                    notch1bCRISPR8-notch1bCRISPR
                    1 - 2 of 2
                    Show
                    Fish
                    No data available
                    Antibodies
                    No data available
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    DsRedEFGDsRed
                    EGFPEFGEGFP
                    mCherryEFGmCherry
                    1 - 3 of 3
                    Show
                    Mapping
                    No data available
                    Your Input Welcome
                    We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
                    Citation
                    Zhong, J., Xiao, C., Chen, Q., Pan, X., Xu, T., Wang, Y., Hou, W., Liu, L., Cao, F., Wang, Y., Li, X., Zhou, L., Yang, H., Yang, Y., Zhao, C. (2023) Zebrafish functional xenograft vasculature platform identifies PF-502 as a durable vasculature normalization drug. iScience. 26:107734107734.