ArticleProceedings of the National Academy of Sciences of the United States of America2002
In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 143 citations in OpenAlex.
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- Light-enhanced VEGFFrontiers in immunology · 2023Article
- Advances on Delivery of Cytotoxic Enzymes as Anticancer Agents.Molecules (Basel, Switzerland) · 2022Review
- Spatial maps of hepatocellular carcinoma transcriptomes highlight an unexplored landscape of heterogeneity and a novel gene signature for survival.Cancer cell international · 2022Article
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- Toxic proteins application in cancer therapy.Molecular biology reports · 2021Review
- The Role of VEGF Receptors as Molecular Target in Nuclear Medicine for Cancer Diagnosis and Combination Therapy.Cancers · 2021Review
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- Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research.Journal of clinical medicine · 2020Review
- Advances on Tumor-Targeting Delivery of Cytotoxic Proteins.ACS pharmacology & translational science · 2020Review
- YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA.Frontiers in oncology · 2019Article
- Membrane reorganization after photochemical internalization to release transferrin-biofunctionalized polystyrene microparticles.Scientific reports · 2018Article
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- Targeting of Tumor Neovasculature with GrB/VEGFBiomedicines · 2017Review
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- Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET.Molecular imaging and biology · 2015Article
- Design of an EGFR-targeting toxin for photochemical delivery: in vitro and in vivo selectivity and efficacy.Oncogene · 2015Article
- Efficient Inhibition of Ovarian Cancer by Gelonin Toxin Gene Delivered by Biodegradable Cationic Heparin-polyethyleneimine Nanogels.International journal of medical sciences · 2015Article
- Immunotoxins constructed with ribosome-inactivating proteins and their enhancers: a lethal cocktail with tumor specific efficacy.Current pharmaceutical design · 2014Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Vascular endothelial growth factor (VEGF) plays a key role in the growth and metastasis of solid tumors. We generated a fusion protein containing VEGF(121) linked by a flexible G(4)S tether to the toxin gelonin (rGel) and expressed this as a soluble protein in bacteria. Purified VEGF(121)/rGel migrated as an 84-kDa homodimer under nonreducing conditions. VEGF(121)/rGel bound to purified, immobilized Flk-1, and the binding was competed by VEGF(121). Both VEGF(121)/rGel and VEGF(121) stimulated cellular kinase insert domain receptor (KDR) phosphorylation. The VEGF(121)/rGel fusion construct was highly cytotoxic to endothelial cells overexpressing the KDR/Flk-1 receptor. The IC(50) of the construct on dividing endothelial cells expressing 10(5) or more KDR/Flk-1 receptors per cell was 0.5-1 nM, as compared with 300 nM for rGel itself. Dividing endothelial cells overexpressing KDR were approximately 60-fold more sensitive to VEGF(121)/rGel than were nondividing cells. Endothelial cells overexpressing FLT-1 were not sensitive to the fusion protein. Human melanoma (A-375) or human prostate (PC-3) xenografts treated with the fusion construct demonstrated a reduction in tumor volume to 16% of untreated controls. The fusion construct localized selectively to PC-3 tumor vessels and caused thrombotic damage to tumor vessels with extravasation of red blood cells into the tumor bed. These studies demonstrate the successful use of VEGF(121)/rGel fusion construct for the targeted destruction of tumor vasculature in vivo.
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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.