ArticleJournal of neuro-oncology2012
Intracerebral infusion of the bispecific targeted toxin DTATEGF in a mouse xenograft model of a human metastatic non-small cell lung cancer.
Article in Journal of neuro-oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator.Biomedicines · 2024Review
- Dr.Nod: computational framework for discovery of regulatory non-coding drivers in tissue-matched distal regulatory elements.Nucleic acids research · 2023Article
- Review
- The Urokinase Receptor (uPAR) as a "Trojan Horse" in Targeted Cancer Therapy: Challenges and Opportunities.Cancers · 2021Review
- Fibrinolytic System and Cancer: Diagnostic and Therapeutic Applications.International journal of molecular sciences · 2021Review
- Targeted Diphtheria Toxin-Based Therapy: A Review Article.Frontiers in microbiology · 2019Review
- Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications.Frontiers in oncology · 2018Review
- Immunotoxin Therapies for the Treatment of Epidermal Growth Factor Receptor-Dependent Cancers.Toxins · 2016Review
- Plasma membrane gp96 enhances invasion and metastatic potential of liver cancer via regulation of uPAR.Molecular oncology · 2015Article
- Molecular determinants of lung cancer metastasis to the central nervous system.Translational lung cancer research · 2013Review
- The many spaces of uPAR: delivery of theranostic agents and nanobins to multiple tumor compartments through a single target.Theranostics · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this study is to investigate the anti-cancer effect of the bispecific diphtheria toxin (DT) based immunotoxin DTATEGF, which targets both the epidermal growth factor (EGF) receptor (EGFR) and the urokinase-type plasminogen activator (uPA) receptor (uPAR) in vitro and in vivo when delivered by convection-enhanced delivery (CED) via an osmotic minipump in a human metastatic non-small cell lung cancer (NSCLC) brain tumor mouse xenograft model. The effects of the bispecific immunotoxin DTATEGF, and monospecific DTAT, DTEGF and control DT at various concentrations were tested for their ability to inhibit the proliferation of human metastatic NSCLC PC9-BrM3 cells in vitro by MTT assay. A xenograft model of human metastatic NSCLC intracranial model was established in nude mice using the human NSCLC PC9-BrM3 cell line genetically marked with a firefly luciferase reporter gene. One microgram of DTATEGF in the treatment group or control DT in the control group was delivered intracranially by CED via an osmotic minipump. The bioluminescent imaging (BLI) was performed at day 7, 14, 1 month, 2 months, and 3 months. Kaplan-Meier survival curves for the two groups were generated. The brain tissue samples were stained by hematoxylin and eosin for histopathological assessment. In vitro, DTATEGF could selectively kill PC9-BrM3 cells and showed an IC(50) less than 0.001 nM, representing a more than 100- to 1000-fold increase in activity as compared to monospecific DTAT and DTEGF. In vivo, mice with tumors were treated intracranially with drug via CED where the results showed the treatment was successful in providing a survival benefit with the median survival of mice treated with DTATEGF being significantly prolonged relative to controls (87 vs. 63 days, P = 0.006). The results of these experiments indicate that DTATEGF kills the NSCLC PC9-BrM3 cell line in vitro, and when it is delivered via CED intracranially, it is highly efficacious against metastatic NSCLC brain tumors. DTATEGF is a safe and effective drug where further preclinical and clinical development is warranted for the management of metastatic brain tumors.
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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.