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Updated: Aug 30, 2026
Monitoring Stub1-Mediated Pexophagy
Published on: May 12, 2023
Long-term inhibition of glioma growth by systemic administration of human PEX
M Pluderi1, V Lucini, D Caronzolo
1Neurosurgery, Department of Neurological Sciences, University of Milan, Milan, Italy.
Aim:
The growth of gliomas depends on the balance of factors stimulating or inhibiting angiogenesis, tumor cell invasion and proliferation. The administration of endogenous inhibitors to experimental human gliomas in animal models resulted in a significant inhibition of tumor growth. It is becoming apparent that resistance can develop over time to many types of endogenous inhibitors and seems to be influenced by the tumor type and system of delivery.
Methods:
We recently isolated a potent endogenous inhibitor, called human PEX, from human glioma cells in culture. Human PEX is a potent inhibitor of angiogenesis, tumor and endothelial cell proliferation and migration. In this paper, we investigated the ability of human PEX to sustain inhibition of glioma growth for a prolonged period of time. We initially developed a recombinant form of the inhibitor and showed that this form had similar in vitro and in vivo activities to the natural one. Human PEX was then administered to nude mice intracranial human glioma model, in combination with metronomic chemotherapy, for a period of 185 days, starting 15 days after tumor cells implantation.
Results:
Our data showed that the systemic administration of human PEX mantained a very prolonged inhibition of glioma growth (50% survival of animals treated with 2 mg/kg/days was 160 days vs 24 days of the control) and had a synergistic effect with low dose chemotherapy. Histological analysis of tumors, showed that treatment with PEX was associated with a decrease of vascularity, cell proliferation, and increase in apoptosis.
Conclusion:
These data indicate that human PEX controls tumor growth by separate mechanisms. In addition, treatment with PEX produced well delineated tumors, indicating the persistence of a direct anti-invasive effect of the molecule even after a prolonged period of treatment.
Insights
Human PEX, a novel endogenous inhibitor, significantly prolonged glioma growth inhibition in mice. This molecule demonstrated synergistic effects with chemotherapy, offering a promising new avenue for glioma treatment.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Glioma growth is regulated by a balance of pro-angiogenic and anti-angiogenic factors.
- Endogenous inhibitors can impede glioma progression, but resistance can develop.
- Human PEX is a newly isolated endogenous inhibitor with potent anti-angiogenic and anti-proliferative properties.
Purpose of the Study:
- To investigate the sustained efficacy of human PEX in inhibiting glioma growth over an extended period.
- To evaluate the synergistic potential of human PEX when combined with metronomic chemotherapy.
- To assess the anti-invasive capabilities of human PEX in a preclinical glioma model.
Main Methods:
- A recombinant form of human PEX was developed and validated for in vitro and in vivo activity.
- Human PEX was administered systemically to nude mice with intracranial human gliomas.
- Treatment involved combination therapy with metronomic chemotherapy for 185 days, starting 15 days post-implantation.
Main Results:
- Systemic human PEX administration resulted in prolonged glioma growth inhibition, extending median survival significantly compared to controls.
- A synergistic effect was observed between human PEX and low-dose metronomic chemotherapy.
- Histological analysis revealed decreased tumor vascularity, reduced cell proliferation, and increased apoptosis in PEX-treated tumors.
Conclusions:
- Human PEX effectively controls glioma growth through multiple mechanisms, including anti-angiogenesis, anti-proliferation, and anti-invasion.
- Sustained treatment with human PEX led to well-delineated tumors, suggesting a persistent anti-invasive effect.
- Human PEX represents a promising therapeutic agent for sustained glioma growth control.
