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  • AFPep, a Novel Agent with Potential of Development for Treatment of Glioblastoma

    Final Number:
    1585

    Authors:
    Fassil B. Mesfin MD PhD; Natalie Dowell-Mesfin PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2015 Annual Meeting

    Introduction: Glioblastoma Multiforme (GBM) is the most frequent malignant primary tumor of the central nervous system. Patients with a diagnosis of glioblastoma have a poor prognosis despite advances in cancer treatment and surgical techniques. Consequently, new therapeutic agents are in demand for management. Recently, AFPep has been shown to have an effect on the proliferation, migration and invasion of glioblastoma cells. AFPep is a nine amino acid sequence cyclic analog of Alpha-fetoprotein (AFP), which is a glycoprotein produced during pregnancy by the fetal yolk sac and by fetal liver. AFPep is a peptide derived from a natural product and is well tolerated in animal studies. The data reported in this abstract showed a potential of development of AFPep for treatment of GBM.

    Methods: AFPep was synthesized commercially . The anti-proliferative effect of APep was determined in MTT growth inhibition assay against cultured U87 human GBM. Chemotactic migration of GBM cells in response to serum was carried out by using a modified Boyden chamber assay and matrigel invasion assay. The in vivo anti-proliferative effect of AFPep was determined using human GBM xenografts growth assay using SCID mice.

    Results: This study showed that AFPep inhibits the proliferation of cultured human glioblastoma cells in a dose-dependent manner with an IC50 of 1 nM. Tamoxifen also had a dose-dependent inhibitory effect with the IC50 of 5 µM. Treatment of SCID mice bearing U87 xenografts with 4 mg/Kg/day AFPep resulted in a significant inhibition of tumor growth. In addition, AFPep (10-6M to 10-4M) inhibited the invasion of U87 cells in a dose dependent manner in the Matrigel chemoinvasion assay.

    Conclusions: The data reported here showed that AFPep inhibits the growth and invasion of human glioblastoma. Therefore, AFPep can be developed as chemotherapeutic agent for treatment of patients with GBM.

    Patient Care: This is a basic science research with real potential of developing a novel therapeutic agent, AFPep for treatment of patients with glioblastoma.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance and demand for new therapeutic agents for treatment patient with GBM 2) Discuss a potential development of novel agent AFPep for treatment of patients with GBM.

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