Long-term inhibition of glioma growth by systemic administration of human PEX

M. Pluderi, V. Lucini, D. Caronzolo, M. Pannacci, F. Costa, G. Carrabba, C. Giussani, S. Grosso, F. Colleoni, F. Scaglione, R. Villani, A. Bikfalvi, L. Bello

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)69-78
Number of pages10
JournalJournal of Neurosurgical Sciences
Volume47
Issue number2
Publication statusPublished - Jun 2003

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Glioma
Growth
Neoplasms
Cell Proliferation
Drug Therapy
Angiogenesis Inhibitors
Nude Mice
Cell Movement
Therapeutics
Endothelial Cells
Animal Models
Cell Culture Techniques
Apoptosis

Keywords

  • Angiogenesis inhibitors
  • Endogenous inhibitors
  • Glioma, therapy

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Long-term inhibition of glioma growth by systemic administration of human PEX. / Pluderi, M.; Lucini, V.; Caronzolo, D.; Pannacci, M.; Costa, F.; Carrabba, G.; Giussani, C.; Grosso, S.; Colleoni, F.; Scaglione, F.; Villani, R.; Bikfalvi, A.; Bello, L.

In: Journal of Neurosurgical Sciences, Vol. 47, No. 2, 06.2003, p. 69-78.

Research output: Contribution to journalArticle

Pluderi, M, Lucini, V, Caronzolo, D, Pannacci, M, Costa, F, Carrabba, G, Giussani, C, Grosso, S, Colleoni, F, Scaglione, F, Villani, R, Bikfalvi, A & Bello, L 2003, 'Long-term inhibition of glioma growth by systemic administration of human PEX', Journal of Neurosurgical Sciences, vol. 47, no. 2, pp. 69-78.
Pluderi, M. ; Lucini, V. ; Caronzolo, D. ; Pannacci, M. ; Costa, F. ; Carrabba, G. ; Giussani, C. ; Grosso, S. ; Colleoni, F. ; Scaglione, F. ; Villani, R. ; Bikfalvi, A. ; Bello, L. / Long-term inhibition of glioma growth by systemic administration of human PEX. In: Journal of Neurosurgical Sciences. 2003 ; Vol. 47, No. 2. pp. 69-78.
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AU - Pluderi, M.

AU - Lucini, V.

AU - Caronzolo, D.

AU - Pannacci, M.

AU - Costa, F.

AU - Carrabba, G.

AU - Giussani, C.

AU - Grosso, S.

AU - Colleoni, F.

AU - Scaglione, F.

AU - Villani, R.

AU - Bikfalvi, A.

AU - Bello, L.

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N2 - 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.

AB - 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.

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