Combinatorial Administration of Molecules That Simultaneously Inhibit Angiogenesis and Invasion Leads to Increased Therapeutic Efficacy in Mouse Models of Malignant Glioma
- Lorenzo Bello1,
- Valeria Lucini2,
- Francesco Costa1,
- Mauro Pluderi1,
- Carlo Giussani1,
- Francesco Acerbi1,
- Giorgio Carrabba1,
- Marilou Pannacci2,
- Dario Caronzolo2,
- Silvia Grosso2,
- Svetlana Shinkaruk4,
- Federica Colleoni2,
- Xavier Canron3,
- Giustino Tomei1,
- Gerard Deleris4 and
- Andreas Bikfalvi3
- 1Neurosurgery, Department of Neurological Sciences, University of Milano, Ospedale Maggiore di Milano, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy; 2 Department of Pharmacology, University of Milano, Milan, Italy; 3 INSERM Unit EMI 0113, Molecular Angiogenesis Laboratory, University of Bordeaux I, Talence, France; and 4 Groupe de Chimie Bio-Organique (Institut National de la Santé et de la Recherche Médicale U 577), Université Victor Segalen Bordeaux 2, Bordeaux Cedex, France
Abstract
Purpose: We investigated the ability of the combinatorial administration of different inhibitors with activities on glioma angiogenesis, migration, and proliferation to produce a prolonged inhibition of glioma growth.
Experimental Design: We combined inhibitors affecting solely tumor angiogenesis (PF-4/CTF, cyclo-VEGI) or inhibitors affecting both angiogenesis and invasion together (PEX, PF-4/DLR).
Results: When administered in combination, these drugs produced a prolonged and increased inhibition of glioma growth independently from the type of inhibitor used. The combinatory administration was more effective than the administration of a single inhibitor alone, and a strong therapeutic response was reached with a significantly lower amount of protein. The strongest inhibition was observed when human PEX and PF-4/DLR, which affect both glioma angiogenesis and invasion by separate mechanisms, were combined.
Conclusions: This supports the concept that prolonged glioma growth inhibition can be achieved by simultaneous delivery of molecules that target both tumor and endothelial cells and acting by separate mechanisms.
Footnotes
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Grant support: Associazione Italiana Ricerca sul Cancro, Progetto Oncologia, Compagnia di San Paolo, Torino, Italy, Fondazione Italo Monzino, Milan, Italy, Progetto Galileo, CRUI, Italy (L. Bello); the “Ligue contre le Cancer” (“Equipe Labelisée”), the “Conseil Regional D’Aquitaine” (A. Bikfalvi); and the “Ligue contre le Cancer” and the “Conseil Régional d’Aquitaine” (G. Deleris).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: L. Bello and V. Lucini contributed equally to this work.
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Requests for reprints: Lorenzo Bello, Neurosurgery, Department of Neurological Sciences, University of Milano, Ospedale Maggiore Policlinico, Istituto di Ricovero e Cura a Carattere Scientifico, Via Francesco Sforza 35, 20122 Milan, Italy. Phone: 39-02-5503-5502; Fax: 39-02-5990-2239; E-mail: lorenzo.bello{at}unimi.it
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- Accepted March 26, 1904.
- Received February 1, 1904.
- Revision received March 18, 1904.
