This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bello, L. Articles by Bikfalvi, A. Search for Related Content PubMed PubMed Citation Articles by Bello, L. Articles by Bikfalvi, A.

Suppression of Malignant Glioma Recurrence in a Newly Developed Animal Model by Endogenous Inhibitors¹

Neurosurgery, Department of Neurological Sciences, University of Milano, Ospedale Maggiore Policlinico, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy [L. B., C. G., G. C., M. P., G. T., R. V.]; Department of Pharmacology, University of Milan, Milan 20122, Italy [V. L., M. P., D. C., F. S.]; Institut National de la Santé et de la Recherche Médicale, Unit EPI 0113, Molecular Mechanisms of Angiogenesis, University of Bordeaux I, Talence, France [A. B.]; and Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts [R. S. C.]

Glioma recurrences develop at the borders of the surgical cavity and are the main cause of their poor prognosis. There are no therapeutic advances to reduce the incidence of recurrence or animal models that closely mimic the clinical scenario to evaluate novel therapeutics. This work investigates the efficacy of endogenous inhibitors, in preventing the recurrence of human malignant gliomas, in a newly developed animal model of glioma surgical resection. We developed a nude mice model in which human glioma xenografts were microsurgically removed. After surgery, small islets of tumor cells persisted in the normal brain parenchyma, grew, and formed a recurrence. As inhibitors we used PEX and a fragment of platelet factor 4 (PF-4/CTF), which were administered systemically on a daily basis or in metronomic combination with chemotherapy for 120 days. Treatment was started 1 or 15 days after tumor removal. PEX or PF-4/CTF produced a significant improvement in survival, and delayed the appearance of glioma recurrence. Survival of animals that received daily PEX or PF-4/CTF was similar to that of animals that received metronomic PEX or PF-4/CTF and chemotherapy, respectively. The effect of treatment was dependent on the time at which the treatment was initiated. The highest level of inhibition was observed when the treatment was administered 1 day after surgical resection and when PEX was used as the inhibitor (120 days versus 35 days of the control). Tumors treated with PEX or PF-4/CTF were small and well delineated, with few vessels. Postsurgical administration of PEX or PF-4/CTF significantly reduces the incidence human malignant glioma recurrences for a long period of time.

This article has been cited by other articles:

				O. Benny, S.-K. Kim, K. Gvili, I. S. Radzishevsky, A. Mor, L. Verduzco, L. G. Menon, P. M. Black, M. Machluf, and R. S. Carroll In vivo fate and therapeutic efficacy of PF-4/CTF microspheres in an orthotopic human glioblastoma model FASEB J, February 1, 2008; 22(2): 488 - 499. [Abstract] [Full Text] [PDF]

				S. Sarkar, R. K. Nuttall, S. Liu, D. R. Edwards, and V. W. Yong Tenascin-C Stimulates Glioma Cell Invasion through Matrix Metalloproteinase-12 Cancer Res., December 15, 2006; 66(24): 11771 - 11780. [Abstract] [Full Text] [PDF]

				J. Zhang, S. Sarkar, and V.W. Yong The chemokine stromal cell derived factor-1 (CXCL12) promotes glioma invasiveness through MT2-matrix metalloproteinase Carcinogenesis, December 1, 2005; 26(12): 2069 - 2077. [Abstract] [Full Text] [PDF]

				S. R. Perri, J. Nalbantoglu, B. Annabi, Z. Koty, L. Lejeune, M. Francois, M. R. Di Falco, R. Beliveau, and J. Galipeau Plasminogen Kringle 5-Engineered Glioma Cells Block Migration of Tumor-Associated Macrophages and Suppress Tumor Vascularization and Progression Cancer Res., September 15, 2005; 65(18): 8359 - 8365. [Abstract] [Full Text] [PDF]

				O. Benny, M. Duvshani-Eshet, T. Cargioli, L. Bello, A. Bikfalvi, R. S. Carroll, and M. Machluf Continuous Delivery of Endogenous Inhibitors from Poly(Lactic-Co-Glycolic Acid) Polymeric Microspheres Inhibits Glioma Tumor Growth Clin. Cancer Res., January 15, 2005; 11(2): 768 - 776. [Abstract] [Full Text] [PDF]

				L. Bello, V. Lucini, F. Costa, M. Pluderi, C. Giussani, F. Acerbi, G. Carrabba, M. Pannacci, D. Caronzolo, S. Grosso, et al. Combinatorial Administration of Molecules That Simultaneously Inhibit Angiogenesis and Invasion Leads to Increased Therapeutic Efficacy in Mouse Models of Malignant Glioma Clin. Cancer Res., July 1, 2004; 10(13): 4527 - 4537. [Abstract] [Full Text] [PDF]

				N. O. Schmidt, M. Ziu, G. Carrabba, C. Giussani, L. Bello, Y. Sun, K. Schmidt, M. Albert, P. Mcl. Black, and R. S. Carroll Antiangiogenic Therapy by Local Intracerebral Microinfusion Improves Treatment Efficiency and Survival in an Orthotopic Human Glioblastoma Model Clin. Cancer Res., February 15, 2004; 10(4): 1255 - 1262. [Abstract] [Full Text] [PDF]

				L. Zilberberg, S. Shinkaruk, O. Lequin, B. Rousseau, M. Hagedorn, F. Costa, D. Caronzolo, M. Balke, X. Canron, O. Convert, et al. Structure and Inhibitory Effects on Angiogenesis and Tumor Development of a New Vascular Endothelial Growth Inhibitor J. Biol. Chem., September 12, 2003; 278(37): 35564 - 35573. [Abstract] [Full Text] [PDF]

				C. Giussani, G. Carrabba, M. Pluderi, V. Lucini, M. Pannacci, D. Caronzolo, F. Costa, M. Minotti, G. Tomei, R. Villani, et al. Local Intracerebral Delivery of Endogenous Inhibitors by Osmotic Minipumps Effectively Suppresses Glioma Growth in Vivo Cancer Res., May 15, 2003; 63(10): 2499 - 2505. [Abstract] [Full Text] [PDF]