Continuous local delivery of interferon-β stabilizes tumor vasculature in an orthotopic glioblastoma xenograft resection model

Jason W. Denbo, Regan Williams, W. Shannon Orr, Thomas L. Sims, Catherine Y. Ng, Junfang Zhou, Yunyu Spence, Christopher L. Morton, Amit C. Nathwani, Christopher Duntsch, Lawrence Pfeffer, Andrew M. Davidoff

Research output: Contribution to journalArticle

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Abstract

Background: High-grade glioblastomas have immature, leaky tumor blood vessels that impede the efficacy of adjuvant therapy. We assessed the ability of human interferon (hIFN)-β delivered locally via gene transfer to effect vascular stabilization in an orthotopic model of glioblastoma xenograft resection. Methods: Xenografts were established by injecting 3 grade IV glioblastoma cell lines (GBM6-luc, MT330-luc, and SJG2-luc) into the cerebral cortex of nude rats. Tumors underwent subtotal resection, and then had gel foam containing an adeno-associated virus vector encoding either hIFN-β or green fluorescence protein (control) placed in the resection cavity. The primary endpoint was stabilization of tumor vasculature, as evidenced by CD34, α-SMA, and CA IX staining. Overall survival was a secondary endpoint. Results: hIFN-β treatment altered the tumor vasculature of GBM6-luc and SJG2-luc xenografts, decreasing the density of endothelial cells, stabilizing vessels with pericytes, and decreasing tumor hypoxia. The mean survival for rats with these neoplasms was not improved, however. In rats with MT330-luc xenografts, hIFN-β resulted in tumor regression with a 6-month survival of 55% (INF-β group) and 9% (control group). Conclusion: The use of AAV hIFN-β in our orthotopic model of glioblastoma resection stabilized tumor vasculature and improved survival in rats with MT330 xenografts.

Original languageEnglish (US)
Pages (from-to)497-504
Number of pages8
JournalSurgery
Volume150
Issue number3
DOIs
StatePublished - Sep 1 2011

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Glioblastoma
Heterografts
Interferons
Neoplasms
Survival
Nude Rats
Vascular Tissue Neoplasms
Pericytes
Dependovirus
Cerebral Cortex
Blood Vessels
Endothelial Cells
Fluorescence
Gels
Staining and Labeling
Cell Line
Control Groups
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Continuous local delivery of interferon-β stabilizes tumor vasculature in an orthotopic glioblastoma xenograft resection model. / Denbo, Jason W.; Williams, Regan; Orr, W. Shannon; Sims, Thomas L.; Ng, Catherine Y.; Zhou, Junfang; Spence, Yunyu; Morton, Christopher L.; Nathwani, Amit C.; Duntsch, Christopher; Pfeffer, Lawrence; Davidoff, Andrew M.

In: Surgery, Vol. 150, No. 3, 01.09.2011, p. 497-504.

Research output: Contribution to journalArticle

Denbo, JW, Williams, R, Orr, WS, Sims, TL, Ng, CY, Zhou, J, Spence, Y, Morton, CL, Nathwani, AC, Duntsch, C, Pfeffer, L & Davidoff, AM 2011, 'Continuous local delivery of interferon-β stabilizes tumor vasculature in an orthotopic glioblastoma xenograft resection model', Surgery, vol. 150, no. 3, pp. 497-504. https://doi.org/10.1016/j.surg.2011.07.044
Denbo, Jason W. ; Williams, Regan ; Orr, W. Shannon ; Sims, Thomas L. ; Ng, Catherine Y. ; Zhou, Junfang ; Spence, Yunyu ; Morton, Christopher L. ; Nathwani, Amit C. ; Duntsch, Christopher ; Pfeffer, Lawrence ; Davidoff, Andrew M. / Continuous local delivery of interferon-β stabilizes tumor vasculature in an orthotopic glioblastoma xenograft resection model. In: Surgery. 2011 ; Vol. 150, No. 3. pp. 497-504.
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abstract = "Background: High-grade glioblastomas have immature, leaky tumor blood vessels that impede the efficacy of adjuvant therapy. We assessed the ability of human interferon (hIFN)-β delivered locally via gene transfer to effect vascular stabilization in an orthotopic model of glioblastoma xenograft resection. Methods: Xenografts were established by injecting 3 grade IV glioblastoma cell lines (GBM6-luc, MT330-luc, and SJG2-luc) into the cerebral cortex of nude rats. Tumors underwent subtotal resection, and then had gel foam containing an adeno-associated virus vector encoding either hIFN-β or green fluorescence protein (control) placed in the resection cavity. The primary endpoint was stabilization of tumor vasculature, as evidenced by CD34, α-SMA, and CA IX staining. Overall survival was a secondary endpoint. Results: hIFN-β treatment altered the tumor vasculature of GBM6-luc and SJG2-luc xenografts, decreasing the density of endothelial cells, stabilizing vessels with pericytes, and decreasing tumor hypoxia. The mean survival for rats with these neoplasms was not improved, however. In rats with MT330-luc xenografts, hIFN-β resulted in tumor regression with a 6-month survival of 55{\%} (INF-β group) and 9{\%} (control group). Conclusion: The use of AAV hIFN-β in our orthotopic model of glioblastoma resection stabilized tumor vasculature and improved survival in rats with MT330 xenografts.",
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AU - Ng, Catherine Y.

AU - Zhou, Junfang

AU - Spence, Yunyu

AU - Morton, Christopher L.

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AU - Pfeffer, Lawrence

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N2 - Background: High-grade glioblastomas have immature, leaky tumor blood vessels that impede the efficacy of adjuvant therapy. We assessed the ability of human interferon (hIFN)-β delivered locally via gene transfer to effect vascular stabilization in an orthotopic model of glioblastoma xenograft resection. Methods: Xenografts were established by injecting 3 grade IV glioblastoma cell lines (GBM6-luc, MT330-luc, and SJG2-luc) into the cerebral cortex of nude rats. Tumors underwent subtotal resection, and then had gel foam containing an adeno-associated virus vector encoding either hIFN-β or green fluorescence protein (control) placed in the resection cavity. The primary endpoint was stabilization of tumor vasculature, as evidenced by CD34, α-SMA, and CA IX staining. Overall survival was a secondary endpoint. Results: hIFN-β treatment altered the tumor vasculature of GBM6-luc and SJG2-luc xenografts, decreasing the density of endothelial cells, stabilizing vessels with pericytes, and decreasing tumor hypoxia. The mean survival for rats with these neoplasms was not improved, however. In rats with MT330-luc xenografts, hIFN-β resulted in tumor regression with a 6-month survival of 55% (INF-β group) and 9% (control group). Conclusion: The use of AAV hIFN-β in our orthotopic model of glioblastoma resection stabilized tumor vasculature and improved survival in rats with MT330 xenografts.

AB - Background: High-grade glioblastomas have immature, leaky tumor blood vessels that impede the efficacy of adjuvant therapy. We assessed the ability of human interferon (hIFN)-β delivered locally via gene transfer to effect vascular stabilization in an orthotopic model of glioblastoma xenograft resection. Methods: Xenografts were established by injecting 3 grade IV glioblastoma cell lines (GBM6-luc, MT330-luc, and SJG2-luc) into the cerebral cortex of nude rats. Tumors underwent subtotal resection, and then had gel foam containing an adeno-associated virus vector encoding either hIFN-β or green fluorescence protein (control) placed in the resection cavity. The primary endpoint was stabilization of tumor vasculature, as evidenced by CD34, α-SMA, and CA IX staining. Overall survival was a secondary endpoint. Results: hIFN-β treatment altered the tumor vasculature of GBM6-luc and SJG2-luc xenografts, decreasing the density of endothelial cells, stabilizing vessels with pericytes, and decreasing tumor hypoxia. The mean survival for rats with these neoplasms was not improved, however. In rats with MT330-luc xenografts, hIFN-β resulted in tumor regression with a 6-month survival of 55% (INF-β group) and 9% (control group). Conclusion: The use of AAV hIFN-β in our orthotopic model of glioblastoma resection stabilized tumor vasculature and improved survival in rats with MT330 xenografts.

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