Intra-arterial bevacizumab with blood brain barrier disruption in a glioblastoma xenograft model

Jan Karl Burkhardt, Alejandro Santillan, Christoph P. Hofstetter, Paul Christos, Nick Berry, Benjamin J. Shin, Conor P. Foley, Demirkan B. Gürsel, Douglas J. Ballon, Y. Pierre Gobin, John A. Boockvar

Research output: Contribution to journalArticle

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Abstract

Purpose: In this study we investigated the treatment response and survival of intra-arterial (IA) compared to intra-peritoneal (IP) delivery of bevacizumab (BV) in a glioblastoma (GBM) xenograft mouse model. Methods: 3×105 U87-Luc cells were stereotactically implanted into the cortex of 35 nude mice and grouped for treatment (n = 7 in each group): IP saline (group 1), single IP BV (group 2), biweekly IP BV for 3 weeks (group 3), single intra-arterial (IA) BV alone (group 4) and single IA BV with blood brain barrier disruption (BBBD) (group 5). Tumor growth was monitored every 3 to 4 days using bioluminescence imaging (BLI) and survival was analyzed by the Kaplan Meier method. Tumor tissue was analyzed using H&E staining and immunohistochemistry. Results: Based on BLI, BV treated mice showed a delayed tumor growth over time compared to control. Kaplan Meier analysis demonstrated a median survival time of 28 days for group 1, 31 days for group 2, 34 days for group 3, 36 days for group 4 and 36 days for group 5 (p<0.0001). Mice treated with repeated IP BV (p = 0.003) or single IA BV with (p = 0.015) or without (p = 0.005) BBBD showed a significant survival benefit compared to single IP BV treated mice. Post mortem analysis revealed a histological pattern with a more discontinuous border between tumor and mouse brain in the repeated IP BV and single IA BV with or without BBBD treated mice compared to the sharply defined edges of single IP BV treated and control mice. Conclusions: In this study we showed a significant survival benefit of repeated IP BV and single IA BV with or without BBBD treated mice compared to single IP BV treated and control mice in a U87 xenograft model.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalJournal of Experimental Therapeutics and Oncology
Volume10
Issue number1
StatePublished - Aug 3 2012

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Glioblastoma
Blood-Brain Barrier
Heterografts
Bevacizumab
Neoplasms
Kaplan-Meier Estimate
Growth
Nude Mice
Brain Neoplasms

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Cancer Research

Cite this

Burkhardt, J. K., Santillan, A., Hofstetter, C. P., Christos, P., Berry, N., Shin, B. J., ... Boockvar, J. A. (2012). Intra-arterial bevacizumab with blood brain barrier disruption in a glioblastoma xenograft model. Journal of Experimental Therapeutics and Oncology, 10(1), 31-37.
Burkhardt, Jan Karl ; Santillan, Alejandro ; Hofstetter, Christoph P. ; Christos, Paul ; Berry, Nick ; Shin, Benjamin J. ; Foley, Conor P. ; Gürsel, Demirkan B. ; Ballon, Douglas J. ; Gobin, Y. Pierre ; Boockvar, John A. / Intra-arterial bevacizumab with blood brain barrier disruption in a glioblastoma xenograft model. In: Journal of Experimental Therapeutics and Oncology. 2012 ; Vol. 10, No. 1. pp. 31-37.
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abstract = "Purpose: In this study we investigated the treatment response and survival of intra-arterial (IA) compared to intra-peritoneal (IP) delivery of bevacizumab (BV) in a glioblastoma (GBM) xenograft mouse model. Methods: 3×105 U87-Luc cells were stereotactically implanted into the cortex of 35 nude mice and grouped for treatment (n = 7 in each group): IP saline (group 1), single IP BV (group 2), biweekly IP BV for 3 weeks (group 3), single intra-arterial (IA) BV alone (group 4) and single IA BV with blood brain barrier disruption (BBBD) (group 5). Tumor growth was monitored every 3 to 4 days using bioluminescence imaging (BLI) and survival was analyzed by the Kaplan Meier method. Tumor tissue was analyzed using H&E staining and immunohistochemistry. Results: Based on BLI, BV treated mice showed a delayed tumor growth over time compared to control. Kaplan Meier analysis demonstrated a median survival time of 28 days for group 1, 31 days for group 2, 34 days for group 3, 36 days for group 4 and 36 days for group 5 (p<0.0001). Mice treated with repeated IP BV (p = 0.003) or single IA BV with (p = 0.015) or without (p = 0.005) BBBD showed a significant survival benefit compared to single IP BV treated mice. Post mortem analysis revealed a histological pattern with a more discontinuous border between tumor and mouse brain in the repeated IP BV and single IA BV with or without BBBD treated mice compared to the sharply defined edges of single IP BV treated and control mice. Conclusions: In this study we showed a significant survival benefit of repeated IP BV and single IA BV with or without BBBD treated mice compared to single IP BV treated and control mice in a U87 xenograft model.",
author = "Burkhardt, {Jan Karl} and Alejandro Santillan and Hofstetter, {Christoph P.} and Paul Christos and Nick Berry and Shin, {Benjamin J.} and Foley, {Conor P.} and G{\"u}rsel, {Demirkan B.} and Ballon, {Douglas J.} and Gobin, {Y. Pierre} and Boockvar, {John A.}",
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Burkhardt, JK, Santillan, A, Hofstetter, CP, Christos, P, Berry, N, Shin, BJ, Foley, CP, Gürsel, DB, Ballon, DJ, Gobin, YP & Boockvar, JA 2012, 'Intra-arterial bevacizumab with blood brain barrier disruption in a glioblastoma xenograft model', Journal of Experimental Therapeutics and Oncology, vol. 10, no. 1, pp. 31-37.

Intra-arterial bevacizumab with blood brain barrier disruption in a glioblastoma xenograft model. / Burkhardt, Jan Karl; Santillan, Alejandro; Hofstetter, Christoph P.; Christos, Paul; Berry, Nick; Shin, Benjamin J.; Foley, Conor P.; Gürsel, Demirkan B.; Ballon, Douglas J.; Gobin, Y. Pierre; Boockvar, John A.

In: Journal of Experimental Therapeutics and Oncology, Vol. 10, No. 1, 03.08.2012, p. 31-37.

Research output: Contribution to journalArticle

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T1 - Intra-arterial bevacizumab with blood brain barrier disruption in a glioblastoma xenograft model

AU - Burkhardt, Jan Karl

AU - Santillan, Alejandro

AU - Hofstetter, Christoph P.

AU - Christos, Paul

AU - Berry, Nick

AU - Shin, Benjamin J.

AU - Foley, Conor P.

AU - Gürsel, Demirkan B.

AU - Ballon, Douglas J.

AU - Gobin, Y. Pierre

AU - Boockvar, John A.

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Y1 - 2012/8/3

N2 - Purpose: In this study we investigated the treatment response and survival of intra-arterial (IA) compared to intra-peritoneal (IP) delivery of bevacizumab (BV) in a glioblastoma (GBM) xenograft mouse model. Methods: 3×105 U87-Luc cells were stereotactically implanted into the cortex of 35 nude mice and grouped for treatment (n = 7 in each group): IP saline (group 1), single IP BV (group 2), biweekly IP BV for 3 weeks (group 3), single intra-arterial (IA) BV alone (group 4) and single IA BV with blood brain barrier disruption (BBBD) (group 5). Tumor growth was monitored every 3 to 4 days using bioluminescence imaging (BLI) and survival was analyzed by the Kaplan Meier method. Tumor tissue was analyzed using H&E staining and immunohistochemistry. Results: Based on BLI, BV treated mice showed a delayed tumor growth over time compared to control. Kaplan Meier analysis demonstrated a median survival time of 28 days for group 1, 31 days for group 2, 34 days for group 3, 36 days for group 4 and 36 days for group 5 (p<0.0001). Mice treated with repeated IP BV (p = 0.003) or single IA BV with (p = 0.015) or without (p = 0.005) BBBD showed a significant survival benefit compared to single IP BV treated mice. Post mortem analysis revealed a histological pattern with a more discontinuous border between tumor and mouse brain in the repeated IP BV and single IA BV with or without BBBD treated mice compared to the sharply defined edges of single IP BV treated and control mice. Conclusions: In this study we showed a significant survival benefit of repeated IP BV and single IA BV with or without BBBD treated mice compared to single IP BV treated and control mice in a U87 xenograft model.

AB - Purpose: In this study we investigated the treatment response and survival of intra-arterial (IA) compared to intra-peritoneal (IP) delivery of bevacizumab (BV) in a glioblastoma (GBM) xenograft mouse model. Methods: 3×105 U87-Luc cells were stereotactically implanted into the cortex of 35 nude mice and grouped for treatment (n = 7 in each group): IP saline (group 1), single IP BV (group 2), biweekly IP BV for 3 weeks (group 3), single intra-arterial (IA) BV alone (group 4) and single IA BV with blood brain barrier disruption (BBBD) (group 5). Tumor growth was monitored every 3 to 4 days using bioluminescence imaging (BLI) and survival was analyzed by the Kaplan Meier method. Tumor tissue was analyzed using H&E staining and immunohistochemistry. Results: Based on BLI, BV treated mice showed a delayed tumor growth over time compared to control. Kaplan Meier analysis demonstrated a median survival time of 28 days for group 1, 31 days for group 2, 34 days for group 3, 36 days for group 4 and 36 days for group 5 (p<0.0001). Mice treated with repeated IP BV (p = 0.003) or single IA BV with (p = 0.015) or without (p = 0.005) BBBD showed a significant survival benefit compared to single IP BV treated mice. Post mortem analysis revealed a histological pattern with a more discontinuous border between tumor and mouse brain in the repeated IP BV and single IA BV with or without BBBD treated mice compared to the sharply defined edges of single IP BV treated and control mice. Conclusions: In this study we showed a significant survival benefit of repeated IP BV and single IA BV with or without BBBD treated mice compared to single IP BV treated and control mice in a U87 xenograft model.

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