Local non-viral gene delivery of apoptin delays the onset of paresis in an experimental model of intramedullary spinal cord tumor

W. A. Pennant, S. An, S. J. Gwak, S. Choi, D. T. Banh, A. B.L. Nguyen, H. Y. Song, Y. Ha, J. S. Park

Research output: Contribution to journalArticle

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Abstract

Objective:The objective of this study is to evaluate the safety and efficacy of a tumor-specific apoptosis-inducing gene, apoptin, as delivered by the non-viral carrier, PAM-RG4, in an animal model of spinal cord tumor.Methods:Male Sprague-Dawley rats were given a 2.5-μl intramedullary injection of C6 glioma (100 000) cells and randomized into three groups (day 0). On day 5, animals received a 7.5-μl intramedullary injection of Dulbecco's modified Eagle's medium (Group 1; n=7), PAM-RG4/control gene polyplex (Group 2; n=7), or PAM-RG4/apoptin gene polyplex (Group 3; n=8). Hindlimb functional strength was assessed every other day for the duration of the study. The spinal cords of killed animals were collected and hematoxylin-eosin stained.Results:Following treatment, animals that received apoptin had significantly higher mean functional hindlimb scores than those of sham control animals, showing a level of preserved hindlimb function throughout the study. In addition, Group 1 (sham control) and Group 2 (control gene) animals had median survival scores lower than those of animals receiving apoptin. Histopathological analysis showed marked retardation of tumor progression in apoptin-treated animals compared with sham controls.Conclusion:Our study suggests that apoptin is safe for use in the mammalian spinal cord as well as effective in slowing the progression of tumor growth in the spinal cord. The significant slowing of tumor progression, as manifested by the preserved hindlimb function, coupled with the reduction in tumor volume, shows local non-viral delivery of apoptin could serve as an emerging therapy for the treatment of intramedullary spinal cord tumors.

Original languageEnglish
Pages (from-to)3-8
Number of pages6
JournalSpinal Cord
Volume52
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

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Spinal Cord Neoplasms
Paresis
Theoretical Models
Hindlimb
Genes
Spinal Cord
Neoplasms
Eagles
Injections
Hematoxylin
Eosine Yellowish-(YS)
Tumor Burden
Glioma
Sprague Dawley Rats
Therapeutics
Animal Models
Apoptosis
Safety
Control Groups
Growth

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Pennant, W. A., An, S., Gwak, S. J., Choi, S., Banh, D. T., Nguyen, A. B. L., ... Park, J. S. (2014). Local non-viral gene delivery of apoptin delays the onset of paresis in an experimental model of intramedullary spinal cord tumor. Spinal Cord, 52(1), 3-8. https://doi.org/10.1038/sc.2013.106
Pennant, W. A. ; An, S. ; Gwak, S. J. ; Choi, S. ; Banh, D. T. ; Nguyen, A. B.L. ; Song, H. Y. ; Ha, Y. ; Park, J. S. / Local non-viral gene delivery of apoptin delays the onset of paresis in an experimental model of intramedullary spinal cord tumor. In: Spinal Cord. 2014 ; Vol. 52, No. 1. pp. 3-8.
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abstract = "Objective:The objective of this study is to evaluate the safety and efficacy of a tumor-specific apoptosis-inducing gene, apoptin, as delivered by the non-viral carrier, PAM-RG4, in an animal model of spinal cord tumor.Methods:Male Sprague-Dawley rats were given a 2.5-μl intramedullary injection of C6 glioma (100 000) cells and randomized into three groups (day 0). On day 5, animals received a 7.5-μl intramedullary injection of Dulbecco's modified Eagle's medium (Group 1; n=7), PAM-RG4/control gene polyplex (Group 2; n=7), or PAM-RG4/apoptin gene polyplex (Group 3; n=8). Hindlimb functional strength was assessed every other day for the duration of the study. The spinal cords of killed animals were collected and hematoxylin-eosin stained.Results:Following treatment, animals that received apoptin had significantly higher mean functional hindlimb scores than those of sham control animals, showing a level of preserved hindlimb function throughout the study. In addition, Group 1 (sham control) and Group 2 (control gene) animals had median survival scores lower than those of animals receiving apoptin. Histopathological analysis showed marked retardation of tumor progression in apoptin-treated animals compared with sham controls.Conclusion:Our study suggests that apoptin is safe for use in the mammalian spinal cord as well as effective in slowing the progression of tumor growth in the spinal cord. The significant slowing of tumor progression, as manifested by the preserved hindlimb function, coupled with the reduction in tumor volume, shows local non-viral delivery of apoptin could serve as an emerging therapy for the treatment of intramedullary spinal cord tumors.",
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Local non-viral gene delivery of apoptin delays the onset of paresis in an experimental model of intramedullary spinal cord tumor. / Pennant, W. A.; An, S.; Gwak, S. J.; Choi, S.; Banh, D. T.; Nguyen, A. B.L.; Song, H. Y.; Ha, Y.; Park, J. S.

In: Spinal Cord, Vol. 52, No. 1, 01.01.2014, p. 3-8.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Local non-viral gene delivery of apoptin delays the onset of paresis in an experimental model of intramedullary spinal cord tumor

AU - Pennant, W. A.

AU - An, S.

AU - Gwak, S. J.

AU - Choi, S.

AU - Banh, D. T.

AU - Nguyen, A. B.L.

AU - Song, H. Y.

AU - Ha, Y.

AU - Park, J. S.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objective:The objective of this study is to evaluate the safety and efficacy of a tumor-specific apoptosis-inducing gene, apoptin, as delivered by the non-viral carrier, PAM-RG4, in an animal model of spinal cord tumor.Methods:Male Sprague-Dawley rats were given a 2.5-μl intramedullary injection of C6 glioma (100 000) cells and randomized into three groups (day 0). On day 5, animals received a 7.5-μl intramedullary injection of Dulbecco's modified Eagle's medium (Group 1; n=7), PAM-RG4/control gene polyplex (Group 2; n=7), or PAM-RG4/apoptin gene polyplex (Group 3; n=8). Hindlimb functional strength was assessed every other day for the duration of the study. The spinal cords of killed animals were collected and hematoxylin-eosin stained.Results:Following treatment, animals that received apoptin had significantly higher mean functional hindlimb scores than those of sham control animals, showing a level of preserved hindlimb function throughout the study. In addition, Group 1 (sham control) and Group 2 (control gene) animals had median survival scores lower than those of animals receiving apoptin. Histopathological analysis showed marked retardation of tumor progression in apoptin-treated animals compared with sham controls.Conclusion:Our study suggests that apoptin is safe for use in the mammalian spinal cord as well as effective in slowing the progression of tumor growth in the spinal cord. The significant slowing of tumor progression, as manifested by the preserved hindlimb function, coupled with the reduction in tumor volume, shows local non-viral delivery of apoptin could serve as an emerging therapy for the treatment of intramedullary spinal cord tumors.

AB - Objective:The objective of this study is to evaluate the safety and efficacy of a tumor-specific apoptosis-inducing gene, apoptin, as delivered by the non-viral carrier, PAM-RG4, in an animal model of spinal cord tumor.Methods:Male Sprague-Dawley rats were given a 2.5-μl intramedullary injection of C6 glioma (100 000) cells and randomized into three groups (day 0). On day 5, animals received a 7.5-μl intramedullary injection of Dulbecco's modified Eagle's medium (Group 1; n=7), PAM-RG4/control gene polyplex (Group 2; n=7), or PAM-RG4/apoptin gene polyplex (Group 3; n=8). Hindlimb functional strength was assessed every other day for the duration of the study. The spinal cords of killed animals were collected and hematoxylin-eosin stained.Results:Following treatment, animals that received apoptin had significantly higher mean functional hindlimb scores than those of sham control animals, showing a level of preserved hindlimb function throughout the study. In addition, Group 1 (sham control) and Group 2 (control gene) animals had median survival scores lower than those of animals receiving apoptin. Histopathological analysis showed marked retardation of tumor progression in apoptin-treated animals compared with sham controls.Conclusion:Our study suggests that apoptin is safe for use in the mammalian spinal cord as well as effective in slowing the progression of tumor growth in the spinal cord. The significant slowing of tumor progression, as manifested by the preserved hindlimb function, coupled with the reduction in tumor volume, shows local non-viral delivery of apoptin could serve as an emerging therapy for the treatment of intramedullary spinal cord tumors.

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