TNF-α gene and proton radiotherapy in an orthotopic brain tumor model

  • Authors:
    • D. S. Gridley
    • J. R. Baer
    • J. D. Cao
    • G. M. Miller
    • D. W. Kim
    • T. M. Timiryasova
    • I. Fodor
    • J. M. Slater
  • View Affiliations

  • Published online on: August 1, 2002     https://doi.org/10.3892/ijo.21.2.251
  • Pages: 251-259
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Abstract

The major goal of this study was to evaluate the safety and efficacy of TNF-α gene therapy (pGL1-TNF-α) in combination with proton radiation in an orthotopic brain tumor model. C6 glioma cells were implanted into the left hemibrain of athymic rats (day 0). On day 5, pGL1-TNF-α (19 μg/10 μl) was injected into the same site; appropriate control groups were included. Proton irradiation (10 Gy, single fraction) was performed 18-20 h thereafter and, on day 10, a portion of animals from each group was assayed. Nearly all tumor-bearing groups had lower body mass compared to those without tumor; brain mass was somewhat increased with plasmid (pGL1-TNF-α or pWS4) injection (p<0.05). Histopathological analysis of brain sections revealed that rats receiving pGL1-TNF-α/proton irradiation had the smallest tumors and lowest number of mitotic tumor cells, although survival time for animals kept long-term was not significantly prolonged. A decline in leukocyte populations was noted with combination treatment compared to controls (p<0.05), but no differences were found compared to groups receiving each modality alone. Based on DNA synthesis, the pGL1-TNF-α/proton irradiated group had the highest levels of leukocyte activation. The highest percentage of lymphocytes expressing the CD71 activation marker occurred with pGL1-TNF-α, whereas the proton-irradiated group had the highest percentage of activated NK cells (NK1.1+/CD71+). No significant differences were found in erythrocyte and thrombocyte numbers, hemoglobin, and hematocrit. Overall, the data indicate that pGL1-TNF-α/proton treatment results in a measurable antitumor effect and is safe under the conditions used.

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August 2002
Volume 21 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Gridley DS, Baer JR, Cao JD, Miller GM, Kim DW, Timiryasova TM, Fodor I and Slater JM: TNF-α gene and proton radiotherapy in an orthotopic brain tumor model. Int J Oncol 21: 251-259, 2002
APA
Gridley, D.S., Baer, J.R., Cao, J.D., Miller, G.M., Kim, D.W., Timiryasova, T.M. ... Slater, J.M. (2002). TNF-α gene and proton radiotherapy in an orthotopic brain tumor model. International Journal of Oncology, 21, 251-259. https://doi.org/10.3892/ijo.21.2.251
MLA
Gridley, D. S., Baer, J. R., Cao, J. D., Miller, G. M., Kim, D. W., Timiryasova, T. M., Fodor, I., Slater, J. M."TNF-α gene and proton radiotherapy in an orthotopic brain tumor model". International Journal of Oncology 21.2 (2002): 251-259.
Chicago
Gridley, D. S., Baer, J. R., Cao, J. D., Miller, G. M., Kim, D. W., Timiryasova, T. M., Fodor, I., Slater, J. M."TNF-α gene and proton radiotherapy in an orthotopic brain tumor model". International Journal of Oncology 21, no. 2 (2002): 251-259. https://doi.org/10.3892/ijo.21.2.251