Survivin-associated adaptive response in radiation therapy

David J. Grdina, Jeffrey S. Murley, Richard C. Miller, Helena J. Mauceri, Harold G. Sutton, Jian-Jian Li, Gayle E. Woloschak, Ralph R. Weichselbaum

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Adaptive responses can be induced in cells by very low doses of ionizing radiation resulting in an enhanced resistance to much larger exposures. The inhibitor of apoptosis protein, survivin, has been implicated in many adaptive responses to cellular stress. Computerized axial tomography used in image-guided radiotherapy to position and monitor tumor response uses very low radiation doses ranging from 0.5 to 100 mGy. We investigated the ability of these very low radiation doses administered along with two 2 Gy doses separated by 24 hours, a standard conventional radiotherapy dosing schedule, to initiate adaptive responses resulting in the elevation of radiation resistance in exposed cells. Human colon carcinoma (RKO36), mouse sarcoma (SA-NH), along with transformed mouse embryo fibroblasts, wild type or cells lacking functional tumor necrosis factor receptors 1 and 2 were used to assess their relative ability to express an adaptive response when grown either to confluence in vitro or as tumors in the flank of C57BL/6 mice. The survival of each of these cells was elevated from 5% to 20% (P ≤ 0.05) as compared to cells not receiving a 100 mGy or lesser dose. In addition, the cells exposed to 100 mGy exhibited elevations in survivin levels, reductions in apoptosis frequencies, and loss of an adaptive response if transfected with survivin siRNA. This survivinmediated adaptive response has the potential for affecting outcomes if regularly induced throughout a course of image guided radiation therapy.

Original languageEnglish (US)
Pages (from-to)4418-4428
Number of pages11
JournalCancer Research
Volume73
Issue number14
DOIs
StatePublished - Jul 15 2013

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Radiotherapy
Image-Guided Radiotherapy
Radiation
Receptors, Tumor Necrosis Factor, Type II
Inhibitor of Apoptosis Proteins
Ionizing Radiation
Inbred C57BL Mouse
Sarcoma
Small Interfering RNA
Neoplasms
Cell Survival
Appointments and Schedules
Colon
Embryonic Structures
Fibroblasts
Tomography
Apoptosis
Carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Grdina, D. J., Murley, J. S., Miller, R. C., Mauceri, H. J., Sutton, H. G., Li, J-J., ... Weichselbaum, R. R. (2013). Survivin-associated adaptive response in radiation therapy. Cancer Research, 73(14), 4418-4428. https://doi.org/10.1158/0008-5472.CAN-12-4640

Survivin-associated adaptive response in radiation therapy. / Grdina, David J.; Murley, Jeffrey S.; Miller, Richard C.; Mauceri, Helena J.; Sutton, Harold G.; Li, Jian-Jian; Woloschak, Gayle E.; Weichselbaum, Ralph R.

In: Cancer Research, Vol. 73, No. 14, 15.07.2013, p. 4418-4428.

Research output: Contribution to journalArticle

Grdina, DJ, Murley, JS, Miller, RC, Mauceri, HJ, Sutton, HG, Li, J-J, Woloschak, GE & Weichselbaum, RR 2013, 'Survivin-associated adaptive response in radiation therapy', Cancer Research, vol. 73, no. 14, pp. 4418-4428. https://doi.org/10.1158/0008-5472.CAN-12-4640
Grdina DJ, Murley JS, Miller RC, Mauceri HJ, Sutton HG, Li J-J et al. Survivin-associated adaptive response in radiation therapy. Cancer Research. 2013 Jul 15;73(14):4418-4428. https://doi.org/10.1158/0008-5472.CAN-12-4640
Grdina, David J. ; Murley, Jeffrey S. ; Miller, Richard C. ; Mauceri, Helena J. ; Sutton, Harold G. ; Li, Jian-Jian ; Woloschak, Gayle E. ; Weichselbaum, Ralph R. / Survivin-associated adaptive response in radiation therapy. In: Cancer Research. 2013 ; Vol. 73, No. 14. pp. 4418-4428.
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