Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria

Chetan Bettegowda; Long H. Dang; Ross Abrams; David L Huso; Larry Dillehay; Ian Cheong; Nishant Agrawal; Scott Borzillary; J. Michael McCaffery; E. Latice Watson; Kuo Shyan Lin; Fred Bunz; Kwamena Baidoo; Martin Pomper; Kenneth W. Kinzler; Bert Vogelstein; Shibin Zhou

doi:10.1073/pnas.2036598100

Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria

Chetan Bettegowda, Long H. Dang, Ross Abrams, David L Huso, Larry Dillehay, Ian Cheong, Nishant Agrawal, Scott Borzillary, J. Michael McCaffery, E. Latice Watson, Kuo Shyan Lin, Fred Bunz, Kwamena Baidoo, Martin Pomper, Kenneth W. Kinzler, Bert Vogelstein, Shibin Zhou

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Abstract

The low level of oxygenation within tumors is a major cause of radiation treatment failures. We theorized that anaerobic bacteria that can selectively destroy the hypoxic regions of tumors would enhance the effects of radiation. To test this hypothesis, we used spores of Clostridium novyi-NT to treat transplanted tumors in mice. The bacteria were found to markedly improve the efficacy of radiotherapy in several of the mouse models tested. Enhancement was noted with external beam radiation derived from a Cs-137 source, systemic radioimmunotherapy with an I-131-conjugated monoclonal antibody, and a previously undescribed form of experimental brachytherapy using plaques loaded with 1-125 seeds. C. novyi-NT spores added little toxicity to the radiotherapeutic regimens, and the combination resulted in long-term remissions in a significant fraction of animals.

Original language	English (US)
Pages (from-to)	15083-15088
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	100
Issue number	25
DOIs	https://doi.org/10.1073/pnas.2036598100
State	Published - Dec 9 2003

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Bettegowda, C., Dang, L. H., Abrams, R., Huso, D. L., Dillehay, L., Cheong, I., Agrawal, N., Borzillary, S., McCaffery, J. M., Watson, E. L., Lin, K. S., Bunz, F., Baidoo, K., Pomper, M., Kinzler, K. W., Vogelstein, B., & Zhou, S. (2003). Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria. Proceedings of the National Academy of Sciences of the United States of America, 100(25), 15083-15088. https://doi.org/10.1073/pnas.2036598100

Bettegowda, C, Dang, LH, Abrams, R, Huso, DL, Dillehay, L, Cheong, I, Agrawal, N, Borzillary, S, McCaffery, JM, Watson, EL, Lin, KS, Bunz, F, Baidoo, K, Pomper, M, Kinzler, KW , Vogelstein, B & Zhou, S 2003, 'Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 25, pp. 15083-15088. https://doi.org/10.1073/pnas.2036598100

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abstract = "The low level of oxygenation within tumors is a major cause of radiation treatment failures. We theorized that anaerobic bacteria that can selectively destroy the hypoxic regions of tumors would enhance the effects of radiation. To test this hypothesis, we used spores of Clostridium novyi-NT to treat transplanted tumors in mice. The bacteria were found to markedly improve the efficacy of radiotherapy in several of the mouse models tested. Enhancement was noted with external beam radiation derived from a Cs-137 source, systemic radioimmunotherapy with an I-131-conjugated monoclonal antibody, and a previously undescribed form of experimental brachytherapy using plaques loaded with 1-125 seeds. C. novyi-NT spores added little toxicity to the radiotherapeutic regimens, and the combination resulted in long-term remissions in a significant fraction of animals.",

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AU - Cheong, Ian

AU - Agrawal, Nishant

AU - Borzillary, Scott

AU - McCaffery, J. Michael

AU - Watson, E. Latice

AU - Lin, Kuo Shyan

AU - Bunz, Fred

AU - Baidoo, Kwamena

AU - Pomper, Martin

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Zhou, Shibin

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Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria

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