DOI: 10.1073/pnas.030545097. Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy

Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy

10.1073/pnas.030545097

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent endogenous activator of the cell death pathway and functions by activating the cell surface death receptors 4 and 5 (DR4 and DR5). TRAIL is nontoxicin vivoand preferentially kills neoplastically transformed cells over normal cells by an undefined mechanism. Radiotherapy is a common treatment for breast cancer as well as many other cancers. Here we demonstrate that ionizing radiation can sensitize breast carcinoma cells to TRAIL-induced apoptosis. This synergistic effect is p53-dependent and may be the result of radiation-induced up-regulation of the TRAIL-receptor DR5. Importantly, TRAIL and ionizing radiation have a synergistic effect in the regression of established breast cancer xenografts. Changes in tumor cellularity and extracellular space were monitoredin vivoby diffusion-weighted magnetic resonance imaging (diffusion MRI), a noninvasive technique to produce quantitative images of the apparent mobility of water within a tissue. Increased water mobility was observed in combined TRAIL- and radiation-treated tumors but not in tumors treated with TRAIL or radiation alone. Histological analysis confirmed the loss of cellularity and increased numbers of apoptotic cells in TRAIL- and radiation-treated tumors. Taken together, our results provide support for combining radiation with TRAIL to improve tumor eradication and suggest that efficacy of apoptosis-inducing cancer therapies may be monitored noninvasively, using diffusion MRI.

Bibliography

Chinnaiyan, A. M., Prasad, U., Shankar, S., Hamstra, D. A., Shanaiah, M., Chenevert, T. L., Ross, B. D., & Rehemtulla, A. (2000). Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. Proceedings of the National Academy of Sciences, 97(4), 1754â1759.

Authors 8

Arul M. Chinnaiyan (first)
Uttara Prasad (additional)
Sunita Shankar (additional)
Daniel A. Hamstra (additional)
Murthy Shanaiah (additional)
Thomas L. Chenevert (additional)
Brian D. Ross (additional)
Alnawaz Rehemtulla (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:14 a.m.)
Indexed	3 weeks, 5 days ago (Aug. 6, 2025, 9:06 a.m.)
Issued	25 years, 6 months ago (Feb. 4, 2000)
Published	25 years, 6 months ago (Feb. 4, 2000)
Published Online	25 years, 6 months ago (Feb. 4, 2000)
Published Print	25 years, 6 months ago (Feb. 15, 2000)

Funders 0

None

BibTeX

@article{Chinnaiyan_2000, title={Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.030545097}, DOI={10.1073/pnas.030545097}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Chinnaiyan, Arul M. and Prasad, Uttara and Shankar, Sunita and Hamstra, Daniel A. and Shanaiah, Murthy and Chenevert, Thomas L. and Ross, Brian D. and Rehemtulla, Alnawaz}, year={2000}, month=feb, pages={1754–1759} }

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