Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation

Abstract The prostate is a hormone-responsive organ where testicular androgens drive the proliferation and survival of prostatic cells, ensuring the development and functioning of this gland throughout life. Androgen deprivation therapy leads to apoptosis of prostatic cells and organ regression, and...

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Autores principales:	Ali H. Zahalka, N. Patrik Brodin, Maria Maryanovich, Xizhe Wang, Kara L. Watts, Sandra Pinho, Chandan Guha, Paul S. Frenette
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d8d0c1c0ea7404b996afc6c0621714d
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spelling	oai:doaj.org-article:6d8d0c1c0ea7404b996afc6c0621714d2021-12-02T16:36:12ZUsing CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation10.1038/s41598-021-86067-82045-2322https://doaj.org/article/6d8d0c1c0ea7404b996afc6c0621714d2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86067-8https://doaj.org/toc/2045-2322Abstract The prostate is a hormone-responsive organ where testicular androgens drive the proliferation and survival of prostatic cells, ensuring the development and functioning of this gland throughout life. Androgen deprivation therapy leads to apoptosis of prostatic cells and organ regression, and is a cornerstone of prostate cancer and benign prostatic hypertrophy treatment. For several decades, androgen deprivation has been used as an adjuvant to external beam radiotherapy, however, emerging data suggests that the low rates of epithelial proliferation in the castrated prostate imparts radio-resistance. As proliferating cells exhibit increased sensitivity to radiation, we hypothesized that short bursts of synchronized epithelial proliferation, which can be achieved by exogeneous testosterone supplementation prior to targeted high-dose radiation, would maximize sustained prostate ablation, while minimizing damage to surrounding tissues. To test this hypothesis, we designed a novel computed-tomography (CT)-guided stereotactic prostate radiation therapy (CT-SPRT) technique to deliver a single high-dose 25 Gy fraction of X-ray radiation. Sustained prostatic cell ablation was assessed post CT-SPRT by measuring prostate weight, epithelial cell number, and relative contributions of luminal and basal epithelial populations in control and testosterone-pretreated glands. CT-SPRT was safely delivered with no observed damage to surrounding rectal and bladder tissues. Importantly, castrated mice that received a pulse of testosterone to induce synchronous cell proliferation prior to CT-SPRT exhibited significant sustained gland ablation compared to control mice. These results provide new insights in stereotactic radiotherapy sensitivity to maximize prostatic cell ablation and improve our understanding of prostate gland regeneration that can potentially lead to improved non-invasive therapies for benign prostatic hypertrophy and prostate cancer.Ali H. ZahalkaN. Patrik BrodinMaria MaryanovichXizhe WangKara L. WattsSandra PinhoChandan GuhaPaul S. FrenetteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ali H. Zahalka N. Patrik Brodin Maria Maryanovich Xizhe Wang Kara L. Watts Sandra Pinho Chandan Guha Paul S. Frenette Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation
description	Abstract The prostate is a hormone-responsive organ where testicular androgens drive the proliferation and survival of prostatic cells, ensuring the development and functioning of this gland throughout life. Androgen deprivation therapy leads to apoptosis of prostatic cells and organ regression, and is a cornerstone of prostate cancer and benign prostatic hypertrophy treatment. For several decades, androgen deprivation has been used as an adjuvant to external beam radiotherapy, however, emerging data suggests that the low rates of epithelial proliferation in the castrated prostate imparts radio-resistance. As proliferating cells exhibit increased sensitivity to radiation, we hypothesized that short bursts of synchronized epithelial proliferation, which can be achieved by exogeneous testosterone supplementation prior to targeted high-dose radiation, would maximize sustained prostate ablation, while minimizing damage to surrounding tissues. To test this hypothesis, we designed a novel computed-tomography (CT)-guided stereotactic prostate radiation therapy (CT-SPRT) technique to deliver a single high-dose 25 Gy fraction of X-ray radiation. Sustained prostatic cell ablation was assessed post CT-SPRT by measuring prostate weight, epithelial cell number, and relative contributions of luminal and basal epithelial populations in control and testosterone-pretreated glands. CT-SPRT was safely delivered with no observed damage to surrounding rectal and bladder tissues. Importantly, castrated mice that received a pulse of testosterone to induce synchronous cell proliferation prior to CT-SPRT exhibited significant sustained gland ablation compared to control mice. These results provide new insights in stereotactic radiotherapy sensitivity to maximize prostatic cell ablation and improve our understanding of prostate gland regeneration that can potentially lead to improved non-invasive therapies for benign prostatic hypertrophy and prostate cancer.
format	article
author	Ali H. Zahalka N. Patrik Brodin Maria Maryanovich Xizhe Wang Kara L. Watts Sandra Pinho Chandan Guha Paul S. Frenette
author_facet	Ali H. Zahalka N. Patrik Brodin Maria Maryanovich Xizhe Wang Kara L. Watts Sandra Pinho Chandan Guha Paul S. Frenette
author_sort	Ali H. Zahalka
title	Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation
title_short	Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation
title_full	Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation
title_fullStr	Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation
title_full_unstemmed	Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation
title_sort	using ct-guided stereotactic prostate radiation therapy (ct-sprt) to assess sustained murine prostate ablation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6d8d0c1c0ea7404b996afc6c0621714d
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Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation

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