Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation
Autor: | Xizhe Wang, N. Patrik Brodin, Maria Maryanovich, Kara L. Watts, Ali H. Zahalka, Chandan Guha, Sandra Pinho, Paul S. Frenette |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine medicine.drug_class medicine.medical_treatment Science Urogenital models Contrast Media Radiosurgery Article Muscle hypertrophy Androgen deprivation therapy Mice 03 medical and health sciences Prostate cancer 0302 clinical medicine Prostate medicine Animals Humans Testosterone External beam radiotherapy Cell Proliferation Multidisciplinary business.industry Disease Management Prostatic Neoplasms Androgen medicine.disease Urogenital diseases Experimental models of disease Radiation therapy Disease Models Animal 030104 developmental biology medicine.anatomical_structure Preclinical research 030220 oncology & carcinogenesis Cancer research Medicine Tomography X-Ray Computed business Radiotherapy Image-Guided |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-7 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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