Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy

Tumati,Vasu; Mathur,Sanjeev; Song,Kwang; Hsieh,Jer-Tsong; Zhao,Dawen; Takahashi,Masaya; Dobin,Timothy; Gandee,Leah; Solberg,Timothy   D.; Habib,Amyn  A.; Saha,Debabrata

doi:10.3892/ijo.2013.1858

Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy

Authors:
- Vasu Tumati
- Sanjeev Mathur
- Kwang Song
- Jer-Tsong Hsieh
- Dawen Zhao
- Masaya Takahashi
- Timothy Dobin
- Leah Gandee
- Timothy D. Solberg
- Amyn A. Habib
- Debabrata Saha
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Affiliations: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA, Uniformed Services University of Health Sciences (USUHS), Bethesda, MD 20814, USA, Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA, Department of Advanced Imaging, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Published online on: March 19, 2013 https://doi.org/10.3892/ijo.2013.1858
Pages: 1613-1619

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Abstract

The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.

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