title: Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy.
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.
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Vasu
authors.initials: V
authors.lastname: Tumati
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Mathur
authors.forename: Kwang
authors.initials: K
authors.lastname: Song
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.forename: Dawen
authors.initials: D
authors.lastname: Zhao
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.forename: Timothy
authors.initials: T
authors.lastname: Dobin
authors.forename: Leah
authors.initials: L
authors.lastname: Gandee
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Solberg
authors.forename: Amyn A
authors.initials: AA
authors.lastname: Habib
authors.forename: Debabrata
authors.initials: D
authors.lastname: Saha
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D061089:Radiotherapy, Image-Guided; D051381:Rats; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
chemical_list: C462952:DAB2IP protein, human; D020703:ras GTPase-Activating Proteins