Yusuke Aoki1,2,3, Noriyuki Masaki1,2, Yasunori Tome3, Yutaro Kubota1,2, Yasuyo Aoki1, Michael Bouvet2, Kotaro Nishida3, Robert M Hoffman4,2. 1. AntiCancer Inc, San Diego, CA, U.S.A. 2. Department of Surgery, University of California, San Diego, La Jolla, CA, U.S.A. 3. Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. 4. AntiCancer Inc, San Diego, CA, U.S.A.; yastome@med.u-ryukyu.ac.jp.
Abstract
BACKGROUND/AIM: Although the 5-year survival rate for localized prostate cancer is nearly 100%, prognosis for patients with metastases, of which the bone is the most common site, is poor. In order to evaluate efficacy of treatments against metastatic prostate cancer, experimental tibia-bone-metastasis mouse models of prostate cancer have been previously established. In the present study, we used a novel procedure for establishment of an experimental tibiabone metastasis mouse model, with human PC-3 prostate cancer expressing green fluorescent protein (GFP), that more closely matches prostate cancer growing in the bone. MATERIALS AND METHODS: PC-3 human prostate cancer cells, labeled with GFP, were initially subcutaneously injected into the flank of five male nude mice to obtain tumor tissues. Once the tumor tissue grew larger than 10 mm in diameter, the tumor tissue was harvested and minced into fragments of 1 mm3 A 1-mm hole was made in the proximal left tibia of eight male nude mice, using the tip of a 5-mm blade, and a tumor fragment was implanted into the hole for an exact fit. Tumor size was measured once a week, by non-invasive imaging of GFP fluorescence. The mice were sacrificed four weeks after tumor implantation. RESULTS: Tumors grew in 8 out of 8 mice (100%). All tumors were non-invasively detectable with GFP fluorescence, through the skin. Increased tumor growth in the tibia was observed every week. CONCLUSION: The establishment in the tibia of the novel experimental bone-metastatic mouse model of human prostate cancer enables facile screening, in a clinically-relevant system, of improved therapeutics for this recalcitrant disease.
BACKGROUND/AIM: Although the 5-year survival rate for localized prostate cancer is nearly 100%, prognosis for patients with metastases, of which the bone is the most common site, is poor. In order to evaluate efficacy of treatments against metastatic prostate cancer, experimental tibia-bone-metastasis mouse models of prostate cancer have been previously established. In the present study, we used a novel procedure for establishment of an experimental tibiabone metastasis mouse model, with human PC-3 prostate cancer expressing green fluorescent protein (GFP), that more closely matches prostate cancer growing in the bone. MATERIALS AND METHODS: PC-3 human prostate cancer cells, labeled with GFP, were initially subcutaneously injected into the flank of five male nude mice to obtain tumor tissues. Once the tumor tissue grew larger than 10 mm in diameter, the tumor tissue was harvested and minced into fragments of 1 mm3 A 1-mm hole was made in the proximal left tibia of eight male nude mice, using the tip of a 5-mm blade, and a tumor fragment was implanted into the hole for an exact fit. Tumor size was measured once a week, by non-invasive imaging of GFP fluorescence. The mice were sacrificed four weeks after tumor implantation. RESULTS: Tumors grew in 8 out of 8 mice (100%). All tumors were non-invasively detectable with GFP fluorescence, through the skin. Increased tumor growth in the tibia was observed every week. CONCLUSION: The establishment in the tibia of the novel experimental bone-metastatic mouse model of human prostate cancer enables facile screening, in a clinically-relevant system, of improved therapeutics for this recalcitrant disease.
Authors: M Yang; E Baranov; P Jiang; F X Sun; X M Li; L Li; S Hasegawa; M Bouvet; M Al-Tuwaijri; T Chishima; H Shimada; A R Moossa; S Penman; R M Hoffman Journal: Proc Natl Acad Sci U S A Date: 2000-02-01 Impact factor: 11.205
Authors: D W Burton; J Geller; M Yang; P Jiang; I Barken; R H Hastings; R M Hoffman; L J Deftos Journal: Prostate Date: 2005-02-15 Impact factor: 4.104
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Authors: Karim Fizazi; NamPhuong Tran; Luis Fein; Nobuaki Matsubara; Alfredo Rodriguez-Antolin; Boris Y Alekseev; Mustafa Özgüroğlu; Dingwei Ye; Susan Feyerabend; Andrew Protheroe; Peter De Porre; Thian Kheoh; Youn C Park; Mary B Todd; Kim N Chi Journal: N Engl J Med Date: 2017-06-04 Impact factor: 91.245