Igarashi Kentaro, Kawaguchi Kei, Kiyuna Tasuku, Miyake Kentaro, Miyake Masuyo, Li Yunfeng, Nelson Scott D, Dry Sarah M, Singh Arun S, Elliott Irmina A, Russell Tara A, Eckardt Mark A, Yamamoto Norio, Hayashi Katsuhiro, Kimura Hiroaki, Miwa Shinji, Tsuchiya Hiroyuki, Eilber Fritz C, Hoffman Robert M
AntiCancer, Inc., San Diego, California, USA.
Department of Surgery, University of California, San Diego, California, USA.
Oncotarget. 2017 Dec 4;9(8):7774-7781. doi: 10.18632/oncotarget.22892. eCollection 2018 Jan 30.
Relapsed osteosarcoma is a recalcitrant tumor. A patient's cisplatinum (CDDP)-resistant relapsed osteosarcoma lung metastasis was previously established orthotopically in the distal femur of mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the PDOX models were randomized into the following groups when tumor volume reached 100 mm: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i.p.) injection, weekly, for 2 weeks); gemcitabine (GEM) (100 mg/kg, i.p., weekly, for 2 weeks) combined with docetaxel (DOC) (20 mg/kg, i.p., once); temozolomide (TEM) (25 mg/kg, p.o., daily, for 2 weeks) combined with irinotecan (IRN) (4 mg/kg i.p., daily for 2 weeks). Tumor size and body weight were measured with calipers and a digital balance twice a week. After 2 weeks, all treatments significantly inhibited tumor growth except CDDP compared to the untreated control: CDDP: = 0.093; GEM+DOC: = 0.0002, TEM+IRN: < 0.0001. TEM combined with IRN was significantly more effective than either CDDP ( = 0.0001) or GEM combined with DOC ( = 0.0003) and significantly regressed the tumor volume compared to day 0 ( = 0.003). Thus the PDOX model precisely identified the combination of TEM-IRN that could regress the CDDP-resistant relapsed metastatic osteosarcoma PDOX.
复发性骨肉瘤是一种顽固性肿瘤。先前已将一名患者的顺铂（CDDP）耐药复发性骨肉瘤肺转移灶原位植入小鼠股骨远端，建立了患者来源的原位异种移植（PDOX）模型。在本研究中，当肿瘤体积达到100 mm³时，将PDOX模型随机分为以下几组：G1组，未治疗的对照组；G2组，CDDP（6 mg/kg，腹腔内（i.p.）注射，每周一次，共2周）；吉西他滨（GEM）（100 mg/kg，i.p.，每周一次，共2周）联合多西他赛（DOC）（20 mg/kg，i.p.，一次）；替莫唑胺（TEM）（25 mg/kg，口服，每日一次，共2周）联合伊立替康（IRN）（4 mg/kg i.p.，每日一次，共2周）。每周用卡尺和电子天平测量肿瘤大小和体重两次。2周后，与未治疗的对照组相比，除CDDP外，所有治疗均显著抑制肿瘤生长：CDDP：P = 0.093；GEM+DOC：P = 0.0002，TEM+IRN：P < 0.0001。与CDDP（P = 0.0001）或GEM联合DOC（P = 0.0003）相比，TEM联合IRN显著更有效，并且与第0天相比，肿瘤体积显著缩小（P = 0.003）。因此，PDOX模型准确地确定了TEM-IRN联合用药可使CDDP耐药的复发性转移性骨肉瘤PDOX肿瘤体积缩小。
