Temozolomide combined with irinotecan regresses a cisplatinum-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) precision-oncology mouse model.
Temozolomide combined with irinotecan regresses a cisplatinum-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) precision-oncology mouse model.
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DOI：
10.18632/oncotarget.22892
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发表时间：
2018-01-30
期刊：
影响因子：
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通讯作者：
Hoffman RM
中科院分区：
文献类型：
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作者：
Igarashi K;Kawaguchi K;Kiyuna T;Miyake K;Miyake M;Li Y;Nelson SD;Dry SM;Singh AS;Elliott IA;Russell TA;Eckardt MA;Yamamoto N;Hayashi K;Kimura H;Miwa S;Tsuchiya H;Eilber FC;Hoffman RM
复发性骨肉瘤是一种恶性肿瘤。患者的顺铂（CDDP）耐药复发性骨肉瘤肺转移先前建立原位在小鼠股骨远端建立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 mm 3时，将PDOX模型随机分为以下组：G1，对照，不治疗; G2，CDDP（6 mg/kg，腹膜内（i. p.）注射，每周，持续2周）;吉西他滨（GEM）（100 mg/kg，i. p.，每周，持续2周）与多西他赛（DOC）（20 mg/kg，i. p.，一次）;替莫唑胺（TEM）（25 mg/kg，p.o.，每日，持续2周）与伊立替康（IRN）（4 mg/kg腹膜内，每日2次）。每周两次用卡尺和数字天平测量肿瘤大小和体重。2周后，与未处理的对照相比，除CDDP外，所有处理均显著抑制肿瘤生长：CDDP：p = 0.093; GEM+DOC：p = 0.0002，TEM+IRN：p < 0.0001。TEM联合IRN比CDDP（p = 0.0001）或GEM联合DOC（p = 0.0003）显著更有效，并且与第0天相比显著缩小了肿瘤体积（p = 0.003）。因此，PDOX模型精确地鉴定了可以使CDDP抗性复发性转移性骨肉瘤PDOX消退的TEM-IRN的组合。
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 mm3: 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: p = 0.093; GEM+DOC: p = 0.0002, TEM+IRN: p < 0.0001. TEM combined with IRN was significantly more effective than either CDDP (p = 0.0001) or GEM combined with DOC (p = 0.0003) and significantly regressed the tumor volume compared to day 0 (p = 0.003). Thus the PDOX model precisely identified the combination of TEM-IRN that could regress the CDDP-resistant relapsed metastatic osteosarcoma PDOX.