A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology.
A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology.
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DOI：
10.18632/oncotarget.19095
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发表时间：
2017-09-22
期刊：
影响因子：
--
通讯作者：
Hoffman RM
中科院分区：
文献类型：
--
作者：
Igarashi K;Murakami T;Kawaguchi K;Kiyuna T;Miyake K;Zhang Y;Nelson SD;Dry SM;Li Y;Yanagawa J;Russell TA;Singh AS;Tsuchiya H;Elliott I;Eilber FC;Hoffman RM
在本研究中，我们评估了trabectedin（TRAB）和替莫唑胺（TEM）与顺铂（CDDP）相比，对CDDP治疗失败的患者骨肉瘤肺转移的患者源性原位异种移植（PDOX）的疗效。将从患者切除的骨肉瘤原位植入小鼠股骨远端以建立PDOX模型，当肿瘤体积达到约100 mm 3时，将其随机分为以下组：G1，对照组，不治疗; G2，CDDP（6 mg/kg，腹腔注射，每周一次，持续2周）; G3，TRAB（0.15 mg/kg，静脉注射，每周一次，持续2周）; G4，TEM（25 mg/kg，口服，每日一次，持续14天）。分别用卡尺和数字天平测量肿瘤大小和体重，每周两次。在治疗开始后第14天，与未治疗的对照相比，TEM和TRAB而不是CDDP显著抑制肿瘤体积：对照（G1）：814.5±258.8 mm 3; CDDP（G2）：608.6±126.9 mm 3; TRAB（G3）：286.6±133.0 mm 3; TEM（G4）：182.9±69.1 mm 3。CDDP与对照，p=0.07; TRAB与对照，p=0.0004; TEM与对照，p =0.0002; TRAB与CDDP，p =0.0002; TEM与CDDP，p =0.00003。本研究的结果表明，在辅助CDDP治疗后复发的骨肉瘤肺转移的PDOX模型已经确定了用于这种恶性疾病的潜在高效药物，同时准确地维持了患者肿瘤的CDDP抗性，从而证明了骨肉瘤PDOX模型用于精确肿瘤学的潜力。
In the present study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to cisplatinum (CDDP) on a patient-derived orthotopic xenogrraft (PDOX) of a lung-metastasis from an osteosarcoma of a patient who failed CDDP therapy. Osteosarcoma resected from the patient was implanted orthotopically in the distal femur of mice to establish PDOX models which were randomized into the following groups when tumor volume reached approximately 100 mm3: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0.15 mg/kg, intravenous injection, weekly, for 2 weeks); G4, TEM (25 mg/kg, oral, daily, for 14 days). Tumor size and body weight were measured with calipers and a digital balance, respectively, twice a week. On day 14 after initiation of treatment, TEM and TRAB, but not CDDP, significantly inhibited tumor volume compared to untreated control: control (G1): 814.5±258.8 mm3; CDDP (G2): 608.6±126.9 mm3; TRAB (G3): 286.6±133.0 mm3; TEM (G4): 182.9±69.1 mm3. CDDP vs. control, p=0.07; TRAB vs. control, p=0.0004; TEM vs. control p =0.0002; TRAB vs. CDDP, p =0.0002; TEM vs. CDDP, p =0.00003. The results of the present study show that a PDOX model of an osteosarcoma lung-metastasis that recurred after adjuvant CDDP-treatment has identified potentially, highly-effective drugs for this recalcitrant disease, while accurately maintaining the CDDP resistance of the tumor in the patient, thereby demonstrating the potential of the osteosarcoma PDOX model for precision oncology.
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DOI：
10.1073/pnas.89.12.5645
发表时间：
1992-06-15
影响因子：
11.1
作者：
FU, XY;GUADAGNI, F;HOFFMAN, RM
通讯作者：
HOFFMAN, RM
影响因子：
4.3
作者：
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通讯作者：
Blagosklonny, MV
DOI：
10.1073/pnas.88.20.9345
发表时间：
1991-10-01
影响因子：
11.1
作者：
FU, XY;BESTERMAN, JM;HOFFMAN, RM
通讯作者：
HOFFMAN, RM
影响因子：
3.7
作者：
Hiroshima Y;Zhang Y;Zhang N;Maawy A;Mii S;Yamamoto M;Uehara F;Miwa S;Yano S;Murakami T;Momiyama M;Chishima T;Tanaka K;Ichikawa Y;Bouvet M;Murata T;Endo I;Hoffman RM
通讯作者：
Hoffman RM
DOI：
10.1089/lap.2013.0418
发表时间：
2014-04-01
影响因子：
1.3
作者：
Hiroshima, Yukihiko;Maawy, Ali;Hoffman, Robert M.
通讯作者：
Hoffman, Robert M.