Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors.
Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors.
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SCID小鼠性别对儿童脑肿瘤原位PDX模型中致瘤性、异种移植物生长和药物反应的影响
DOI：
10.1016/j.canlet.2020.08.035
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发表时间：
2020-11-28
期刊：
影响因子：
9.7
通讯作者：
Li, Xiao-Nan
中科院分区：
文献类型：
--
作者：
Qi, Lin;Kogiso, Mari;Du, Yuchen;Zhang, Huiyuan;Braun, Frank K.;Huang, Yulun;Teo, Wan-Yee;Lindsay, Holly;Zhao, Sibo;Baxter, Patricia;Zhao, Xiumei;Yu, Litian;Liu, Zhigang;Zhang, Xingding;Su, Jack M. F.;Adesina, Adekunle;Yang, Jianhua;Chintagumpala, Murali;Perlaky, Laszlo;Man, Chris Tsz-Kwong;Lau, Ching C.;Li, Xiao-Nan
脑肿瘤是儿童癌症相关死亡的主要原因。临床相关动物对于新疗法开发至关重要。为了解决动物性别对致瘤率、异种移植物生长和体内药物反应的潜在影响，我们回顾性分析了我们建立的99个患者来源的原位异种移植小鼠模型（原位PDX或PDOX）。来自27个患者肿瘤，包括5个胶质母细胞瘤（GBM）、11个髓母细胞瘤（MB）、4个室管膜瘤（EPN）、4个非典型畸胎瘤/横纹肌样肿瘤（ATRT）和3个弥漫性内在脑桥胶质瘤（DIPG），其被直接植入年龄匹配的大约相等数量的雄性和雌性动物（n = 310）脑中的匹配位置。（在2周龄差异内）SCID小鼠，雄性小鼠成瘤率为50.6 ± 21.5%，雌性小鼠成瘤率为52.7 ± 23.5%，动物生存时间雄性为192.6 ± 31.7天，雌性小鼠为173.9 ± 34.5天（P = 0.46）。一旦建立，将PDOX肿瘤连续亚移植至VII代。来自59个PDOX模型的1，595只小鼠的分析第II代和第VII代期间（18个GBM、18个MB、5个ATRT、6个EPN、7个DIPG和5个PENT），雄性之间6种不同肿瘤类型的肿瘤摄取率相似动物存活时间雄性为96.7 ± 23.3天，雌性为99.7 ± 20天（P = 0.25）。来自7只GBM、2只MB、1只ATRT、1只EPN、2只DIPG和1只PNET的共计284只小鼠接受了一系列标准和研究药物/化合物治疗。雄性小鼠的总生存时间为106.9 ± 25.7天，雌性小鼠为110.9 ± 31.8天（P = 0.41），不同类型/模型的小鼠分别分析时观察到相似的结果。总之，我们的数据表明，SCID小鼠的性别对动物模型开发和体内药物反应没有重大影响，两种性别的SCID小鼠都适合使用。
Brain tumor is the leading cause of cancer related death in children. Clinically relevant animals are critical for new therapy development. To address the potential impact of animal gender on tumorigenicity rate, xenograft growth and in vivo drug responses, we retrospectively analyzed 99 of our established patient derived orthotopic xenograft mouse models (orthotopic PDX or PDOX). From 27 patient tumors, including 5 glioblastomas (GBMs), 11 medulloblastomas (MBs), 4 ependymomas (EPNs), 4 atypical teratoid/rhabdoid tumors (ATRTs) and 3 diffuse intrinsic pontine gliomas (DIPGs), that were directly implanted into matching locations in the brains of approximately equal numbers of male and female animals (n = 310) in age-matched (within 2-week age-difference) SCID mice, the tumor formation rate was 50.6 ± 21.5% in male and 52.7 ± 23.5% in female mice with animal survival times of 192.6 ± 31.7 days in male and 173.9 ± 34.5 days in female mice (P = 0.46) regardless of pathological diagnosis. Once established, PDOX tumors were serially subtransplanted for up to VII passage. Analysis of 1,595 mice from 59 PDOX models (18 GBMs, 18 MBs, 5 ATRTs, 6 EPNs, 7 DIPGs and 5 PENTs) during passage II and VII revealed similar tumor take rates of the 6 different tumor types between male (85.4 ± 15.5%) and female mice (84.7 ± 15.2%) (P = 0.74), and animal survival times were 96.7 ± 23.3 days in male mice and 99.7 ± 20 days in female (P = 0.25). A total of 284 mice from 7 GBM, 2 MB, 1 ATRT, 1 EPN, 2 DIPG and 1 PNET were treated with a series of standard and investigational drugs/compounds. The overall survival times were 106.9 ± 25.7 days in male mice, and 110.9 ± 31.8 days in female mice (P = 0.41), similar results were observed when different types/models were analyzed separately. In conclusion, our data demonstrated that the gender of SCID mice did not have a major impact on animal model development nor drug responses in vivo, and SCID mice of both genders are appropriate for use.
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影响因子：
7.3
作者：
Dobson THW;Tao RH;Swaminathan J;Maegawa S;Shaik S;Bravo-Alegria J;Sharma A;Kennis B;Yang Y;Callegari K;Haltom AR;Taylor P;Kogiso M;Qi L;Khatua S;Goldman S;Lulla RR;Fangusaro J;MacDonald TJ;Li XN;Hawkins C;Rajaram V;Gopalakrishnan V
通讯作者：
Gopalakrishnan V
影响因子：
14
作者：
Truong D;Fiorelli R;Barrientos ES;Melendez EL;Sanai N;Mehta S;Nikkhah M
通讯作者：
Nikkhah M
影响因子：
64.8
作者：
Hovestadt, Volker;Smith, Kyle S.;Northcott, Paul A.
通讯作者：
Northcott, Paul A.
影响因子：
15.9
作者：
Liu, Zhigang;Zhao, Xiumei;Li, Xiao-Nan
通讯作者：
Li, Xiao-Nan
影响因子：
6.2
作者：
Krishnatry, Rahul;Zhukova, Nataliya;Tabori, Uri
通讯作者：
Tabori, Uri