Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors. (28th November 2020)

• Record Type: Journal Article
• Authors: 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 MF.; Adesina, Adekunle; Yang, Jianhua; Chintagumpala, Murali; Perlaky, Laszlo; Tsz-Kwong Man, Chris; Lau, Ching C.; Li, Xiao-Nan
• Is Part Of: Cancer letters. Volume 493(2020)
• Page Start: 197
• Page End: 206
• Publication Date: 2020-11-28
• Subjects: Gender -- Brain tumor -- Tumorigenicity -- Survival time -- Drug treatment; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.08.035
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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. Highlights: A retrospective analysis of 99 PDOX models of various types of pediatric brain tumors demonstrated that the gender of SCID mice did not have a major impact on animal model development and xenograft growth, nor on drug responses in vivo. SCID mice of both genders are appropriate PDOX model development and preclinical drug testing of pediatric brain tumors.