Impact Of Scid Mouse Gender On Tumorigenicity, Xenograft Growth And Drug-Responses In Patient Derived Orthotopic Xenograft Models (Pdox) Of Malignant Brain Tumors

Brain tumor is the leading cause of cancer related death in children. To develop new therapies and to understand tumor biology, many efforts are made to develop patient derived orthotopic xenograft mouse models (PDOX). There are, however, some concerns about the potential impact of animal genders on tumor take rate, xenograft growth and in vivo drug responses. To systematically analyze such impact, we retrospectively examined >1,000 mice of 59 PDOX models, including glioblastoma (GBM), medulloblastoma (MB), primitive neuroectodermal tumor (PENT) and ependymoma (EPN) and diffuse intrinsic pontine glioma (DIPG), in which there were age-matched (within 2 wks differences) with relatively even numbers of male and female animals. All the animals were injected with identical number of tumor cells (1x10^5) in the mouse brains matching that in human patients. Animals were monitored daily and euthanized when they were moribund. Differences between male and female mice were analyzed by t-test. In 25 GBM models (15 adult and 10 pediatric) involving 419 mice, there was an average of number of mice was 17.8±9.5 mice per model (male: female = 9.88±5.8:7.93±3.6) (P>0.05). In 26 MB models with total 488 mice, the average animal number was 17.24±8.8 mice per model (male:female= 9.54±5.34 :7.71±3.45) (P>0.05). The tumor take rate was near >95% in both male and female mice (P>0.05). In GBM models, the survival times was 94.1±21.7 days in male mice and 92.3±20.8 days in female (P>0.05); wherease in MB models, they were 134.95±39.86 day in male and 121.08±31.68 days in female mice (P>0.05). The impact of animal gender on drug responses in vivo is essential to the preclinical drug testing. A total of 468 mice from 11 GBM, 5 MB, 3 EPN, 3 DIPG and 2 PNET were treated a series of standard and investigational drugs/compounds, including radiation, oncolytic virus (SVV-001), ABT888, BMI1-inhibitor, MLN8237, TMZ, Flavopiridol, SYC-435, SYC-719, SYC-836, Olig 2 inhibitor, VPA, SAHA, Echinomycin, MCB613, and PARPi. The overall survival times were 104.55±23.63 day in male mice, and 98.64±25.66 in female mice (P>0.05). The only model that exhibited the increased responses in male mice was found in IC-2305GBM treated with TMZ and PTC-596 (P Citation Format: Lin Qi, Mari Kogiso, Yuchen Du, Huiyuan Zhang, Frank Braun, Holly Lindsay, Sibo Zhao, Sarah Injac, Patricia Baxter, Zhigang Liu, Yujing Zhang, Jack Su, Adekunle Adesina, Andrew Walter, Jeffery Murray, Javad Nazarian, Will Parsons, Murali Chintagumpala, Xiao-nan Li. Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-responses in patient derived orthotopic xenograft models (PDOX) of malignant brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2821. doi:10.1158/1538-7445.AM2017-2821