OBJECT: Diffuse brainstem tumors are the most difficult type of pediatric CNS malignancy to treat. These inoperable lesions are treated with radiation alone or in combination with chemotherapy, and the survival rate is less than 10%. It is therefore essential to develop a reliable animal model to screen new therapeutic agents for the treatment of this type of tumor. METHODS: A multipotent human glioblastoma stemlike neurosphere line, 060919, was established from a surgically resected glioblastoma specimen; when cells were implanted intracranially into athymic nude mice, they formed invasive, vascular tumors that exhibited the features of glioblastoma. Ten female Fischer 344 rats received an injection of 75,000 F98 rat glioma cells and 10 female athymic nude rats received an injection of 75,000 060919 human glioblastoma stemlike cells in the pontine tegmentum of the brainstem. A control group of 5 female Fischer rats received an injection of saline in the same location as the animals in the tumor groups. Kaplan-Meier curves were generated for survival, and brains were processed postmortem for histopathological investigation. RESULTS: Both F98 cells and 060919 cells grew in 100% of the animals injected. Median survival of animals injected with F98 was 15 days, consistent with the authors' previous reports on the establishment of the brainstem tumor model using the F98 rat glioma line. Median survival of animals injected with 060919 was 31 days. Histopathological analysis of the tumors confirmed the presence of brainstem lesions in animals that received brainstem injections of F98 and in animals that received brainstem injections of 060919. The 060919 brainstem tumors histologically resembled glioblastoma. CONCLUSIONS: Tumor take and median survival were consistent for animals injected in the brainstem with either the established F98 rat glioma cell line or the 060919 human glioblastoma stemlike neurosphere line. Histopathological features of the 060919 brainstem tumors resembled glioblastoma. Establishment of this human glioblastoma stemlike brainstem animal model will improve the evaluation and identification of more efficacious agents for the treatment of high-grade brainstem tumors.
OBJECT: Diffuse brainstem tumors are the most difficult type of pediatric CNS malignancy to treat. These inoperable lesions are treated with radiation alone or in combination with chemotherapy, and the survival rate is less than 10%. It is therefore essential to develop a reliable animal model to screen new therapeutic agents for the treatment of this type of tumor. METHODS: A multipotent humanglioblastoma stemlike neurosphere line, 060919, was established from a surgically resected glioblastoma specimen; when cells were implanted intracranially into athymic nude mice, they formed invasive, vascular tumors that exhibited the features of glioblastoma. Ten female Fischer 344 rats received an injection of 75,000 F98 ratglioma cells and 10 female athymic nude rats received an injection of 75,000 060919 humanglioblastoma stemlike cells in the pontine tegmentum of the brainstem. A control group of 5 female Fischer rats received an injection of saline in the same location as the animals in the tumor groups. Kaplan-Meier curves were generated for survival, and brains were processed postmortem for histopathological investigation. RESULTS: Both F98 cells and 060919 cells grew in 100% of the animals injected. Median survival of animals injected with F98 was 15 days, consistent with the authors' previous reports on the establishment of the brainstem tumor model using the F98 ratglioma line. Median survival of animals injected with 060919 was 31 days. Histopathological analysis of the tumors confirmed the presence of brainstem lesions in animals that received brainstem injections of F98 and in animals that received brainstem injections of 060919. The 060919 brainstem tumors histologically resembled glioblastoma. CONCLUSIONS:Tumor take and median survival were consistent for animals injected in the brainstem with either the established F98 ratglioma cell line or the 060919 humanglioblastoma stemlike neurosphere line. Histopathological features of the 060919 brainstem tumors resembled glioblastoma. Establishment of this humanglioblastoma stemlike brainstem animal model will improve the evaluation and identification of more efficacious agents for the treatment of high-grade brainstem tumors.
Authors: Alexandra Borodovsky; Alan K Meeker; Ewen F Kirkness; Qi Zhao; Charles G Eberhart; Gary L Gallia; Gregory J Riggins Journal: J Neurooncol Date: 2014-12-04 Impact factor: 4.130
Authors: Jeffrey V Brower; Daniel J Indelicato; Philipp R Aldana; Eric Sandler; Ronny Rotondo; Nancy P Mendenhall; Robert B Marcus; Zhong Su Journal: Acta Oncol Date: 2013-02-20 Impact factor: 4.089
Authors: Zev A Binder; I-Mei Siu; Charles G Eberhart; Colette Ap Rhys; Ren-Yuan Bai; Verena Staedtke; Hao Zhang; Nicolas R Smoll; Steven Piantadosi; Sara G Piccirillo; Francesco Dimeco; Jon D Weingart; Angelo Vescovi; Alessandro Olivi; Gregory J Riggins; Gary L Gallia Journal: PLoS One Date: 2013-10-16 Impact factor: 3.240
Authors: Zev A Binder; Kelli M Wilson; Vafi Salmasi; Brent A Orr; Charles G Eberhart; I-Mei Siu; Michael Lim; Jon D Weingart; Alfredo Quinones-Hinojosa; Chetan Bettegowda; Amin B Kassam; Alessandro Olivi; Henry Brem; Gregory J Riggins; Gary L Gallia Journal: PLoS One Date: 2016-03-30 Impact factor: 3.240