Characterization of an Orthotopic Rat Model of Glioblastoma Using Multiparametric Magnetic Resonance Imaging and Bioluminescence Imaging

Le, Trung; Lim, Heeseung; Hamilton, Amanda M.; Parkins, Katie M.; Chen, Yuanxin; Scholl, Timothy J.; Ronald, John A.

doi:10.18383/j.tom.2018.00012

Cited by 13 publications

(8 citation statements)

References 47 publications

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“…Complete gene ontology list based on up-regulated genes after ARRY-520 treatment of LU-NB-2 PDX cells. References (53)(54)(55) View/request a protocol for this paper from Bio-protocol.…”

Section: Statistical Analysesmentioning

confidence: 99%

Therapeutic targeting of KSP in preclinical models of high-risk neuroblastoma

et al. 2020

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Neuroblastoma is a childhood malignancy with often dismal prognosis; relapse is common despite intense treatment. Here, we used human tumor organoids representing multiple MYCN-amplified high-risk neuroblastomas to perform a high-throughput drug screen with approved or emerging oncology drugs. Tumor-selective effects were calculated using drug sensitivity scores. Several drugs with previously unreported anti-neuroblastoma effects were identified by stringent selection criteria. ARRY-520, an inhibitor of kinesin spindle protein (KSP), was among those causing reduced viability. High expression of the KSP-encoding gene KIF11 was associated with poor outcome in neuroblastoma. Genome-scale loss-of-function screens in hundreds of human cancer cell lines across 22 tumor types revealed that KIF11 is particularly important for neuroblastoma cell viability. KSP inhibition in neuroblastoma patient-derived xenograft (PDX) cells resulted in the formation of abnormal monoastral spindles, mitotic arrest, up-regulation of mitosis-associated genes, and apoptosis. In vivo, KSP inhibition caused regression of MYCN-amplified neuroblastoma PDX tumors. Furthermore, treatment of mice harboring orthotopic neuroblastoma PDX tumors resulted in increased survival. Our results suggested that KSP inhibition could be a promising treatment strategy in children with high-risk neuroblastoma.

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“…Complete gene ontology list based on up-regulated genes after ARRY-520 treatment of LU-NB-2 PDX cells. References (53)(54)(55) View/request a protocol for this paper from Bio-protocol.…”

Section: Statistical Analysesmentioning

confidence: 99%

Therapeutic targeting of KSP in preclinical models of high-risk neuroblastoma

et al. 2020

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“…Grade IV gliomas, also called glioblastoma (GB), represent the most common and aggressive form of malignant primary brain tumors in adults, with an average age-adjusted incidence of 3.2 cases per 100,000 people [3]. GB account for approximately 15% of all central nervous system tumors and approximately 50% of all gliomas [1,2,4]. The current standard of care for newly diagnosed GB patients consists of maximum safe surgical resection, followed by radiation therapy, with concomitant and adjuvant chemotherapy with temozolomide [5].…”

Section: Introductionmentioning

confidence: 99%

Comparison of In Vivo and Ex Vivo Magnetic Resonance Imaging in a Rat Model for Glioblastoma-Associated Epilepsy

et al. 2021

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Magnetic resonance imaging (MRI) is frequently used for preclinical treatment monitoring in glioblastoma (GB). Discriminating between tumors and tumor-associated changes is challenging on in vivo MRI. In this study, we compared in vivo MRI scans with ex vivo MRI and histology to estimate more precisely the abnormal mass on in vivo MRI. Epileptic seizures are a common symptom in GB. Therefore, we used a recently developed GB-associated epilepsy model from our group with the aim of further characterizing the model and making it useful for dedicated epilepsy research. Ten days after GB inoculation in rat entorhinal cortices, in vivo MRI (T2w and mean diffusivity (MD)), ex vivo MRI (T2w) and histology were performed, and tumor volumes were determined on the different modalities. The estimated abnormal mass on ex vivo T2w images was significantly smaller compared to in vivo T2w images, but was more comparable to histological tumor volumes, and might be used to estimate end-stage tumor volumes. In vivo MD images displayed tumors as an outer rim of hyperintense signal with a core of hypointense signal, probably reflecting peritumoral edema and tumor mass, respectively, and might be used in the future to distinguish the tumor mass from peritumoral edema—associated with reactive astrocytes and activated microglia, as indicated by an increased expression of immunohistochemical markers—in preclinical models. In conclusion, this study shows that combining imaging techniques using different structural scales can improve our understanding of the pathophysiology in GB.

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“…We established an intracranial C6 GBM model as previously described [ 22 ]. The rats were anaesthetized with 3% isoflurane (792632, Sigma-Aldrich, USA) in an airtight chamber.…”

Section: Methodsmentioning

confidence: 99%

Resveratrol Enhances the Radiosensitivity by Inducing DNA Damage and Antitumor Immunity in a Glioblastoma Rat Model under 3 T MRI Monitoring

Qian

Mao

et al. 2022

Journal of Oncology

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Glioblastoma (GBM) is the most common intracranial tumor with characteristic of malignancy. Resveratrol, a natural originated polyphenolic compound, has been reported to act as a potential radiosensitizer in cancer therapy. Magnetic resonance imaging (MRI) is the first choice for the diagnosis, pathological grading, and efficacy evaluation of GBM. In this study, MRI was applied to observe whether resveratrol could intensify the anti-GBM tumor effect by enhancing antitumor immunity during radiotherapy. We established an intracranial C6 GBM model in SD rats, treated with radiation and resveratrol. The increased body weight, the inhibition on mortality, and tumor volume in radiated- GBM rats were further enhanced by resveratrol addition, while the pathological damage of brain was alleviated. The modulation of radiation on inflammation, cell cycle, and apoptosis was strengthened by resveratrol; and Ki-67, PD-L1, and cell cycle- and apoptosis-related protein expressions were also improved by cotreatment. Besides, cotreatment attenuated DNA damage and induced G0/G1-phase cell arrest of GBM rats, accompanied with the changed expression of ATM-AKT-STAT3 pathway-related proteins. Moreover, the percentages of CD3+CD8+T cells and IFN-γ+CD8+T cells were enhanced, while (CD4+CD25+Foxp3)/CD4+T cells were decreased by radiation or resveratrol, which was strengthened by cotreatment. The modulation effect of cotreatment on CD3, Foxp3, and IFN-γ levels was also stronger than radiation or resveratrol alone. To conclude, resveratrol enhanced the effect of radiotherapy by inducing DNA damage and antitumor immunity in the intracranial C6 GBM.

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Characterization of an Orthotopic Rat Model of Glioblastoma Using Multiparametric Magnetic Resonance Imaging and Bioluminescence Imaging

Cited by 13 publications

References 47 publications

Therapeutic targeting of KSP in preclinical models of high-risk neuroblastoma

Therapeutic targeting of KSP in preclinical models of high-risk neuroblastoma

Comparison of In Vivo and Ex Vivo Magnetic Resonance Imaging in a Rat Model for Glioblastoma-Associated Epilepsy

Resveratrol Enhances the Radiosensitivity by Inducing DNA Damage and Antitumor Immunity in a Glioblastoma Rat Model under 3 T MRI Monitoring

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