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Intracranial injectable tumor model: technical advancements.

ABSTRACT: Background and Objectives Few simulation models are available that provide neurosurgical trainees with the challenge of distorted skull base anatomy despite increasing importance in the acquisition of safe microsurgical and endoscopic techniques. We have previously reported a unique training model for skull base neurosurgery where a polymer is injected into a cadaveric head where it solidifies to mimic a skull base tumor for resection. This model, however, required injection of the polymer under direct surgical vision via a complicated alternative approach to that being studied, prohibiting its uptake in many neurosurgical laboratories. Conclusion We report our updated skull base tumor model that is contrast-enhanced and may be easily and reliably injected under fluoroscopic guidance. We have identified a map of burr holes and injection corridors available to place tumor at various intracranial sites. Additionally, the updated tumor model allows for the creation of mass effect, and we detail the variation of polymer preparation to mimic different tumor properties. These advancements will increase the practicality of the tumor model and ideally influence neurosurgical standards of training.

SUBMITTER: Gragnaniello C

PROVIDER: S-EPMC4176537 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Project description:BackgroundAlthough meningioma is the most common primary brain tumor, treatments rely on surgery and radiotherapy, and recurrent meningiomas have no standard therapeutic options due to a lack of clinically relevant research models. Current meningioma cell lines or organoids cannot reflect biological features of patient tumors since they undergo transformation along culture and consist of only tumor cells without microenvironment. We aim to establish patient-derived meningioma organoids (MNOs) preserving diverse cell types representative of the tumor microenvironment.MethodsThe biological features of MNOs were evaluated using WST, LDH, and collagen-based 3D invasion assays. Cellular identities in MNOs were confirmed by immunohistochemistry (IHC). Genetic alteration profiles of MNOs and their corresponding parental tumors were obtained by whole-exome sequencing.ResultsMNOs were established from four patients with meningioma (two grade 1 and two grade 2) at a 100% succession rate. Exclusion of enzymatic dissociation-reaggregation steps endowed MNOs with original histology and tumor microenvironment. In addition, we used a liquid media culture system instead of embedding samples into Matrigel, resulting in an easy-to-handle, cost-efficient, and time-saving system. MNOs maintained their functionality and morphology after long-term culture (> 9 wk) and repeated cryopreserving-recovery cycles. The similarities between MNOs and their corresponding parental tumors were confirmed by both IHC and whole-exome sequencing. As a representative application, we utilized MNOs in drug screening, and mifepristone, an antagonist of progesterone receptor, showed prominent antitumor efficacy with respect to viability, invasiveness, and protein expression.ConclusionTaken together, our MNO model overcame limitations of previous meningioma models and showed superior resemblance to parental tumors. Thus, our model could facilitate translational research identifying and selecting drugs for meningioma in the era of precision medicine.

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Intracranial injectable tumor model: technical advancements.

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