Abstract
BackgroundGliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown. Patient-derived xenograft (PDX) models have been used widely to model tumor progression, and subsequently to validate biomarkers and inform potential therapeutic regimens. Here, we report for the first time the successful development of a PDX model of secondary GSM.MethodsTissue obtained from a tumor resection revealed a secondary GSM arising from GBM. The clinical, radiological, and histopathological records of the patient were retrospectively reviewed. Samples obtained from surgery were cultured ex vivo and/or implanted subcutaneously in immunocompromised mice. Histopathological features between the primary GBM, secondary GSM, and GSM PDX are compared.ResultsIn explant culture, the cells displayed a spindle-shaped morphology under phase contrast microscopy, consistent with the sarcomatous component. GSM samples were subcutaneously engrafted into immunocompromised mice after single-cell suspension. Xenografts of serial passages showed enhanced growth rate with increased in vivo passage. We did not observe any histopathological differences between the secondary GSM and its serial in vivo passages of PDX tumors.ConclusionsOur PDX model for GSM retained the histopathological characteristics of the engrafted tumor from the patient. It may provide valuable information to facilitate molecular and histopathological modelling of GSM and be of significant implication in future research to establish precise cancer medicine for this highly malignant tumor.
Highlights
Gliosarcoma (GSM) is a rare and aggressive subtype of glioblastoma multiforme (GBM), comprising up to 2.4% of GBM cases, and typically affecting the 50–70 age group with a male preponderance [1]
GSM is classified as a World health organization (WHO) grade IV lesion, and when compared to the usual progression of GBM, GSM carries a greater tendency of intra- and extracranial metastasis, invasion of cerebral lobes, and generally a worse prognosis
The currently accepted management approach for GSM is derived from the conventional treatment strategy of GBM: maximally safe surgical resection followed by chemoirradiation and adjuvant chemotherapy using temozolomide (TMZ)
Summary
Gliosarcoma (GSM) is a rare and aggressive subtype of glioblastoma multiforme (GBM), comprising up to 2.4% of GBM cases, and typically affecting the 50–70 age group with a male preponderance [1]. GSM is classified as a WHO grade IV lesion, and when compared to the usual progression of GBM, GSM carries a greater tendency of intra- and extracranial metastasis, invasion of cerebral lobes, and generally a worse prognosis. They are further classified into primary de novo GSM and secondary GSM (secondary to a recurrent or radiationinduced GBM), with a recent review noting different median survivals between the two (25 vs 53 weeks) [1]. Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. We report for the first time the successful development of a PDX model of secondary GSM
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