The cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM) have also shown palbociclib to be efficacious. In this study, we investigated palbociclib in combination with radiation therapy (RT) for treating GBM. We tested palbociclib (with and without RT) on four patient-derived cell lines (PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the cell cycle and apoptosis using flow cytometry, in vitro. Balb/c nude mice were intracranially injected with the PDCL, GBM-L1 and treated orally with palbociclib (with and without RT). Overall survival was measured. Palbociclib treatment resulted in a significant increase in the percentage of cells in the G1 cell cycle phase. Apoptotic cell death, measured by Annexin V was induced. Palbociclib combined with RT acted synergistically with the significant impediment of colony formation. The oral treatment of mice with palbociclib did not show any significant survival advantage when compared to control mice, however when combined with RT, a survival advantage of 8 days was observed. Our results support the use of palbociclib as an adjuvant treatment to RT and warrant translation to the clinic.
Objectives: Biphenotypic sinonasal sarcoma (BSNS), previously low-grade sinonasal sarcoma with neural and myogenic features, is a rare tumor of the sinonasal tract first described in 2012. Due to its rarity, limited literature is available in providing clinicians with a standardized treatment regimen, particularly in cases of positive surgical margins. This article aims to provide a clinical review of the currently available reported cases of BSNS, as well as presenting clinical, radiologic, and pathologic details of 2 novel cases. Methods: Online electronic databases include PubMed and Embase where queried for reports of biphenotypic sinonasal sarcoma or low-grade sinonasal sarcoma with neural and myogenic features. Two previously unpublished cases were included in the results. Data including clinical presentation, epidemiologic data, radiologic evaluation, intraoperative details, histopathology, treatment modality, and postoperative follow-up information were included. Results: A total of 100 previously published cases were identified in 12 prior articles. Mean age at presentation was 52.9 years. Extrasinonasal extension was observed in 27.4% of cases with most common site of extension being cribriform plate. Forty-seven cases included treatment details with surgical excision being the most common modality. Recurrence rates were identical for both surgical excision alone and surgical excision with adjuvant radiotherapy (33.3%). Conclusions: Biphenotypic sinonasal sarcoma is a slow-growing tumor that is amenable to surgical resection. Recurrence rates are similar between surgical excision and surgical excision with adjuvant radiation therapy, but limited data in reported cases preclude a determination of treatment superiority.
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