Abstract | PURPOSE: METHODS: In vitro cell culture, ex vivo slice culture and in vivo cell line-derived orthotopic xenograft animal models of AM/RIM were utilized to assess treatment efficacy with palbociclib plus radiation. Treatment effects were examined by immunoblot, cell viability, apoptosis, and cell cycle progression. RESULTS: The in vitro and ex vivo studies demonstrate that palbociclib plus radiation treatment reduced proliferation and has additional effects on cell cycling, including induction of an RB-associated G (1) arrest in Rb+ AM and RIM cells, but not in Rb- cells. Our results also demonstrated reduced CDK4 and CDK6 expression as well as reduced E2F target gene expression (CCNA2 and CCNE2) with the combination therapy. MRI results in vivo demonstrated reduced tumor size at 5 weeks when treated with 14 days palbociclib (10 mg/kg) plus 6 Gy radiation compared to saline-treated tumors. Finally, no hepatic toxicity was found after treatments. CONCLUSION: A pre-clinical murine model provides preclinical evidence for use of palbociclib plus radiation as a therapeutic agent for Rb+ meningiomas.
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Authors | A Das, M Alshareef, J L Martinez Santos, G B F Porto, D G McDonald, L K Infinger, W A Vandergrift 3rd, S M Lindhorst, A K Varma, S J Patel, D Cachia |
Journal | Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
(Clin Transl Oncol)
Vol. 22
Issue 11
Pg. 2017-2025
(Nov 2020)
ISSN: 1699-3055 [Electronic] Italy |
PMID | 32253706
(Publication Type: Evaluation Study, Journal Article)
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Chemical References |
- Antineoplastic Agents
- Piperazines
- Pyridines
- Retinoblastoma Protein
- Cyclin-Dependent Kinase 4
- Cyclin-Dependent Kinase 6
- palbociclib
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Topics |
- Animals
- Antineoplastic Agents
(therapeutic use)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Combined Modality Therapy
- Cyclin-Dependent Kinase 4
(antagonists & inhibitors)
- Cyclin-Dependent Kinase 6
(antagonists & inhibitors)
- Humans
- Male
- Meningeal Neoplasms
(therapy)
- Meningioma
(therapy)
- Mice
- Neoplasms, Radiation-Induced
(therapy)
- Piperazines
(therapeutic use)
- Pyridines
(therapeutic use)
- Retinoblastoma Protein
(metabolism)
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