ABSTRACT
The traditional classification, diagnosis, and treatment of intracranial aneurysms are based on the characteristics of their vascular lumen. However, in the past few years, some advances in MRI technology with high-resolution imaging can assess the pathology of intracranial vascular walls. Compared with traditional methods of computed tomography angiography, magnetic resonance angiograhpy, and digital subtraction angiography, high resolution magnetic resonance imaging technology can help us to newly understand the disease by directly evaluating the characteristics of vascular wall, such as aneurysm wall thickness, inflammation, enhancement, permeability and hemodynamics. At present, high-resolution magnetic resonance imaging is increasingly used in clinic to assess the rupture risk of intracranial aneurysms, which is of great significance for guiding the diagnosis and treatment of intracranial aneurysms.
Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Aneurysm, Ruptured/diagnostic imaging , Cerebral Angiography , Humans , Intracranial Aneurysm/diagnostic imaging , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Risk Assessment , TechnologyABSTRACT
Dysregulation of retinoblastoma (Rb) signaling pathway have been established as a requirement for glioblastoma (GBM) initiation and progression, which suggests that blockade of CDK4/6-Rb signaling axis for GBM treatment. Palbociclib, a selective inhibitor of the cyclin-dependent kinases CDK4/6, has been applied for breast cancer treatment. However, its efficacy against glioblastoma has not been well clarified. Here, effects of CDK4/6 inhibitors on various kinds of GBM cell lines are investigated and the functional mechanisms are identified. Data showed that cells with diverse PTEN status respond to palbociclib differently. Gain-of-function and loss-of-function studies indicated that PTEN enhanced the sensitivity of GBM cells to palbociclib in vitro and in vivo, which was associated with suppressions of Akt and ERK signaling and independent of Rb signaling inhibition. Hence, our findings support that palbociclib selectively.
ABSTRACT
Genomic studies have established a set of three core-signaling pathways, receptor tyrosine kinase (RTK), p53 and retinoblastoma (Rb) signaling pathways, contributing glioblastoma (GBM) and revealed that dysregulation of at least two pathways is required for GBM progression. In the present study, we investigate efficacy of combination of palbociclib, cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, and erlotinib, epidermal growth factor receptor (EGFR) inhibitor in GBM cell systems with different p53 status. Cell proliferation and colony formation assays showed that the combination treatment synergistically suppressed GBM cell proliferation. LN229 cells with mutant p53 and wild-type PTEN were more sensitive to the combination treatment. Further studies indicated that the synergetic anti-GBM effects were due to cell apoptosis induction and cell cycle arrest at G1 phase. Signaling examination indicated that levels of p-Rb and p-4E-BP1 significantly decreased by the combination treatment; however, Akt and MAPK signaling were differentially suppressed among the three GBM cell lines. Hence, our data demonstrate that palbociclib and erlotinib exert synergistic anti-GBM activity, providing pre-clinical evidence and a proof-ofconcept that usage of the combination of EGFR and CDK4/6 inhibitors for GBM treatment.
