Human Schwannomas Express Activated Platelet-Derived Growth Factor Receptors and c-kit and Are Growth Inhibited by Gleevec (Imatinib Mesylate)

Abstract

Schwannomas, although benign, can be fatal or give rise to significant morbidity due to an unpredictable growth rate.

Gene-expression profiling elucidates molecular signaling networks that can be therapeutically targeted in vestibular schwannoma

“…13,34 Additionally, receptor tyrosine kinases such as stem cell factor receptor (c-KIT) and platelet-derived growth factor receptor (PDGFR)-a and -b, have been demonstrated to be overexpressed and overactivated in sporadic and NF2-associated peripheral and vestibular schwannomas. 22,30 Preclinical targeting of c-KIT, PDGFR-a, and PDGFR-b with imatinib and nilotinib using the immortalized NF2-null VS cell line HEI-193 demonstrated that receptor tyrosine kinase (RTK) inhibition increased apoptosis, and cell cycle arrest decreased anchorage-independent growth. 22,30 The transcriptome of schwannoma remains poorly understood, as inappropriate control tissues or insufficient sample numbers were used in the few published studies investigating gene expression in this condition.…”

“…22,30 Preclinical targeting of c-KIT, PDGFR-a, and PDGFR-b with imatinib and nilotinib using the immortalized NF2-null VS cell line HEI-193 demonstrated that receptor tyrosine kinase (RTK) inhibition increased apoptosis, and cell cycle arrest decreased anchorage-independent growth. 22,30 The transcriptome of schwannoma remains poorly understood, as inappropriate control tissues or insufficient sample numbers were used in the few published studies investigating gene expression in this condition. Thus, identification of novel recurring alterations in schwannoma is limited leading to a poor fundamental understanding of core signaling pathways that are activated, which may serve as therapeutic targets.…”

The microtubule binding drug EM011 inhibits the growth of paediatric low grade gliomas

“…The cells were loaded in a haemocytometer and counted microscopically. The percentage viability was calculated from the average count for live cells (those that exclude trypan blue) and dead cells (those that allow uptake of typan blue) as previously described [17].…”

“…Cell cycle analysis 2 Â 10 5 Cells were grown in each well of 6-well plates and exposed to varying drug doses daily. Prior to analysis, cells were stained with propidium iodide and analysed by flow cytometry as previously described [17] using the BD FACS canto II software.…”

“…Soft agarose assays over an 18 day period in 24 well plates were performed as previously described [17]. Cells were then stained with 0.005% crystal violet for 2 h at room temperature, followed by quantification of the number of colonies with a compound microscope.…”