Abstract |
Neurofibromatosis type 2 (NF2) is an autosomal dominant disease that is characterized mainly by schwannomas, as well as menigiomas and gliomas. The NF2 gene product merlin/ schwannomin acts as a tumor suppressor. Schwann cells derived from NF2 schwannomas showed an enhanced proliferation rate, and electrophysological studies revealed larger K(+) outward currents as compared with controls. Schwann cells isolated from schwannomas of NF2 patients or multiorgan donors were treated with different concentrations of the K(+) current blockers quinidine, tetraethylammonium chloride, and 4-aminopyridine and K(+) outward currents and proliferation rates of these cells were compared. K(+) outward currents of both cell types can be blocked by quinidine. Importantly, treatment with quinidine reduces proliferation of NF2 Schwann cells in a concentration dependent manner but did not reduce proliferation of normal Schwann cells. Therefore, the use of quinidine or quinidine-like components would possibly provide a novel adjuvant therapeutic option for NF2 patients to slow down or freeze growth of schwannomas.
|
Authors | C Rosenbaum, M Kamleiter, P Grafe, L Kluwe, V Mautner, H W Müller, C O Hanemann |
Journal | Neurobiology of disease
(Neurobiol Dis)
Vol. 7
Issue 4
Pg. 483-91
(Aug 2000)
ISSN: 0969-9961 [Print] United States |
PMID | 10964617
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright 2000 Academic Press. |
Chemical References |
- Antineoplastic Agents
- Potassium Channel Blockers
- Potassium Channels
- Quinidine
|
Topics |
- Antineoplastic Agents
(pharmacology)
- Cell Division
(drug effects, physiology)
- Cells, Cultured
- Drug Screening Assays, Antitumor
- Humans
- Neurilemmoma
(drug therapy, physiopathology)
- Neurofibromatosis 2
(drug therapy, physiopathology)
- Potassium Channel Blockers
- Potassium Channels
(physiology)
- Quinidine
(pharmacology, therapeutic use)
- Schwann Cells
(drug effects, physiology)
|