Reversal of chemoresistance in malignant gliomas by calcium antagonists: correlation with the expression of multidrug-resistant p-glycoprotein.
J Neurosurg
; 81(4): 587-94, 1994 Oct.
Article
en En
| MEDLINE
| ID: mdl-7931593
ABSTRACT
Resistance to multiple drugs is often observed in malignant gliomas. The authors used a microtiter tetrazolium test to analyze primary in vitro chemoresistance and chemosensitivity of 15 early cultures of human malignant glioma exposed to 50 micrograms/ml (1,4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a (ACNU), 50 micrograms/ml cisplatin, 1 microgram/ml vincristine, or combinations of these chemotherapeutic agents. Primary chemoresistance was observed in 87% of tumors for ACNU, in 87% for cisplatin, and in 83% for vincristine. All tumors were examined for expression of multidrug-resistant p-glycoprotein, a transport protein of 170,000 D, by means of immunohistochemical staining with the JSB-1 antibody on paraffinized tumor sections. Eight of 15 specimens (53%) showed positive staining for the monoclonal antibody. Primary chemoresistance was overcome by addition of the calcium antagonists verapamil or nimodipine to the cultures if the original tumor expressed p-glycoprotein (p < 0.01 for verapamil, p < 0.05 for nimodipine). In tumors not expressing p-glycoprotein, addition of calcium antagonists to the cell cultures did not influence primary chemoresistance. It is concluded from these data that addition of calcium antagonists to the adjuvant chemotherapy of malignant gliomas might overcome primary chemoresistance in tumors expressing the multidrug-resistant phenotype.
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Colección:
01-internacional
Asunto principal:
Verapamilo
/
Nimodipina
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Glioblastoma
/
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
Límite:
Humans
Idioma:
En
Revista:
J Neurosurg
Año:
1994
Tipo del documento:
Article
País de afiliación:
Alemania