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In vitro analysis of BCNU‐sensitivity in human malignant gliomas
Author(s) -
Gerosa Massimo A.,
Rosenblum Mark L.,
Stevai Gabriella,
Tommasi Marina,
Corte Vincenzo Della,
Licata Claudio,
Bricolo Albino,
Tridente Giuseppe
Publication year - 1985
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.1985.tb00893.x
Subject(s) - nitrosourea , carmustine , lomustine , in vitro , anaplastic astrocytoma , cancer research , pharmacology , glioma , chemistry , cross resistance , cell culture , chemotherapy , medicine , biology , astrocytoma , biochemistry , vincristine , cyclophosphamide , genetics
– Like all chloroethyl‐nitrosoureas of major clinical use, 1,3 bis‐(2‐chloroethyl)‐l‐nitrosourea (BCNU) – which is one of the most effective chem‐otherapeutic agents for CNS malignancies – biologically degrades into active alkylating and carbamoylating moieties. Using a human brain tumor stem cell assay, we analyzed a series of anaplastic astrocytomas of pediatric age, characterized by different degrees of BCNU‐resistance. Early (2–4) passage cultures from these tumors were treated in vitro with model drugs for alkylation (BCNU, CHLZ (2‐[3‐(2‐chloroethyl)‐3‐nitrosoureido]‐2‐deoxy‐D‐glucopyranose), ENU (N‐ethyl‐N‐nitrosourea), cross‐linking (BCNU, CHLZ) and carbamoylation BHCNU (1,3 bis (trans‐4‐hydrocyclohexyl)‐l‐nitrosourea): dose‐schedules were compatible with clinically achievable levels. Results of chemosensitivity tests confirmed that – as previously reported in malignant gliomas of the adult – cellular resistance to BCNU was closely related to the cross‐linking activity of alkylating species. However, in pediatric gliomas the levels of cell kill after treatment with the purely carbamoylating agent BHCNU, even at the highest doses tested, were lower than expected.