Multidrug resistance in glioblastoma. Chemosensitivity testing and immunohistochemical demonstration of P-glycoprotein.
Chemosensitivity of previously untreated glioblastomas to mitoxantrone, methotrexate, ACNU and BCNU was tested on cultured tissue. Sixteen of 62 tumors were partially chemosensitive in vitro. The monoclonal antibody C 219 was used to demonstrate the presence of p-glycoprotein in the 16 sensitive and five highly resistant glioblastomas. All 21 tumors identically expressed p-glycoprotein. These results show that untreated glioblastomas primarily express p-glycoprotein even if they are at least partially chemosensitive in vitro. Therefore, immunohistochemical demonstration of p-glycoprotein with the monoclonal antibody C 219 can not provide reliable information on short term resistance of the individual tumors to antineoplastic drugs. P-glycoprotein expression could, however, help to explain the disappointing overall long-term efficacy of chemotherapy by showing the existence of cell populations with early drug resistance in these tumors.
Leweke
F
F
Neurologic Clinic, Justus Liebig University, Giessen, Germany.
Damian
M S
MS
Schindler
C
C
Schachenmayr
W
W
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002330:Carmustine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008727:Methotrexate / Q000494:pharmacology; D008942:Mitoxantrone / Q000494:pharmacology; D015376:Nimustine / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D015376:Nimustine; D008942:Mitoxantrone; D002330:Carmustine; D008727:Methotrexate