Japanese Journal of Clinical Oncology, Vol 29, Issue 11 527-534, Copyright © 1999 by Foundation for Promotion of Cancer Research
M Nagane, A Asai, S Shibui, H Oyama, K Nomura and Y Kuchino
BACKGROUND: In addition to traditional modalities such as surgical
intervention and radiotherapy, chemotherapy is a common therapeutic method
for human malignant brain tumors. However, the effectiveness of
chemotherapy is frequently hampered by cancer cell chemoresistance,
resulting in an unsatisfactory outcome. To overcome this disadvantage, the
proper selection of efficacious anticancer agents is required. METHODS: The
expression levels of chemoresistance-related genes, MGMT, mdr1, MRP, MTIIA
and GST-pi, in 28 surgical specimens of human brain tumors and in 10 human
glioma cell lines were examined by Northern blot analysis. In addition, the
SD10 values of human glioma cell lines against ACNU, CDDP, ADM and VP16
were estimated by a cell survival assay. RESULTS: The expression levels of
each of the chemoresistance-related genes, except MRP, were generally
higher in brain tumors than those in non-neoplastic brain tissues. MGMT
expression correlated exclusively with ACNU resistance in all glioma cell
lines examined (p = 0.0002). The transcriptional level of mdr1 in the tumor
cells correlated with the SD10 values of VCR (p = 0.04) and ADM (p =
0.034). In contrast, the expression levels of MTIIA and GST-pi did not
correlate with resistance to any of the drugs tested. A correlation of MRP
mRNA expression with multidrug resistance was not apparent in the 10 cell
lines tested. CONCLUSIONS: The data indicate that knowledge of the
expression levels of MGMT and mdr1 may be particularly useful for a more
rational selection of drugs which are not influenced by these resistance
genes and which have improved efficacy against human brain tumors.
ORIGINAL ARTICLE
Expression pattern of chemoresistance-related genes in human malignant brain tumors: a working knowledge for proper selection of anticancer drugs
Department of Neurosurgery, National Cancer Center Hospital, Tokyo, Japan.
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