Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin Journal Article
| Authors: | Abolhoda, A.; Wilson, A. E.; Ross, H.; Danenberg, P. V.; Burt, M.; Scotto, K. W. |
| Article Title: | Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin |
| Abstract: | Overexpression of P-glycoprotein (Pgp), a multidrug transporter encoded by the MDR1 gene, is associated with chemoresistance in some human solid tumor malignancies. To date, analyses of MDR1 levels in solid tumors have examined constitutive increases in expression at relapse. In the present study, we have evaluated the acute induction of MDR1 gene expression in a solid human tumor as a function of time in response to in vivo exposure to chemotherapy. Five patients with unresectable sarcoma pulmonary metastases underwent isolated single lung perfusion with doxorubicin. Relative MDR1 gene expression was measured in metastatic tumor nodules and normal lung specimens after initiation of chemoperfusion. In four of five patients, a 3-15-fold (median, 6.8) increase in MDR1 RNA levels was detected in tumors at 50 min after administration of doxorubicin. In contrast, normal lung samples had very low levels of MDR1 RNA prior to perfusion, and no acute increases were observed after therapy. These findings demonstrate, for the first time, that MDR1 gene expression can be rapidly activated in human tumors after transient in vivo exposure to cytotoxic chemotherapy. |
| Keywords: | adult; clinical article; controlled study; human tissue; protein expression; bone neoplasms; middle aged; clinical trial; doxorubicin; antineoplastic agents; gene; reverse transcription polymerase chain reaction; computer assisted tomography; controlled clinical trial; gene expression; lung neoplasms; sarcoma; lung metastasis; gene expression regulation, neoplastic; messenger rna; reverse transcriptase polymerase chain reaction; neoplasm metastasis; intraarterial drug administration; high performance liquid chromatography; phase 1 clinical trial; multidrug resistance; glycoprotein p; genes, mdr; humans; human; male; female; priority journal; article; lung perfusion |
| Journal Title: | Clinical Cancer Research |
| Volume: | 5 |
| Issue: | 11 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1999-11-01 |
| Start Page: | 3352 |
| End Page: | 3356 |
| Language: | English |
| PUBMED: | 10589744 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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