Collateral methotrexate resistance in cisplatin-selected murine leukemia cells
Braz. j. med. biol. res
;
32(7): 827-33, July 1999.
Article
in English
| LILACS
| ID: lil-234887
RESUMO
Resistance to anticancer drugs is a major cause of failure of many therapeutic protocols. A variety of mechanisms have been proposed to explain this phenomenon. The exact mechanism depends upon the drug of interest as well as the tumor type treated. While studying a cell line selected for its resistance to cisplatin we noted that the cells expressed a >25,000-fold collateral resistance to methotrexate. Given the magnitude of this resistance we elected to investigate this intriguing collateral resistance. From a series of investigations we have identified an alteration in a membrane protein of the resistant cell as compared to the sensitive cells that could be the primary mechanism of resistance. Our studies reviewed here indicate decreased tyrosine phosphorylation of a protein (molecular mass = 66) in the resistant cells, which results in little or no transfer of methotrexate from the medium into the cell. Since this is a relatively novel function for tyrosine phosphorylation, this information may provide insight into possible pharmacological approaches to modify therapeutic regimens by analyzing the status of this protein in tumor samples for a better survival of the cancer patients
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Leukemia L1210
/
Methotrexate
/
Cisplatin
/
Antineoplastic Agents
Type of study:
Practice guideline
Limits:
Animals
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
1999
Type:
Article
/
Congress and conference
Similar
MEDLINE
...
LILACS
LIS