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Advances in Brief

Multidrug Resistance Protein (MRP) Expression in Retinoblastoma Correlates with the Rare Failure of Chemotherapy despite Cyclosporine for Reversal of P-Glycoprotein

Helen S. L. Chan, Ying Lu, Thomas M. Grogan, George Haddad, David R. Hipfner, Susan P. C. Cole, Roger G. Deeley, Victor Ling and Brenda L. Gallie
Helen S. L. Chan
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Ying Lu
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Thomas M. Grogan
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George Haddad
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David R. Hipfner
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Susan P. C. Cole
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Roger G. Deeley
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Victor Ling
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Brenda L. Gallie
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DOI:  Published June 1997
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Abstract

Failure of chemotherapy associated with expression of the multidrug resistance protein p170 frequently occurs in retinoblastoma (RB). Despite using cyclosporine, which inhibits p170 and improves our chemotherapy results, rare failures occur. In nonmetastatic primarily enucleated RBs, we show expression of p170 in 3 of 18 samples and expression of multidrug resistance protein (MRP), the second protein associated with resistance to chemotherapy, in 1 of 18 samples. All three RBs that failed chemotherapy without cyclosporine expressed MRP with p170. All three RBs that were enucleated immediately when chemotherapy failed despite the addition of cyclosporine expressed only MRP. One RB enucleated 2 years after failing chemotherapy with cyclosporine, despite radiation and salvage chemotherapy, expressed both p170 and MRP. Two metastatic RBs that expressed both p170 and MRP at diagnosis and at recurrence failed chemotherapy without cyclosporine, whereas one metastatic RB that expressed neither protein was cured by chemotherapy without cyclosporine. MRP may result in failure of chemotherapy despite the elimination of p170-expressing clones by cyclosporine.

Footnotes

  • ↵1 Supported by grants from the National Cancer Institute of Canada (to H. S. L. C., V. L., B. L. G., R. G. D., and S. P. C. C.); Medical Research Council of Canada (to H. S. L. C., S. P. C. C., R. G. D., V. L., and B. L. G)0; Elsa U. Pardee Foundation (to H. S. L. C.); Sandoz Canada, Inc., Hospital for Sick Children Pediatric Consultants and Research Institute, Atkinson Charitable Foundation (to H. S. L. C.); Canadian Genetic Diseases Network; Retinoblastoma Family Association; and Royal Arch Masons of Canada (to B. L. G.); and by NIH USPHS Grant CA37130 (to V. L.) and National Cancer Institute Grants CA32102 and CA17094 (to T. M. G.). S. P. C. C. is a Senior Scientist of the Ontario Cancer Treatment and Research Foundation. R. G. D. is the Stauffer Research Professor of Queen's University. B. L. G. is a Distinguished Scientist of the Medical Research Council of Canada.

  • ↵2 To whom requests for reprints should be addressed. Phone: (416) 813-5872; Fax: (416) 813-5327.

  • Received February 17, 1997.
  • Accepted April 30, 1997.
  • ©1997 American Association for Cancer Research.
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June 1997
Volume 57, Issue 12
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Multidrug Resistance Protein (MRP) Expression in Retinoblastoma Correlates with the Rare Failure of Chemotherapy despite Cyclosporine for Reversal of P-Glycoprotein
Helen S. L. Chan, Ying Lu, Thomas M. Grogan, George Haddad, David R. Hipfner, Susan P. C. Cole, Roger G. Deeley, Victor Ling and Brenda L. Gallie
Cancer Res June 15 1997 (57) (12) 2325-2330;

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Multidrug Resistance Protein (MRP) Expression in Retinoblastoma Correlates with the Rare Failure of Chemotherapy despite Cyclosporine for Reversal of P-Glycoprotein
Helen S. L. Chan, Ying Lu, Thomas M. Grogan, George Haddad, David R. Hipfner, Susan P. C. Cole, Roger G. Deeley, Victor Ling and Brenda L. Gallie
Cancer Res June 15 1997 (57) (12) 2325-2330;
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