Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling-Reference-Cited by-同舟云学术

Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling

Published:2006-11-02 Issue:5 Volume:109 Page:2165-2173
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Sin Sang-Hoon¹²,Roy Debasmita¹²,Wang Ling¹²,Staudt Michelle R.¹²,Fakhari Farnaz D.¹²,Patel Dhavalkumar D.¹²³⁴,Henry David⁵⁶,Harrington William J.⁷⁸,Damania Blossom A.¹²,Dittmer Dirk P.¹²

Affiliation:

1. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill;

2. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill;

3. Department of Medicine, University of North Carolina at Chapel Hill;

4. Thurston Arthritis Research Center, University of North Carolina at Chapel Hill;

5. Department of Medicine, University of Pennsylvania, Philadelphia;

6. Joan Karnell Cancer Center, University of Pennsylvania, Philadelphia;

7. Sylvester Cancer Center, University of Miami, FL;

8. Department of Medicine, University of Miami, FL

Abstract

AbstractThe antitumor potency of the mTOR inhibitor rapamycin (sirolimus) is the subject of intense investigations. Primary effusion lymphoma (PEL) appears as an AIDS-defining lymphoma and like Kaposi sarcoma has been linked to Kaposi sarcoma–associated herpesvirus (KSHV). We find that (1) rapamycin is efficacious against PEL in culture and in a murine xenograft model; (2) mTOR, its activator Akt, and its target p70S6 kinase are phosphorylated in PEL; (3) rapamycin inhibits mTOR signaling as determined by S6 phosphorylation; (4) KSHV transcription is unaffected; (5) inhibition of IL-10 signaling correlates with drug sensitivity; and (6) addition of exogenous IL-10 or IL-6 can reverse the rapamycin growth arrest. This validates sirolimus as a new treatment option for PEL.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/109/5/2165/1478535/zh800507002165.pdf

Reference63 articles.

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