Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling
| Autor: | Farnaz D. Fakhari, Blossom Damania, Dhavalkumar D. Patel, Sang Hoon Sin, William J. Harrington, Dirk P. Dittmer, Ling Wang, David H. Henry, Debasmita Roy, Michelle R. Staudt |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Lymphoma
Transcription Genetic viruses Immunology Biology Biochemistry Mice immune system diseases hemic and lymphatic diseases Cell Line Tumor medicine Animals Humans RNA Messenger Autocrine signalling Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Sirolimus Neoplasia Cell growth RPTOR virus diseases Cell Biology Hematology biochemical phenomena metabolism and nutrition medicine.disease Virology Xenograft Model Antitumor Assays Autocrine Communication Herpesvirus 8 Human Cancer research Disease Progression Phosphorylation Cytokines Primary effusion lymphoma medicine.drug |
| Popis: | The 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. |
| Databáze: | OpenAIRE |
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