Work

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

Year: 2006

Type: article

Abstract: 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.

Source: Blood

DOI: 10.1182/blood-2006-06-028092

Authors: Sang-Hoon Sin, Debasmita Roy, Ling Wang, Michelle R. Staudt, Farnaz D. Fakhari, Dhavalkumar D. Patel, David Henry, William J. Harrington, Blossom A. Damania, Dirk P. Dittmer

Institutions: University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, University of Pennsylvania, University of Miami, Sylvester Comprehensive Cancer Center

Language: English

Topic: Viral-associated cancers and disorders

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Leukemia and Lymphoma Society, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research

Awards: G1465922187, G164741270, G1815638046, Viral Infection and Primary Pulmonary Hypertension, G2579308029, G3879490787, Role of CX3CR1 in the anti-tumor effects of NK cells, G4150258224, G5398899240, G5414952080, G605456412, Role of KSHV Viral Proteins in Signaling and Pathogenesis, G7699855597, Southeast Regional Centers of Excellence for Biodefense & Emerging Infectious Di, G9000158818, G9000162070, G9000253134, ART Modulation of Viral Pathogenesis

OpenAlex ID: W2099904968

FWCI: 5.422

Cites: 67

Cited by: 171

Related to: 10