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Targeting of survivin by nanoliposomal ceramide induces complete remission in a rat model of NK-LGL leukemia

  1. Author:
    Liu, X.
    Ryl, L.
    Yang, J.
    Liao, A. J.
    Aliaga, C.
    Watts, R.
    Tan, S. F.
    Kaiser, J.
    Shanmugavelandy, S. S.
    Rogers, A.
    Loughran, K.
    Petersen, B.
    Yuen, J.
    Meng, F. X.
    Baab, K. T.
    Jarbadan, N. R.
    Broeg, K.
    Zhang, R. R.
    Liao, J. S.
    Sayers, T. J.
    Kester, M.
    Loughran, T. P.

  2. Author Address

    [Liu, Xin; Ryland, Lindsay; Yang, Jun; Liao, Aijun; Aliaga, Cesar; Watts, Rebecca; Tan, Su-Fern; Rogers, Andrew; Loughran, Kathleen; Petersen, Bailey; Yuen, Jonathan; Meng, Fanxue; Baab, Kendall Thomas; Jarbadan, Nancy Ruth; Broeg, Kathleen; Zhang, Ranran; Liao, Jason; Kester, Mark; Loughran, Thomas P., Jr.] Penn State Univ, Coll Med, Penn State Hershey Canc Inst, Hershey, PA 17033 USA. [Ryland, Lindsay; Kaiser, James; Shanmugavelandy, Sriram S.; Kester, Mark] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. [Liao, Aijun] China Med Univ, Shengjing Hosp, Dept Hematol, Shenyang, Peoples R China. [Sayers, Thomas Joseph] NCI, SAIC Frederick, Expt Immunol Lab, Frederick, MD 21701 USA.;Liu, X, Penn State Univ, Coll Med, Penn State Hershey Canc Inst, CH74,Rm 4401,500 Univ Dr,POB 850, Hershey, PA 17033 USA.;Xliu2@hmc.psu.edu
    1. Year: 2010
    2. Date: Nov
  2. Journal: Blood
    1. 116
    2. 20
    3. Pages: 4192-4201
  4. Type of Article: Article
  5. ISSN: 0006-4971
  1. Abstract:

    The natural killer (NK) type of aggressive large granular lymphocytic (LGL) leukemia is a fatal illness that pursues a rapid clinical course. There are no effective therapies for this illness, and pathogenetic mechanisms remain undefined. Here we report that the survivin was highly expressed in both aggressive and chronic leukemic NK cells but not in normal NK cells. In vitro treatment of human and rat NK-LGL leukemia cells with cell-permeable, short-chain C-6-ceramide (C-6) in nanoliposomal formulation led to caspase-dependent apoptosis and diminished survivin protein expression, in a time-and dose-dependent manner. Importantly, systemic intravenous delivery of nanoliposomal ceramide induced complete remission in the syngeneic Fischer F344 rat model of aggressive NK-LGL leukemia. Therapeutic efficacy was associated with decreased expression of survivin in vivo. These data suggest that in vivo targeting of survivin through delivery of nanoliposomal C-6-ceramide may be a promising therapeutic approach for a fatal leukemia. (Blood. 2010;116(20):4192-4201)

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External Sources

  1. View Full Text
  2. DOI: 10.1182/blood-2010-02-271080
  3. View record in Web of Science®
  4. WOS: 000284359400027

Library Notes

  1. Fiscal Year: FY2010-2011
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