Publications (2)12.28 Total impact
-
Article: Targeting of survivin by nanoliposomal ceramide induces complete remission in a rat model of NK-LGL leukemia.
[show abstract] [hide abstract]
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 C₆-ceramide (C₆) 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 C₆-ceramide may be a promising therapeutic approach for a fatal leukemia.Blood 11/2010; 116(20):4192-201. · 9.90 Impact Factor -
Article: Growth of human pancreatic cancer is inhibited by down-regulation of gastrin gene expression.
[show abstract] [hide abstract]
ABSTRACT: This study evaluated the effects of gastrin messenger RNA (mRNA) down-regulation on growth of human pancreatic cancer. Gastrin expression was examined in human pancreatic cancer cell lines by reverse transcriptase-polymerase chain reaction, and peptide expression was assessed by immunocytochemistry. Gastrin was down-regulated using either stable transfection of an antisense gastrin cDNA or 1 of 3 shRNA (short hairpin RNA) constructs. Tumor formation was evaluated after either subcutaneous or orthotopic injections into nude mice. The effect of nanoliposomes loaded with gastrin siRNA (small interfering RNA) was tested in mice bearing pancreatic tumors. Stable transfection of gastrin antisense or shRNAs into BxPC-3 cells resulted in clones with more than 90% reduction in gastrin mRNA. Tumor growth rate and incidence of metastases in both wild-type and transfected pancreatic cancer cells were directly proportional to the degrees of gastrin mRNA expression. Immunofluorescence analysis confirmed that gastrin peptide levels were decreased in antisense and shRNA tumors. Gastrin knockdown clones had lower Ki-67 and increased cleaved caspase-3 staining, consistent with known effects of gastrin on proliferation and apoptosis. Tumors in mice treated with gastrin siRNA were smaller than controls. These results suggest that RNAi targeting of gastrin could serve as an effective treatment for pancreatic cancer.Pancreas 08/2009; 38(5):e151-61. · 2.39 Impact Factor
