Liposome-incorporated Grb2 antisense oligodeoxynucleotide increases the survival of mice bearing bcr-abl-positive leukemia xenografts

  • Authors:
    • Ana M. Tari
    • Yolanda Gutiérrez-Puente
    • Giuseppe Monaco
    • Clifton Stephens
    • Tong Sun
    • Michael Rosenblum
    • John Belmont
    • Ralph Arlinghaus
    • Gabriel Lopez-Berestein
  • View Affiliations

  • Published online on: November 1, 2007     https://doi.org/10.3892/ijo.31.5.1243
  • Pages: 1243-1250
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Abstract

We previously demonstrated that liposome-incorporated antisense oligodeoxynucleotide specific for the grb2 mRNA (L-Grb2) inhibited Grb2 protein expression and the proliferation of bcr-abl-positive leukemia cell lines. To determine whether L-Grb2 has the potential of being a therapeutic modality against bcr-abl-positive leukemia, we studied the tissue distribution of L-Grb2 in normal mice before studying its effects in mice bearing bcr-abl-positive leukemia xenografts. L-Grb2 was widely distributed in the body. The highest tissue concentrations of L-Grb2 were found in the spleen and liver, which are the organs where the tumor mass of bcr-abl-positive leukemia is mainly found. At 4 h post-injection, the amount of L-Grb2 detected per g of tissue was 64 µg in spleen and 50 µg in liver. Intravenous injection of bcr-abl-positive 32D mouse leukemia cells into radiated NOD/scid mice caused a lethal leukemia syndrome; we determined whether L-Grb2 could prolong the survival of mice bearing such xenografts. One day after leukemia cell inoculation, mice received twice weekly intravenous injections of L-Grb2. At an injection dose of 15 mg of L-Grb2 per kg of mouse body weight, 80% of mice treated with L-Grb2 survived to 48 days (end of study) whereas 0% of mice treated with the same dose of liposomal control oligonucleotide survived; the mean survival duration of these groups was 44 and 20 days, respectively. Our data indicate that L-Grb2 prolonged the survival of mice bearing bcr-abl-positive leukemia xenografts. L-Grb2 may be used as a novel cancer therapeutic modality.

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November 2007
Volume 31 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Tari, A.M., Gutiérrez-Puente, Y., Monaco, G., Stephens, C., Sun, T., Rosenblum, M. ... Lopez-Berestein, G. (2007). Liposome-incorporated Grb2 antisense oligodeoxynucleotide increases the survival of mice bearing bcr-abl-positive leukemia xenografts. International Journal of Oncology, 31, 1243-1250. https://doi.org/10.3892/ijo.31.5.1243
MLA
Tari, A. M., Gutiérrez-Puente, Y., Monaco, G., Stephens, C., Sun, T., Rosenblum, M., Belmont, J., Arlinghaus, R., Lopez-Berestein, G."Liposome-incorporated Grb2 antisense oligodeoxynucleotide increases the survival of mice bearing bcr-abl-positive leukemia xenografts". International Journal of Oncology 31.5 (2007): 1243-1250.
Chicago
Tari, A. M., Gutiérrez-Puente, Y., Monaco, G., Stephens, C., Sun, T., Rosenblum, M., Belmont, J., Arlinghaus, R., Lopez-Berestein, G."Liposome-incorporated Grb2 antisense oligodeoxynucleotide increases the survival of mice bearing bcr-abl-positive leukemia xenografts". International Journal of Oncology 31, no. 5 (2007): 1243-1250. https://doi.org/10.3892/ijo.31.5.1243