TY - JOUR
T1 - Liposome-incorporated Grb2 antisense oligodeoxynucleotide increases the survival of mice bearing bcr-abl-positive leukemia xenografts
AU - Tari, Ana M.
AU - Gutiérrez-Puente, Yolanda
AU - Monaco, Giuseppe
AU - Stephens, Clifton
AU - Sun, Tong
AU - Rosenblum, Michael
AU - Belmont, John
AU - Arlinghaus, Ralph
AU - Lopez-Berestein, Gabriel
PY - 2007/11
Y1 - 2007/11
N2 - 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 postinjection, 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.
AB - 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 postinjection, 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.
KW - Antisense oligodeoxynucleotide
KW - Bcr-abl
KW - Grb2
UR - http://www.scopus.com/inward/record.url?scp=38449110056&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38449110056&partnerID=8YFLogxK
M3 - Article
C2 - 17912453
AN - SCOPUS:38449110056
SN - 1019-6439
VL - 31
SP - 1243
EP - 1250
JO - International journal of oncology
JF - International journal of oncology
IS - 5
ER -