Early detection of chemoresistance in vivo through the use of a radiolabeled antisense oligonucleotide
| Autor: | Muriel, Touboul, Anne-Sophie, Gauchez, Amaury Du Moulinet, D'Hardemare, Joël, Lunardi, Jean-Robert, Deverre, Claude, Pernin, Jean-Paul, Mathieu, Jean-Philippe, Vuillez, Daniel, Fagret |
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| Rok vydání: | 2003 |
| Předmět: |
Ovarian Neoplasms
Dose-Response Relationship Drug Mice Nude Nucleic Acid Hybridization Middle Aged Oligonucleotides Antisense Iodine Radioisotopes Kinetics Mice Drug Stability Tumor Cells Cultured Animals Humans Polyethyleneimine Female Tissue Distribution ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger Genes MDR K562 Cells |
| Zdroj: | Anticancer research. 22(6A) |
| ISSN: | 0250-7005 |
| Popis: | Radiolabeled antisense oligonucleotide to target the mRNA of the hmdr1 gene for diagnostic purposes is a new concept for evaluating the chemoresistance of tumors in vivo.An 18 mer complementary to the zone which contains the translation initiation codon of the hmdr1 gene was modified using one phosphoramidate group and one dimethoxytrityle group at the 5' and 3'ends. It permitted probe radiolabeling by 125I. Chemical modifications made to the antisense probe ensured the stability in biological media tested by incubation with human serum at 37 degrees C from 5 minutes to 24 hours. These modifications did not interfere with recognition of the target. Retention of the antisense probe followed the expression level of the target transcript in in vitro and in vivo studies. In vitro, after a 2-hour incubation in the presence of K562--sensitive (S) and- resistant (R) cell lines, uptake was respectively 4.27 +/- 0.96% ID/mg protein and 7.78 +/- 0.46% ID/mg protein (p0.001). In vivo, the ratios between radioactivity found in the tumor and that found in the striated muscle and in the blood were, respectively, 20 and 3 for IGR OV1 resistant tumor and 1 and 0.3 for the sensitive one.In our study, resistant cell lines and tumor showed greater retention of the specific probe than the sensitive ones. This constitutes a further advance towards non invasive imaging of resistant genes involved in chemoresistance. These results are encouraging: the current trend in innovative cancer therapy is moving towards targeting the genes of interest. |
| Databáze: | OpenAIRE |
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