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EP1016 Evaluation of the antitumor effect of dioxade on the change in the content of free DNA in the blood
  1. I Vasilyeva1,
  2. V Bespalov1,
  3. A Semenov1,
  4. G Tochilnikov1,
  5. A Stukov1,
  6. K Senchik2 and
  7. G Gafton2
  1. 1Research Laboratory of Cancer Prevention and Oncopharmacology
  2. 2Department of General Oncology and Urology, N.N. Petrov Medical Research Center of Oncology, Saint-Petersburg, Russian Federation

Abstract

Introduction/Background Tumor growth is characterized by a modified ratio of apoptotic and mitotic indexes. Purpose of research was to assess the cfDNA levels change during tumor growth and the effect of antitumor drug from group of acetylated cytostatic dioxadet in a model of transplanted ascites ovarian cancer (OC) in female rats.

Methodology Tumor was transplanted intraperitoneally to 12-week-old Wistar rats (n=20) by introducing 1×107 tumor cells in 0.5 ml of saline. 48 h after OC inoculation dioxadet at the maximum tolerated dose of 1.5 mg/kg b.w. was injected intraperitoneally to rats (n=10) and saline was injected intraperitoneally to control rats (n=10). The results were evaluated by the increase in median survival (MS) of rats and by the content of cfDNA. Blood from rats was taken from the peripheral vein at intervals of 0, 2, 4, 6 and 8 days after inoculation and EDTA-plasma was separated. The cfDNA content was measured by ELISA assay.

Results The blood plasma cfDNA level of rats initially, before OC transplantation, was 1.6±0.33 ng/µl, without changing within 2 days, was significantly higher after 6 days (9.84±3.96 ng/µl, p<0.01) and remained elevated after 8 days. 2 days after the dioxadet administration the cfDNA level in the experimental group was lower than in the control group (0.78±0.33 vs 2.33±1.17 ng/µl, p<0.025), but 6 and 8 days after OC transplantation the cfDNA level did not differ significantly from the baseline. MS of rats treated with dioxadet was 46.0 days, control - 29.5 days (p=0.0049).

Conclusion A significant (56%) increase in rat’s life expectancy caused by dioxadet is accompanied by cfDNA level decrease in the 2 days after injection of the drug. Thus, the measurement of cfDNA can be used to assess the effectiveness of the cytostatic effect in the clinic.

Disclosure Nothing to disclose.

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