Info

aData represent means ± SD.

bp = 0.05 vs the combined DFMO treatment groups (10 and 14 wk). cp < 0.05 vs each of the remaining groups. (Reproduced with permission from ref. 44.)

Fig. 3. Growth in nude mice of orthotopically implanted green fluorescent protein-tagged MDA-MB-435 breast cancer cells. A total of 1 x 106 cells in 0.1 mL Hank's balanced salt solution were injected in athymic mice in the absence and in the presence of DFMO treatment (2% in drinking H2O). Growth curve analysis using a linear model revealed no statistically significant difference between control and DFMO treatment. (Reproduced from ref. 44 with permission of Springer Science and Business Media.)

Days 10 16 24 31 38 45

Fig. 3. Growth in nude mice of orthotopically implanted green fluorescent protein-tagged MDA-MB-435 breast cancer cells. A total of 1 x 106 cells in 0.1 mL Hank's balanced salt solution were injected in athymic mice in the absence and in the presence of DFMO treatment (2% in drinking H2O). Growth curve analysis using a linear model revealed no statistically significant difference between control and DFMO treatment. (Reproduced from ref. 44 with permission of Springer Science and Business Media.)

different experimental systems of breast cancer metastasis. Preliminary unpublished data indicate that DFMO treatment significantly reduces skeletal metastasis from MDA-MB-435 cells injected in the left ventricle of the heart of athymic mice. In addition, DFMO administration also reduces the incidence of pulmonary metastasis in mice injected iv with MDA-MB-231 human breast cancer cells (unpublished observations).

As discussed previously, AdoMetDC may be an additional important target in the development of optimal antipolyamine therapy for prevention of metastasis. SAM486A has already been shown to have antimetastatic activity against melanoma in nude mice (45). We are particularly interested in the combined inhibition of ODC and AdoMetDC to optimize polyamine depletion and antitumor action. We have recently observed that combined treatment with DFMO and SAM486A not only had a synergistic inhibitory effect on tumor cell proliferation, but also on invasiveness in matrigel (35). We are testing whether the combined administration of these two compounds has an antimetastatic effect superior to the individual treatments.

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