Ompound in the bone. H Highest probably intact, show their respective targets to significant absorption thwart and / or anti-tumor activity of t. The current results indicate that our approach to the bridge, the unique chemical hydrolytic stability PIK-90 can t by chemical modifications VER Can be changed the first suitable method for specific delivery of antineoplastic agents against tumors in bone sites to be. MBC 11 was from both immunocompetent and immunodeficient M Mice tolerated well. We observed that show Mice t Resembled for 49 days with a maximum of 500 g / day treated MBC 11 has no weight loss or urea nitrogen and creatinine. In addition, there were hemoglobin H, White S Blutk rperchen, Modify platelets, reticulocytes in dogs given five matched t Iv at doses of up to 75 mg / kg / day MBC 11.
MBC 11 is effective to the tumor burden and bone Erh Increase bone volume in M Nozzles reduce with a breast cancer-induced bone disease. No significant difference was observed between NPI-2358 high and low doses, suggesting that the 11-MBC concentrations used in this study can, over the linear range of the dose-response curve. The absence of a dose-response relationship k Nnte that be The Gr e of the sample in some groups of animals and the variability of t between the relatively high levels of luciferase for the selected hlten treatment groups. We have also observed that MBC 11, no inhibitory effect on the formation of lung metastases, with the compound had, s term, to release the drug in the bone chamber and targeted skeletal tumor burden.
Our in vivo and in vitro studies suggest that zoledronic acid and etidronate are associated with a high level of anti-tumor activity of t, and support previous observations that these high concentrations of cytotoxic activity for their t are required. Similar to previous investigators, we observed that a high Ma inhibits the growth of zoledronate of different types of multiple myeloma cells in vitro. We observed that much lower MBC 11 levels significantly inhibited the proliferation of multiple myeloma cells indicating that MBC 11100 1000 times more potent than zoledronate or etidronate, to inhibit cell proliferation of multiple myeloma. These results are consistent with published results have shown that MBC 11 100 st time Was more strongly inhibited than zoledronate in breast cancer cell growth.
Shown in contrast to previous results, the positive effects in both iv and sc administration of zoledronate on bone and lung metastases and survival time, we observed no significant benefit of zoledronic acid on bone and lung metastases or survival in vivo. Other studies have shown that intravenously Se zoledronate reduced bone metastases and the lung at 22 days and modest, but significant survival at 5 days in Mice inoculated 4T1 agrees on. Clinical use of zoledronate inhibited tumor growth of the skeleton in the mouse model B02/GFP.2, but a strong dose of zoledronic acid has no effect on tumor progression in extramedull Re space. Zoledronate also the survival of 12 days, engaged in the model of myeloma 5T2MM agrees on. The absence of a significant survival advantage in the zoledronate in our study is likely Differences in the cumulative dose, route of administration and types of animal models used in each study. Reinholz et al. Page 10 bones. Author manuscript, increases available in PMC 2011 1 July. PA Author Manuscript NIH-PA Author Manuscript NIH NIH