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BMS-247550, a novel epothilone derivative, is being developed by Bristol-Myers Squibb Company (BMS) as an anticancer agent for the treatment of patients with malignant tumors. BMS-247550 is a semisynthetic analogue of the natural product epothilone B and has a mode of action analogous to that of paclitaxel (i.e., microtubule stabilization). In vitro, it is(More)
In order to better understand colon cancer, a model system reflecting the heterogenous nature of this disease was developed and used in the development of new cytotoxic and non-cytotoxic therapeutic approaches. A large bank of colon carcinoma cell lines was established from primary human colon carcinomas and grouped based on their tumorigenicity in athymic(More)
The anticancer agents 4'-demethylepipodophyllotoxin-4-(4,6-O-ethylidene-beta-D-glucopyra noside (etoposide) (VP16-213) and 4'-demethylepipodophyllotoxin-4-(4,6-O-thenylidene-beta-D-gl ucopyranoside (teniposide) (VM26) produce cytotoxicity by inhibiting type II topoisomerase, resulting in an accumulation of DNA breaks. By using alkaline elution techniques to(More)
Studies suggest that the anticancer drugs VP16-213 and VM26 produce cytotoxicity by inducing protein-associated DNA breakage in vivo through interaction with a yet unknown nuclear component. The effects of these drugs and their congeners on topoisomerase activities was investigated. VP16-213, VM26, and congeners active toward inducing DNA breaks also(More)
Eleutherobin is a novel natural product isolated from a marine soft coral that is extremely potent for inducing tubulin polymerization in vitro and is cytotoxic for cancer cells with an IC50 similar to that of paclitaxel. This compound is cross-resistant along with other multidrug-resistant agents against P-glycoprotein-expressing cells and is(More)
Very low concentrations of paclitaxel, a clinically active anticancer agent isolated from the bark of the Pacific yew tree, were found to produce micronuclei in human colon carcinoma cells, suggesting inhibition of mitotic spindle assembly or function. The possibility that paclitaxel acts at the level of the mitotic spindle was investigated by evaluating(More)
BMY25282, a newly designed analogue of mitomycin C (MMC) with the substitution of an amidine group at position 7 of MMC, can circumvent MMC resistance in a series of human colonic carcinoma cells that were selected for resistance to MMC (J.K.V. Willson et al., Cancer Res., 45:5281-5286, 1985). In this study MMC resistance was found to be associated with an(More)
Nuclear matrices from undifferentiated and differentiated Friend erythroleukemia cells have been obtained by a method which removes DNA in a physiological buffer. These matrices preserved the characteristic topographical distribution of condensed and diffuse "chromatin" regions, as do nuclei in situ or isolated nuclei. Histone H1 was released from the(More)
Fourteen congeners of podophyllotoxin were evaluated for their abilities to induce DNA breakage and inhibit growth of A549 human lung adenocarcinoma cells. Among the congeners studied were VP16-213, VM26, alpha-peltatin, beta-peltatin, and picropodophyllotoxin. Alkaline elution methods were used to assess DNA break frequencies following 1-h exposure to(More)
An actinomycete, strain C-38,383, was selected in a screening program for the isolation of novel antitumor agents. A yellow crystalline product, named rebeccamycin, was isolated from the mycelium and was found to have activity against P388 leukemia, L1210 leukemia and B16 melanoma implanted in mice. Rebeccamycin inhibits the growth of human lung(More)