Issues

The antibody-linked maytansinoid DM1 conjugate and its intracellular metabolites bind to microtubule ends and suppress microtubule dynamics with high potency at subnanomolar concentrations, thus arresting mitosis and inhibiting tumor cell proliferation. Using immunofluorescence microscopy, the MCF7 breast cancer cell is shown arrested in an abnormal mitosis after incubation with 340 pmol/L of the metabolite S-methyl DM1 (the concentration that half-maximally arrests mitosis) and exhibits uncongressed chromosomes (blue) located at one of the spindle poles which is marked by anti-pericentrin staining (red). Microtubules are green. For details, see articles by Oroudjev and colleagues on page 2700 and Lopus and colleagues on page 2689.