We have used RNA aptamer:gelonin conjugates to target and specifically destroy cells overexpressing the known cancer biomarker prostate-specific membrane antigen (PSMA). Aptamer:toxin conjugates have an IC 50 of 27 nmol/L and display an increased potency of at least 600-fold relative to cells that do not express PSMA. The aptamer not only promotes uptake into target cells but also decreases the toxicity of gelonin in non-target cells. These results validate the notion that ''escort aptamers'' may be useful for the treatment of specific tumors expressing unique antigen targets. (Cancer Res 2006; 66(12): 5989-92)
SUMMARYThe distribution of F-actin in the fission yeast Schizosaccharomyces pombe was investigated by fluorescence microscopy using rhodamine-conjugated phalloidin. Fluorescence was seen either at the ends of the cell or at the cell equator. End staining was predominantly in the form of dots whilst equatorial actin was resolved as a filamentous band. The different staining patterns showed a close correlation with the known pattern of cell wall deposition through the cell cycle. In small, newly divided cells actin was localized at the single growing cell end whilst initiation of bipolar cell growth was coincident with the appearance of actin at both ends of the cell. As cells ceased to grow and entered cell division, a ring of actin was seen to anticipate the deposition of the septum at cytokinesis. The relationship between actin and cell wall deposition was further confirmed in three temperature-sensitive cell division cycle (cdc) mutants; cdc 10, cdc 11 and cdc 13. Immunofluor escence microscopy of S. pombe with an anti-tubulin antibody revealed a system of cytoplasmic microtubules extending between the cell ends. The function of these was investigated in the coldsensitive, benomyl-resistant mutant ben A. In cold-grown cells actin was seen to form conspicuous filamentous rings around the nucleus. The origin of these and the possible role of microtubules in the cell-cycle-dependent rearrangements of F-actin are discussed.
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