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Although a good correlation has been found between chromosome damage induced by UV in human lymphocytes and sister chromatid exchanges (SCE) in peripheral blood lymphocytes from the same subjects in the chromosomal aberration (CA) test, that correlation was not evident in a separate SCE study. The CA test and SCE analysis in human peripheral blood lymphocytes may be used to determine the characteristics of the UV-induced cellular repair processes occurring in chromosomes of human lymphocytes. Peripheral blood lymphocytes in blood samples from young volunteers were exposed to 10 mJ/cm2 dose of UV light in the presence or absence of the repair inhibitor methotrexate (MTX) during the SCE analysis. The ability of lymphocytes exposed to ultraviolet light to undergo spontaneous repair is unaffected by MTX. Both the SCE frequency and the UV-induced CA frequency decrease, with increasing time from UV exposure to metaphase analysis, indicating that some damage is repaired in the chromosomes with time. The data showed that the fraction of unrejoined SCEs in cultured human lymphocytes was more than 45% and declined to 12% of the total number of SCEs after exposure to UV for 20 h. This report shows that a modified method for the detection of UV-induced genotoxic damage in human lymphocytes with the use of MTX has resulted in an increase in the correlation between CA frequency and SCE frequency in human lymphocytes with increasing time from the UV exposure to the metaphase analysis. The increased correlation with SCEs after 10 h is in contrast to a similar study where the correlation was greatest after 40 h.Phase III study of FK778 (alvespimycin) given in combination with vinorelbine in patients with advanced soft tissue sarcoma.
The clinical benefit of chemotherapy in advanced soft tissue sarcomas (STS) is limited. Alvespimycin (FK778) is a cell-cycle selective inhibitor that has demonstrated activity in a variety of tumor types, including STS. The dose limiting toxicities of alvespimycin are neutropenia, fever and
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