Cytogenetics of gynecologic neoplasms.
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Biomedical subjects
Publications and source records attributed to N Auersperg.
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The etiology and early events in the progression of epithelial ovarian carcinomas are among the least understood of all major human malignancies. There are no adequate means for early detection of these neoplasms and, as a result, they are usually diagnosed in late stages. The purpose of this review is to point out some of the peculiar problems and limitations that have hampered progress in ovarian carcinogenesis research and to summarize new approaches and recent advances in our understanding of this process. The review first presents an overview of the properties of the ovarian surface epithelium (OSE) which is thought to be the source of epithelial ovarian carcinomas, followed by a discussion of recent research based on human OSE. This includes sections on methodology for the attainment and study of OSE, investigations of OSE from women with predisposing mutations, and attempts to convert normal OSE to malignancy. This overview is followed by a discussion of the contributions, potential, and limitations of animal models. The knowledge gained by these approaches will likely lead to improvements in our ability to prevent, diagnose, and treat ovarian cancer.
Cultured human umbilical vein endothelial cells (HUVECs) are a valuable model for investigation of endothelial functions, but they enter senescence at low passage. Transfection of early passage HUVECs with the early genes of SV40 greatly extends the replicative potential of these cells, but eventually results in marked changes in growth, morphology, and biochemistry. Here we report a modified approach that appears to have overcome the problem of late passage decline after transfection. Plasmid pX-8 containing the SV40 early genes was transfected into passage four HUVECs. At passage five, these transfectants were cloned by limiting dilution and selected on the basis of both morphological and biochemical resemblance to their untransfected counterparts. Two clones that expressed factor VIII and in which the basal and the tumor necrosis factor-alpha inducible levels of interleukin 6 and endothelial adhesion molecules were normal were chosen. Vimentin and fibronectin distribution in these clones resembled untransfected cells. At passage 25, growth pattern changes were becoming evident, but recloning these late passage clones recovered numerous subclones of normal, cobblestone appearance. Two of these were further characterized and found to resemble their original parental clone by all of the biochemical criteria listed above. These subclones appeared to transform more rapidly than the parental clone, but repeated subcloning again rescued clones with normal morphologies and normal biochemical characteristics. We conclude that periodic recloning may indefinitely perpetuate lines that are useful equivalents of their original counterparts.
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