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C L Goolsby

Publications and source records attributed to C L Goolsby.

22 records · Page 2Linked to original sources

Flow cytometric DNA analysis of carcinoid tumors of the ileum and appendix.

Although all carcinoid tumors are considered potentially malignant, the biologic behaviors of appendiceal and ileal carcinoids are distinctly different. Appendiceal carcinoids often behave in a benign fashion, whereas ileal carcinoids pursue an aggressive course with frequent metastasis. Whether differences in DNA ploidy are related to this disparity in tumor behavior was addressed in this study. Flow cytometric DNA analyses were performed on paraffin blocks from 11 ileal and seven appendiceal carcinoid tumor cases. The mean coefficient of variation for all samples was 3.4 +/- 0.7. DNA aneuploidy was seen in two of the appendiceal cases and in six of the ileal cases. Metastases were seen in one of the appendiceal carcinoid cases, and that tumor was aneuploid. In six cases of carcinoid of the ileum, metastases were seen; of these, five tumors were aneuploid. In the ileal cases, despite the low number of cases examined, the correlation between DNA aneuploidy and metastases nearly reached statistical significance (P = .07) and showed a much stronger correlation than tumor size and metastases (P = .4). Although no statistical significance was reached in this study, the results are highly suggestive of DNA aneuploidy being an important predictor of malignant behavior in carcinoids of the ileum.

Adult↗

Viral and cellular oncogene expression during progressive malignant transformation of SV40 transformed human fibroblasts.

In vitro investigation of the multistep neoplastic progression which occurs during transformation of human cells has been hindered by resistance of human cells to both immortalization and tumorigenicity (Mut. Res. 199; 273, 1988). Previously our laboratory established a cell line, HSF4-T12, by transfection of normal human foreskin fibroblasts with the plasmid pSV3-neo which contains the early genes of simian virus 40 (SV40). A multistep progression in karyotypic alterations and transformed phenotype occurred resulting in a neoplastic cell line that was immortal, transformed, and tumorigenic. We have examined changes in the SV40 proteins, large T (T-antigen) and small t (t-antigen) antigens, and in the cellular protein, p53, during progressive transformation of these cells. Total viral protein expression relative to total cellular protein increased following immortalization of HSF4-T12 as did the ratio of T-antigen to t-antigen. Interestingly, no significant change in DNA content accompanied immortalization. However, during the progressive in vitro transformation of HSF4-T12 which occurred primarily post-immortalization, DNA index increased to 1.6 but only small additional increases in T-antigen expression were seen. No consistent or critical role for t-antigen in development of the tumorigenic phenotype was found in this system.

Antigens, Viral, Tumor↗

Karyotype evolution in a simian virus 40-transformed tumorigenic human cell line.

Normal human foreskin fibroblasts (HSF4) were transfected using the pSV3-neo plasmid. A pool of 10 G418-resistant colonies, HSF4-T12, showed a progressive increase in the expression of a number of in vitro transformation markers with passage in culture and became immortalized. Although no tumors were formed when cells were injected subcutaneously into nude mice, this cell line produced progressive tumors when cells were injected into preimplanted Gelfoam sponges in the mice. When these tumors were cultured in vitro and subsequently injected subcutaneously, progressive tumors were produced with median latency periods as short as 4 weeks. Three phases of cytogenetic change could be distinguished. At early passages after transfection. HSF4-T12 exhibited many random chromosomal changes. At a time just after immortalization, both flow karyotype and G-banded analyses showed the appearance of balanced clonal rearrangements. These included t(2;4), t(2;14), t(3;?), 6p-, i(6p), 8p-, t(14;15), i(15), and t(18;?). These clonal rearrangements were stable with passage in culture, and less variability from cell to cell was noted. The only consistent chromosomal loss observed was -Y. Analysis of three independent tumors showed characteristic loss of chromosomal material rather than balanced chromosomal rearrangements. Frequent loss of 6q and chromosomes #13, 15, 20, and Y was noted.

Animals↗

Cell bioprocessing in space: applications of analytical cytology.

Cell bioprocessing in space consists of the preparation, cultivation, purification and investigation of cells and their products in the microgravity environment of orbital space flight. Inertial acceleration is used as an independent variable to explore the limits of specific bioprocessing functions, such as cell growth and secretion, gravity-dependent phenomena in cell bioreactors, cell fusion, the influence of thermal convection on processes at cellular dimensions, the electrophoretic separation of cell subpopulations and subcellular particles, and two-phase partitioning of cells, bioparticles, and macromolecules. Analytical cytology techniques are under development for on-orbit application to future cell growth and separation experiments, such as those anticipated in the Space Station era.

Acceleration↗