PubMed · 15017994
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Guido Adler, Peter M Schlag. 2004. Time for progress.. https://doi.org/10.1159/000077180
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In this work, we shed new light on the highly debated issue of chromatin fragmentation in cryopreserved cells. Moreover, for the first time, we describe replicating cell-specific DNA damage and higher-order chromatin alterations after freezing and thawing. We identified DNA structural changes associated with the freeze-thaw process and correlated them with the viability of frozen and thawed cells. We simultaneously evaluated DNA defects and the higher-order chromatin structure of frozen and thawed cells with and without cryoprotectant treatment. We found that in replicating (S phase) cells, DNA was preferentially damaged by replication fork collapse, potentially leading to DNA double strand breaks (DSBs), which represent an important source of both genome instability and defects in epigenome maintenance. This induction of DNA defects by the freeze-thaw process was not prevented by any cryoprotectant studied. Both in replicating and non-replicating cells, freezing and thawing altered the chromatin structure in a cryoprotectant-dependent manner. Interestingly, cells with condensed chromatin, which was strongly stimulated by dimethyl sulfoxide (DMSO) prior to freezing had the highest rate of survival after thawing. Our results will facilitate the design of compounds and procedures to decrease injury to cryopreserved cells.
BACKGROUND: The aim of this study was to evaluate whether photodynamic therapy (PDT) with verteporfin is able to induce tumor cell necrosis in human uveal melanomas. METHODS: On four eyes with an uveal melanoma, PDT with verteporfin was performed on the tumor 2-3 days before planned enucleation. The eyes were evaluated histologically. RESULTS: In two melanomas with only mild pigmentation some effects after PDT were detected on tumor tissue in a depth up to 2.5 mm at light doses > or =100 J/cm(2). Histologically, vascular occlusion and thrombosis in tumor vessels were observed. In the heavily pigmented melanoma no tumor necrosis was induced with the above-mentioned parameters. CONCLUSION: Depending on treatment parameters and tumor pigmentation, PDT with verteporfin is able to induce tumor necrosis in human uveal melanomas. Based on these results it is possible that PDT can become an adjuvant treatment method for uveal melanoma.
In this study, we demonstrate that 17beta-estradiol (E(2)) inhibits human insulin receptor (IR) gene expression in a dose- and time-dependent manner in U-937 human promonocytic cells. Using cells transfected with the -1819 to -271 bp fragment of the human IR promoter (wild type promoter) and treated with E(2), we show that this repression is regulated at the transcriptional level. The steroid was also found to diminish the insulin responsiveness of the cells in terms of cell survival, DNA synthesis, glucose transport, and glucose oxidation, this last effect possibly involving reduced phosphatidylinositol 3-kinase (PI3-kinase) activity. These data provide new information on the molecular mechanisms of estrogen-inducing insulin resistance in human cells.