Biomedical subjects

Rheem D Medh

Publications and source records attributed to Rheem D Medh.

3 recordsLinked to original sources

PubMed2003

Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis.

Three closely related clones of leukemic lymphoid CEM cells were compared for their gene expression responses to the glucocorticoid dexamethasone (Dex). All three contained receptors for Dex, but only two responded by undergoing apoptosis. After a time of exposure to Dex that ended late in the interval preceding onset of apoptosis, gene microarray analyses were carried out. The results indicate that the expression of a limited, distinctive set of genes was altered in the two apoptosis-prone clones, not in the resistant clone. That clone showed altered expression of different sets of genes, suggesting that a molecular switch converted patterns of gene expression between the two phenotypes: apoptosis-prone and apoptosis-resistant. The results are consistent with the hypothesis that altered expression of a distinctive network of genes after glucocorticoid administration ultimately triggers apoptosis of leukemic lymphoid cells. The altered genes identified provide new foci for study of their role in cell death.

Apoptosis↗

PubMed2002

Microarray-based expression profiling of normal and malignant immune cells.

Recent advances in gene microarray technology have facilitated global analyses of gene expression profiles in normal and malignant immune cells. Great strides have been made in our understanding of molecular differences among various types of immune cells, the process of T and B cell activation, and the genomic changes that convert normal cells to malignant ones. Genomic analysis has become a crucial aspect of cancer classification, diagnosis, therapy, and prognosis. This technology has the potential to reveal the comprehensive transcriptional alterations that dictate fundamental biological processes such as signal transduction in response to specific stimuli, cell growth, differentiation, and apoptosis. While reaping the benefits of genomic analyses, it is important to realize its limitations with respect to accuracy of interpretation, reproducibility, and signal detection. It is crucial to optimize signals for individual probe-target pairs and to develop a uniform set of criteria for data analyses. The development of a public-access database of results from individual laboratories will pave the way for identifying discrepancies and advancing scientific breakthroughs.

Gene Expression Profiling↗

PubMedDate not supplied

Glucocorticoids and polyamine inhibitors synergize to kill human leukemic CEM cells.

Glucocorticoids are well-known apoptotic agents in certain classes of lymphoid cell malignancies. Reduction of intracellular polyamine levels by use of inhibitors that block polyamine synthesis slows or inhibits growth of many cells in vitro. Several such inhibitors have shown efficacy in clinical trials, though the toxicity of some compounds has limited their usefulness. We have tested the effects of combinations of the glucocorticoid dexamethasone (Dex) and two polyamine inhibitors, difluoromethylornithine (DFMO) and methyl glyoxal bis guanylhydrazone (MGBG), on the clonal line of human acute lymphoblastic leukemia cells, CEM-C7-14. Dex alone kills these cells, though only after a delay of at least 24 hours. We also evaluated a partially glucocorticoid-resistant c-Myc-expressing CEM-C7-14 clone. We show that Dex downregulates ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis. Pretreatment with the ODC inhibitor DFMO, followed by addition of Dex, enhances steroid-evoked kill slightly. The combination of pretreatment with sublethal concentrations of both DFMO and the inhibitor of S-adenosylmethionine decarboxylase, MGBG, followed by addition of Dex, results in strong synergistic cell kill. Both the rapidity and extent of cell kill are enhanced compared to the effects of Dex alone. These results suggest that use of such combinations in vivo may result in apoptosis of malignant cells with lower overall toxicity.

Apoptosis↗