Search PubMed⌕ Search

Biomedical subjects

G Salomons

Publications and source records attributed to G Salomons.

3 recordsLinked to original sources
PubMed1999

Glucocorticoid induced apoptosis in leukemia.

Lymphoid and leukemic cells are uniquely sensitive to the lytic actions of glucocorticoid hormones which activate a programmed cell death in these cells. The response to glucocorticoids is sensitive to modulations at each step of hormone action: cellular uptake, binding and activation of cytosolic receptors, nuclear translocation and transcriptional activity of the activated receptor and the expression levels of pro- and anti-apoptotic genes. This review, based mainly on our studies with leukemic cells in tissue culture and on clinical observations in childhood acute lymphoblastic leukemia, summarizes the potential impact of these checkpoints in the treatment of this disease. In addition, we will discuss interventions that may reverse resistance or promote sensitivity to apoptosis of leukemic cells by glucocorticoid hormones.

Apoptosis↗
PubMed1998

Involvement of the glucocorticoid receptor in stress-induced apoptosis of leukemic cells.

Glucocorticoid (GC) hormones induce apoptosis in lymphoid and leukemic cells by binding and activating cytosolic GC receptors. Because physiological stress often causes hormone-free GC receptor activation, we have investigated if stress-induced apoptosis of lymphoid cells is also mediated by the activation of the GC receptor pathway. In S49 T lymphoma cells, heat shock and deprivation of growth factors or nutrients caused nuclear translocation and loss of agonist binding capacity of GC receptors, similar to that in cells incubated with the glucocorticoid dexamethasone (DEX). In variant S49 H.2 cells, cross-resistance to DEX, temperature shocks and growth factor deprivation were associated with a higher threshold for hormone-dependent and -independent receptor activation in situ and with impaired in vitro activation of cytosolic receptors. Cross-resistance to DEX, low serum and heat shock was abrogated, however, by pharmacological sensitization of GC receptor activation with the drug meta-iodobenzylguanidine (MIBG). Sensitive S49 cells and resistant variants did not differ in the expression levels of the apoptosis-regulating genes bax, bad, bcl-X and bcl-2, the status of the p53 gene nor in a different requirement for the growth factors II-2, IL-4 or IL-9. The results suggest that ligand-independent activation of the GC receptor is a central signalling and controlling event in some forms of stress-induced apoptosis, assigning a novel function to the GC receptor in the regulation of lymphoid and leukemic cell numbers.

3-Iodobenzylguanidine↗