First description of single-pass albumin dialysis combined with cytokine adsorption in fulminant liver failure and hemophagocytic syndrome resulting from generalized herpes simplex virus 1 infection

Tyrosine kinase inhibitors (TKI), erlotinib and gefitinib are small molecule inhibitors which are used for the treatment of lung cancer. But, the development of drug resistance has been reported as one of the major setbacks in oncology. This study focused on the mechanisms leading to secondary resistance by assessing the gene expression of BCL2 family proteins which are associated with the intrinsic apoptotic signaling pathway. 8 genes were investigated in erlotinib and gefitinib treated cells by real time PCR and protein analysis by western blotting. The cells were exposed to the test drugs 48 h prior to RNA or protein isolation. It was observed that BIM-EL, a pro-apoptotic protein was up-regulated in cells sensitive to the drugs but not in the resistant cells. On the other hand BCL2-?, an anti-apoptotic protein was up-regulated in the resistant cells and not in the sensitive cells. BCL2-? revealed a counter-regulation effect on BIM-EL and this effect is probably one of the causes of secondary resistance to erlotinib and gefitinib.