Xiap downregulation together with wild type p reconstitution, however, not only further increased p content, but significantly increased apoptosis in these otherwise pdeficient cells.This is consistent with the observation that, although adenoviral infection efficiency was close to, only about of the cells were apoptotic hafter infection. Xiap downregulation not only induces apoptosis but also sensitizes chemoresistant wild type p hOSE cancer cells to the proapoptotic action of cisplatin.These findings provide a new concept for the development of novel therapeutic approaches in the treatment of chemoresistant hOSE cancer.Click on Request Permissions which will take you to the Copyright Clearance Centers Downloaded from cancerres.aacrjournals.org on April. American Association for Cancer Research. We have developed a lowmolecularweight EGFR tyrosine kinase inhibitor. The level of expression of EGFR did not determine xenograft tumor sensitivity to ZD.Flunisolide Longterm ZD treatment of mice bearing A xenografts was well tolerated, and ZD completely inhibited tumor growth and induced regression of established tumors.No drugresistant tumors appeared during ZD treatment, but some tumors regrew after drug withdrawal.The issue of toxicity could be addressed only with the inhibitors at hand, but attenuation, rather than complete blockade, of the abnormally active signal in tumors, implied by the high levels of EGFR expression, could provide an opportunity to define an acceptable therapeutic ratio between efficacy and toxicity.An alternative approach to targeting these growth factor receptors involves inhibition of their TK activity. The costs of publication of this article were defrayed in part by the payment of page charges.The abbreviations used are: EGFR, epidermal growth factor receptor; TK, tyrosine kinase; TKI, tyrosine kinase inhibitor; RTK, receptor tyrosine kinase; MEK, mitogenactivated proteinextracellular signalrelated kinase kinase; ERK, extracellular signalrelated kinase; MAPK, mitogenactivated protein kinase; MTT, diphenyltetrazolium bromide; HUVEC, human umbilical vascular endothelial cell; FGF, fibroblast growth factor; VEGF, vascular endothelial growth factor; TGF, transforming growth factor. Medium was replaced with l of acid alcohol per well.Cell growth was calculated by subtracting the mean day absorbance value from the mean absorbance value at day. Cell growth inhibition was confirmed, with KB cells grown under similar conditions in well dishes, by trypsinization and cell counting. Expression of phosphorylated EGFR varied among the selected tumor cell lines markedly increased tyrosine phosphorylation of EGFR in all four cell lines. Incubation with ZD for hbefore EGF stimulation produced a dosedependent inhibition of EGFR autophosphorylation in all of the tumor cell lines. Similarly, ZD inhibited the growth of A lung tumor xenografts in a dosedependent manner.A more stringent test was provided by tumors that were month old at the start of therapy.The cells were harvested by use of a well plate harvester. Mice were housed in airfiltered laminar flow cabinets and handled using aseptic procedures with a h light cycle and food and water ad libitum.Fragments of tumor tissue or tumor cells under Letermovir anesthesia.Tumors were allowed to establish growth, and at a designated time after implantation, treatment with ZD commenced.The maximum dose of ZD administered was mgkg; this dose did not induce any significant adverse effect on body weight or produce any other signs of toxicity.