Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD1839 (‘Iressa’)

Treatment schedule is of importance when gefitinib is combined with irradiation of glioma and endothelial cellsin vitro

“…Cells in the G 0 -G 1 phase are known to be more resistant to irradiation than cells in other phases of the cell cycle [14]. In a previous study, pre-treatment with gefitinib for 24 h prior to irradiation had radio-protective effects on 251MG cells, which supports our results seen after the same treatment schedule [12]. However, the same study also demonstrated that with short-pre-treatment with gefitinib prior to irradiation, radio-sensitizing effects was achieved in the same cell line.…”

“…Two pre-treatment schedules; 1) administration of gefitinib 30 min prior to single dose irradiation, followed by continuous incubation in presence of the drug for 6 days after irradiation, and 2) administration of gefitinib 24 h prior to single dose irradiation, without following incubation with gefitinib after the initial administration were used. To investigate the sensitivity to gefitinib in the postirradiation phase a third treatment schedule was used; 3) administration of gefitinib for varying length of time (2,4,8,12, and 24 h) after exposure to irradiation, followed by incubation with gefitinib for 6 days after the initial treatment.…”

“…Recently published data from a clinical phase II trial of gefitinib in recurrent glioblastoma demonstrated no objective tumor response [11]. An in vitro study on human glioma cells suggested that inhibition of EGFR signaling by gefitinib can be combined with radiotherapy as a beneficial therapeutic strategy, and also provided new data on the importance of timing of drug administration and irradiation interactions [12].…”

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

“…Gene therapy targeting TK domain in glioma therapy EGFR gene consists of 28 exons and encodes a 170 kDa of glycoprotein, comprising an extracellular region (encoded by exons 1-16), a membrane spanning region (encoded by exon 17) and an intracellular region (encoded by exons [18][19][20][21][22][23][24][25][26][27][28]. 19 The extracellular portion of EGFR is Figure 5 Compare to the group of PBS and psiRNA-scr, tumor growth in nude mice in the group of psiRNA-EGFR and panti-EGFR were inhibited (Po0.001) (a), EGFR expression of tumors was downregulated (b), GFAP expression was upregulated (c), apoptosis cells become obvious by TUNEL staining (d), and PCNA expression was downregulated (Po0.001) (e).…”

“…The antisense, dominant-negative or EGFR TK inhibitor could effectively inhibit tumor growth, induce apoptosis and cell cycle arrest, and enhance the radiosensitization of gliomas. [25][26][27][28] Using an antisense construct complementary to the 3 0 -coding region of EGFR mRNA (AS-3 0 ,552 bp), Pu et al 25 have demonstrated that exogenous antisense EGFR cDNA can successfully inhibit proliferation and induce apoptosis in C6 glioma cells in vitro, and stereotactically delivery of lipofectin-mediated antisense construct can prolong survival time of tumor-bearing rats. In addition, studies by Ng have demonstrated that antisense EGFR construct transfected into U87 glioma cell can impair the proliferation, reduce the soft agarose growth activities, induce G0/G1 arrest, and upregulate the expression of GFAP.…”