OBJECTIVE: We investigated whether the @entity1862 -induced loss of double-minute chromosomes containing amplified @entity12841 ( @entity12841 ) genes would lead to a loss of @entity7433 of a @entity463 multiforme cell line. METHODS: @entity463 were treated in vitro with 0 (HU0) or 100 micromol/L (HU100) @entity1862 and then injected into the flanks of @entity19 . Survival and @entity5 volumes were evaluated. Pulsed-field gel electrophoresis, Southern blot hybridization, and slot-blot analysis were used to determine @entity12841 amplification levels. Flow cytometry and immunofluorescent staining were used for cell-cycle analysis and @entity12841 protein expression. RESULTS: Prior to injection, HU100 cells lost 95% of their amplified @entity12841 genes and developed into @entity5 6 weeks after injection versus 3 weeks for HU0 cells. @entity19 with @entity5 had a median survival of 62 days versus 43 days for control @entity19 with @entity5 . Pulse-field gel electrophoresis analysis showed that @entity5 had reamplified the @entity12841 gene as double-minute chromosomes of the same size as those originally present before @entity1862 treatment. When HU100 cells were cultured in the absence of @entity1862 , the @entity12841 gene also reamplified. HU100 cells grew at less than half the rate of untreated HU0 control cells in culture and showed a decreased number of cells entering the cell cycle. Immunofluorescent staining of HU150 (150 micromol/L) cells showed decreased @entity12841 protein expression. CONCLUSION: The @entity12841 gene is important for @entity7433 in @entity19 and growth in culture. @entity1862 induces the loss of double-minute chromosome-amplified @entity12841 genes against a selection gradient and significantly delays the onset of @entity5 . These results support the potential use of low-dose @entity1862 for the treatment of @entity1 @entity463 multiforme.

The @entity1862 -induced loss of double-minute chromosomes containing amplified epidermal growth factor receptor genes reduces the @entity7433 and growth of XXXX @entity463 multiforme.

@entity1 :: ('9606', 'Species') :: ['human'] @entity12841 :: ('13649(Tax:10090)', 'Gene') :: ['EGFR', 'epidermal growth factor receptor'] @entity1862 :: ('MESH:D006918', 'Chemical') :: ['Hydroxyurea', 'hydroxyurea'] @entity7433 :: ('MESH:D002471', 'Disease') :: ['tumorigenicity'] @entity19 :: ('10090', 'Species') :: ['mice', 'nude mice', 'Mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['HU0 tumors', 'tumor', 'HU100 tumors', 'tumors'] @entity463 :: ('MESH:D005909', 'Disease') :: ['Glioblastoma multiforme cells', 'glioblastoma']
@entity1 :: (9606,Species) :: ['human']
