PMID- 16675563
OWN - NLM
STAT- MEDLINE
DCOM- 20060821
LR  - 20150204
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 12
IP  - 9
DP  - 2006 May 1
TI  - Genomic alterations in human malignant glioma cells associate with the cell 
      resistance to the combination treatment with tumor necrosis factor-related 
      apoptosis-inducing ligand and chemotherapy.
PG  - 2716-29
AB  - PURPOSE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is 
      currently under clinical development as a cancer therapeutic agent. Many human 
      malignant glioma cells, however, are resistant to TRAIL treatment. We, therefore, 
      investigated the genomic alterations in TRAIL-resistant malignant glioma cells. 
      EXPERIMENTAL DESIGN: Seven glioma cell lines and two primary cultures were first 
      analyzed for their sensitivity to TRAIL and chemotherapy and then examined for 
      the genomic alterations in key TRAIL apoptotic genes by comparative genomic 
      hybridization (CGH), G-banding/spectral karyotyping, and fluorescence in situ 
      hybridization (FISH). RESULTS: CGH detected loss of the chromosomal regions that 
      contain the following genes: 8p12-p23 (DR4 and DR5), 2q33-34 (caspase-8), 11q13.3 
      (FADD), 22q11.2 (Bid), and 12q24.1-q24.3 (Smac/DIABLO) in TRAIL-resistant cell 
      lines. Spectral karyotyping showed numerical and structural aberrations involving 
      the chromosomal regions harboring these genes. A combination of 
      G-banding/spectral karyotyping and FISH further defined the loss or gain of gene 
      copy of these genes and further showed the simultaneous loss of one copy of 
      DR4/DR5, caspase-8, Bid, and Smac in two near-triploid cell lines that were 
      resistant to the combination treatment with TRAIL and chemotherapy. Loss of the 
      caspase-8 locus was also detected in a primary culture in correlation with the 
      culture resistance to the combined TRAIL and chemotherapy treatment. CONCLUSIONS: 
      The study identifies chromosomal alterations in TRAIL apoptotic genes in the 
      glioma cells that are resistant to the treatment with TRAIL and chemotherapy. 
      These genetic alterations could be used to predict the responsiveness of 
      malignant gliomas to TRAIL-based therapies in clinical treatment of the tumors.
FAU - Li, Yueh-Chun
AU  - Li YC
AD  - Department of Biomedical Sciences, Chung Shan Medical University, Taichung, 
      Taiwan.
FAU - Tzeng, Ching-Cherng
AU  - Tzeng CC
FAU - Song, Jin H
AU  - Song JH
FAU - Tsia, Fuu-Jen
AU  - Tsia FJ
FAU - Hsieh, Lie-Jiau
AU  - Hsieh LJ
FAU - Liao, Shu-Ju
AU  - Liao SJ
FAU - Tsai, Chang-Hai
AU  - Tsai CH
FAU - Van Meir, Erwin G
AU  - Van Meir EG
FAU - Hao, Chunhai
AU  - Hao C
FAU - Lin, Chyi-Chyang
AU  - Lin CC
LA  - eng
GR  - CA86335/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Brain Neoplasms/*drug therapy/*genetics
MH  - Cell Line, Tumor
MH  - Chromosome Banding
MH  - Chromosome Mapping
MH  - Drug Resistance, Neoplasm
MH  - Glioma/*drug therapy/*genetics
MH  - Humans
MH  - In Situ Hybridization
MH  - Karyotyping
EDAT- 2006/05/06 09:00
MHDA- 2006/08/22 09:00
CRDT- 2006/05/06 09:00
PHST- 2006/05/06 09:00 [pubmed]
PHST- 2006/08/22 09:00 [medline]
PHST- 2006/05/06 09:00 [entrez]
AID - 12/9/2716 [pii]
AID - 10.1158/1078-0432.CCR-05-1980 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2006 May 1;12(9):2716-29. doi: 10.1158/1078-0432.CCR-05-1980.