PMID- 14678959
OWN - NLM
STAT- MEDLINE
DCOM- 20040227
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 23
DP  - 2003 Dec 1
TI  - Glutathione S-transferase pi amplification is associated with cisplatin 
      resistance in head and neck squamous cell carcinoma cell lines and primary 
      tumors.
PG  - 8097-102
AB  - PURPOSE: The purpose is to evaluate the association of glutathione S-transferase 
      pi (GST-pi) amplification and cisplatin resistance in head and neck cancer. 
      EXPERIMENTAL DESIGN: An analysis of chromosomal abnormalities in 10 head and neck 
      cancer cell lines by comparative genomic hybridization was performed. GST-pi 
      amplification and expression were evaluated in head and neck cell lines and 
      paraffin-embedded tissue by fluorescence in situ hybridization (FISH) and 
      immunohistochemistry. RESULTS: Changes in the DNA copy number were seen in all 10 
      cell lines by comparative genomic hybridization. The most frequent chromosomal 
      alterations were: gain at 3q; loss at 3p; gain at 8q; loss of 18q; gain at 20q; 
      loss at 8p; and gain of 11q11-q13. Using FISH, 9 of 10 cell lines showed 
      increased GST-pi copy number. GST-pi amplification was detected in 7 of 10 cell 
      lines. Five were relatively cisplatin resistant, and 2 were relatively cisplatin 
      sensitive (mean IC(50), 11.2 and 2.75 microM). Two relatively cisplatin-sensitive 
      cell lines showed GST-pi gain and another relatively cisplatin-sensitive cell 
      line had predominantly two copies of the gene. In 10 tumor specimens, 4 had two 
      copies of GST-pi. All 4 had a complete response to neoadjuvant chemotherapy, 3 of 
      whom are alive >50 months from treatment compared with 2 patients showing GST-pi 
      amplification. Neither responded to chemotherapy, and both died of disease <9 
      months from diagnosis. CONCLUSIONS: Using FISH, GST-pi amplification is a common 
      event in head and neck squamous cell carcinoma and may be associated with 
      cisplatin resistance and poor clinical outcomes in head and neck cancer patients 
      treated with cisplatin-based therapy.
FAU - Cullen, Kevin J
AU  - Cullen KJ
AD  - Department of Oncology, Lombardi Cancer Center, Washington, DC 20057, USA. 
      cullenk@georgetown.edu
FAU - Newkirk, Kenneth A
AU  - Newkirk KA
FAU - Schumaker, Lisa M
AU  - Schumaker LM
FAU - Aldosari, Naji
AU  - Aldosari N
FAU - Rone, Janice D
AU  - Rone JD
FAU - Haddad, Bassem R
AU  - Haddad BR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.5.1.18 (GSTP1 protein, human)
RN  - EC 2.5.1.18 (Glutathione S-Transferase pi)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biopsy
MH  - Carcinoma, Squamous Cell/drug therapy/*enzymology/genetics/pathology
MH  - Cell Line, Tumor
MH  - Chromosome Aberrations
MH  - Cisplatin/administration & dosage/*pharmacology
MH  - Drug Resistance, Neoplasm
MH  - Fluorouracil/administration & dosage
MH  - Gene Amplification
MH  - Glutathione S-Transferase pi
MH  - Glutathione Transferase/biosynthesis/*genetics
MH  - Head and Neck Neoplasms/drug therapy/*enzymology/genetics/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Nucleic Acid Hybridization
EDAT- 2003/12/18 05:00
MHDA- 2004/02/28 05:00
CRDT- 2003/12/18 05:00
PHST- 2003/12/18 05:00 [pubmed]
PHST- 2004/02/28 05:00 [medline]
PHST- 2003/12/18 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Dec 1;63(23):8097-102.