PMID- 17634410
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 110
IP  - 9
DP  - 2007 Nov 1
TI  - Expression of CYP3A4 as a predictor of response to chemotherapy in peripheral 
      T-cell lymphomas.
PG  - 3345-51
AB  - Peripheral T-cell lymphomas (PTCLs) are aggressive tumors in which the current 
      therapy based on multiagent chemotherapy is not successful. Since cytochrome P450 
      3A subfamily (CYP3A) enzymes are involved in the inactivation of chemotherapy 
      drugs, we hypothesized that CYP3A and P-glycoprotein (MDR1) expression in these 
      lymphomas could result in a poor clinical response. We measured tumoral CYP3A and 
      MDR1 mRNA content in 44 T-cell lymphomas, finding a large variation in CYP3A 
      expression. Multiplex polymerase chain reaction (PCR) analysis and fluorescence 
      in situ hybridization (FISH) analysis showed genomic gains affecting CYP3A and 
      MDR1 genes in T-cell lines and primary tumors, suggesting that this could be the 
      mechanism underlying the tumoral expression variation. To test whether the 
      tumoral expression of CYP3A and/or MDR1 could influence PTCL treatment outcome, 
      their expression levels were compared with the clinical response and survival of 
      the patients, finding that a high tumoral expression of CYP3A4 was significantly 
      associated with a lower complete remission rate. This was further investigated 
      with cell lines stably expressing CYP3A4 that exhibited an increased resistance 
      to doxorubicin and etoposide. In conclusion, a high CYP3A4 tumoral expression 
      could be useful to predict poor response to the standard PTCL chemotherapy; in 
      these cases alternative chemotherapy combinations or doses should be explored.
FAU - Rodriguez-Antona, Cristina
AU  - Rodriguez-Antona C
AD  - Hereditary Endocrine Cancer Group, Spanish National Cancer Centre, C/Melchor 
      Fernandez Almagro no. 3, 28029 Madrid, Spain.
FAU - Leskela, Susanna
AU  - Leskela S
FAU - Zajac, Magdalena
AU  - Zajac M
FAU - Cuadros, Marta
AU  - Cuadros M
FAU - Alves, Javier
AU  - Alves J
FAU - Moneo, Maria Victoria
AU  - Moneo MV
FAU - Martin, Carmen
AU  - Martin C
FAU - Cigudosa, Juan Cruz
AU  - Cigudosa JC
FAU - Carnero, Amancio
AU  - Carnero A
FAU - Robledo, Mercedes
AU  - Robledo M
FAU - Benitez, Javier
AU  - Benitez J
FAU - Martinez-Delgado, Beatriz
AU  - Martinez-Delgado B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070718
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (ABCB1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Antineoplastic Agents)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 80168379AG (Doxorubicin)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - EC 1.14.14.55 (CYP3A4 protein, human)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics
MH  - Antineoplastic Agents/*therapeutic use
MH  - Chromosomes, Human, Pair 7
MH  - Cytochrome P-450 CYP3A
MH  - Cytochrome P-450 Enzyme System/*genetics
MH  - Doxorubicin/therapeutic use
MH  - Drug Resistance, Neoplasm/genetics
MH  - Etoposide/therapeutic use
MH  - Gene Duplication
MH  - Gene Expression
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Jurkat Cells
MH  - Lymphoma, T-Cell, Peripheral/*diagnosis/*drug therapy/*genetics/mortality
MH  - Prognosis
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Tumor Cells, Cultured
EDAT- 2007/07/20 09:00
MHDA- 2007/12/14 09:00
CRDT- 2007/07/20 09:00
PHST- 2007/07/20 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/07/20 09:00 [entrez]
AID - S0006-4971(20)42332-8 [pii]
AID - 10.1182/blood-2007-02-075036 [doi]
PST - ppublish
SO  - Blood. 2007 Nov 1;110(9):3345-51. doi: 10.1182/blood-2007-02-075036. Epub 2007 
      Jul 18.