PMID- 16528528
OWN - NLM
STAT- MEDLINE
DCOM- 20070103
LR  - 20131121
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 58
IP  - 6
DP  - 2006 Dec
TI  - Gene expression of ferredoxin reductase predicts outcome in patients with 
      metastatic colorectal cancer treated by 5-fluorouracil plus leucovorin.
PG  - 794-801
AB  - PURPOSE: Ferredoxin reductase (FDXR) is a putative contributor to p53-mediated 
      apoptosis from 5-fluorouracil (5-FU) through the generation of oxidative stress 
      in the mitochondria. However, the influence of FDXR gene expression levels on the 
      outcome of 5-FU chemotherapy has been relatively little studied. The aim of this 
      study is to investigate the association between FDXR gene expressions and the 
      clinical outcome when treated by 5-FU chemotherapy, as well as the correlation of 
      FDXR gene expressions and p53 mutation. METHODS: Pre-chemotherapeutic fresh 
      frozen samples of 33 patients with metastatic colorectal cancer, who received 
      bolus 5-FU and leucovorin (LV) as first line chemotherapy, were studied. FDXR 
      gene expression and p53 mutation were evaluated by real-time RT-PCR and direct 
      sequencing, respectively. RESULTS: FDXR gene expression was significantly higher 
      in responding tumors compared with non-responding ones (P=0.0379). Patients with 
      FDXR values above the cutoff value of 13.52 had a statistically longer survival 
      than those with FDXR gene expressions below the cutoff value (P=0.0148). The 9 
      tumors with wild-type p53 had statistically higher FDXR gene expressions than the 
      14 tumors with mutant-type p53 which had sequence alterations within the "hot 
      spot" codons, the L2-L3 loops, or frameshift (P=0.0463). CONCLUSIONS: FDXR gene 
      expression did not affect clinical outcome in patients with wild-type p53 tumors, 
      whereas, among patients with p53 mutant-type tumors, patients with tumors with 
      low FDXR gene expression had a worse outcome than those with a high FDXR gene 
      expression (P=0.0200). FDXR gene expression, which is regulated at least in part 
      by p53, is associated with both response and survival when metastatic colorectal 
      cancer is treated with 5-FU plus LV. In addition, analysis of p53 mutation 
      combined with FDXR gene expression might be useful in estimating the outcome in 
      5-FU-treated patients.
FAU - Ichikawa, Wataru
AU  - Ichikawa W
AD  - Department of General and Digestive Surgery, Saitama Medical School, 38, 
      Moro-Hongo, Moroyama, Iruma, 350-049, Saitama, Japan. wataru@saitama-med.ac.jp
FAU - Ooyama, Akio
AU  - Ooyama A
FAU - Toda, Etsuko
AU  - Toda E
FAU - Sugimoto, Yoshikazu
AU  - Sugimoto Y
FAU - Oka, Toshinori
AU  - Oka T
FAU - Takahashi, Takehiro
AU  - Takahashi T
FAU - Shimizu, Michio
AU  - Shimizu M
FAU - Sasaki, Yasutsuna
AU  - Sasaki Y
FAU - Hirayama, Renzo
AU  - Hirayama R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060310
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 1.18.1.2 (Ferredoxin-NADP Reductase)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Colorectal Neoplasms/*drug therapy/enzymology/genetics/pathology
MH  - DNA Mutational Analysis
MH  - Ferredoxin-NADP Reductase/*genetics
MH  - Fluorouracil/administration & dosage
MH  - Frameshift Mutation/genetics
MH  - Gene Expression/*genetics
MH  - Gene Expression Regulation, Enzymologic/genetics
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Leucovorin/administration & dosage
MH  - Middle Aged
MH  - Mutation, Missense/genetics
MH  - Neoplasm Metastasis
MH  - Prognosis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Tumor Suppressor Protein p53/genetics
EDAT- 2006/03/11 09:00
MHDA- 2007/01/04 09:00
CRDT- 2006/03/11 09:00
PHST- 2005/12/13 00:00 [received]
PHST- 2006/02/16 00:00 [accepted]
PHST- 2006/03/11 09:00 [pubmed]
PHST- 2007/01/04 09:00 [medline]
PHST- 2006/03/11 09:00 [entrez]
AID - 10.1007/s00280-006-0217-6 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2006 Dec;58(6):794-801. doi: 
      10.1007/s00280-006-0217-6. Epub 2006 Mar 10.