UNASSIGNED: 2008 Background: Expression of key enzymes in chemotherapy drug pathways correlates with @entity14 response following treatment. No prior research has simultaneously described the patterns of expression in @entity14 for @entity1487 , @entity2600 and @entity901 pathways. Characterizing relative expression levels of these enzymes is a first step towards definitively predicting @entity5 responsiveness to chemotherapy. METHODS: Twelve genes known to influence @entity5 response to chemotherapy were selected from the pharmacogenetic pathways of @entity1487 , @entity2600 and @entity902 agents. Genes included intracellular targets, DNA repair enzymes, drug transporters and metabolizers. Gene expression was examined in primary @entity14 and adjacent normal mucosa in 51 @entity1 with stage III or IV disease using TaqMan RT-PCR. Relative expression levels were calculated with b-actin as control using a method to account for differing polymerase amplification efficiencies. RESULTS: @entity16981 , @entity11833 _ 2, @entity4191 , TOP1, and @entity6912 were significantly over-expressed in @entity5 cells relative to normal mucosa, while @entity2602 , @entity24265 and @entity10430 were under-expressed (p < 0.05, Wilcoxon matched pairs test). Expression of @entity1262 , @entity1015 and @entity5322 did not differ significantly between @entity5 and normal tissues. Expression of enzymes regulating @entity902 -agent metabolism and DNA repair were co-regulated. Using differential expression relative to normal mucosa as a marker for @entity5 resistance, predicted @entity5 response rates were calculated. 19.6% of @entity5 were predicted responsive to single-agent @entity2600 , 7.8% to @entity1487 , and 15.7% to @entity901 . Two-thirds were predicted resistant to all three drugs. CONCLUSIONS: Significant differences in gene expression were found between @entity14 and normal mucosa. Distinct sensitivity subgroups existed among the 51 @entity1 with pathologically homogenous disease. These preliminary observations allow further research to correlate multivariate gene expression with clinical outcomes in order to develop a model for predicting response to chemotherapy, eventually resulting in @entity1 -specific treatment. [Table: see text].

Modeling the response of @entity14 ( XXXX ) to common chemotherapy using multivariate gene expression.

@entity901 :: ('MESH:C030110', 'Chemical') :: ['oxaliplatin'] @entity1 :: ('9606', 'Species') :: ['patient', 'patients'] @entity11833 :: ('2067', 'Gene') :: ['ERCC1'] @entity6912 :: ('54658', 'Gene') :: ['UGT1A1'] @entity2600 :: ('MESH:C051890', 'Chemical') :: ['irinotecan'] @entity1262 :: ('5243', 'Gene') :: ['ABCB1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity5322 :: ('1576', 'Gene') :: ['CYP3A4'] @entity10430 :: ('9429', 'Gene') :: ['ABCG2'] @entity16981 :: ('7298', 'Gene') :: ['TYMS'] @entity1015 :: ('1890', 'Gene') :: ['ECGF'] @entity2602 :: ('8824', 'Gene') :: ['CES2'] @entity14 :: ('MESH:D015179', 'Disease') :: ['CRC', 'colorectal adenocarcinoma'] @entity4191 :: ('2950', 'Gene') :: ['GSTP1'] @entity24265 :: ('1806', 'Gene') :: ['DPYD'] @entity902 :: ('MESH:D010984', 'Chemical') :: ['platinum'] @entity1487 :: ('MESH:D005472', 'Chemical') :: ['5-fluorouracil', '5-FU']
@entity14 :: (MESH:D015179,Disease) :: ['CRC']
