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Expression of Folate Pathway Genes in Stage III Colorectal Cancer Correlates with Recurrence Status following Adjuvant Bolus 5-FU-Based Chemotherapy.

Artikel i vetenskaplig tidskrift
Författare Elisabeth Odin
Arvid Sondén
Bengt Gustavsson
Göran Carlsson
Yvonne Wettergren
Publicerad i Molecular medicine (Cambridge, Mass.)
Volym 21
Sidor 597-60
ISSN 1528-3658
Publiceringsår 2015
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för kirurgi
Core Facilities, Bioinformatics
Sidor 597-60
Språk en
Länkar dx.doi.org/10.2119/molmed.2014.0019...
Ämneskategorier Cancer och onkologi, Kirurgi

Sammanfattning

Colorectal cancer is commonly treated with 5-fluorouracil and 5-formyltetrahydrofolate (leucovorin). Metabolic action of leucovorin requires several enzymatic steps that are dependent on expression of corresponding coding genes. To identify folate pathway genes with possible impact on leucovorin metabolism, a retrospective study was performed on 193 patients with stage III colorectal cancer. Relative expression of 22 genes putatively involved in leucovorin transport, polyglutamation, and metabolism was determined in tumor and mucosa samples using quantitative real-time polymerase chain reaction. After surgery, patients received adjuvant 5-fluorouracil-based bolus chemotherapy with leucovorin during six months, and were followed for 3-5 years. Cox regression analysis showed that high tumoral expression of the genes SLC46A1/PCFT (proton-coupled folate transporter) and SLC19A1/RFC-1 (reduced folate carrier 1) correlated significantly (p<0.001 and p<0.01, respectively) with decreased risk of recurrent disease, measured as disease-free survival (DFS). These two genes are involved in transport of folates into the cells, and function optimally at different pH. We conclude that SLC46A1/PCFT and SLC19A1/RFC-1 are associated with DFS of patients with colorectal cancer and hypothesize that poor response to 5-fluorouracil plus leucovorin therapy in some patients may be linked to low expression of these genes. Such patients might need a more intensified therapeutic approach than those with high gene expression. Future prospective studies will determine if the expression of any of these genes can be used to predict response to leucovorin.

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