Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential of gene expression profiles to predict the response to neoadjuvant chemotherapy in patients with advanced adenocarcinoma of the esophagus was analyzed. Paraffin-embedded endoscopic esophageal tumor biopsies of 38 patients with advanced esophageal adenocarcinoma (Barrett's adenocarcinoma) were included. All patients underwent two cycles of cisplatin and fluorouracil (5-FU) therapy with or without additional paclitaxel (taxol) followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU-metabolism associated genes thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), MAP7, ELF3, as well as of platinum and taxane associated related genes caldesmon, excision cross-complementing genes (ERCC1 and ERCC4) HER2-neu, DNA damage-inducible gene 45 (GADD45) and multidrug resistance genes (MDR1, MRP1) were determined using real-time RT-PCR. Expression levels were correlated with the histopathological response to chemotherapy assessed in surgically resected specimens. Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (p = 0.012), Caldesmon (p = 0.016), MRP1 (p = 0.007) and MDR1 (p = 0.025). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (p = 0.013 and p = 0.015, respectively). Additionally, intratumoral heterogeneity of gene expression of selected genes (TP, DPD, MTHFR, HER2-neu, Caldesmon, ERCC4, MRP1) was additionally verified in 9 untreated Barrett's adenocarcinoma by examination of 5 distinct tumor areas and was observed in 12.7% (5.6%-23.5%, CI 95%) of all cases analyzed. Our results indicate that determination of mRNA levels of a few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with advanced adenocarcinoma of the esophagus.
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PMID:[Prediction of response to neoadjuvant chemotherapy in Barrett's carcinoma by quantitative gene expression analysis]. 1689 54

Multimodal treatment protocols are increasingly employed to improve the survival of patients with locally advanced adenocarcinomas of the upper gastrointestinal tract, however, only 30-40% per year of the patients respond to 5-FU and cisplatin-based neoadjuvant chemotherapy. The goal of our studies is the identification of reliable genetic markers, on the genomic DNA-level, mRNA, or protein level that could predict response of upper gastrointestinal carcinomas prior to neoadjuvant chemotherapy. In esophageal carcinomas, a higher gene expression of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in folate metabolism, was more frequently found in responding patients. In addition high gene expression of caldesmon and of the two drug carrier proteins, MRP1 and MDR1 was associated with response to therapy. By performing a genome-wide profiling on the protein level in a small group of patients, new potential markers were identified, which have to be validated in ongoing studies. In gastric carcinomas, mutations of the p53 gene revealed no association with response or survival, but tumors with a high rate of loss of heterozygosity (LOH), determined by microsatellite analysis, showed a better response to a cisplatin-based chemotherapy. Analysis of expression of 5-FU-(e.g., TS, DPD, and TP) and cisplatin-(e.g., ERCC1, ERCC4, GADD45A, and KU80) related genes, demonstrated an association of DPD expression with response and survival. The combined consideration of TP and GADD45 gene expression, showed the most obvious association with therapy response in this tumor. Our studies point to promising markers with potential use for chemotherapy response prediction of adenocarcinomas of the upper gastrointestinal tract, but prospective studies for validation are necessary.
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PMID:Prediction of response to neoadjuvant chemotherapy in carcinomas of the upper gastrointestinal tract. 1716 61

Increasingly, multimodal treatment protocols are being employed to improve the survival of patients with locally advanced adenocarcinomas of the upper gastrointestinal tract; however, only 30%-40% of the patients respond to 5-fluoro-uracil (5-FU) and cisplatin-based neoadjuvant chemotherapy. The goal of our studies is the identification of reliable genetic markers--on the genomic DNA, messenger RNA (mRNA), or protein level-that could predict response of upper gastrointestinal carcinomas prior to neoadjuvant chemotherapy. In esophageal carcinomas, a higher gene expression of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in folate metabolism, was more frequently found in responding patients. In addition high gene expression of caldesmon and of the two drug carrier proteins MRP1 and MDR1 was associated with response to therapy. By performing a genome-wide profiling on the protein level in a small group of patients, new potential markers were identified that will have to be validated in ongoing studies. In gastric carcinomas, mutations of the p53 gene revealed no association with response or survival, but tumors with a high rate of loss of heterozygosity, as determined by microsatellite analysis, showed a better response to a cisplatin-based chemotherapy. Analysis of the expression of 5-fluorouracil (5-FU) (TS, DPD, TP)- and cisplatin (ERCC1, ERCC4, GADD45A, KU80)-related genes demonstrated an association of DPD expression with response and survival. The combined consideration of TP and GADD45 gene expression showed the most obvious association with therapy response in this tumor. Our studies point to promising markers with potential use for chemotherapy response prediction of adenocarcinomas of the upper gastrointestinal tract, but prospective studies for validation are necessary.
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PMID:Prediction of response to neoadjuvant chemotherapy in carcinomas of the upper gastrointestinal tract. 1760 14