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)

Serious and endometrioid carcinomas differ dramatically in their clinical behavior; however, the specific significance of villoglandular (papillary) differentiation in endometrioid carcinoma has been studied rarely. We compared the clinicopathologic features and genetic alterations in 28 villoglandular endometrioid carcinomas compared with 60 nonvilloglandular endometrioid carcinomas and 60 healthy women. The study revealed a slight increase in the frequency of early-stage disease in villoglandular tumors compared with nonvilloglandular tumors. No differences were observed in the age at onset or cellular grade. The oncogene and susceptibility gene analyses revealed a positive association of K-ras oncogene mutation and germline variants of the cytochrome P-450 1A1 (CYP1A1) gene and an inverse association of the p53PIN3 variant with villoglandular carcinomas, whereas no differences were observed in the c-erbB2/neu oncogene amplification or the methylenetetrahydrofolate reductase germline variant. Finally, a positive association was found between CYP1A1 and methylenetetrahydrofolate reductase variants and the presence of papillary differentiation in the myometrial component. The results suggest that the villoglandular differentiation pattern arises without aggressive clinicopathologic features in a genetic background of transforming and carcinogen-metabolism genes, characteristic of estrogen-related endometrial tumors (type 1) not exhibiting an unfavorable prognosis.
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PMID:Clinicopathologic features and genetic alterations in endometrioid carcinoma of the uterus with villoglandular differentiation. 1007 8

Endometrial polyps and endometrial neoplasms are a recognized complication of chronic tamoxifen treatment. This study describes an endometrial carcinoma that developed in a woman receiving low-dose tamoxifen treatment for breast cancer. Little is known about steroid receptor status, somatic alterations in oncogenes and tumor suppressor genes, and inherited susceptibility in endometrial carcinomas associated with tamoxifen use. In the present case, the endometrial carcinoma was negative for estrogen receptors and weakly positive for progesterone receptors. In addition, analysis of K-ras, c-erbB2/neu, cyclin D1, and p53 status revealed a codon 12 point mutation in the K-ras oncogene. The patient was determined not to be a carrier of germ-line mutations in cytochrome P-450 1A1 (CYP1A1), an estrogen-metabolizing gene previously associated with enhanced endometrial cancer risk, but she was a carrier of a methylenetetrahydrofolate reductase gene variant related with putative alterations in DNA methylation.
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PMID:Endometrial carcinoma in tamoxifen-treated breast cancer patient: clinicopathological, immunohistochemical, and genetic analysis. 1054 49

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