Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assayed thymidylate synthase (TS) activity in normal and malignant gynecologic tissues. TS activity in the normal cervix, secretory endometrium, and ovaries from a total of 61 patients was 1.00 +/- 0.52 pmol/g tissue (mean +/- SD). Thus the upper limit (mean + 2SD) of TS activity in normal gynecologic tissue was 2.00 pmol/g tissue. TS activity was generally higher in malignant tissue than in normal tissue, and particularly high activity was detected in cervical cancer. TS activity in endometrial cancer was relatively low, but activity in poorly and moderately differentiated tumors was significantly elevated compared to well differentiated tumors. These findings suggest that cervical cancer is a highly proliferative tumor and that in endometrial cancer, cell proliferation is more rapid in poorly differentiated tumors than in well differentiated ones.
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PMID:Thymidylate synthase activity in normal and malignant gynecologic tissues. 149 11

The antitumor effects of tegafur and UFT, fluorinated pyrimidines, were investigated in endometrial carcinoma bearing mice. Following administration of tegafur and UFT, each at a clinical dosage, the levels of 5-fluorouracil (5-Fu) and the inhibition of thymidylate synthase (TS) activity in the tumor tissue were measured. As a result, the mean levels of 5-Fu in the tumor tissue were approximately six times higher in the UFT group (29.2 +/- 10.7 ng/g) than in the tegafur group (4.9 +/- 4.8 ng/g) (p less than 0.01). The UFT group showed a mean inhibition of TS activity in the tumor tissue significantly higher (61.60 +/- 2.02%) than did the tegafur group (56.08 +/- 4.87%) (p less than 0.05). Hence, not only the higher tumor tissue levels of 5-Fu but also the higher inhibition of TS activity in the UFT group as compared with the tegafur group suggested that UFT had more potent antitumor effect.
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PMID:[Level of inhibition of thymidylate synthase activity and 5-fluorouracil in tumor tissues after administration of UFT or tegafur]. 253 Feb 93

Previous studies from our laboratory indicated that expression of the MLH1 DNA mismatch repair (MMR) gene was necessary to restore cytotoxicity and an efficient G(2) arrest in HCT116 human colon cancer cells, as well as Mlh1(-/-) murine embryonic fibroblasts, after treatment with 5-fluoro-2'-deoxyuridine (FdUrd). Here, we show that an identical phenomenon occurred when expression of MSH2, the other major MMR gene, was restored in HEC59 human endometrial carcinoma cells or was present in adenovirus E1A-immortalized Msh2(+/+) (compared with isogenic Msh2(-/-)) murine embryonic stem cells. Because MMR status had little effect on cellular responses (i.e. G(2) arrest and lethality) to the thymidylate synthase inhibitor, Tomudex, and a greater level of [(3)H]FdUrd incorporation into DNA was found in MMR-deficient cells, we concluded that the differential FdUrd cytotoxicity between MMR-competent and MMR-deficient cells was mediated at the level of DNA incorporation. Analyses of ATPase activation suggested that the hMSH2-hMSH6 heterodimer only recognized FdUrd moieties (as the base 5-fluorouracil (FU) in DNA) when mispaired with guanine, but not paired with adenine. Furthermore, analyses of incorporated FdUrd using methyl-CpG-binding domain 4 glycosylase indicated that there was more misincorporated FU:Gua in the DNA of MMR-deficient HCT116 cells. Our data provide the first demonstration that MMR specifically detects FU:Gua (in the first round of DNA replication), signaling a sustained G(2) arrest and lethality.
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PMID:DNA mismatch repair-dependent response to fluoropyrimidine-generated damage. 1561 Oct 52

We comprehensively evaluated genetic variants in the thymidylate synthase (TYMS) gene in association with endometrial cancer risk in a population-based case-control study of 1,199 incident endometrial cancer cases and 1,212 age frequency-matched population controls. Exposure information was obtained via in-person interview, and DNA samples (blood or buccal cell) were collected. Genotyping of 11 haplotype-tagging single nucleotide polymorphisms (SNP) for the TYMS gene plus the 5-kb flanking regions was done for 1,028 cases and 1,003 controls by using the Affymetrix MegAllele Targeted Genotyping System. Of 11 haplotype-tagging SNPs identified, 7 that are located in flanking regions of the TYMS gene are also in the ENOSF1 (rTS) gene. The SNP rs3819102, located in the 3'-flanking region of the TYMS gene and in an intron of the ENOSF1 gene, was associated with risk of endometrial cancer. The odds ratio (95% confidence interval) for the CC genotype was 1.5 (1.0-2.2) compared with the TT genotype. Haplotype TTG in block 2 of the TYMS gene, which includes SNPs rs10502289, rs2298583, and rs2298581 (located in introns of the ENOSF1 gene), was associated with a marginally significant decrease in risk of endometrial cancer under the dominant model (odds ratio, 0.8; 95% confidence interval, 0.6-1.0). This study suggests that genetic polymorphisms in the TYMS or ENOSF1 genes may play a role in the development of endometrial cancer among Chinese women.
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PMID:Association of thymidylate synthase gene with endometrial cancer risk in a Chinese population. 1919 Jan 36