Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thymidylate synthase (TS) [TYMS; OMIM reference number (188,350)] is normally considered to be a cytoplasmic enzyme. However, a few reports have suggested it may also be present in the nucleus. To explore this in more detail, we used a highly specific polyclonal antibody to TS and a combination of techniques, including immunocytochemistry, confocal microscopy, cell fractionation, and Western blotting. We developed cell line HeLa-55, a HeLa derivative that grossly overexpresses TS. Although the vast majority of TS was in the cytoplasm, some TS also was seen in the nucleus. TS in parental HeLa cells and in normal human fibroblasts was seen exclusively in the cytoplasm. HeLa-55 cells exposed to 5-fluorodeoxyuridine were fractionated and examined by Western blotting. Interestingly, both free TS and the ternary complex of TS were seen in the cytoplasmic fraction but only free TS was detected in the nuclear fraction. Amongst different cell lines examined, HCT-15 and normal fibroblasts showed no nuclear TS, HCC-2998 and SW-620 showed a small amount of nuclear TS, and HT-29, RKO, and HCT-116 showed a strong nuclear TS signal. Nuclear staining was clearly evident in some clinical colorectal specimens, both normal and malignant. This staining was definitively shown to be TS by competition with recombinant TS protein. A putative leucine-rich nuclear export sequence was identified but its function could not be confirmed. We conclude that small amounts of TS protein is present in the nucleus of some cell types but further work is needed to determine the significance of this observation.
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PMID:Nuclear expression of thymidylate synthase in colorectal cancer cell lines and clinical samples. 1595 25

Thymidylate synthase (TYMS) and dihydropyrimidine dehydrogenase (DPYD) are associated with the response of tumors to fluoropyrimidines. The aim of the present study was to investigate the association between the levels of TYMS and DPYD mRNAs and the efficacy of S-1 for treating patients with HCC. A total of 35 patients with HCC who received S-1 upon recurrence (S-1 group) and 20 patients who never received a fluoropyrimidine (control group) were studied. The levels of TYMS and DPYD mRNA in surgically resected specimens were determined using reverse transcription-polymerase chain reaction assays. Overall survival (OS) time of S-1 group patients with high levels of DPYD mRNA was significantly longer compared with that of patients with low levels (median 501 days vs. 225 days; P=0.016). Similarly, the OS time of those patients with high levels of TYMS mRNA was significantly longer compared with those with low levels (median 503 days vs. 239 days; P=0.0076). By contrast, there was no difference in OS time of the control group between patients with high and low levels of DPYD and TYMS mRNAs. The levels of TYMS and DPYD mRNAs may serve as predictive markers for patients with HCC who receive S-1 chemotherapy.
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PMID:Elevated levels of mRNAs encoding dihydropyrimidine dehydrogenase and thymidylate synthase are associated with improved survival of patients with hepatocellular carcinoma treated with S-1. 2869 54