Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q96S42 (nodal)
 22,877 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibitors of thymidylate synthetase, 5-fluoro-2'-deoxyuridine (FUDR) and 5-fluorouracil (FU), enhanced in vitro thymidine labeling of human breast carcinoma cells. Their use resulted in an increase in the measured thymidine labeling index (TLI) of breast carcinomas by increasing detectability of labeled nuclei in autoradiographs. The TLI was measured with FU or FUDR enhancement in primary breast carcinomas from nine women younger than age 50, and from 30 women 50 years or older. The mean and geometric mean TLI were 8.0 and 6.3 respectively for the younger group, and 4.0 and 2.8 respectively for the older group. Similar significant age-associated differences were noted in a series of 133 TLI measurements without FU or FUDR. The TLI was not significantly correlated with primary breast carcinoma size or number of axillary nodal metastases. The capacity to form axillary metastases must be related to factors other than the rate of cell replication in breast carcinomas.
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PMID:Thymidine labeling index of human breast carcinoma. Enhancement of in vitro labeling by 5-fluorouracil and 5-fluoro-2'-deoxyuridine. 14 21

We analyzed the relationship between clinical response to neo-adjuvant chemotherapy including 5-fluorouracil (5-FU) in patients with hypopharyngeal carcinoma (HPC) and thymidylate synthase (TS) expression in their tumors. TS expression was evaluated with immunohistochemical staining techniques on biopsy specimens from HPC patients. TS immunostaining was divided into four levels (TS0-TS3) according to its level and pattern. The relationship between prognosis, tumor size, nodal status, differentiation of tumor cells and TS expression were also investigated. There was a statistically significant association between the level of TS expression and tumor size (p < 0.01). In terms of the effectiveness of chemotherapy, tumor differentiation, nodal status and prognosis, a statistical difference was not found in TS expression. These results suggest that the level of TS expression may show the degree of tumor proliferation, but may not necessarily be useful to obtain a response to chemotherapy including other drugs, e.g., cisplatin and other derivatives of platinum.
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PMID:[Thymidylate synthase expression in patients with hypopharyngeal carcinoma]. 964 15

The immunohistochemical expression of thymidylate synthase (TS) and thymidine phosphorylase (TP) was investigated in 116 of early gastric cancer, in order to know whether or not these reflect malignity in an early stage. The materials conditioned on early gastric cancer with submucosal invasion and over 1 cm2 in size, were 57 with and 59 without lymph node metastasis. They were divided into two by the depth of invasion. The expressions of TS and TP in these group were compared with corresponding histopathological findings. Overall expressions of TS and TP were 54.3% and 34.5%, respectively. The TS-expression was not related with the depth of invasion and lymph node metastasis. The TP-expression, however, showed significant difference between with and without lymph node metastasis, and was so on the depth of submucosal invasion in the group without the nodal metastasis. Multivariate analysis showed that mucosal spread bordering 4 cm2 in size (p = 0.024) and lymphatic permeation (p = 0.099) in TS-expression, and lymph node metastasis (p = 0.041), submucosal invasion (p = 0.076) and venous permeation (p = 0.111) in TP-expression were the noticeable factors regarding to their high expression rates. Although these results were considered not to exceed gastric resection on the prognosis, they might be applicable as one of the indicators in postoperative follow-up on the minor resection of early gastric cancer such as EMR or local resection.
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PMID:[The expression of thymidylate synthase and thymidine phosphorylase in the early-stage of gastric cancer]. 1006 95

To investigate prognostic indicators for gastric adenocarcinomas in advanced stage, we have carried out immunohistochemical determination of thymidylate synthase (TS) in carcinoma tissues. Sixty seven cases of curatively resected gastric carcinoma, under 70 years old at the time of surgery, who had been in the same grade of invasion and lymph nodal involvements (pT3/pN2, Stage IIIB), and had underwent postoperative 5FU-related chemotherapy for a long period were extracted from the files of our hospital. Formalin-fixed and paraffin-embedded specimens were stained with an antibody for human TS (polyclonal). A positive signal was always compared with some types of inflammatory cells in the same slide because of their constantly strong signal. Normal control tissue used was human bone marrow containing blastic cells. Both staining intensity and the fraction of positively stained carcinoma cells were examined in each case, and then the results were summarized with respect to fraction of positively stained carcinoma cells. The present study indicates that the TS-negative group had better survival than the positive group (p < 0.05), the 5 year survival rates being 42.3% and 25.1%, respectively, which suggests that the frequency of TS-positive carcinoma cells could also be a prognostic indicator.
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PMID:Immunohistochemical detection of thymidylate synthase in advanced gastric cancer: a prognostic indicator in patients undergoing gastrectomy followed by adjuvant chemotherapy with 5-fluoropyrimidines. 1021 96

Although the expression of thymidylate synthase (TS) in metastatic colorectal cancer (CRC) may be a better predictor of response to 5-fluorouracil chemotherapy than TS expression in primary CRC, this enzyme has not been well studied in tumor-draining regional lymph nodes. We retrospectively examined TS expression in 12 primary CRC lesions (pT3) and matched sentinel lymph nodes. Of the 8 primary tumors that were TS-positive, 50 per cent (4/8) had tumor-positive lymph nodes and 50 per cent (4/8) had tumor-negative nodes. Of the 4 primary tumors that were TS-negative, 75 per cent (3/4) had tumor-positive nodes and 25 per cent (1/4) had tumor-negative nodes [kappa = -0.1386, 95 per cent confidence interval: (-0.4820, 0.2048), P = 0.4284]. Of the 8 TS-positive primaries, 25 per cent (2/8) had TS-positive nodes and 75 per cent (6/8) had TS-negative nodes. Of the 4 TS-negative primaries, 50 per cent (2/4) had TS-positive nodes and 50 per cent (2/4) had TS-negative nodes [kappa = -0.0131, 95 per cent confidence interval: (-0.2958, 0.2696), P = 0.9274]. Two of the three TS-negative primaries that had metastasized to regional lymph nodes were associated with TS-positive lymph nodes. Our findings indicate that expression of TS by a primary CRC does not correlate with nodal metastases or nodal TS expression. Nodal expression of TS may be important in predicting response to 5-fluorouracil when a primary CRC is TS-negative.
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PMID:Differential expression of thymidylate synthase in colorectal tumors and matched lymph nodes: impact on adjuvant treatment. 1457 Mar 75

TNM staging in colon cancer has several limitations. Prognostic molecular markers are now being developed to address these limitations. The aim of this study was to identify a combination of genes and markers whose expression is predictive of nodal status and outcome in colon cancer. The expression of 12 genetic markers were examined in 66 node-positive and 65 node-negative T3 colon cancers. Gene expression was quantified using real-time polymerase chain reaction. Microsatellite instability status was available through the registry. Association with lymph node status was examined using univariate and multivariate logistic regression. Thymidylate synthase expression was statistically significantly associated with lymph node status (odds ratio 0.36; 95% confidence interval: 0.16-0.81). Microsatellite instability and the other genes were not associated with nodal status. Multiple logistic regression did not identify a significant multivariate predictive model. Decreased expression of thymidylate synthase is associated with a higher risk of lymph node metastasis in patients with T3 colon cancers. Microsatellite instability and the expression of other genes are not predictive of nodal status in this population. Thymidylate synthase gene expression may help identify patients at greater risk for progression of disease.
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PMID:Molecular predictors of lymph node metastasis in colon cancer: increased risk with decreased thymidylate synthase expression. 1633 76

We analysed the expression of microsatellite instability, p53, p21, vascular endothelial growth factor and thymidylate synthase (TS) in pretreatment biopsy specimens from 57 locally advanced rectal cancers. The aim of the study was to correlate the expression of these markers with pathological response. Nineteen patients were treated with preoperative concomitant radiotherapy (RT) and fluorouracil/oxaliplatin-based chemotherapy (RCT), while 38 had RT alone. Pathological complete remission (pCR) and microfoci residual tumour (micR) occurred more frequently in patients treated with RCT (P=0.002) and in N0 tumours (P=0.004). Among patients treated with RCT, high TS levels were associated with a higher response rate (pCR+micR; P=0.015). No such correlation was found in the RT group. The other molecular factors were of no predictive value. Multivariate analysis confirmed a significant interaction between nodal status and the probability of achieving a pathological response (P=0.023) and between TS expression and treatment, indicating that a high TS level is predictive of a higher pathological response in the RCT subset (P=0.007). This study shows that lymph node status is the most important predictive factor of tumour response to preoperative treatment. Thymidylate synthase expression assessed immunohistochemically from pretreatment tumour biopsies may be a useful predictive marker of rectal tumour response to preoperative RCT.
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PMID:Biological predictive factors in rectal cancer treated with preoperative radiotherapy or radiochemotherapy. 1808 84

We evaluated the usefulness of the level of thymidylate synthase(TS)and dihydropyrimidine dehydrogenase(DPD) activity as prognostic factors and indicators for selection of chemotherapy regimens. Between November 1997 and March 1999, fifty-seven patients with stages I - IIIa primary breast cancer were registered. Using recurrence risk categories, they were classified into TAM monotherapy, TAM+oral 5-FU, and TAM+CMF groups(each were standard regimens at the time), and underwent postoperative adjuvant chemotherapy. The relationship between prognosis and the TS level and DPD activity, in addition to conventional risk factors, was examined. The recurrence-free survival time curve showed significant differences when stratified by tumor diameter, ER expression, and TS levels, but not by menopausal status, nodal status, surgical method, p53 expression, DPD activity, or HER2 expression. These results suggest that the TS level is useful as a prognostic factor for breast cancer.
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PMID:[Clinical significance of intratumoral TS levels and DPD activity in breast cancer]. 1929 64

Data mining on public domain identified that thymidylate synthetase (TYMS) and dihydrofolate reductase (DHFR) transcripts were significantly higher expressed in nasopharyngeal carcinoma (NPC). In the folate pathway, TYMS catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate [5,10-CH2=THF, derived from tetrahydrofolate (THF)], as a cofactor. This function maintains the thymidine-5-prime monophosphate pool critical for DNA replication and repair and, THF is generated from dihydrofolate (DHF) through the activity of DHFR. Immunoexpression of TYMS and DHFR were retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high TYMS (50%) expressions were correlated with primary tumor (p=0.008) and AJCC stage (p=0.006), and high DHFR (50%) expression were correlated with nodal status (p=0.039) and AJCC stage (p=0.029) (7th American Joint Committee on Cancer), respectively. In multivariate analyses, high TYMS expression emerged as an independent prognosticator for worse disease-specific survival (p<0.001), distal metastasis-free survival (p=0.002) and local recurrence-free survival (p<0.001), along with AJCC stage. Therefore, TYMS expression is common and associated with adverse prognosticators and might confer tumor aggressiveness through dysregulation of the nucleotide biosynthetic process.
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PMID:Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma. 2372 96