ArticleBritish journal of cancer2001
Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma.
Article in British journal of cancer, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Role of biological markers in the clinical outcome of colon cancer.British journal of cancer · 2002Trial
- The novel anti-cancer fluoropyrimidine NUC-3373 is a potent inhibitor of thymidylate synthase and an effective DNA-damaging agent.Cancer chemotherapy and pharmacology · 2023Article
- Article
- Therapeutic Targeting of Mitochondrial One-Carbon Metabolism in Cancer.Molecular cancer therapeutics · 2020Review
- Cellular Mechanisms Accounting for the Refractoriness of Colorectal Carcinoma to Pharmacological Treatment.Cancers · 2020Review
- A novel intraperitoneal therapy for gastric cancer with DFP-10825, a unique RNAi therapeutic targeting thymidylate synthase, in a peritoneally disseminated xenograft model.Cancer medicine · 2019Article
- Deoxyuracil in DNA and disease: Genomic signal or managed situation?DNA repair · 2019Review
- Nuclear Folate Metabolism.Annual review of nutrition · 2018Review
- Dietary Uridine Decreases Tumorigenesis in theCurrent developments in nutrition · 2018Article
- Targeting nuclear thymidylate biosynthesis.Molecular aspects of medicine · 2017Review
- Distinct gene expression profiles of proximal and distal colorectal cancer: implications for cytotoxic and targeted therapy.The pharmacogenomics journal · 2015Article
- Thymidylate synthase expression and p21(WAF1)/p53 phenotype of colon cancers identify patients who may benefit from 5-fluorouracil based therapy.Cellular oncology (Dordrecht, Netherlands) · 2014Article
- Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5-fluorouracil on human colon cancer cells.Cancer science · 2013Article
- Cancer of the colon and rectum: potential effects of sex-age interactions on incidence and outcome.Medical science monitor : international medical journal of experimental and clinical research · 2013Article
- Trafficking of intracellular folates.Advances in nutrition (Bethesda, Md.) · 2011Review
- Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor.Virchows Archiv : an international journal of pathology · 2009Article
- Predictive value of Ki67 and p53 in locally advanced rectal cancer: correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy.World journal of gastroenterology · 2008Article
- The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer.International journal of colorectal disease · 2007Review
- Schedule-dependent activity of 5-fluorouracil and irinotecan combination in the treatment of human colorectal cancer: in vitro evidence and a phase I dose-escalating clinical trial.British journal of cancer · 2007Article
- Genetic factors influencing pyrimidine-antagonist chemotherapy.The pharmacogenomics journal · 2005Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thymidylate synthase (TS) is a key enzyme in DNA synthesis and is inhibited by metabolites of the chemotherapeutic agent 5-fluorouracil (5FU). Nuclear expression of TS in human tissue in vivo has not been characterised and its clinicopathological correlates in malignancy are unknown. 52 cases of primary colorectal carcinoma (CRC) and 24 cases of matched metastatic carcinoma were studied immunohistochemically using the monoclonal antibody TS106. The degree of nuclear TS immunostaining correlated closely with levels of TS mRNA expression amongst 10 CRCs studied. Strong nuclear immunostaining was seen in normal basal crypt colonocytes and germinal centre cells, and in a varying proportion of adenocarcinoma cells. Amongst the primary carcinomas, higher TS nuclear expression was associated with prominent extracellular mucin production and right-sided location. Higher TS nuclear expression also showed a significant association with poorer response to protracted venous infusional 5FU therapy. There was no clear association between TS nuclear expression and Ki67 or p53 expression assessed immunohistochemically. There was a strong positive correlation between TS nuclear expression in primary and metastatic CRC but the latter generally showed higher expression than matched primary tumour tissue. These findings confirm the nuclear expression of TS protein in human cells in vivo and provide new insight into how such expression may relate to the behaviour of CRCs.
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Registered trials
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