Trial reportGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2003
Prediction of sensitivity to fluoropyrimidines by metabolic and target enzyme activities in gastric cancer.
Trial report in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- The Impact of the Expression Level of Intratumoral Dihydropyrimidine Dehydrogenase on Chemotherapy Sensitivity and Survival of Patients in Gastric Cancer: A Meta-Analysis.Disease markers · 2017Pooled it
- Molecular mechanism of MLCK1 inducing 5-Fu resistance in colorectal cancer cells through activation of TNFR2/NF-κB pathway.Discover oncology · 2024Article
- Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma.Cancers · 2020Review
- Large-Scale TransgenicGenetics · 2020Article
- Choice of Capecitabine or S1 in Combination with Oxaliplatin based on Thymidine Phosphorylase and Dihydropyrimidine Dehydrogenase Expression Status in Patients with Advanced Gastric Cancer.Journal of gastric cancer · 2019Article
- Dihydropyrimidine dehydrogenase predicts survival and response to interferon-α in hepatocellular carcinoma.Cell death & disease · 2018Article
- Article
- Screening of lymph nodes metastasis associated lncRNAs in colorectal cancer patients.World journal of gastroenterology · 2014Article
- A long-time survivor of alpha-fetoprotein-producing gastric cancer successfully treated by fluoropyrimidine-based chemotherapy: a case study.Clinical journal of gastroenterology · 2009Article
- Comparison of alternate-day versus consecutive-day treatment with S-1: assessment of tumor growth inhibition and toxicity reduction in gastric cancer cell lines in vitro and in vivo.International journal of clinical oncology · 2008Article
- Chemotherapy sensitivity and resistance testing: to be "standard" or to be individualized, that is the question.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2006Review
- Molecular markers for gastric adenocarcinoma: an update.Molecular diagnosis & therapy · 2006Review
- Histological complete response in advanced gastric cancer after 2 weeks of S-1 administration as neoadjuvant chemotherapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2006Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThis study was designed to investigate the role of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) in tumor progression and sensitivity to 5-fluorouracil (5-FU).
methodsA total of 275 tumor samples from 275 patients with gastric cancer were utilized in this study. TS activity was determined in 130 samples by 5-fluorodeoxyuridine monophosphate binding assay. DPD activity was measured in 140 samples by radioenzymatic assay, and TP protein level was determined in 157 samples by an enzyme-linked immunosorbent assay (ELISA) system. These parameters were compared with several clinicopathologic factors and sensitivity to 5-FU determined by in-vitro ATP assay. The antitumor activities of 5-FU, uracil plus tegafur (UFT), and 1M tegafur--0.4 M 5-chloro-2,4-dihydroxypyridine--1 M potassium oxonate (S-1 [TS-1]) were also compared, using three human gastric cancer xenografts in nude mice.
resultsThere was no correlation between either TS or TP and sensitivity to 5-FU. However, a weak inverse correlation was found between DPD activity and sensitivity to 5-FU. High DPD activity in tumor resulted in poor prognosis, especially in patients who received 5-FU-based adjuvant chemotherapy. Although TP was significantly correlated with depth of tumor invasion and with lymphatic and venous invasions, TP alone had no impact on survival. On the other hand, TS, as well as peritoneal, hepatic, and lymph node metastases, was selected as an independent prognostic factor in gastric cancer. In the animal model, there was no significant difference in antitumor activities among the drugs in a tumor with low DPD activity. However, S-1 showed superior antitumor activity to 5-FU or UFT in tumors with high DPD activity.
conclusionDPD is considered to be a most important predictive factor of 5-FU sensitivity. The use of DPD inhibitory fluoropyrimidines is strongly recommended for tumors with high DPD activity.
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