Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma

Lee, Sung Wei; Chen, Tzu Ju; Lin, Li; Li, Chien‐Feng; Chen, Li Tzong; Hsing, Chung-Hsi; Hsu, Han Ping; Tsai, Chia‐Jung; Huang, Hsuan Ying; Shiue, Yow Ling

doi:10.1016/j.yexmp.2013.05.006

Cited by 37 publications

(27 citation statements)

References 38 publications

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“…Other studies of THMS in NPC have yielded inconsistent results. In one study by Lee et al, high THMS expressions were correlated with primary tumor site and stage, and high expressions of dihydrofolate reductase were correlated with nodal status and stage. However, this particular study also showed a correlation between high THMS levels and DFS, a finding which our study did not replicate.…”

Section: Discussionmentioning

confidence: 99%

“…The 5‐FU, combined with platinum chemotherapy, yields higher response rates than single‐agent chemotherapy in NPC . Retrospective studies have demonstrated that an overexpression of THMS portends a poorer prognosis in NPC . Intracellular THMS levels have been associated with response to 5‐FU therapy in vitro .…”

Section: Introductionmentioning

confidence: 99%

“…17 Retrospective studies have demonstrated that an overexpression of THMS portends a poorer prognosis in NPC. 18 Intracellular THMS levels have been associated with response to 5-FU therapy in vitro. 19 In patients with gastrointestinal cancers, studies have also shown an inverse relationship between intratumoral THMS levels and response to treatment.…”

Section: Introductionmentioning

confidence: 99%

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ATM, THMS, and RRM1 protein expression in nasopharyngeal carcinomas treated with curative intent

Klimowicz

Jagdis

et al. 2015

Head & Neck

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ATM, THMS, and RRM1 protein expression in nasopharyngeal carcinomas treated with curative intent

Klimowicz

Jagdis

et al. 2015

Head & Neck

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“…TS is an enzyme that plays an important role in DNA biosynthesis and repair. Evidence from in vitro and in vivo studies indicates that TS contributes to cancer development through cell cycle regulation (20). More poorly differentiated carcinomas exhibit higher rates of tumor cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Thymidine phosphorylase affects clinical outcome following surgery and mRNA expression levels of four key enzymes for 5‑fluorouracil metabolism in patients with stage�I and II non‑small cell lung cancer

et al. 2018

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The expression levels of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS) and orotate phosphoribosyltransferase (OPRT) may predict the clinical efficacy of 5-fluorouracil-based chemotherapy in patients with cancer. We herein investigated the differences in the mRNA levels of these enzymes in non-small-cell lung cancer (NSCLC) and evaluated their prognostic value for NSCLC treated by surgical resection. The intratumoral mRNA levels of TP, DPD, TS, and OPRT were quantified in 66 patients with pathological stage I and II NSCLC (adenocarcinoma or squamous cell carcinoma) following complete resection according to the Danenberg Tumor Profile method. The TP level was the only significant prognostic factor for disease-specific survival (DSS) following complete resection; the mean TP mRNA level differed significantly between the high and low mRNA expression groups. The DSS at 5 years was significantly higher in the low TP mRNA compared with that in the high TP mRNA expression group (83.4 vs. 58.6%, respectively; P=0.005). A Cox proportional hazards model revealed that pathological stage, sex, and TP expression were independent prognostic factors for DSS in patients with stage I and II NSCLC following complete resection. Thus, TP level may be used to monitor treatment efficacy and predict the outcome of NSCLC patients.

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“…Resultant imbalance in cellular nucleotide pools leads to uracil (and fluorouracil) misincorporation into the DNA and RNA, impaired DNA synthesis and ultimately disruption of cell cycle (Figure 2). TS is overexpressed in multiple tumor types and is frequently associated with poor clinical outcomes [9][10][11][12]. Moreover, TS has been shown to possess oncogenic activity on its own [13].…”

Section: Fluorinated Antimetabolitesmentioning

confidence: 99%

TAS-102: A Novel Antimetabolite for the 21st Century

Uboha

Hochster

2015

Future Oncol.

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TAS-102, a novel antimetabolite combination chemotherapy agent, consists of a rediscovered antimetabolite agent, trifluorothymidine (trifluridine) combined with the metabolic inhibitor of thymidine phosphorylase, tipiracil, in a 1:0.5 molar ratio. Mechanism of action studies suggest that this agent works by incorporation into DNA. Both preclinical and clinical studies demonstrate that this agent is noncross-resistant with 5-fluorouracil. Tipiracil may also have antiangiogenic effects through inhibition of thymidine phosphorylase. Recent randomized Phase II and III trials demonstrate clinical activity (improved progression-free survival, time to decrease in performance status, prolonged overall survival) in metastatic colorectal cancer refractory to all standard agents. Monotherapy with TAS-102 has now been approved for this indication in Japan and in the USA.

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Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma

Cited by 37 publications

References 38 publications

ATM, THMS, and RRM1 protein expression in nasopharyngeal carcinomas treated with curative intent

ATM, THMS, and RRM1 protein expression in nasopharyngeal carcinomas treated with curative intent

Thymidine phosphorylase affects clinical outcome following surgery and mRNA expression levels of four key enzymes for 5‑fluorouracil metabolism in patients with stage�I and II non‑small cell lung cancer

TAS-102: A Novel Antimetabolite for the 21st Century

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