Thymidine phosphorylase levels and dihydropyrimidine dehydrogenase levels in non-small cell lung cancer tissues

Chujo, Masao; Miura, Takashi; Kawano, Yu; Miyawaki, Michiyo; Imakiire, Takanori; Hayashita, Yoji; Kawahara, Katsunobu

doi:10.3892/or.16.4.777

Cited by 7 publications

(8 citation statements)

References 14 publications

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“…TP is overexpressed in oral squamous carcinoma [16], oesophageal [4], gastric [17], breast [18], lung [19][20][21], colorectal [22], bladder [23], and cervical cancer [24]. TP is expressed by tumour cells and in the tumour microenvironment by fibroblasts, tumour associated macrophages (TAMs) and lymphocytes [3,4,[17][18][19][20][21][22][23]25].…”

Section: Transcriptional Control Of Tp and Its Upregulation In Cancermentioning

confidence: 99%

Thymidine Phosphorylase in Cancer; Enemy or Friend?

Elamin

Rafee

Osman

et al. 2015

Cancer Microenvironment

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Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme that plays an important role in the pyrimidine pathway.TP catalyzes the conversion of thymidine to thymine and 2-deoxy-α-D-ribose-1-phosphate (dRib-1-P). Although this reaction is reversible, the main metabolic function of TP is catabolic. TP is identical to the angiogenic factor platelet-derived endothelial-cell growth factor (PD-ECGF). TP is overexpressed in several human cancers in response to cellular stressful conditions like hypoxia, acidosis, chemotherapy and radiotherapy. TP has been shown to promote tumor angiogenesis, invasion, metastasis, evasion of the immuneresponse and resistance to apoptosis. Some of the biological effects of TP are dependent on its enzymatic activity, while others are mediated through cytokines like interleukin 10 (IL-10), basic fibroblast growth factor (bFGF) and tumour necrosis factor α (TNFα). Interestingly, TP also plays a role in cancer treatment through its role in the conversion of the oral fluoropyrimidine capecitabine into its active form 5-FU. TP is a predictive marker for fluoropyrimidine response. Given its various biological functions in cancer progression, TP is a promising target in cancer treatment. Further translational research is required in this area.

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Section: Transcriptional Control Of Tp and Its Upregulation In Cancermentioning

confidence: 99%

Thymidine Phosphorylase in Cancer; Enemy or Friend?

Elamin

Rafee

Osman

et al. 2015

Cancer Microenvironment

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“…Although limited information has been available with regard to protein expression measured by ELISA (Nishina et al 2004;Ma et al 2004;Chujo et al 2006;Tsuchida et al 2009), our results provide further evidence that ELISA is a useful method to quantify TS and DPD activities in clinical lung cancer specimens, despite the complexity of the procedure. TS is an essential enzyme for DNA synthesis and controls cell proliferation in a positive manner.…”

Section: Discussionmentioning

confidence: 56%

“…Enzyme-linked immunosorbent assay (ELISA) is a wellknown method for direct quantitation of a given protein and has been used widely to measure proteins in the clinic. In fact, ELISA was used to measure TS and DPD expression levels in lung cancer (Chujo et al 2006;Tsuchida et al 2009). Here, we examined whether TS and DPD expression levels as determined by ELISA in clinical specimens are associated with clinicopathological factors and prognosis in patients with lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Higher Tissue Levels of Thymidylate Synthase Determined by ELISA Are Associated with Poor Prognosis of Patients with Lung Cancer

Shiina

Saito

Sakaizawa

et al. 2017

Tohoku J. Exp. Med.

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Thymidylate synthase (TS) is essential in thymidylate biosynthesis and DNA replication. Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in pyrimidine catabolism and is important in catabolism of 5-fluorouracil (5-FU). The significance of TS and DPD expressed in lung cancer remains controversial. Here we analyzed the relationship between TS and DPD expression and clinicopathological features of lung cancer. Enzyme-linked immunosorbent assays (ELISAs) were used to measure TS and DPD levels in paired tumor and non-tumor lung tissues obtained from 168 patients (107 adenocarcinomas, 39 squamous cell carcinomas, and 22 others), who had operations at the Shinshu University Hospital from 2004 to 2007 and were followed up for a median of 57.0 months. TS and DPD expression levels were higher in tumor tissues, and TS expression levels were significantly lower in adenocarcinomas than those in other subtypes. In addition, patients with low TS levels survived longer compared with patents with high TS levels. By contrast, DPD expression levels were not correlated with overall patient survival. Importantly, patients with low TS and DPD levels exhibited significantly prolonged survival than those with high TS and DPD. Among the 168 patients, 59 patients were treated with tegafur-uracil (UFT), a DPD-inhibitory fluoropyrimidine, and the UFT-treated patients with high TS and high DPD levels showed worst prognosis. Our study demonstrates a significant correlation between low TS expression levels and long-term prognosis of patients with lung cancer. Thus, ELISA is a clinically useful method to measure TS and DPD expression in lung cancer tissues.

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“…The ratio of TP to DPD is considered to be a useful predictor of the efficacy of chemotherapy with 5-FU, since TP converts 5'-deoxy-5-fluorouridine to 5-FU and DPD inactivates 5-FU in tumor tissue (18). Moreover, the ratio of TP to DPD in NSCLC tissue was reported to be higher in squamous cell carcinoma than in adenocarcinoma (19). These findings indicate that chemotherapy with 5-FU is potentially more effective in lung cancer patients with squamous cell carcinoma than in those with adenocarcinoma.…”

Section: Adverse Events Grade Grade 3-4 -----------------------------mentioning

confidence: 84%

A multi-institutional phase II study of combination chemotherapy with S-1 plus cisplatin in patients with advanced non-small cell lung cancer

et al. 2011

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Abstract. S-1 is an oral anticancer fluoropyrimidine agent designed to elevate anticancer activity with a decrease in gastrointestinal toxicity. We conducted a phase II study to evaluate the efficacy and safety of combination chemotherapy with S-1 plus cisplatin in patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients were treated with S-1 administered orally at 40 mg/m 2 twice a day for 21 consecutive days, and cisplatin (60 mg/m 2 ) infused intravenously on day 8, repeated every 5 weeks. Of the 44 patients enrolled in the study, 40 were assessable for efficacy and safety. The median number of cycles administered was 3 (range 1-9 cycles). Among the 40 assessable patients, 7 partial responses were observed, with an overall response rate (RR) of 17.5% [95% confidence interval (CI), 5.2-29.8]. Patients with squamous cell carcinoma showed a significantly higher RR (55.5%) than those with adenocarcinoma (9.1%) or other types of NSCLC (0%). The median progression-free survival was 4.3 months (95% CI, 3.4-4.9), the median survival time was 17.9 months (95% CI, 15.0-20.8), and the 1-and 2-year survival rates were 63.3 and 27.3%, respectively. Major grade 3-4 hematologic toxicities were leukocytopenia (7.5%), neutropenia (5.0%), anemia (15.0%) and thrombocytopenia (2.5%). No grade 4 non-hematologic toxicity or treatmentrelated death occurred. These results suggest that combination chemotherapy with S-1 plus cisplatin is a promising therapeutic candidate for patients with advanced NSCLC, particularly squamous cell carcinoma.

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Thymidine phosphorylase levels and dihydropyrimidine dehydrogenase levels in non-small cell lung cancer tissues

Cited by 7 publications

References 14 publications

Thymidine Phosphorylase in Cancer; Enemy or Friend?

Thymidine Phosphorylase in Cancer; Enemy or Friend?

Higher Tissue Levels of Thymidylate Synthase Determined by ELISA Are Associated with Poor Prognosis of Patients with Lung Cancer

A multi-institutional phase II study of combination chemotherapy with S-1 plus cisplatin in patients with advanced non-small cell lung cancer

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