A Novel Approach to Cloning and Expression of Human Thymidylate Synthase

Lv, Yingtao; Du, Pei-Juan; Wang, Qiaoyan; Tan, Yuan Yao; Sun, Zong-Bin; Su, Zhongliang; Kang, Chang‐Hee

doi:10.7314/apjcp.2013.14.12.7523

Cited by 3 publications

(3 citation statements)

References 17 publications

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“…In the same series we now assessed the expression of two other biomarkers with potential prognostic impact: the topoisomerase II alpha (TOP2A), an enzyme responsible for transcription, replication and chromosome condensation and segregation during cell division (Kellner et al 2002); and the thymidylate synthase (TS), an enzyme involved in nucleotide metabolism (Lv et al 2013). TOP2A is also a well-known predictor of efficacy of anthracyclines and topoisomerase inhibitors (Wang et al 2012) and TS is predictive of the efficacy of fluoropyrimidines (Formentini et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

Roca¹,

Berruti²,

Sbiera³

et al. 2017

Endocrine-Related Cancer

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Topoisomerase II alpha (TOP2A) and thymidylate synthase (TS) are known prognostic parameters in several tumors and also predictors of efficacy of anthracyclines, topoisomerase inhibitors and fluoropirimidines, respectively. Expression of and mRNA was assessed in 98 patients with adrenocortical carcinoma (ACC) and protein expression was assessed by immunohistochemistry in a subset of 39 tumors. Ninety-two patients were radically resected for stage II-III disease and 38 of them received adjuvant mitotane. Twenty-six patients with metastatic disease received the EDP-M (etoposide, doxorubicin, Adriamycin, cisplatin plus mitotane). and expression in ACC tissue was directly correlated with the clinical data. Both markers were not associated with either disease free survival (DFS) or overall survival (OS) in multivariate analyses and failed to be associated to mitotane efficacy. Disease response or stabilization to EDP-M treatment was observed in 12/17 (71%) and 1/9 (11%) patients with high and low TOP2A expressing tumors ( = 0.0039) and 9/13 (69%) and 4/13 (31%) patients with high and low TS expressing ACC, respectively ( = 0.049). High TOP2A expression was significantly associated with longer time to progression (TTP) after EDP-M. TOP2A and TS proteins assessed by immunohistochemistry significantly correlated with mRNA expression. Immunohistochemical TOP2A expression was associated with a non-significant better response and longer TTP after EDP-M. TOP2A and TS were neither prognostic nor predictive of mitotane efficacy in ACC patients. The predictive role of TOP2A expression of EDP-M activity suggests a significant contribution of Adriamycin and etoposide for the efficacy of the EDP scheme.

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Section: Introductionmentioning

confidence: 99%

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

Roca¹,

Berruti²,

Sbiera³

et al. 2017

Endocrine-Related Cancer

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“…Chemotherapy is an important therapeutic modality in the treatment of lung adenocarcinoma, however, the efficacy of the currently available therapy is limited ( 1 ). The enzyme, thymidylate synthase (TS), catalyzes the intracellular reaction that provides the sole de novo intracellular source of deoxythymidine monophosphate, or thymidylate, which is required for DNA replication and repair ( 4 , 5 ). The TS protein and messenger RNA levels are elevated in a number of human cancers ( 6 ) and have been found to correlate with poor prognosis in patients with colorectal ( 8 ), breast ( 9 ), head and neck ( 10 ) and pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Predictive value of thymidylate synthase for the prognosis and survival of lung adenocarcinoma patients

et al. 2014

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Chemotherapy represents an important treatment modality for lung adenocarcinoma. Thymidylate synthase (TS) is an essential enzyme in DNA synthesis, and its overexpression has been associated with reduced sensitivity to antifolate agents. The aim of the current study was to investigate the expression of TS and the effect on prognosis in lung adenocarcinoma patients. Adenocarcinoma and adjacent carcinoma tissues were resected from 100 patients with lung adenocarcinoma and the TS levels were detected by immunohistochemical analysis. The values for overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier analysis. The results indicated that the TS protein was expressed predominantly in adenocarcinoma tissues, which exhibited higher TS expression compared with the adjacent tissues (P<0.001). The statistical analysis indicated that TS expression was associated with the clinical stage and history of smoking (P<0.05). The Kaplan-Meier analysis results indicated that the DFS and OS in patients with high TS expression levels were significantly shorter compared with those with low expression levels (P<0.05). In conclusion, the results from this study suggested that TS may serve as an independent predictive factor for survival rate, which may indicate the prognosis of lung adenocarcinoma patients.

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“…Cells may predispose to carcinogenesis if genetic alterations occur in any critical regulatory pathway; the main critical regulatory pathways include regulations of xenobiotic metabolism, control of genomic stability, including deoxyribonucleic acid (DNA) repair mechanisms, cellcycle checkpoints, apoptosis, and control of growth and inflammatory factors (Wu et al, 2004). Thymidylate synthase is one of the enzymes involved in one carbon- Thymidylate synthase (ts) catalyzes the methylation of deoxyuridylate to deoxythymidylate utilizing 5,10methylene-THF as a cofactor (Longley et al, 2003;Lv et al, 2013). ts has three polymorphisms that may affect ts expression; two functionally important polymorphisms; one is a promoter-enhancer region (TSER), containing 2 or 3 tandem repeats of 28 bp units (2R or 3R) (rs34743033; NC_000018.10: 657645-657731) and known to play a role in the transcriptional autoregulation mechanism (Horie et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study

Qasem

Yousef²,

Yousef³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5'UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population. Materials and Methods: An age, gender, and smoking-matched case-control study involving 84 lung cancer cases and 71 controls was conducted. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphism of interest. Results: Individuals bearing the ins/ins genotype were 2.5 times more likely to have lung cancer [(95%CI: 0.98-6.37), p=0.051]. Individuals who were less than or equal to 57 years and carrying ins/ins genotype were 4.6 times more susceptible to lung cancer [OR<57 vs >57years: 4.6 (95%CI: 0.93-22.5), p=0.059)]. Genotypes and alleles of TSER were distributed similarly between cases and controls. Weak linkage disequilibrium existed between the two loci of interest (Lewontin's coefficient [D']) (LC: D' =0.03, r2: 0. 001, p= 0.8; Controls: D' =0.29, r2: 0.08, p=0.02). Carriers of the "3 tandem repeats_insertion" haplotype (3R_ins) were 2 times more likely to have lung cancer [2 (95%CI: 1.13-3.48), p=0.061]. Conclusions: Genetic polymorphism of TS at 3` UTR and its haplotype analysis may modulate the risk of lung cancer in Jordanians. The 6bp ins/del polymorphism of TS at 3 `UTR is more informative than TSER polymorphism in predicting increased risk.

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A Novel Approach to Cloning and Expression of Human Thymidylate Synthase

Cited by 3 publications

References 17 publications

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

Predictive value of thymidylate synthase for the prognosis and survival of lung adenocarcinoma patients

Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study

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