The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression

Akiyama, Shin–ichi; Furukawa, Tatsuhiko; Sumizawa, Tomoyuki; Takebayashi, Yuji; Nakajima, Yuichi; Shimaoka, Shunji; Haraguchi, Masanobu

doi:10.1111/j.1349-7006.2004.tb02193.x

Cited by 96 publications

(87 citation statements)

References 56 publications

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“…As found by the univariate (Table IIa) and multivariate (Table IVa) analyses, the only factor associated with the risk of relapse was disease stage at transplantationpatients transplanted in the advanced stage having a nearly two-fold higher risk of relapse than the rest (HR5 1.8, 95%CI 5 1.2-2.8; P 5 0.010). At 3 years after transplantation, the cumulative incidence of relapse in patients with advanced disease was 35% (95%CI, 27-45) as compared to 18% (95%CI, [14][15][16][17][18][19][20][21][22][23][24][25] in those with early stage disease.…”

Section: Relapse or Progressionmentioning

confidence: 99%

“…Results of the univariate and multivariate regression analyses of factors associated with each specific cause of mortality are displayed in Tables IIc and IVc, respectively. With regard to relapse-related mortality (RRM), the only factor significantly associated with this condition in the multivariate analysis was disease stage at the time of transplantation (P < 0.001). The cumulative incidence of RRM at 3 years was 33% (95%CI, 26-43) for patients with advanced disease at transplant, and 16% (95%CI, [11][12][13][14][15][16][17][18][19][20][21][22] for those with early stage disease. research article…”

Section: Overall Survival and Mortalitymentioning

confidence: 99%

“…Thymidine phosphorylase (TYMP), also known as ECGF1, encodes for a growth factor that plays an important role in cell proliferation and angiogenesis [17,18], though in fact it is also an enzyme that participates in nucleotide synthesis. Specifically, TYMP catalyzes the reversible phosphorolysis of thymidine, thereby regulating the amount of nucleosides within the cells [19] in order to maintain a balanced deoxyribonucleoside triphosphate pool for DNA replication and repair [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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A polymorphism in the TYMP gene is associated with the outcome of HLA‐identical sibling allogeneic stem cell transplantation

et al. 2013

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Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo‐SCT) from an human leukocyte antigen (HLA)‐identical sibling donor. The TYMP genotype of patients correlated with overall survival—carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR = 1.9; P = 0.004). This effect was mostly due to differences in transplant toxicity‐related mortality (HR = 2.5; P = 0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft‐versus‐host disease (GVHD)—carriers of the minor allele being at an increased risk of developing this complication ([HR] = 1.7; P = 0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR = 2.2; P = 0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR = 2.8; P = 0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA‐identical sibling allo‐SCT. Am. J. Hematol. 88:883–889, 2013. © 2013 Wiley Periodicals, Inc.

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Section: Relapse or Progressionmentioning

confidence: 99%

Section: Overall Survival and Mortalitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A polymorphism in the TYMP gene is associated with the outcome of HLA‐identical sibling allogeneic stem cell transplantation

et al. 2013

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“…Cell migration and invasion depend on cellular interactions with the extracellular matrix and are further regulated by factors produced and secreted by tumor cells and the surrounding stromal cells. Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme, identical to the angiogenic factor platelet-derived endothelial cell growth factor (1). TP catalyzes the breakdown of thymidine to thymine and the sugar 2-deoxy-D-ribose-1-phosphate and induces endothelial cell chemotaxis in vitro and angiogenesis in vivo (1).…”

Section: Introductionmentioning

confidence: 99%

“…Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme, identical to the angiogenic factor platelet-derived endothelial cell growth factor (1). TP catalyzes the breakdown of thymidine to thymine and the sugar 2-deoxy-D-ribose-1-phosphate and induces endothelial cell chemotaxis in vitro and angiogenesis in vivo (1). TP modulates both angiogenesis and apoptosis under hypoxic conditions, suggesting that TP plays an important role in cancer progression (2,3).…”

Section: Introductionmentioning

confidence: 99%

Angiogenic Factor Thymidine Phosphorylase Increases Cancer Cell Invasion Activity in Patients with Gastric Adenocarcinoma

Lee

Rha

et al. 2008

Molecular Cancer Research

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We investigated the biological role of thymidine phosphorylase (TP), an angiogenic factor, in gastric cancer cell migration and invasion and explored a therapeutic approach for high TP-expressing tumors using TP enzymatic inhibitor (TPI) and rapamycin. We established TP cDNA overexpressing gastric cancer cell lines (MKN-45/TP and YCC-3/TP) and did invasion and adhesion assays with Matrigel-coated transwell membranes. The related signal pathway using recombinant human TP (rhTP), deoxy-D-ribose (D-dRib), and signal pathway inhibitors (wortmannin, LY294002, and rapamycin) was investigated. First, AGS and MKN-1 gastric cancer cell lines showed dose-dependent up-regulation of invasiveness through Matrigel following treatment with rhTP or D-dRib. TP-overexpressing cancer cell lines displayed increased migration and invasion activity, which doubled with rhTP and D-dRib treatment. This activity depended on the enzymatic activity of TP, and TP stimulated the adhesion of cancer cells onto Matrigel and induced actin filament remodeling. Finally, we showed that this activity is related to increased phosphatidylinositol 3-kinase activity in TP-overexpressing cells and that combination treatment with rapamycin and TP enzymatic inhibitor produces an additive effect to abrogate TP-induced invasion. Taken together, TP increases the migration and invasion of gastric cancer cells, especially in TP-expressing cells. Therapies targeting TP might diminish the propensity for invasion and metastasis in gastric cancer. (Mol Cancer Res 2008;6(10):1554 -66)

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Biomarker‐Responsive Nanosystems for Chronic Disease Theranostics

Wang

et al. 2022

Adv Funct Materials

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Chronic diseases claim millions of lives every year, and it is of great significance to explore and develop advanced drugs to improve the cure rate of chronic diseases. Nanotheranostics are innovative strategies that enable the integration of diagnostic and therapeutic properties into a single nanosystem. Despite great success in nanotheranostics, their applications of nanotheranostics in nanomedicine are still in their infancy. This is because each disease has its corresponding characteristic pathological microenvironment, which motivates the development of endogenous biomarker-responsive nanosystems to meet the requirements of diagnosis and treatment. Herein, recent progress is presented in biomarker-responsive nanosystems and their biomedical applications. First, biomarker-responsive nanosystems are classified into eight subsections according to the type of chronic diseases, including tumors, cardiovascular diseases, neurological diseases, Wilson's diseases, chronic liver diseases, chronic kidney diseases, diabetes mellitus, and rheumatoid arthritis. In the following, a variety of intriguing applications of biomarkers-responsive nanosystems are briefly elaborated, such as biosensing, diagnosis, therapy, combined theranostics, and early evaluation of therapy effect, etc. Finally, the challenges and future directions from research to clinical translation of these responsive nanosystems are also presented.

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The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression

Cited by 96 publications

References 56 publications

A polymorphism in the TYMP gene is associated with the outcome of HLA‐identical sibling allogeneic stem cell transplantation

A polymorphism in the TYMP gene is associated with the outcome of HLA‐identical sibling allogeneic stem cell transplantation

Angiogenic Factor Thymidine Phosphorylase Increases Cancer Cell Invasion Activity in Patients with Gastric Adenocarcinoma

Biomarker‐Responsive Nanosystems for Chronic Disease Theranostics

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