The role of blood platelets in nucleoside metabolism: assay, cellular location and significance of thymidine phosphorylase in human blood

Shaw, Timothy; Smillie, R.H.; MacPhee, Donald G.

doi:10.1016/0027-5107(88)90074-7

Cited by 24 publications

(11 citation statements)

References 40 publications

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“…Blood platelets are one of the richest sources of TP20. Chemotherapy induced thrombocytopenia may reduce the amount of TP and then weak the role of TP.…”

Section: Discussionmentioning

confidence: 99%

Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines

Huang

Chen

et al. 2014

Sci Rep

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The predictive value of thymidine phosphorylase gene variants (TP, also called platelet-derived endothelial cell growth factor) and thrombocytosis were controversial and worthy of further study in gastrointestinal cancer (GIC) patients. We screened all of the common missense single nucleotide polymorphisms (MAF ≥ 0.1) in fluoropyrimidines (FU) pathway genes (including TP, TS, ENOSF1 and DPD). Three of them were selected and genotyped using Sequenom MassARRAY in 141 GIC patients. TP expression was assessed by immunohistochemistry. Our aim was to evaluate the prognostic significance of studied genes and platelet counts in GIC patients. Multivariate analyses indicated in rs11479-T allele carriers, platelet counts negatively correlated to overall survival. In addition, T allele of TP: rs11479 was associated with higher TP expression in cancer tissues. We suggest TP: rs11479 variant combined with platelet counts may be useful prognostic makers in GIC patients receiving first-line FU chemotherapy and thrombopoietin factor should be used with caution in the rs11479 T allele bearing patients.

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“…Blood platelets are one of the richest sources of TP20. Chemotherapy induced thrombocytopenia may reduce the amount of TP and then weak the role of TP.…”

Section: Discussionmentioning

confidence: 99%

Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines

Huang

Chen

et al. 2014

Sci Rep

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“…Although TP is not a secreted protein, high cellular turnover and substantial cell necrosis are thought to occur inside solid tumors, permitting intracellular enzymes to spill into the plasma, thereby raising plasma TP. For these reasons, we assumed that intracellular TP activity was proportional to the amount of D-dRib produced, although we did not directly measure the amount of D-dRib produced in TP-overexpressing cells (21). We observed that the addition of TP or D-dRib promoted invasion of gastric cancer cells and that this activity was more pronounced in TP-overexpressing cells.…”

Section: Discussionmentioning

confidence: 95%

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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“…AZT is an example of a thymidine analog that is not a substrate for thymidine phos phorylase [17]; however, we have shown that it is only as active as IUDR in reducing for mation of viral plaques in human kératino cytes infected with HSV-1. Drugs which combine the features of AZT, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…The studies with IUDR indicate that human kér atinocytes infected in vitro with HSV-1 are useful model system that possess some im portant biochemical features of the human epidermis. We have extended the use of this model to measure the ID5o values of two new thymidine analogs, BVDU and AZT, that were selected because of their difference as substrates for thymidine phosphorylase; BVDU is a substrate for thymidine phos phorylase [16] whereas AZT is not [17]. The ID50 of BVDU in HSV-1-infected human kératinocytes was 0.18 pM (table 3); addi tion of 3 pA/ thymidine reduced the activity of BVDU by threefold (data not shown).…”

Section: Effect O F 6-at and Thymidine On The An Tiviral Activity O Fmentioning

confidence: 99%

Antiviral Activity of 5-Iodo-2’-Deoxyuridine and Related Drugs in Human Keratinocytes Infected in vitro with Herpes simplex Virus Type 1

Reuveni¹,

Bull

Landry

et al. 1991

Skin Pharmacol Physiol

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5-Iodo-2′-deoxyuridine (IUDR) is a potent topical antiviral agent in experimental animals but is less active in man for treating cutaneous viral infections. We have shown here that IUDR is 5 times less active in human keratinocytes infected in vitro with herpes simplex virus type 1 than in guinea pig embryo cells infected in culture. To account, in part, for this difference in activity of IUDR, we measured the capacity of these different cultures to catabolize and thus inactivate the drug. IUDR is catabolized by thymidine phosphorylase; activity of this enzyme was very high in human keratinocytes in vitro but was very low in guinea pig embryo cells. The antiviral activity of IUDR in human keratinocytes, however, was not increased by inhibiting thymidine phosphorylase; inhibiting thymidine phosphorylase apparently increased the availability of thymidine that would compete with IUDR and, indeed, the activity of IUDR in infected cells was reduced by addition of thymidine to the medium. These data indicate that the catabolism of IUDR and related analogs alters antiviral activity in human keratinocytes.

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The role of blood platelets in nucleoside metabolism: assay, cellular location and significance of thymidine phosphorylase in human blood

Cited by 24 publications

References 40 publications

Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines

Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines

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

Antiviral Activity of 5-Iodo-2’-Deoxyuridine and Related Drugs in Human Keratinocytes Infected in vitro with Herpes simplex Virus Type 1

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