Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour angiogenesis is a complex multistep process regulated by a number of angiogenic factors. One such factor, platelet-derived endothelial cell growth factor has recently been shown to be thymidine phosphorylase (TP). TP catalyses the reversible phosphorylation of thymidine to deoxyribose-1-phosphate and thymine. Although known to be generally elevated in tumours, the expression of this enzyme in breast carcinomas is unknown. Therefore, we used ribonuclease protection assays and immunohistochemistry to examine the expression of TP in 240 primary breast carcinomas. Nuclear and/or cytoplasmic TP expression was observed in the neoplastic tumour epithelium in 53% of tumours. Immunoreactivity was also often present in the stromal, inflammatory and endothelial cell elements. Although endothelial cell staining was usually focal, immunoreactivity was observed in 61% of tumours and was prominent at the tumour periphery, an area where tumour angiogenesis is most active. Tumour cell TP expression was significantly inversely correlated with grade (P = 0.05) and size (P = 0.003) but no association was observed with other tumour variables. These findings suggest that TP is important for remodelling the existing vasculature early in tumour development, consistent with its chemotactic non-mitogenic properties, and that additional angiogenic factors are more important for other angiogenic processes like endothelial cell proliferation. Relapse-free survival was higher in node-positive patients with elevated TP (P = 0.05) but not in other patient groups. This might be due to the potentiation of chemotherapeutic agents like methotrexate by TP. Therefore, this enzyme might be a prediction marker for response to chemotherapy.
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PMID:The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium. 856 30

Considerable evidence indicates that the microvascular changes observed in psoriasis are a result of angiogenesis. Vascular proliferation is driven by the local production of molecules which have angiogenic activity. Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PDECGF/TP) is a potent angiogenic factor active in in vivo angiogenesis assays and overexpressed in several tumour types. We have demonstrated by ribonuclease protection analysis a consistently high degree of PDECGF/TP mRNA production in lesional psoriatic skin, while immunohistochemical studies revealed strong PDECGF/TP immunoreactivity in lesional epidermis, with nuclear staining present in basal keratinocytes and cytoplasmic immunoreactivity in suprabasal layers. Non-lesional skin showed minimal PDECGF/TP mRNA production and weak epidermal immunostaining. These results indicate a potential role for PDECGF/TP in the pathophysiology of psoriasis, and reveal a target for antiangiogenesis therapy in the treatment of this disease.
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PMID:Overexpression of the angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase in psoriatic epidermis. 947 Aug 99