Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leflunomide, a novel immunomodulatory drug, has two biochemical activities: inhibition of tyrosine phosphorylation and inhibition of pyrimidine nucleotide synthesis. In the present study, we first showed that A77 1726 [N-(4-trifluoromethylphenyl-2-cyano-3-hydroxycrotoamide)], the active metabolite of leflunomide, was more effective at inhibiting the tyrosine kinase activity of platelet-derived growth factor (PDGF) receptor than that of epidermal growth factor (EGF) receptor, and had no effect on the tyrosine kinase activity of the fibroblast growth factor receptor. In the presence of exogenous uridine, A77 1726 was more effective at inhibiting the PDGF-stimulated proliferation of PDGF receptor-overexpressing C6 glioma than the EGF-stimulated proliferation of EGF receptor-overexpressing A431 cells. In vivo studies demonstrated that leflunomide treatment strongly inhibited the growth of the C6 glioma but had only a modest effect on the growth of the A431 tumor. Uridine co-administered with leflunomide did not reverse the antitumor activity of leflunomide on C6 and A431 tumors significantly. Quantitation of nucleotide levels in the tumor tissue revealed that leflunomide treatment significantly reduced pyrimidine nucleotide levels in the fast-growing C6 glioma but had no effect on the relatively slow-growing A431 tumor. Whereas uridine co-administration normalized pyrimidine nucleotide levels, it had minimal effects on the antitumor activity of leflunomide in both tumor models. Immunohistochemical analysis revealed that leflunomide treatment significantly reduced the number of proliferating cell nuclear antigen-positive cells in C6 glioma, and that uridine only partially reversed this inhibition. These results collectively suggest that the in vivo antitumor effect of leflunomide is largely independent of its inhibitory effect on pyrimidine nucleotide synthesis. The possibility that leflunomide exerts its antitumor activity by inhibition of tyrosine phosphorylation or by a yet unidentified mode of action is discussed.
 ...
PMID:In vitro and in vivo antitumor activity of a novel immunomodulatory drug, leflunomide: mechanisms of action. 1051 84

We analyzed the interim results of prognostic significance of pyrimidine nucleoside phosphorylase (PyNPase), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) in 5-FU-based chemotherapy for breast cancer. In surgical specimens of tumor tissues and normal mammary gland tissues from 102 breast cancer patients, TS, PyNPase, and DPD activities were measured, and p53 and c-erbB-2 overexpression were also examined. TS, d-Thd-Pase/Urd-Pase (PyNPase), and DPD activities were significantly higher in tumor tissues than in normal tissues. There was a strong correlation between d-Thd-Pase and Urd-Pase in tumor tissues. No relationship was found between patient characteristics and any of the enzyme activities. PyNPase activities were significantly higher in the tissues having a c-erbB-2 overexpression of 75% (4+) or more than in those having less than 75%, and the tissues with a p53 of 50% (3+) or more had significantly higher TS activities than those with less than 50%. However, the other parameters showed no significant difference. The data obtained so far suggest no clear correlation between the activity of any of these enzymes and prognosis.
 ...
PMID:[Significance of tissue PyNPase, TS, and DPD activities in breast cancer]. 1221 67