title: Chemopreventive effect of leflunomide against Ehrlich's solid tumor grown in mice: Effect on EGF and EGFR expression and tumor proliferation.
abstract: i)
  
  
  OBJECTIVE
  The current study aimed to examine the effect of leflunomide on tumoral expression of epidermal growth factor and its receptor (EGFR) in Ehrlich's ascites carcinoma (EAC) grown in mice. ii)
  
  
  METHODS
  Mice were injected subcutaneously with EAC cells and allocated into four groups; Group i: EAC control group. Groups ii-iv: mice treated with leflunomide (3, 10 or 30mg/kg/day, p.o.), respectively. Pharmacologic treatments were initiated at day 8 and continued for 14days. iii)
  
  
  RESULTS
  Treatment with leflunomide evoked antitumor properties as indicated by reduction in tumor mass, histopathological score, number of intratumoral PCNA immunopositive nuclei. Leflunomide (3, 10 or 30mg/kg) exerted an anti-inflammatory effect as indicated by the reduction in serum tumor necrosis factor-α. Furthermore, leflunomide demonstrated anti-angiogenic activity which was expressed as a decline in serum vascular endothelial growth factor and down-regulation of intratumoral EGF protein and mRNA expression as well as EGFR expression in addition to suppression of immunostaining for the endothelial marker, CD31. iv)
  
  
  CONCLUSIONS
  Taken together, the present results demonstrated that leflunomide possessed anti-angiogenic and anti-proliferative activity against EAC solid tumors that might be correlated to down regulation of EGF and EGFR. Further, the current data indicated that leflunomide may have utility in the management of human cancer.
authors.affiliation: Department of Biochemistry, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Hoda I
authors.initials: HI
authors.lastname: Bahr
authors.affiliation: Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Eman A
authors.initials: EA
authors.lastname: Toraih
authors.affiliation: Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Eman A
authors.initials: EA
authors.lastname: Mohammed
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Hala M F
authors.initials: HM
authors.lastname: Mohammad
authors.affiliation: Department of Histology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Eman A I
authors.initials: EA
authors.lastname: Ali
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt. Electronic address: Sawsan_zaytoon@pharm.suez.edu.eg.
authors.forename: Sawsan A
authors.initials: SA
authors.lastname: Zaitone
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D007555:Isoxazoles; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000077339:Leflunomide
keywords: Angiogenesis; Ehrlich's carcinoma; Epidermal growth factor; Leflunomide; Mice; Tumor proliferation