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Publication : Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft model.

First Author  Abramson LP Year  2003
Journal  J Pediatr Surg Volume  38
Issue  3 Pages  336-42; discussion 336-42
PubMed ID  12632345 Mgi Jnum  J:115508
Mgi Id  MGI:3691876 Doi  10.1053/jpsu.2003.50104
Citation  Abramson LP, et al. (2003) Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft model. J Pediatr Surg 38(3):336-42; discussion 336-42
abstractText  BACKGROUND/PURPOSE: Pigment epithelium-derived factor (PEDF), a potent endogenous inhibitor of angiogenesis, is highly expressed in the kidney. The authors postulated that systemic administration of PEDF would decrease Wilms' tumor growth in a xenograft model, and increased renal vascularity would result in a mouse null for PEDF. METHODS: Tumors were induced in athymic mice using human anaplastic Wilms' tumor cells. Purified PEDF protein or vehicle was administered for 7 days beginning 2 to 3 weeks after inoculation. Tumors were stained with anti-PEDF and anti-Factor VIII antibodies. Mitoses and microvascular density (MVD) were counted per high-power field (hpf). PEDF-null mice were generated on a SV129/C57Bl6 background. Wild-type and null kidneys were assessed for MVD. RESULTS: Mean tumor weight in the 2-week group was 60% less than controls (P <.05). The MVD and mitotic count in treated tumors were significantly less than controls (P <.05). PEDF stained strongly in normal kidneys but was minimal to absent in Wilms' tumor. PEDF-null kidneys had increased MVD compared with wild-type (P <.05). CONCLUSIONS: PEDF is expressed strongly in normal murine kidney, and loss of its angioinhibitory activity may contribute to pathologic angiogenesis in Wilms' tumor. Systemic PEDF suppresses WT growth by targeting both the tumor cells and its associated vasculature.
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