Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium–derived factor in a xenograft model
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 wo...
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| Veröffentlicht in: | Journal of pediatric surgery 2003-03, Vol.38 (3), p.336-342 |
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| creator | Abramson, Lisa P. Stellmach, Veronica Doll, Jennifer A. Cornwell, Mona Arensman, Robert M. Crawford, Susan E. |
| description | 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 |
| doi_str_mv | 10.1053/jpsu.2003.50104 |
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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. J Pediatr Surg 38:336-342. Copyright 2003, Elsevier Science (USA). All rights reserved.</description><identifier>ISSN: 0022-3468</identifier><identifier>EISSN: 1531-5037</identifier><identifier>DOI: 10.1053/jpsu.2003.50104</identifier><identifier>PMID: 12632345</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>anaplasia ; angiogenesis inhibitors ; Angiogenesis Inhibitors - therapeutic use ; Animals ; Eye Proteins ; Humans ; Kidney - blood supply ; Kidney - secretion ; Kidney Neoplasms - blood supply ; Kidney Neoplasms - drug therapy ; Kidney Neoplasms - pathology ; Mice ; Mice, Knockout ; Mice, Nude ; Mitotic Index ; Neoplasm Transplantation ; Neovascularization, Pathologic - drug therapy ; Nerve Growth Factors ; pigment epithelium–derived factor ; Proteins - genetics ; Proteins - secretion ; Proteins - therapeutic use ; Recombinant Proteins - therapeutic use ; Serpins - deficiency ; Serpins - genetics ; Serpins - secretion ; Serpins - therapeutic use ; Tumor Cells, Cultured - transplantation ; Wilms Tumor - blood supply ; Wilms Tumor - drug therapy ; Wilms Tumor - pathology ; Wilms' tumor ; xenograft ; Xenograft Model Antitumor Assays</subject><ispartof>Journal of pediatric surgery, 2003-03, Vol.38 (3), p.336-342</ispartof><rights>2003</rights><rights>Copyright 2003, Elsevier Science (USA). All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c343t-df4dee135b18d7169165d1129422d6b48ae2f599e8c3ee1deab3b4c3c1d21f013</citedby><cites>FETCH-LOGICAL-c343t-df4dee135b18d7169165d1129422d6b48ae2f599e8c3ee1deab3b4c3c1d21f013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022346802631124$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12632345$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abramson, Lisa P.</creatorcontrib><creatorcontrib>Stellmach, Veronica</creatorcontrib><creatorcontrib>Doll, Jennifer A.</creatorcontrib><creatorcontrib>Cornwell, Mona</creatorcontrib><creatorcontrib>Arensman, Robert M.</creatorcontrib><creatorcontrib>Crawford, Susan E.</creatorcontrib><title>Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium–derived factor in a xenograft model</title><title>Journal of pediatric surgery</title><addtitle>J Pediatr Surg</addtitle><description>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. J Pediatr Surg 38:336-342. Copyright 2003, Elsevier Science (USA). All rights reserved.</description><subject>anaplasia</subject><subject>angiogenesis inhibitors</subject><subject>Angiogenesis Inhibitors - therapeutic use</subject><subject>Animals</subject><subject>Eye Proteins</subject><subject>Humans</subject><subject>Kidney - blood supply</subject><subject>Kidney - secretion</subject><subject>Kidney Neoplasms - blood supply</subject><subject>Kidney Neoplasms - drug therapy</subject><subject>Kidney Neoplasms - pathology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Nude</subject><subject>Mitotic Index</subject><subject>Neoplasm Transplantation</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Nerve Growth Factors</subject><subject>pigment epithelium–derived factor</subject><subject>Proteins - genetics</subject><subject>Proteins - secretion</subject><subject>Proteins - therapeutic use</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Serpins - deficiency</subject><subject>Serpins - genetics</subject><subject>Serpins - secretion</subject><subject>Serpins - therapeutic use</subject><subject>Tumor Cells, Cultured - transplantation</subject><subject>Wilms Tumor - blood supply</subject><subject>Wilms Tumor - drug therapy</subject><subject>Wilms Tumor - pathology</subject><subject>Wilms' tumor</subject><subject>xenograft</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0022-3468</issn><issn>1531-5037</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10L1u2zAUhmEiaFA7TudsBadmksNDirI1FkF-CgTIkiAjQZFHCg1JVEnKSbbcQ--wVxI5NtCpE5eHH3BeQs6ALYFJcbEZ4rjkjImlZMDyIzIHKSCTTKy-kDljnGciL9YzchLjhk1uxeArmQEvBBe5nJP2ybVdPKdp7HygTfAv6Zm6SOM4DAFjREurN6r75HTfON9g7wwdXNNhnygOLj1j68bu7_sfi8FtJ15rk6Yp11NNX7H3TdB1op232J6S41q3Eb8d3gV5vL56uLzN7u5vfl3-vMuMyEXKbJ1bRBCygrVdQVFCIS0AL3PObVHla428lmWJayMmZ1FXosqNMGA51AzEgvzY7w7B_x4xJtW5aLBtdY9-jGolWMmlKCZ4sYcm-BgD1moIrtPhTQFTu8BqF1jtAqvPwNOP74fpserQ_vOHohMo9wCnA7cOg4rGYW_QuoAmKevdf8c_AKnIjbM</recordid><startdate>200303</startdate><enddate>200303</enddate><creator>Abramson, Lisa P.</creator><creator>Stellmach, Veronica</creator><creator>Doll, Jennifer A.</creator><creator>Cornwell, Mona</creator><creator>Arensman, Robert M.</creator><creator>Crawford, Susan E.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200303</creationdate><title>Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium–derived factor in a xenograft model</title><author>Abramson, Lisa P. ; Stellmach, Veronica ; Doll, Jennifer A. ; Cornwell, Mona ; Arensman, Robert M. ; Crawford, Susan E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c343t-df4dee135b18d7169165d1129422d6b48ae2f599e8c3ee1deab3b4c3c1d21f013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>anaplasia</topic><topic>angiogenesis inhibitors</topic><topic>Angiogenesis Inhibitors - therapeutic use</topic><topic>Animals</topic><topic>Eye Proteins</topic><topic>Humans</topic><topic>Kidney - blood supply</topic><topic>Kidney - secretion</topic><topic>Kidney Neoplasms - blood supply</topic><topic>Kidney Neoplasms - drug therapy</topic><topic>Kidney Neoplasms - pathology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Nude</topic><topic>Mitotic Index</topic><topic>Neoplasm Transplantation</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Nerve Growth Factors</topic><topic>pigment epithelium–derived factor</topic><topic>Proteins - genetics</topic><topic>Proteins - secretion</topic><topic>Proteins - therapeutic use</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Serpins - deficiency</topic><topic>Serpins - genetics</topic><topic>Serpins - secretion</topic><topic>Serpins - therapeutic use</topic><topic>Tumor Cells, Cultured - transplantation</topic><topic>Wilms Tumor - blood supply</topic><topic>Wilms Tumor - drug therapy</topic><topic>Wilms Tumor - pathology</topic><topic>Wilms' tumor</topic><topic>xenograft</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abramson, Lisa P.</creatorcontrib><creatorcontrib>Stellmach, Veronica</creatorcontrib><creatorcontrib>Doll, Jennifer A.</creatorcontrib><creatorcontrib>Cornwell, Mona</creatorcontrib><creatorcontrib>Arensman, Robert M.</creatorcontrib><creatorcontrib>Crawford, Susan E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pediatric surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abramson, Lisa P.</au><au>Stellmach, Veronica</au><au>Doll, Jennifer A.</au><au>Cornwell, Mona</au><au>Arensman, Robert M.</au><au>Crawford, Susan E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium–derived factor in a xenograft model</atitle><jtitle>Journal of pediatric surgery</jtitle><addtitle>J Pediatr Surg</addtitle><date>2003-03</date><risdate>2003</risdate><volume>38</volume><issue>3</issue><spage>336</spage><epage>342</epage><pages>336-342</pages><issn>0022-3468</issn><eissn>1531-5037</eissn><abstract>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. J Pediatr Surg 38:336-342. Copyright 2003, Elsevier Science (USA). All rights reserved.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12632345</pmid><doi>10.1053/jpsu.2003.50104</doi><tpages>7</tpages></addata></record> |
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| subjects | anaplasia angiogenesis inhibitors Angiogenesis Inhibitors - therapeutic use Animals Eye Proteins Humans Kidney - blood supply Kidney - secretion Kidney Neoplasms - blood supply Kidney Neoplasms - drug therapy Kidney Neoplasms - pathology Mice Mice, Knockout Mice, Nude Mitotic Index Neoplasm Transplantation Neovascularization, Pathologic - drug therapy Nerve Growth Factors pigment epithelium–derived factor Proteins - genetics Proteins - secretion Proteins - therapeutic use Recombinant Proteins - therapeutic use Serpins - deficiency Serpins - genetics Serpins - secretion Serpins - therapeutic use Tumor Cells, Cultured - transplantation Wilms Tumor - blood supply Wilms Tumor - drug therapy Wilms Tumor - pathology Wilms' tumor xenograft Xenograft Model Antitumor Assays |
| title | Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium–derived factor in a xenograft model |
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