title: Topically applied imiquimod inhibits vascular tumor growth in vivo.
abstract: Vascular tumors occur in approximately 10% of all infants and may be associated with significant morbidity. Available therapies for vascular tumors, such as systemic corticosteroids, vincristine, and interferon-alpha, may cause toxicity, limiting their use to complicated cases. Using a mouse hemangioendothelioma model, we investigated the efficacy and mechanism of action of imiquimod, a topically applied inducer of cytokines. Application of imiquimod cream, whether initiated at the time of cell inoculation or when tumors became visible, significantly decreased tumor growth and increased animal survival in comparison with control mice. Imiquimod-treated tumors showed decreased tumor cell proliferation, increased tumor apoptosis, and increased expression of tissue inhibitor of matrix metalloproteinase-1 with decreased activity of matrix metalloproteinase-9. The demonstration that local application of imiquimod inhibits vascular tumor enlargement in the mouse vascular tumor model suggests a novel, less toxic means of treating infantile hemangioendotheliomas and perhaps other cutaneous vascular tumors.
authors.affiliation: Department of Pediatrics, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60614, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Sidbury
authors.forename: Nicole
authors.initials: N
authors.lastname: Neuschler
authors.forename: Erin
authors.initials: E
authors.lastname: Neuschler
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.forename: Xiao-qi
authors.initials: XQ
authors.lastname: Wang
authors.forename: Richard
authors.initials: R
authors.lastname: Miller
authors.forename: Mark
authors.initials: M
authors.lastname: Tomai
authors.forename: Elena
authors.initials: E
authors.lastname: Puscasiu
authors.forename: Sajiv
authors.initials: S
authors.lastname: Gugneja
authors.forename: Amy S
authors.initials: AS
authors.lastname: Paller
mesh_terms: D000287:Administration, Topical; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D006390:Hemangioendothelioma / Q000188:drug therapy* / Q000473:pathology; D000077271:Imiquimod; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D018809:Proliferating Cell Nuclear Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; D000077271:Imiquimod