Topically applied imiquimod inhibits vascular tumor growth in vivo.
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.
Sidbury
Robert
R
Department of Pediatrics, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60614, USA.
Neuschler
Nicole
N
Neuschler
Erin
E
Sun
Ping
P
Wang
Xiao-qi
XQ
Miller
Richard
R
Tomai
Mark
M
Puscasiu
Elena
E
Gugneja
Sajiv
S
Paller
Amy S
AS
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
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D018809:Proliferating Cell Nuclear Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; D000077271:Imiquimod