Potent inhibition of hemangioma formation in rats by the acyclic nucleoside phosphonate analogue cidofovir.
The acyclic nucleoside phosphonate analogue cidofovir elicited a marked protection against hemangioma growth in newborn rats that had been infected i.p. with a high titer of murine polyomavirus. Untreated, infected rats developed cutaneous, i.m., and cerebral hemangiomas associated with severe hemorrhage and anemia leading to death within 3 weeks postinfection (p.i.). s.c. treatment with cidofovir at 25 mg/kg, once a week, resulted in a complete suppression of hemangioma development and associated mortality when treatment was initiated at 3 days p.i. (100% survival compared with 0% for the untreated animals). Cidofovir still afforded 40% survival and a significant delay in tumor-associated mortality when treatment was started at a time at which cerebral hemangiomas were already macroscopically visible (i.e., 9 days p.i.). Infectious virus or viral DNA was undetectable in the brain at different times p.i. as assessed by means of (a) a DNA-DNA hybridization assay and (b) titration of the brain for infectious virus content, indicating that there was no viral replication in murine polyomavirus-infected rats. Moreover, a semiquantitative PCR for viral protein 1 DNA revealed that the amount of viral protein 1 DNA declined with time after infection to become virtually undetectable at 18 days p.i. Therefore, an antitumor or antiangiogenic effect, rather than inhibition of viral replication, may be the reason for the inhibitory activity of cidofovir in this model. Cidofovir may thus be further explored for the treatment of vascular tumors and, in particular, life-threatening juvenile hemangiomas.
Liekens
S
S
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. Sandra.Liekens@rega.kuleuven.ac.be
Andrei
G
G
Vandeputte
M
M
De Clercq
E
E
Neyts
J
J
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000821:virology; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006391:Hemangioma / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D015994:Incidence; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D011120:Polyomavirus / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D016019:Survival Analysis
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir