Magainin peptides and model amphipathic peptides exhibit antibiotic activity and are also cytolytic for transformed human cells. Here we demonstrate in vitro that MSI-511 (an all-D amino-acid model magainin peptide) and MSI-130 (a margainin analogue) were more lytic for 17 human melanomas than for normal melanocytes. Melanomas established s.c. in athymic nude mice and then injected once with the peptide MSI-511 completely disappeared in 6 out of 9 animals, whereas a control peptide had no effect. Murine skin at the tumor injection site was initially affected, but healed within 2 weeks with minimal scarring. Similarly, accelerated healing was seen in human skin grafted to SCID mice and injected with MSI-511. Our results indicate that lytic magainin peptides can be used for local tumor therapy with minimal long-term damage to normal tissues.
Amebic keratitis produced by Acanthamoeba spp. is an increasingly important ocular infection in extended-use contact lens wearers. Problems associated with the infection are compounded by the lack of effective and well-tolerated chemotherapeutic agents. The magainins, a group of naturally occurring and synthetic membrane-active peptide compounds, have been shown to be active in vitro against a clinical isolate ofAcanthamoeba polyphaga. Two magainins tested extensively had minimal inhibitory and minimal amebicidal values of 20 and 25 ,ug/ml for magainin MSI-103 and 25 and 40 ,ug/ml for magainin MSI-94, respectively. Both amebastatic and amebicidal activities are enhanced by combining the magainins with silver nitrate (200 ,ug/ml) and/or other marginally effective antimicrobial agents. These combinations have activity against both trophic and cystic stages in the Acanthamoeba life cycle and have promise as antimicrobial agents in the treatment of amebic keratitis.Acanthamoeba keratitis, a potentially sight-threatening disease, has been seen in recent years with increasing frequency (23). Initially recognized as a consequence of corneal trauma (12), recent infections have been increasingly associated with daily-wear soft contact lenses, hard lenses, gas-permeable hard lenses, and combined hard-soft lenses. Any departure from recommended contact lens care which exposes the lens or the lens case to a nonsterile environment contaminated with Acanthamoeba spp. can lead to clinical infection (14, 21). Pain and recurrent epithelial breakdown often accompany the course of the disease. Acanthamoeba keratitis is frequently misdiagnosed as a herpes simplex virus or bacterial keratitis, thus delaying the onset of appropriate therapy (4,11,20,27).The life cycle of Acanthamoeba spp. consists of the trophic ameba alternating with a dormant, thick-walled cyst. During infection, both cysts and trophozoites are found within the cornea (12,15
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