Lassa-VSV chimeric virus targets and destroys human and mouse ovarian cancer by direct oncolytic action and by initiating an anti-tumor response.

Ovarian cancer is the third most common female cancer, with poor survival in later stages of metastatic spread. We test a chimeric virus consisting of genes from Lassa and vesicular stomatitis viruses, LASV-VSV; the native VSV glycoprotein is replaced by the Lassa glycoprotein, greatly reducing neurotropism. Human ovarian cancer cells in immunocompromised nude mice were lethal in controls. Chemotherapeutic paclitaxel and cisplatin showed modest cancer inhibition and survival extension. In contrast, a single intraperitoneal injection of LASV-VSV selectively infected and killed ovarian cancer cells, generating long-term survival. Mice with human ovarian cancer cells in brain showed rapid deterioration; LASV-VSV microinjection into brain blocked cancer growth, and generated long-term survival. Treatment of immunocompetent mice with infected mouse ovarian cancer cells blocked growth of non-infected ovarian cancer cells peritoneally and in brain. These results suggest LASV-VSV is a viable candidate for further study and may be of use in the treatment of ovarian cancer.

The Charles River "hairless" rat mutation maps to chromosome 1: allelic with fuzzy and a likely orthologue of mouse frizzy.

Recent evidence has indicated that the recessive mutation affecting hypotrichosis in the Charles River (CR) "hairless" rat does not involve the hairless gene (hr) on rat chromosome 15. To determine if this mutation might be allelic (or orthologous) with any other previously mapped hypotrichosis-generating mutation in mammals, we have produced a panel of backcross rats segregating for the CR hairless rat mutation as well as numerous other markers from throughout the rat genome. Analysis of this panel has located the CR hairless rat's hypotrichosis-generating mutation on chromosome 1, near Myl2, where only the fuzzy mutation in rat (fz) and the frizzy mutation in mouse (fr) have been previously localized. Intercrossing fz/fz and CR hairless rats produced hybrid offspring with abnormal hair, showing that these two rat mutations are allelic. We suggest that the CR hairless rat mutation and fuzzy be renamed frizzy-Charles River (fr(CR)) and frizzy-Harlan (fr(H)), respectively, to reflect their likely orthology with the mouse fr mutation.

GT160-246, a toxin binding polymer for treatment of Clostridium difficile colitis.

GT160-246, a high-molecular-weight soluble anionic polymer, was tested in vitro and in vivo for neutralization of Clostridium difficile toxin A and B activities. Five milligrams of GT160-246 per ml neutralized toxin-mediated inhibition of protein synthesis in Vero cells induced by 5 ng of toxin A per ml or 1.25 ng of toxin B per ml. In ligated rat ileal loops, 1 mg of GT160-246 neutralized fluid accumulation caused by 5 microg of toxin A. At doses as high as 80 mg/loop, cholestyramine provided incomplete neutralization of fluid accumulation caused by 5 microg of toxin A. GT160-246 protected 80% of the hamsters from mortality caused by infection with C. difficile, whereas cholestyramine protected only 10% of animals. Treatment of C. difficile-infected hamsters with metronidazole initially protected 100% of the hamsters from mortality, but upon removal of treatment, 80% of the hamsters had relapses and died. In contrast, removal of GT160-246 treatment did not result in disease relapse in the hamsters. GT160-246 showed no antimicrobial activity in tests with a panel of 16 aerobic bacteria and yeast and 22 anaerobic bacteria and did not interfere with the in vitro activities of most antibiotics. GT160-246 offers a novel, nonantimicrobial treatment of C. difficile disease in humans.

Effect of RenaGel, a non-absorbable, cross-linked, polymeric phosphate binder, on urinary phosphorus excretion in rats.

BACKGROUND: Normalization of serum phosphorus is critical in the treatment of End Stage Renal Failure patients. Aluminum or calcium based phosphate binders, while efficacious, are associated with potential adverse side effects and toxicities. We have developed RenaGel, a novel, non-absorbed hydrogel which binds dietary phosphate leading to increased fecal excretion, decreased absorption and decreased serum phosphorus levels. In this paper, we present results from both in vitro and in vivo studies in which we examined the efficacy of this novel phosphate binder. METHODS: In vitro, RenaGel was suspended in the test solution, and the mixture was stirred for 1 hour at room temperature. The solid was then filtered off, and the residual liquid analyzed for phosphate. In vivo, RenaGel was mixed in rodent feed at different concentrations and fed to normal rats for up to 4 days. Urine was collected and analysed for phosphate content. RESULTS AND CONCLUSIONS: In vitro binding studies demonstrate that RenaGel has an extremely high phosphate binding capacity. At an estimated physiological concentration of 5 mM phosphate, RenaGel binds 2.6 mmole phosphate/g of phosphate binder. The in vivo binding study shows that RenaGel mixed into the diet decreased urinary phosphorus excretion in a dose dependent manner. RenaGel particles with a 23 microns mean diameter are more efficacious than the larger ones. In conclusion, the above studies indicate that RenaGel is a potent phosphate binder. RenaGel contains no calcium or aluminum and offers an alternative to existing phosphate binder treatments.