Ganciclovir

Eight in vitro selection experiments under brincidofovir elicited known cytomegalovirus DNA polymerase amino acid substitutions N408K and V812L, and novel exonuclease domain substitutions D413Y, E303D and E303G, which conferred ganciclovir and cidofovir resistance with 6- to 11-fold resistance to brincidofovir, or 17-fold when E303G was combined with V812L. The new exonuclease domain I resistance mutations selected under brincidofovir pressure add to the single instance previously reported and show the expected patterns of cross resistance.

Chagas' disease carries high morbidity and mortality due to acute parasitemia or cardiac, digestive, cutaneous or neurologic chronic lesions. Latin American countries have the majority of infected or at risk people. Transplanted patients using immunosuppressive agents may develop severe and even fatal forms of the disease. The available treatment causes frequent severe side-effects. A 59 years-old woman with end stage renal disease and positive serology for Chagas` disease, but without any clinical manifestation of this pathology, underwent kidney transplantation from a cadaveric donor and displayed three months later a thigh panniculitis from which a biopsy unveiled amastigote forms of Trypanosoma cruzi. The skin lesions disappeared following treatment with benzonidazole, but the drug was discontinued due to severe pancytopenia. Along with this, infection with E. faecalis and cytomegalovirus were treated with vancomicin and ganciclovir.

BACKGROUND: We report the first case of central nervous system coinfection by human herpes virus-6 (HHV-6) and Toxoplasma gondii, after umbilical cord blood transplantation, in a chronic leukemia myelomonocytic patient.

Glioblastoma multiforme (GBM) is the most commonly occurring primary brain cancer in adults, where its highly infiltrative cells prevent total surgical resection, often leading to tumor recurrence and patient death. Our group has discovered a gene therapy approach for GBM that utilizes high-capacity "gutless" adenoviral vectors encoding regulatable therapeutic transgenes. The herpes simplex type 1-thymidine kinase (TK) actively kills dividing tumor cells in the brain when in the presence of the prodrug, Ganciclovir (GCV), while the FMS-like tyrosine kinase 3 ligand (Flt3L) is an immune-stimulatory molecule under tight regulation by a tetracycline-inducible "Tet-On" activation system that induces anti-GBM immunity. As a prelude to a Phase I clinical trial, we evaluated the safety and efficacy of Food and Drug Administration (FDA)-approved doses of the tetracycline Doxycycline (DOX) allometrically scaled for rats. DOX initiates the expression of Flt3L, which has been shown to recruit dendritic cells (DCs) to the brain tumor microenvironment; an integral first step in the development of anti-tumor immunity.