Data highlight current ranges of industrial exposure to 3,3′-DBZ in Germany and demonstrate
the applicability check details of biological monitoring to minimize this exposure. Effective biological monitoring was achieved by a combination of monitoring hemoglobin adducts with spot samplings of urinary 3,3′-DBZ excretion in cases of reported exposure periods. Data presented might help to identify biological guidance values (BGV/BAR) for 3,3′-DBZ-exposed individuals.”
“BACKGROUND: Glioblastoma is a fatal brain tumor in needing urgent effective therapy. Treatments with both oncolytic viruses and immunotherapy have shown preclinical efficacy and clinical promise. We sought to exploit possible synergies between oncolytic herpes simplex virus type 1 (oHSV-1) infection of intracranial gliomas and delivery Bindarit molecular weight of
immune-stimulating fms-like tyrosine kinase 3 ligand (Flt3L) by engineering a herpes vector to express the cytokine.
OBJECTIVE: To construct an oHSV-1 vector that expresses high levels of Flt3L and examine its antiglioma efficacy in an immunocompetent murine model.
METHODS: G47 Delta and a bacterial artificial chromosome system were used to generate a novel oHSV-1, termed G47 Delta-Flt3L, expressing Flt3L. Cytokine expression was confirmed, and G47 Delta-Flt3L was injected intratumorally into MK-0518 solubility dmso established intracranial CT-2A gliomas in syngeneic C57/Bl6 mice. Animals were followed for survival and assessed by the Kaplan-Meier method.
RESULTS: G47 Delta-Flt3L expressed high levels of Flt3L in culture. Expression of
Flt3L affected neither viral replication nor had a cytotoxic effect on CT2A glioma cells. Direct inoculation into intracerebral CT2A glioma cells resulted in high levels of detectable Flt3L in mouse blood and was superior to parental G47 Delta in prolonging survival in glioma-bearing animals.
CONCLUSION: Treatment with G47 Delta-Flt3L improves survival of glioma-bearing mice.”
“Homing endonucleases recognize specific long DNA sequences and catalyze double-stranded breaks that significantly stimulate homologous recombination, representing an attractive tool for genome targeting and editing. We previously described a two-plasmid selection system that couples enzymatic DNA cleavage with the survival of host cells, and enables directed evolution of homing endonucleases with altered cleavage sequence specificity. Using this selection system, we successfully evolved mutant I-SceI homing endonucleases with greatly increased cleavage activity towards a new target DNA sequence that differs from the wild-type cleavage sequence by 4 bp. The most highly evolved mutant showed a survival rate similar to 100-fold higher than that of wild-type I-SceI enzyme.