G207 is a conditionally replicating derivative of herpes simplex virus type1 (HSV-1) engineered with deletions of both ICP34.5 loci and a lacZ insertion disabling the ICP6 gene. G207 exhibits an efficient oncolytic activity in vitro and in vivo, yet minimal toxicity in normal tissue, and is now in clinical trial for malignant glioma. According to the results of clinical trials, however, although G207 was proved to be safe, the efficacy was not so impressive. Deletion of the ICP34.5 gene coding for virulence made G207 extremely safe, but it markedly reduced the cytotoxicity mediated by HSV-1. To enhance the therapeutic efficacy of G207 without diminishing its safety, we used a defective vector containing Musashi1 promoter/ICP34.5, with G207 as helper virus. P/musashi1 was functional selectively in human glioma cell lines (U87MG, U251, T98G) in this study and dvM345 showed a much higher therapeutic efficacy both in culture and in the in vivo glioma model, than G207 alone, without diminishing its favorable toxicity profile. These results suggest that transcriptional regulation of ICP34.5 by P/musashi1 can be used to target HSV-1 virulence toward gliomas while maintaining the desirable neuroattenuated phenotype.
Rhinacanthus nasutus (L.) KURZ (Acanthaceae) is a shrub widely distributed in South China and India. In this study, the antiproliferative activity of the ethanol extract of root and aqueous extract of leaves of R. nasutus, and the supposed active moiety rhinacanthin C was assessed in vitro using the human cervical carcinoma cell line HeLa, its MDR1-overexpressing subline Hvr100-6, human prostate carcinoma PC-3 cells and human bladder carcinoma T24 cells. Rhinacanthin C was chemically synthesized and its content in the R. nasutus extracts was determined by HPLC with a photodiode array detector. The antiproliferative activity of the R. nasutus extracts was also assessed in vivo using sarcoma 180-bearing mice. It was suggested that 1) the in vitro antiproliferative activity of rhinacanthin C was comparable with or slightly weaker than that of 5-FU, 2) rhinacanthin C showed antiproliferative activity for MDR1-overexpressing Hvr100-6 cells, similarly to parent HeLa cells, 3) the in vitro antiproliferative activity of the ethanol extract of root R. nasutus was due to rhinacanthin C, whereas that of the aqueous extract of leaves of R. nasutus was due to constituents other than rhinacanthin C, and 4) both of the R. nasutus extracts showed in vivo antiproliferative activity after oral administration once daily for 14 d.
Mineral carbonation using alkaline wastes is an attractive approach to CO 2 utilization. Owing to the difference between waste CO 2 and feedstock CO 2 , developing CO 2 utilization technologies without CO 2 purification and pressurization is a promising concept. This study investigated a potential method for CO 2 utilization via direct aqueous carbonation of synthesized concrete fines under atmospheric pressure and low CO 2 concentration. The carbonation reaction with different solid−liquid ratios and different concentrations of introduced CO 2 was examined in detail. Under basic conditions, a CO 2 uptake of 0.19 g-CO 2 /g-concrete fines demonstrated that direct aqueous carbonation of concrete fines under atmospheric pressure and low CO 2 concentration is effective. The CaCO 3 concentration, degree of carbonation, and reaction mechanism were clarified. Furthermore, characterization of the carbonated products was used to evaluate ways of utilizing the carbonated products.
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