ABSTRACT
ZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a "nonself" label in tumor cells and then turn the tumor cells from the "self" state into the "nonself" state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.
Subject(s)
Adenoviridae/genetics , Immunotherapy/methods , Interleukins/metabolism , Melanoma/genetics , Animals , Disease Models, Animal , Female , Humans , Mice , Mice, NudeABSTRACT
OBJECTIVE: To confirm AcrAB-TolC system mediated the multiple antimicrobial resistance in Salmonella typhimurium. METHODS: One-step knock-out of chromosomal method was used, to disrupt chromosomal genes, in Salmonella typhimurium wild strain X2. The acrAB gene and tolC gene were knocked out and two mutants of the delta acrABX2 and delta tolCX2 were produced. RESULTS: Results of E-test to two mutation strains and their parent strain showed that delta acrABX2 and delta tolCX2 were resistant to vancomycin and susceptible to amikacin and cephalothin, which was similar to their parents isolate X2, but (acrABX2 and (tolCX2 were susceptible to other eleven antimicrobial agents, while the parents isolate X2 was resistant to those. CONCLUSION: multiple antimicrobial resistance in Salmonella typhimurium. It suggested that the AcrAB-TolC system mediated the multiple antimicrobial resistance in Salmonella typhimurium.
Subject(s)
Bacterial Proteins/genetics , Carrier Proteins/genetics , Drug Resistance, Multiple, Bacterial/genetics , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Gene Knockout Techniques , Mutation , Vancomycin ResistanceABSTRACT
OBJECTIVE: To determine and analyse the composition of cellular fatty acids of Burkholderia gladioli. METHODS: The cellular fatty acids composition of different pathovar strains of Burkholderia gladioli were determined by GC method and analyzed by MIDI-FAME. RESULTS: The results showed that the composition of cellular fatty acids of these strains, including original food poison strains of, were similar and were identified as, and this confirmed the conclusion that Pseudomonas cocovenenans subsp farinofermentans and Burkholderia cocovenenan were the junior synonym of Burkholdria gladioli. It was interesting to find that fatty acids of C16: 0.20H, C18: 1.20H and C16: 1.20H were related to the Bongkrekic acid (BA) producing of Pseudomonas cocovenenans subsp farinofermentans. CONCLUSION: It provide more data for the study of the mechanism of BA production and pathogenesis.
