195 research outputs found
Options to relieve the transport network and to shift road traffic to environmentally sounder means of traffic. Summary
Cultivo do milho em sistema de corte e trituração da capoeira na região Nordeste do Pará efeito da época do preparo de área.
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Effects of slash & burn vs. slash & mulch on water, solute, and sediment dynamics at the watershed level.
Manejo de vegetação secundária na Amazônia visando ao aumento da sustentabilidade do uso agrícola do solo.
Qualitative and quantitative patterns of variation in throughfall in spontaneous and enriched secondary vegetation under fallow in Northeastern Para State Brazil.
Entwicklung und Analyse von Optionen zur Entlastung des Verkehrsnetzes und zur Verlagerung von Straßenverkehr auf umweltfreundlichere Verkehrsträger. Endbericht zum TA-Projekt
Avaliação da sustentabilidade das formas de manejo da agricultura itinerante com ou sem queima da capoeira no Nordeste do Pará.
Characterization of a novel novobiocin analogue as a putative Cterminal inhibitor of heat shock protein 90 in prostate cancer cells
PURPOSE: Hsp90 is important in the folding, maturation and stabilization of pro-tumorigenic client proteins and represents a viable drug target for the design of chemotherapies. Previously, we reported the development of novobiocin analogues designed to inhibit the C-terminal portion of Hsp90, which demonstrated the ability to decrease client protein expression. We now report the characterization of the novel novobiocin analogue, F-4, which demonstrates improved cytotoxicity in prostate cancer cell lines compared to the N-terminal inhibitor, 17-AAG. MATERIALS AND METHODS: LNCaP and PC-3 cells were treated with 17-AAG or F-4 in anti-proliferative, apoptosis, cell cycle and cytotoxicity assays. Western blot and prostate specific antigen (PSA) ELISAs were used to determine client protein degradation, induction of Hsp90 and to assess the functional status of the androgen receptor (AR) in response to F-4 treatment. Surface Plasmon Resonance (SPR) was also used to determine the binding properties of F-4 to Hsp90. RESULTS: F-4 demonstrated improved potency and efficacy compared to novobiocin in anti-proliferative assays and decreased expression of client proteins. PSA secretion was inhibited in a dose-dependent manner that paralleled a decrease in AR expression. The binding of F-4 to Hsp90 was determined to be saturable with a binding affinity (Kd) of 100 µM. In addition, superior efficacy was demonstrated by F-4 compared to 17-AAG in experiments measuring cytotoxicity and apoptosis. CONCLUSIONS: These data reveal distinct modes of action for N-terminal and C-terminal Hsp90 inhibitors, which may offer unique therapeutic benefits for the treatment of prostate cancer
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