22 research outputs found
In vitro optimization of non-small cell lung cancer activity with troxacitabine, L-1,3-dioxolane-cytidine, prodrugs
No full textl-1,3-Dioxolane-cytidine, a potent anticancer agent against leukemia, has limited efficacy against solid tumors, perhaps due to its hydrophilicity. Herein, a library of prodrugs were synthesized to optimize in vitro antitumor activity against non-small cell lung cancer. N4-Substituted fatty acid amide prodrugs of 10-16 carbon chain length demonstrated significantly improved antitumor activity over l-1,3-dioxolane-cytidine. These in vitro results suggest that the in vivo therapeutic efficacy of l-1,3-dioxolane-cytidine against solid tumors may be improved with prodrug strategie
Lipophilic Prodrugs and Formulations of Conventional (Deoxy) Nucleoside and Fluoropyrimidine Analogs in Cancer
No full textAbstract B65: Overexpression of MRP4 or MRP5 confers resistance to the nucleoside analogs cytarabine and troxacitabine, but not gemcitabine
No full textOverexpression of MRP4 (ABCC4) and MRP5 (ABCC5) confer resistance to the nucleoside analogs cytarabine and troxacitabine, but not gemcitabine
No full textHematodinium sp. infection in Norway lobster Nephrops norvegicus and its effects on meat quality
No full textHematodinium and Hematodinium-like species have emerged in the last 3 decades
as important parasitic pathogens of crustaceans worldwide, causing a significant economic loss to
fisheries and related markets. In some species (notably the Tanner crab Chionoecetes bairdi), the
parasite reportedly causes the cooked meat to taste bitter and aspirin-like. The bitter taste,
together with the gross pathology of the infection, renders these crabs unmarketable. Surprisingly, no organoleptic tests have ever been conducted to date, and the cause for the bitter taste is
still unknown. Nevertheless, it is generally assumed that the bitter taste occurs widely in cooked
meats and products derived from crustaceans infected with Hematodinium. In the present study,
we analysed the meat quality and organoleptic attributes after capture and during storage of Norway lobsters Nephrops norvegicus from Scottish waters that were either asymptomatic or symptomatic of patent Hematodinium infection. Results from the sensory evaluation of the cooked product indicate that tail meat from symptomatic N. norvegicus is bland in flavour and aftertaste, and
more friable or sloppier in texture than meat from asymptomatic animals. As a consequence,
infected meat tends to be less palatable, although surprisingly no bitter taste is reported. From an
analytical point of view, tail meat from patently infected animals is at an advanced stage of auto -
lysis, while no difference in microbial load is detected. These results suggest that Norway lobsters
heavily infected with Hematodinium are of inferior marketing quality even after the tails have
been cooked
Reservoir computing with output feedback
No full textReinhart RF. Reservoir computing with output feedback. Bielefeld: Bielefeld University; 2011.A dynamical system approach to forward and inverse modeling is proposed. Forward and inverse models are trained in associative recurrent neural networks that are based on non-linear random projections. Feedback of estimated outputs into such reservoir networks is a key ingredient in the context of bidirectional association but entails the problem of error amplification. Robust training of reservoir networks with output feedback is achieved by a novel one-shot learning and regularization method for input-driven recurrent neural networks. It is shown that output feedback enables the implementation of ambiguous inverse models by means of multi-stable dynamics. The proposed methodology is applied to movement generation of robotic manipulators in a feedforward-feedback control framework
Modulation of signaling enhances the efficacy of the combination of satraplatin and erlotinib
No full textThe active metabolite (JM118) of the oral platinum analog satraplatin (JM216) was investigated for potential synergism with erlotinib, an epidermal growth factor receptor (EGFR) inhibitor. JM118 sensitivity of 7 cancer cell lines (ovarian: 2008, A2780; colon: Lovo92, WiDr; lung: A549, SW1573; epidermoid: A431), was enhanced most pronounced when JM118 preceded erlotinib, which was associated with increased formation of DNA-platinum adducts. The combination increased G2/M phase accumulation and enhanced apoptosis. JM118 increased the phosphorylation of the cell cycle proteins CDK2 and CHK1 after 24 hr exposure. JM118/erlotinib enhanced Erk and Akt phosphorylation after 2 hr. JM118 significantly decreased the phosphorylation of PTEN, VEGFR, EPHA1, ERBB4, FGF-R, andSTAT3 by 20 (PTEN) to >90% (STAT3). Erlotinib enhanced the effects of JM118, even in cells with mutations in Ras. The mechanism of synergy involved a combination of effects on platinum-DNA adduct formation, cell cycle distribution and signalin
Metabolism and accumulation of the lipophilic deoxynucleoside analogs elacytarabine and CP-4126
No full textSulfasalazine Down-Regulates the Expression of the Angiogenic Factors Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase and Interleukin-8 in Human Monocytic-Macrophage THP1 and U937 Cells
No full textAntiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models
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