Human glioblastoma multiforme: p53 reactivation by a novel MDM2 inhibitor

Cancer development and chemo-resistance are often due to impaired functioning of the p53 tumor suppressor through genetic mutation or sequestration by other proteins. In glioblastoma multiforme (GBM), p53 availability is frequently reduced because it binds to the Murine Double Minute-2 (MDM2) oncoprotein, which accumulates at high concentrations in tumor cells. The use of MDM2 inhibitors that interfere with the binding of p53 and MDM2 has become a valid approach to inhibit cell growth in a number of cancers; however little is known about the efficacy of these inhibitors in GBM. We report that a new small-molecule inhibitor of MDM2 with a spirooxoindolepyrrolidine core structure, named ISA27, effectively reactivated p53 function and inhibited human GBM cell growth in vitro by inducing cell cycle arrest and apoptosis. In immunoincompetent BALB/c nude mice bearing a human GBM xenograft, the administration of ISA27 in vivo activated p53, inhibited cell proliferation and induced apoptosis in tumor tissue. Significantly, ISA27 was non-toxic in an in vitro normal human cell model and an in vivo mouse model. ISA27 administration in combination with temozolomide (TMZ) produced a synergistic inhibitory effect on GBM cell viability in vitro, suggesting the possibility of lowering the dose of TMZ used in the treatment of GBM. In conclusion, our data show that ISA27 releases the powerful antitumor capacities of p53 in GBM cells. The use of this MDM2 inhibitor could become a novel therapy for the treatment of GBM patients

A Probabilistic Model For Sensor Validation

The validation of data from sensors has become an important issue in the operation and control of modern industrial plants. One approach is to use knowledge based techniques to detect inconsistencies in measured data. This article presents a probabilistic model for the detection of such inconsistencies. Based on probability propagation, this method is able to find the existence of a possible fault among the set of sensors. That is, if an error exists, many sensors present an apparent fault due to the propagation from the sensor (s) with a real fault. So the fault detection mechanism can only tell if a sensor has a potential fault, but it can not tell if the fault is real or apparent. So the central problem is to develop a theory, and then an algorithm, for distinguishing real and apparent faults, given that one or more sensors can fail at the same time. This article then, presents an approach based on two levels: (i) probabilistic reasoning, to detect a potential fault, and (ii) cons..

The use of spray drying technology to reduce bitter taste of casein hydrolysate

The utilization of protein hydrolysates in food systems is frequently hindered due to their bitterness and hygroscopicity. Spray drying technology could be an alternative for reducing these problems. The aim of this work was to reduce or to mask the casein hydrolysate bitter taste using spray drying and mixtures of gelatin and soy protein isolate (SPI) as carriers. Six formulations were studied: three with 20% of hydrolysate and 80% of mixture (gelatine/SPI at proportions of 50/50, 40/60 and 60/40%) and three with 30% of hydrolysate and 70% of mixture (gelatine/SPI at proportions of 50/50, 40/60 and 60/40%). The spray-dried formulations were evaluated by SEM, hygroscopicity, thermal behavior (DSC), dissolution, and bitter taste, by a trained sensory panel using a paired-comparison test (free samples vs. spray-dried samples); all samples were presented in powder form. SEM analysis showed mostly spherically shaped particles, with many concavities and some particles with pores. All formulations were oil and water compatible and showed lower hygroscopicity values than free casein hydrolysate. At Aw 0.83, the free hydrolysate showed Tg about 25 °C lower than the formulations, indicating that the formulations may be more stable at Aw ≥ 0.65 since the glass transition should be prevented. The sensory panel found the formulations, tasted in the powder form, to be less bitter (P < 0.05) than the free casein hydrolysate. These results indicated that spray drying of casein hydrolysate with mixtures of gelatin and SPI was successful to attenuate the bitterness of casein hydrolysate. Thus, spray drying widens the possibilities of application of casein hydrolysates244336340FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP05/56674-3; 06/56714-

Production and properties of casein hydrolysate microencapsulated by spray drying with soybean protein isolate

The aim of this work was to encapsulate casein hydrolysate by spray drying with soybean protein isolate (SPI) as wall material to attenuate the bitter taste of that product. Two treatments were prepared: both with 12 g/100 g solids and containing either two proportions of SPI: hydrolysate (70:30 and 80:20), called M1 and M2, respectively. The samples were evaluated for morphological characteristics (SEM), particle size, hygroscopicity, solubility, hydrophobicity, thermal behavior and bitter taste with a trained sensory panel using a paired-comparison test (non-encapsulated samples vs. encapsulated samples). Microcapsules had a continuous wall, many concavities, and no porosity. Treatments M1 and M2 presented average particle sizes of 11.32 and 9.18 mu m, respectively. The wall material and/or the microencapsulation raised the hygroscopicity of the hydrolysate since the free hydrolysate had hygroscopicity of 53 g of water/100 g of solids and M1 and M2 had 106.99 and 102.19 g of water/100 g of solids, respectively. However, the hydrophobicity decreases, the absence of a peak in encapsulated hydrolysates, and the results of the panel sensory test considering the encapsulated samples less bitter (p < 0.05) than the non-encapsulated, showed that spray drying with SPI was an efficient method for microencapsulation and attenuation of the bitter taste of the casein hydrolysate. (c) 2008 Elsevier Ltd. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[051 56674-3

Microencapsulation of casein hydrolysate by complex coacervation with SPI/pectin

The aim of this work was to encapsulate casein hydrolysate by complex coacervation with soybean protein isolate (SPI)/pectin. Three treatments were studied with wall material to core ratio of 1:1, 1:2 and 1:3. The samples were evaluated for morphological characteristics, moisture, hygroscopicity, solubility, hydrophobicity, surface tension, encapsulation efficiency and bitter taste with a trained sensory panel using a paired comparison test. The samples were very stable in cold water. The hydrophobicity decreased inversely with the hydrolysate content in the microcapsule. Encapsulated samples had lower hygroscopicity values than free hydrolysate. The encapsulation efficiency varied from 91.62% to 78.8%. Encapsulated samples had similar surface tension, higher values than free hydrolysate. The results of the sensory panel test considering the encapsulated samples less bitter (P < 0.05) than the free hydroly-state, showed that complex coacervation with SPI/pectin as wall material was an efficient method for microencapsulation and attenuation of the bitter taste of the hydrolysate. (C) 2009 Elsevier Ltd. All rights reserved.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)[05/56674-3