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351.
352.
Accordi B Espina V Giordan M VanMeter A Milani G Galla L Ruzzene M Sciro M Trentin L De Maria R te Kronnie G Petricoin E Liotta L Basso G 《PloS one》2010,5(10):e13552
Background
In spite of leukemia therapy improvements obtained over the last decades, therapy is not yet effective in all cases. Current approaches in Acute Lymphoblastic Leukemia (ALL) research focus on identifying new molecular targets to improve outcome for patients with a dismal prognosis. In this light phosphoproteomics seems to hold great promise for the identification of proteins suitable for targeted therapy.Methodology/Principal Findings
We employed Reverse Phase Protein Microarrays to identify aberrantly activated proteins in 118 pediatric B-cell precursor (BCP)-ALL patients. Signal transduction pathways were assayed for activation/expression status of 92 key signalling proteins. We observed an increased activation/expression of several pathways involved in cell proliferation in poor clinical prognosis patients. MLL-rearranged tumours revealed BCL-2 hyperphosphorylation through AMPK activation, which indicates that AMPK could provide a functional role in inhibiting apoptosis in MLL-rearranged patients, and could be considered as a new potential therapeutic target. Second, in patients with poor clinical response to prednisone we observed the up-modulation of LCK activity with respect to patients with good response. This tyrosine-kinase can be down-modulated with clinically used inhibitors, thus modulating LCK activity could be considered for further studies as a new additional therapy for prednisone-resistant patients. Further we also found an association between high levels of CYCLIN E and relapse incidence. Moreover, CYCLIN E is more expressed in early relapsed patients, who usually show an unfavourable prognosis.Conclusions/Significance
We conclude that functional protein pathway activation mapping revealed specific deranged signalling networks in BCP-ALL that could be potentially modulated to produce a better clinical outcome for patients resistant to standard-of-care therapies. 相似文献353.
Regional management units for marine turtles: a novel framework for prioritizing conservation and research across multiple scales 总被引:2,自引:0,他引:2
Wallace BP DiMatteo AD Hurley BJ Finkbeiner EM Bolten AB Chaloupka MY Hutchinson BJ Abreu-Grobois FA Amorocho D Bjorndal KA Bourjea J Bowen BW Dueñas RB Casale P Choudhury BC Costa A Dutton PH Fallabrino A Girard A Girondot M Godfrey MH Hamann M López-Mendilaharsu M Marcovaldi MA Mortimer JA Musick JA Nel R Pilcher NJ Seminoff JA Troëng S Witherington B Mast RB 《PloS one》2010,5(12):e15465
Background
Resolving threats to widely distributed marine megafauna requires definition of the geographic distributions of both the threats as well as the population unit(s) of interest. In turn, because individual threats can operate on varying spatial scales, their impacts can affect different segments of a population of the same species. Therefore, integration of multiple tools and techniques — including site-based monitoring, genetic analyses, mark-recapture studies and telemetry — can facilitate robust definitions of population segments at multiple biological and spatial scales to address different management and research challenges.Methodology/Principal Findings
To address these issues for marine turtles, we collated all available studies on marine turtle biogeography, including nesting sites, population abundances and trends, population genetics, and satellite telemetry. We georeferenced this information to generate separate layers for nesting sites, genetic stocks, and core distributions of population segments of all marine turtle species. We then spatially integrated this information from fine- to coarse-spatial scales to develop nested envelope models, or Regional Management Units (RMUs), for marine turtles globally.Conclusions/Significance
The RMU framework is a solution to the challenge of how to organize marine turtles into units of protection above the level of nesting populations, but below the level of species, within regional entities that might be on independent evolutionary trajectories. Among many potential applications, RMUs provide a framework for identifying data gaps, assessing high diversity areas for multiple species and genetic stocks, and evaluating conservation status of marine turtles. Furthermore, RMUs allow for identification of geographic barriers to gene flow, and can provide valuable guidance to marine spatial planning initiatives that integrate spatial distributions of protected species and human activities. In addition, the RMU framework — including maps and supporting metadata — will be an iterative, user-driven tool made publicly available in an online application for comments, improvements, download and analysis. 相似文献354.
Lo Nostro P Ninham BW Milani S Lo Nostro A Pesavento G Baglioni P 《Biophysical chemistry》2006,124(3):208-213
Specific ion effects, representative of near-universal Hofmeister phenomena, are illustrated in three different systems. These are the formation of supramolecular assemblies from cyclodextrins, the optical rotation of L-serine, and the growth rate of two kinds of microorganisms (Staphylococcus aureus and Pseudomonas aeruginosa). The strong specific ion effects can be correlated with the anion polarizabilities and related physico-chemical parameters. The results show the relevance of dispersion (non-electrostatic) forces in these phenomena. 相似文献
355.
356.
357.
Eliana Alves Liliana Costa Carla MB Carvalho Jo?o PC Tomé Maria A Faustino Maria GPMS Neves Augusto C Tomé José AS Cavaleiro ?ngela Cunha Adelaide Almeida 《BMC microbiology》2009,9(1):70
Background
In recent times photodynamic antimicrobial therapy has been used to efficiently destroy Gram (+) and Gram (-) bacteria using cationic porphyrins as photosensitizers. There is an increasing interest in this approach, namely in the search of photosensitizers with adequate structural features for an efficient photoinactivation process. In this study we propose to compare the efficiency of seven cationic porphyrins differing in meso-substituent groups, charge number and charge distribution, on the photodynamic inactivation of a Gram (+) bacterium (Enterococcus faecalis) and of a Gram (-) bacterium (Escherichia coli). The present study complements our previous work on the search for photosensitizers that might be considered good candidates for the photoinactivation of a large spectrum of environmental microorganisms. 相似文献358.
Roberta Carbone Marzia De Marni Andrea Zanardi Simone Vinati Emanuele Barborini Lorenzo Fornasari Paolo Milani 《Analytical biochemistry》2009,394(1):7-12
Protein microarray technologies are rapidly expanding to fulfill current needs of proteome discovery for disease management. Nanostructured materials have been shown to present interesting features when used in biological settings: nanostructured titanium oxide film (ns-TiOx), synthesized by supersonic cluster beam deposition (SCBD), has recently emerged as a biocompatible substrate in different biological assays. The ns-TiOx surface is characterized by a morphology at the nanoscale that can be tuned to modulate specific biomolecule–material interactions. Here we present a systematic characterization of ns-TiOx coatings as protein binding surfaces, comparing their performances with those of most common commercial substrates in protein and antibody microarray assays. Through a robust statistical evaluation of repeatability in terms of coefficient of variation (CV) analysis, we demonstrate that ns-TiOx can be used as reliable substrate for biochips in analytical protein microarray application. 相似文献
359.
Effects of thermal stress on tumor antigenicity and recognition by immune effector cells 总被引:3,自引:0,他引:3
The primary rationale for the application of clinical hyperthermia in the therapy of cancer is based on the direct cytotoxic
effect of heat and the radio-chemosensitization of tumor cells. More recently, additional attention is given to the observation
that heat and heat-shock proteins can activate the host’s immune system. The expression of heat-shock genes and proteins provides
an adaptive mechanism for stress tolerance, allowing cells to survive non-physiologic conditions. However, the same adaptive
mechanism can ultimately favor malignant transformation by interfering with pathways that regulate cell growth and apoptosis.
Cytoprotection and thermotolerance raised the concern that heat-treated tumor cells might also be resistant to attack by immune
effector mechanisms. Many studies, including those from our group, address this concern and document that heat-exposure, although
transiently modulating sensitivity to CTL, do not hinder CTL attack. Moreover, there are promising reports of heat-related
upregulation of NK-activating ligands, rendering those tumors which have lost MHC class I molecules target for NK cell attack.
Heat-induced cytoprotection, therefore, does not necessarily extend protection from cytotoxic immune mechanisms. When interpreting
the effects of heat, it is important to keep in mind that thermal effects on cell physiology are strongly dependent on the
thermal dose, which is a function of the magnitude of change in temperature and the duration of heat exposure. The thermal
dose required to induce cell death in vitro strongly varies from cell type to cell type and depends on microenvironmental
factors (Dewey 1994). Therefore, to dissect the immunological behaviour of a given tumor and its micro-environment at different thermal doses,
it is essential to characterize the thermosensitivity of every single tumor type and assess the proportion of cells surviving
a given heat treatment. In this review, we summarize the pleiotropic effects that heat exposure has on tumor cells. In particular,
we focus on the effects of heat on the antigen presentation of tumor cells and their susceptibility to immune effector mechanisms.
We emphasize that the response to thermal stress is not a one-time point event, but rather a time period starting with the
heat exposure and extending over several days of recovery. In addition, the response of tumor cells and their susceptibility
to immune effector cells is strongly dependent on the model system, on the magnitude and duration of the thermal stress and
on the time of recovery after heat exposure. Consideration of these aspects might help to explain some of the conflicting
results that are reported in the field of thermal stress response.
This article forms part of the Symposium in Writing "Thermal stress-related modulation of tumor cell physiology and immune
responses", edited by Elfriede Noessner. 相似文献
360.
Odetti P Traverso N Monacelli F Menini S Vazzana J Tasso B Pronzato MA Robaudo C Deferrari G 《Free radical research》2006,40(2):207-212
Uraemic subjects undergoing chronic haemodialysis show increased oxidative stress. The use of non-biocompatible filters and reduced antioxidative defences are important sources of reactive oxygen species (ROS) release. The highly oxidative environment accelerates the onset and progression of tissue damage and atherosclerotic cardiovascular disease. The aldehyde 4-hydroxyl-2-nonenal (HNE) is probably the best marker of oxidative stress. In this study, the concentration of plasma HNE was evaluated in eight uremic subjects during two sessions of haemodialysis: the first using a standard biocompatible filter and the second using a filter coated with vitamin E. Baseline plasma levels of HNE were elevated, and dropped during haemodialysis. At the end of the session, however, low levels were maintained only when the vitamin E-modified filter was used. By contrast, a marked increase in HNE was recorded at the end of the session in all subjects who underwent haemodialysis with the conventional filter. This study provides evidence that the vitamin E-coated filter plays a role in counteracting oxidative stress. The chronic use of vitamin E-modified filters in haemodialysed subjects might help to counterbalance oxidative attack and, consequently, contribute to preventing cardiovascular disease. 相似文献