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81.
Modified peptides in anti-cancer vaccines: are we eventually improving anti-tumour immunity? 总被引:1,自引:0,他引:1
Iero M Filipazzi P Castelli C Belli F Valdagni R Parmiani G Patuzzo R Santinami M Rivoltini L 《Cancer immunology, immunotherapy : CII》2009,58(7):1159-1167
The discovery of tumour antigens recognized by T cells and the features of immune responses directed against them has paved
the way to a multitude of clinical studies aimed at boosting anti-tumour T cell immunity as a therapeutic tool for cancer
patients. One of the different strategies explored to ameliorate the immunogenicity of tumour antigens in vaccine protocols
is represented by the use of optimized peptides or altered peptide ligands, whose amino acid sequence has been modified for
improving HLA binding or TCR interaction with respect to native epitopes. However, despite the promising results achieved
with preclinical studies, the clinical efficacy of this approach has not yet met the expectations. Although multiple reasons
could explain the relative failure of altered peptide ligands as more effective cancer vaccines, the possibility that T cells
primed by modified tumour peptides might may be unable to effectively cross-recognize tumour cells has not been sufficiently
addressed. Indeed, the introduction of conservative amino acid substitutions may still produce diverse and unpredictable changes
in the HLA/peptide interface, with consequent modifications of the TCR repertoire that can interact with the complex. This
could lead to the expansion of a broad array of T cells whose TCRs may not necessarily react with equivalent affinity with
the original antigenic epitope. Considering the results presently achieved with this vaccine approach, and the emerging availability
of alternative strategies for boosting anti-tumour immunity, the use of modified tumour peptides could be reconsidered.
This article is a symposium paper from the conference “Immunotherapy—From Basic Research to Clinical Applications”, Symposium
of the Collaborative Research Center (SFB) 685, held in Tübingen, Germany, 6–7 March 2008. 相似文献
82.
Javier Saavedra 《Culture, medicine and psychiatry》2009,33(2):163-184
This study explores qualitative changes in the life narratives of persons diagnosed with paranoid schizophrenia who were receiving
recovery treatment in special care homes in Andalusia, Spain. These narratives are related to patients’ construction of social
identity and the recovery process. Initially, 10 narrative interviews were performed. The first five patients (Group 1) had
lived at the homes for only 3 months, while the other five (Group 2) had been there for 61.4 months. Two years after the initial
interviews, three patients from Group 1 were interviewed once more. The qualitative analysis focuses on two topics: experience
of illness and personal relationships. Long-stay patients create their identities by using more categories related to relationships
and make fewer references to illness than Group 1 subjects. They also make fewer delusive or hallucinatory utterances, and
their narratives have more elements that can be shared in the community than Group 1 narratives. Moreover, long-stay patients
show significant language resources and greater capacity for agency. Results suggest that special care homes provide important
emotional support and a rich, new network. These results are related to the sociocultural characteristics of special care
homes and suggest that the analysis of life narratives could be a very useful instrument for assessing the recovery process.
相似文献
Javier SaavedraEmail: |
83.
Maricel Alvarez Dries Huygens Erick Olivares Isabel Saavedra Miren Alberdi Eduardo Valenzuela 《Physiologia plantarum》2009,136(4):426-436
Drought stress conditions (DC) reduce plant growth and nutrition, restraining the sustainable reestablishment of Nothofagus dombeyi in temperate south Chilean forest ecosystems. Ectomycorrhizal symbioses have been documented to enhance plant nitrogen (N) and phosphorus (P) uptake under drought, but the regulation of involved assimilative enzymes remains unclear. We studied 1-year-old N. dombeyi (Mirb.) Oerst. plants in association with the ectomycorrhizal fungi Pisolithus tinctorius (Pers.) Coker & Couch. and Descolea antartica Sing. In greenhouse experiments, shoot and root dry weights, mycorrhizal colonization, foliar N and P concentrations, and root enzyme activities [glutamate synthase (glutamine oxoglutarate aminotransferase (GOGAT), EC 1.4.1.13-14), glutamine synthetase (GS, EC 6.3.1.2), glutamate dehydrogenase (GDH, EC 1.4.1.2-4), nitrate reductase (NR, EC 1.6.6.1), and acid phosphomonoesterase (PME, EC 3.1.3.1-2)] were determined as a function of soil-water content. Inoculation of N. dombeyi with P. tinctorius and D. antartica significantly stimulated plant growth and increased plant foliar N and P concentrations, especially under DC. Ectomycorrhizal inoculation increased the activity of all studied enzymes relative to non-mycorrhizal plants under drought. We speculate that GDH is a key enzyme involved in the enhancement of ectomycorrhizal carbon (C) availability by fuelling the tricarboxylic acid (TCA) cycle under conditions of drought-induced carbon deficit. All studied assimilative enzymes of the ectomycorrhizal associations, involved in C, N, and P transfers, are closely interlinked and interdependent. The up-regulation of assimilative enzyme activities by ectomycorrhizal fungal root colonizers acts as a functional mechanism to increase seedling endurance to drought. We insist upon incorporating ectomycorrhizal inoculation in existing Chilean afforestation programs. 相似文献
84.
Oscar M. Saavedra Ljubomir Isakovic David B. Llewellyn Lijie Zhan Naomy Bernstein Stephen Claridge Franck Raeppel Arkadii Vaisburg Nadine Elowe Andrea J. Petschner Jubrail Rahil Norman Beaulieu A. Robert MacLeod Daniel Delorme Jeffrey M. Besterman Amal Wahhab 《Bioorganic & medicinal chemistry letters》2009,19(10):2747-2751
The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH– without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N6-amino moiety favors the inhibition of DNMT3b2 enzyme. 相似文献
85.
A. Aires V.R. Mota M.J. Saavedra E.A.S. Rosa R.N. Bennett 《Journal of applied microbiology》2009,106(6):2086-2095
Aims: The aim of the study was to evaluate the in vitro antibacterial activity of glucosinolates and their enzymatic hydrolysis product against bacteria isolated from the human intestinal tract.
Methods and results: Using a disc diffusion bioassay, different doses of intact glucosinolates and their corresponding hydrolysis products were tested. There were clear structure–activity and concentration differences with respect to the in vitro growth inhibition effects as well as differences in the sensitivities of the individual bacteria. The most effective glucosinolate hydrolysis products were the isothiocyanates; sulforaphane and benzyl isothiocyanate were the best inhibitors of growth. Indole-3-carbinol had some inhibitory effects against the Gram-positive bacteria but had no effect, even at the highest dose, against the Gram-negative bacteria. Indole-3-acetonitrile had some inhibitory activity against the Gram-negative bacteria. Glucosinolates, nitriles and amines were ineffective at all the doses used.
Conclusions: Glucosinolate hydrolysis products and specifically the isothiocyanates SFN and BITC have significant antimicrobial activity against Gram-positive and Gram-negative bacteria, and might be useful in controlling human pathogens through the diet.
Significance and Impact of the Study: This the first major in vitro study demonstrating the potential of these natural dietary chemicals as an alternative to, or in combination with, current antibiotic-based therapies for treating infectious diseases. 相似文献
Methods and results: Using a disc diffusion bioassay, different doses of intact glucosinolates and their corresponding hydrolysis products were tested. There were clear structure–activity and concentration differences with respect to the in vitro growth inhibition effects as well as differences in the sensitivities of the individual bacteria. The most effective glucosinolate hydrolysis products were the isothiocyanates; sulforaphane and benzyl isothiocyanate were the best inhibitors of growth. Indole-3-carbinol had some inhibitory effects against the Gram-positive bacteria but had no effect, even at the highest dose, against the Gram-negative bacteria. Indole-3-acetonitrile had some inhibitory activity against the Gram-negative bacteria. Glucosinolates, nitriles and amines were ineffective at all the doses used.
Conclusions: Glucosinolate hydrolysis products and specifically the isothiocyanates SFN and BITC have significant antimicrobial activity against Gram-positive and Gram-negative bacteria, and might be useful in controlling human pathogens through the diet.
Significance and Impact of the Study: This the first major in vitro study demonstrating the potential of these natural dietary chemicals as an alternative to, or in combination with, current antibiotic-based therapies for treating infectious diseases. 相似文献
86.
87.
Bacterial toxin–antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes. 相似文献
88.
Boto A Gallardo JA Hernández R Ledo F Muñoz A Murguía JR Menacho-Márquez M Orjales A Saavedra CJ 《Bioorganic & medicinal chemistry letters》2006,16(23):6073-6077
The discovery of genotoxic amino acids derived from phenylglycine, and possessing halogen substituents, is described. The utility of hypervalent iodine reagents in the synthesis of this class of compounds is highlighted. The mechanism of action of the (haloaryl)glycines was studied in Saccharomyces cerevisiae. 相似文献
89.
Ecological indicators for assessing ecological success of forest restoration: a world review
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Restoration is increasingly being used to reverse degradation and destruction of forest ecosystems. With increasing investment in restoration, there is an urgent need to develop effective programs to assess treatment efficacy and effects. We conducted a global review of forest restoration assessments, in order to identify geographic trends in the locations where assessments have been implemented and the specific ecological attributes (ecosystem composition, structure, and function) and indicators being used to measure effects. We found that the number of forest restoration assessments varied by region and was not related to degree of degradation or restoration need. Some regions, like Africa, which have experienced high rates of forest loss and degradation, had few assessments. The majority (43%) of assessments included indicators for only two of three key ecological attributes (composition‐structure or composition‐function) and assessments on average used fewer than three indicators per attribute. The most commonly employed indicators for composition were richness and abundance of plant species and for structure were height and diameter of trees, variables that are generally relatively easy to measure. The use of functional indicators has been increasing over time and they are now more commonly used than structural indicators. The most common functional indicators were soil functions. Most investigators evaluated treatment effects for 6–10 years after implementation. Our findings related to gaps in analysis of ecological indicators can serve as a guide for developing monitoring and assessment protocols for current global forest restoration initiatives by 2020–2030. 相似文献
90.
Ochoa-Leyva A Barona-Gómez F Saab-Rincón G Verdel-Aranda K Sánchez F Soberón X 《Journal of molecular biology》2011,405(1):143-157
Cellulosomes are large extracellular multi-enzyme complexes that exhibit elevated activity on plant cell-wall polysaccharides. In the present study, the relationships between the conformational flexibility and efficacy of cellulosomes, and the inter-modules linkers of their scaffold protein were investigated. For this purpose, the length of the intrinsically disordered Ser/Thr-rich 50-residue linker connecting a Clostridium thermocellum and a Clostridium cellulolyticum cohesin in a hybrid scaffoldin (Scaf4) was changed by sequences ranging from 4 to 128 residues. The composition was also modified and new linkers composed of series of N, S or repeats of the EPPV motif were generated. Two model cellulases (Cel48F and Cel9G) appended with appropriate dockerins were subsequently bound to the engineered scaffoldins. All the resulting minicomplexes displayed the same activity on crystalline cellulose as the complex based on the initial Scaf4, and were found to be 2-fold more active than Cel48F and Cel9G bound to separate cohesins. Small-angle X-ray scattering assays of the engineered scaffoldins confirmed, however, that the size and the conformational flexibility of some of the new inter-cohesins linkers differed significantly from that of the initial 50 residue linker displayed by the parental Scaf4. Our data suggest that the synergy induced by proximity does not require a specific inter-cohesins sequence or distance. The present study reveals that complexation onto the hybrid scaffoldins modifies the type of soluble sugars released from crystalline cellulose by the selected cellulases, compared to the free enzyme system. 相似文献