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161.
Sonia Fabris Valentina Bollati Luca Agnelli Fortunato Morabito Valeria Motta Giovanna Cutrona Serena Matis Anna Grazia Recchia Vincenzo Gigliotti Massimo Gentile Giorgio Lambertenghi Deliliers Pier Alberto Bertazzi Manlio Ferrarini Antonino Neri Andrea Baccarelli 《Epigenetics》2011,6(2):188-194
Global DNA hypomethylation affecting repeat sequences has been reported in different cancer types. Herein, we investigated the methylation levels of repetitive DNA elements in chronic lymphocytic leukemia (CLL), their correlation with the major cytogenetic and molecular features, and clinical relevance in predicting therapy-free survival (TFS). A quantitative bisulfite-PCR Pyrosequencing method was used to evaluate methylation of Alu, long interspersed nuclear elements-1 (LINE-1) and satellite-α (SAT-α) sequences in 77 untreated early-stage (Binet A) CLL patients. Peripheral B-cells from 7 healthy donors were used as controls. Methylation levels (median %5mC) were lower in B-CLLs compared with controls (21.4 vs. 25.9; 66.8 vs. 85.7; 84.0, vs. 88.2 for Alu, LINE-1 and SAT-α, respectively) (p < 0.001). Among CLL patients, a significant association was observed with 17p13.1 deletion (16.8 vs. 22.4; 51.2 vs. 68.5; 52.6 vs. 85.0, for Alu, LINE-1 and SAT-α) but not with other major genetic lesions, IgVH mutation status, CD38 or ZAP-70 expression. Follow-up analyses showed that lower SAT-α methylation levels appeared to be an independent prognostic marker significantly associated with shorter TFS. Our study extended previous limited evidences in methylation of repetitive sequences in CLL suggesting an important biological and clinical relevance in the disease. 相似文献
162.
Varthaman A Clement M Khallou-Laschet J Fornasa G Gaston AT Dussiot M Caligiuri G Cantor H Kaveri S Nicoletti A 《PloS one》2011,6(6):e21628
T cell-dependent autoimmune diseases are characterized by the expansion of T cell clones that recognize immunodominant epitopes on the target antigen. As a consequence, for a given autoimmune disorder, pathogenic T cell clones express T cell receptors with a limited number of variable regions that define antigenic specificity. Qa-1, a MHC class I-like molecule, presents peptides from the variable region of TCRs to Qa-1-restricted CD8+ T cells. The induction of Vß-specific CD8+ T cells has been harnessed in an immunotherapeutic strategy known as the “T cell vaccination” (TCV) that comprises the injection of activated and attenuated CD4+ T cell clones so as to induce protective CD8+ T cells. We hypothesized that Qa-1-restricted CD8+ regulatory T cells could also constitute a physiologic regulatory arm of lymphocyte responses upon expansion of endogenous CD4+ T cells, in the absence of deliberate exogenous T cell vaccination. We immunized mice with two types of antigenic challenges in order to sequentially expand antigen-specific endogenous CD4+ T cells with distinct antigenic specificities but characterized by a common Vß chain in their TCR. The first immunization was performed with a non-self antigen while the second challenge was performed with a myelin-derived peptide known to drive experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. We show that regulatory Vß-specific Qa-1-restricted CD8+ T cells induced during the first endogenous CD4+ T cell responses are able to control the expansion of subsequently mobilized pathogenic autoreactive CD4+ T cells. In conclusion, apart from the immunotherapeutic TCV, Qa-1-restricted specialized CD8+ regulatory T cells can also be induced during endogenous CD4+ T cell responses. At variance with other regulatory T cell subsets, the action of these Qa-1-restricted T cells seems to be restricted to the immediate re-activation of CD4+ T cells. 相似文献
163.
Capsoni S Covaceuszach S Marinelli S Ceci M Bernardo A Minghetti L Ugolini G Pavone F Cattaneo A 《PloS one》2011,6(2):e17321
During adulthood, the neurotrophin Nerve Growth Factor (NGF) sensitizes
nociceptors, thereby increasing the response to noxious stimuli. The
relationship between NGF and pain is supported by genetic evidence: mutations in
the NGF TrkA receptor in patients affected by an hereditary rare disease
(Hereditary Sensory and Autonomic Neuropathy type IV, HSAN IV) determine a
congenital form of severe pain insensitivity, with mental retardation, while a
mutation in NGFB gene, leading to the aminoacid substitution
R100W in mature NGF, determines a similar loss of pain
perception, without overt cognitive neurological defects (HSAN V). The R100W
mutation provokes a reduced processing of proNGF to mature NGF in cultured cells
and a higher percentage of neurotrophin secreted is in the proNGF form.
Moreover, using Surface Plasmon Resonance we showed that the R100W mutation does
not affect NGF binding to TrkA, while it abolishes NGF binding to p75NTR
receptors. However, it remains to be clarified whether the major impact of the
mutation is on the biological function of proNGF or of mature NGF and to what
extent the effects of the R100W mutation on the HSAN V clinical phenotype are
developmental, or whether they reflect an impaired effectiveness of NGF to
regulate and mediate nociceptive transmission in adult sensory neurons. Here we
show that the R100 mutation selectively alters some of the signaling pathways
activated downstream of TrkA NGF receptors. NGFR100 mutants maintain identical
neurotrophic and neuroprotective properties in a variety of cell assays, while
displaying a significantly reduced pain-inducing activity in
vivo (n = 8–10 mice/group). We also show
that proNGF has a significantly reduced nociceptive activity, with respect to
NGF. Both sets of results jointly contribute to elucidating the mechanisms
underlying the clinical HSAN V manifestations, and to clarifying which receptors
and intracellular signaling cascades participate in the pain sensitizing action
of NGF. 相似文献
164.
165.
In the present study, the decrease in the mean size of specimens over the species flight period in Plecoptera (12 species, 5 families) was analysed, revealing a significant decrease in the adult mean size, for both males and female, in almost all the species without an extended flight-period pattern. Some of the data show that, in addition to temperature, other regulatory factors must govern these variations. Data support the explanation previously proposed for other insect groups that the individuals with appropriate development emerge at the beginning of the flight period or slightly afterwards, when environmental conditions are suitable, whereas individuals with suboptimal size emerge later trying to increase in size but under pressure to emerge during a specific period of the year. Nevertheless, our data suggest that maximum size does not necessarily coincide with the peak flight period (maximum reproductive possibility). 相似文献
166.
Russo L Landi E Tampieri A Natalello A Doglia SM Gabrielli L Cipolla L Nicotra F 《Carbohydrate research》2011,(12):1564-1568
An efficient method for the direct and covalent decoration of granules of nanostructured apatite with a sample monosaccharide is presented; the hydroxyapatite material was directly functionalised with a short azido-containing spacer arm, to which α-propargyl glucopyranoside has been chemoselectively ligated by Huisgen-type cycloaddition. The ‘glycosylated’ hydroxypatite was characterised by its ability to interact with glucose recognising lectins. 相似文献
167.
Gaixia Zhang David Sebastin Xilin Zhang Qiliang Wei Carmelo Lo Vecchio Jihai Zhang Vincenzo Baglio Weichao Wang Shuhui Sun Antonino S. Aric Ana C. Tavares 《Liver Transplantation》2020,10(24)
The oxygen reduction reaction (ORR) is one of the most important reactions in renewable energy conversion and storage devices. The full deployment of these devices depends on the development of highly active, stable, and low‐cost catalysts. Herein, a new hybrid material consisting of Na2Ta8O21?x/Ta2O5/Ta3N5 nanocrystals grown on N‐doped reduced graphene oxide is reported. This catalyst shows a significantly enhanced ORR activity by ≈4 orders of magnitude in acidic media and by ≈2 orders of magnitude in alkaline media compared to individual Na2Ta8O21?x on graphene. Moreover, it has excellent stability in both acid and alkaline media. It also has much better methanol tolerance than the commercial Pt/C, which is relevant to methanol fuel cells. The high ORR activity arises not only from the synergistic effect among the three Ta phases, but also from the concomitant nitrogen doping of the reduced graphene oxide nanosheets. A correlation between ORR activity and nitrogen content is demonstrated. Deep insights into the mechanism of the synergistic effect among these three Ta‐based phases, which boosts the ORR's kinetics, are acquired by combining specific experiments and density functional theory calculations. 相似文献
168.
Alexandre Augusto Pereira Firmino Fernando Campos de Assis Fonseca Leonardo Lima Pepino de Macedo Roberta Ramos Coelho José Dijair Antonino de Souza Jr Roberto Coiti Togawa Orzenil Bonfim Silva-Junior Georgios Joannis Pappas-Jr Maria Cristina Mattar da Silva Gilbert Engler Maria Fatima Grossi-de-Sa 《PloS one》2013,8(12)
169.
Giuseppe Cabibbo Marcello Maida Chiara Genco Nicola Alessi Marco Peralta Giuseppe Butera Massimo Galia Giuseppe Brancatelli Claudio Genova Maurizio Raineri Emanuele Orlando Simona Attardo Antonino Giarratano Massimo Midiri Vito Di Marco Antonio Craxì Calogero Cammà 《PloS one》2013,8(7)
Background
Radio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments.Aim
To assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis.Methods
A cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA.A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients.Results
The overall survival rates were 94%, 80%, 64%, 49%, and 41% at 12, 24, 36, 48 and 60 months, respectively. Complete response (CR) at 1 month (p<0.0001) and serum albumin levels (p = 0.0004) were the only variables indipendently linked to survival by multivariate Cox model. By multivariate analysis, tumor size (p = 0.01) is the only variable associated with an increased likehood of CR.The proportion of major complications after treatment was 4%.Conclusions
RFA is safe and effective for managing HCC with cirrhosis, especially for patients with HCC ≤3 cm and higher baseline albumin levels. Complete response after RFA significantly increases survival. 相似文献170.
Stefano Merler Marco Ajelli Barbara Camilloni Simona Puzelli Antonino Bella Maria Cristina Rota Alberto Eugenio Tozzi Maurizio Muraca Marcello Meledandri Anna Maria Iorio Isabella Donatelli Caterina Rizzo 《PloS one》2013,8(10)