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41.
Matteo Surdo Emanuela Balestra Patrizia Saccomandi Fabiola Di Santo Marco Montano Domenico Di Carlo Loredana Sarmati Stefano Aquaro Massimo Andreoni Valentina Svicher Carlo Federico Perno Francesca Ceccherini-Silberstein 《PloS one》2013,8(7)
Background
Dual/mixed-tropic HIV-1 strains are predominant in a significant proportion of patients, though little information is available regarding their replication-capacity and susceptibility against CCR5-antagonists in-vitro. The aim of the study was to analyze the replication-capacity and susceptibility to maraviroc of HIV-1 clinical isolates with different tropism characteristics in primary monocyte-derived-macrophages (MDM), peripheral-blood-mononuclear-cells (PBMC), and CD4+T-lymphocytes.Methods
Twenty-three HIV-1 isolates were phenotipically and genotipically characterized as R5, X4 or dual (discriminated as R5+/X4, R5/X4, R5/X4+). Phenotypic-tropism was evaluated by multiple-cycles-assay on U87MG-CD4+-CCR5+−/CXCR4+-expressing cells. Genotypic-tropism prediction was obtained using Geno2Pheno-algorithm (false-positive-rate [FPR] = 10%). Replication-capacity and susceptibility to maraviroc were investigated in human-primary MDM, PBMC and CD4+T-cells. AMD3100 was used as CXCR4-inhibitor. Infectivity of R5/Dual/X4-viruses in presence/absence of maraviroc was assessed also by total HIV-DNA, quantified by real-time polymerase-chain-reaction.Results
Among 23 HIV-1 clinical isolates, phenotypic-tropism-assay distinguished 4, 17 and 2 viruses with R5-tropic, dual/mixed-, and X4-tropic characteristics, respectively. Overall, viruses defined as R5+/X4-tropic were found with the highest prevalence (10/23, 43.5%). The majority of isolates efficiently replicated in both PBMC and CD4+T-cells, regardless of their tropism, while MDM mainly sustained replication of R5- or R5+/X4-tropic isolates; strong correlation between viral-replication and genotypic-FPR-values was observed in MDM (rho = 0.710;p-value = 1.4e-4). In all primary cells, maraviroc inhibited viral-replication of isolates not only with pure R5- but also with dual/mixed tropism (mainly R5+/X4 and, to a lesser extent R5/X4 and R5/X4+). Finally, no main differences by comparing the total HIV-DNA with the p24-production in presence/absence of maraviroc were found.Conclusions
Maraviroc is effective in-vitro against viruses with dual-characteristics in both MDM and lymphocytes, despite the potential X4-mediated escape. This suggests that the concept of HIV-entry through one of the two coreceptors “separately” may require revision, and that the use of CCR5-antagonists in patients with dual/mixed-tropic viruses may be a therapeutic-option that deserves further investigations in different clinical settings. 相似文献42.
Adriano Redler Giorgio Di Rocco Domenico Giannotti Francesca Frezzotti Maria Giulia Bernieri Simona Ceccarelli Sirio D’Amici Enrica Vescarelli Anna Paola Mitterhofer Antonio Angeloni Cinzia Marchese 《PloS one》2013,8(8)
Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis. 相似文献
43.
Roberta Grande Domenico Corsi Raffaello Mancini Donatello Gemma Fabrizio Ciancola Isabella Sperduti Lorena Rossi Agnese Fabbri Maria G. Diodoro Enzo Ruggeri Germano Zampa Sara Bianchetti Teresa Gamucci 《PloS one》2013,8(12)
Background
Adjuvant chemotherapy (AC) in Stage II Colon Cancer (CC) is still under debate. Choice should be based on patients and disease characteristics. According to guidelines AC should be considered in high-risk T3N0 patients. No data are available for better option in low-risk patients. The aim of the study is to retrospectively evaluate relapse-free survival (RFS) and disease-free survival (DFS) according to treatment received in T3N0 CC.Methods
RFS and DFS are evaluated with Kaplan-Meier method. Multivariate Cox proportional hazard model was developed using stepwise regression, enter limit and remove limit were p = 0.10 and p = 0.15, respectively.Results
834 patients with T3N0 CC were recruited. Median age was 69 (29–93), M/F 463/371, 335 low-risk patients (40.2%), 387 high-risk (46.4%), 112 unknown (13.4%); 127 (15.2%) patients showed symptoms at diagnosis. Median sampled lymph nodes were 15 (1–76); 353 (42.3%) patients were treated with AC. Median follow up was 5 years (range 3–24). The 5-years RFS was 78.4% and the 5-years DFS was 76.7%. At multivariate analysis symptoms, lymph nodes, and adjuvant chemotherapy were prognostic factors for RFS. AC is prognostic factor for all endpoints.In low-risk group 5-years RFS was 87.3% in treated patients and 74.7% in non-treated patients (p 0.03); in high-risk group was respectively 82.7% and 71.4% (p 0.005).Conclusions
Data confirmed the role of known prognostic factors and suggest the relevance of adjuvant chemotherapy also in low-risk stage II T3N0 CC patients. However, the highest risk in low-risk subgroup should be identified to be submitted to AC. 相似文献44.
45.
46.
Domenico Schillaci Salvatore Petruso Maria Valeria Raimondi Maria Grazia Cusimano Stella Cascioferro Marianna Scalisi 《Biofouling》2013,29(4):433-438
With the goal of discovering new anti-infective agents active against microbial biofilms, this investigation focused on some natural pyrrolomycins, a family of halogenated pyrrole antibiotics. In this study the anti-staphylococcal biofilm activity of pyrrolomycins C, D, F1, F2a, F2b, F3 and of the synthesized related compounds I, II, III were investigated. The susceptibility of six staphylococcal biofilms was determined by methyltiazotetrazolium staining. Most of the compounds were active at concentrations of 1.5 μg ml?1 with significant inhibition percentages. A few of the compounds were active at the lowest screening concentration of 0.045 μg ml?1. The population log reduction of activity against the two best biofilm forming Staphylococcus aureus strains as determined by viable plate counts is also reported. In order to adequately assess the utility of these compounds, their toxicity against human cells was evaluated. It is concluded that pyrrolomycins and synthetic derivatives are promising compounds for developing novel effective chemical countermeasures against staphylococcal biofilms. 相似文献
47.
Filipe Dantas-Torres Riccardo Paolo Lia Gioia Capelli Domenico Otranto 《Experimental & applied acarology》2013,61(1):119-127
It is acknowledged that data from field studies on tick ecology might be biased by collection methods, but actually comparative studies are still limited. Herein we assessed whether the efficiency of flagging and dragging varies according to tick developmental stage, species, season and habitat. Ticks were collected in three sites bordered by an oak forest. The abundance of ticks collected by each collection method varied according to tick species, developmental stage, season, and habitat. Flagging was in general more efficient in collecting adult ticks, especially in spring and winter. Females were more frequently collected by flagging in the meadow and grassland habitats and males in the man-made trail. Flagging collected significantly more adults of Dermacentor marginatus, Hyalomma marginatum, Haemaphysalis inermis and Ixodes ricinus. Flagging was more efficient in collecting D. marginatus and I. ricinus in spring, and H. inermis and I. ricinus females in both spring and winter. In summer and autumn tick abundances were generally similar, with the exception of D. marginatus female in autumn. Flagging was more efficient in collecting D. marginatus adults in the meadow habitat and in the man-made trail, and I. ricinus adults in the meadow and grassland habitats. Dragging was more efficient in grassland for R. turanicus. Our results suggest that variations in terms of collection method performance are associated to factors linked to tick behaviour, habitat characteristics, and climate. Field studies employing these collection methods should take this into account to avoid misleading conclusions about tick population dynamics and tick-borne pathogen transmission risk. 相似文献
48.
49.
Daniela Valenti Domenico De Rasmo Anna Signorile Leonardo Rossi Lidia de Bari Iris Scala Barbara Granese Sergio Papa Rosa Anna Vacca 《生物化学与生物物理学报:疾病的分子基础》2013,1832(4):542-552
A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria. In this study we have tested the potential of epigallocatechin-3-gallate (EGCG) – a natural polyphenol component of green tea – to counteract the mitochondrial energy deficit found in DS cells. We found that EGCG, incubated with cultured lymphoblasts and fibroblasts from DS subjects, rescued mitochondrial complex I and ATP synthase catalytic activities, restored oxidative phosphorylation efficiency and counteracted oxidative stress. These effects were associated with EGCG-induced promotion of PKA activity, related to increased cellular levels of cAMP and PKA-dependent phosphorylation of the NDUFS4 subunit of complex I. In addition, EGCG strongly promoted mitochondrial biogenesis in DS cells, as associated with increase in Sirt1-dependent PGC-1α deacetylation, NRF-1 and T-FAM protein levels and mitochondrial DNA content.In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS. 相似文献
50.