Fibroblast Growth Factor Receptor-2 Expression in Thyroid Tumor Progression: Potential Diagnostic Application

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.     

Evaluation of Relapse-Free Survival in T3N0 Colon Cancer: The Role of Chemotherapy,a Multicentric Retrospective Analysis

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.     

Pyrrolomycins as potential anti-staphylococcal biofilms agents

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.     

Efficiency of flagging and dragging for tick collection

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.     

Genome-wide association mapping of blood cell traits in mice

Genetic variations in blood cell parameters can impact clinical traits. We report here the mapping of blood cell traits in a panel of 100 inbred strains of mice of the Hybrid Mouse Diversity Panel (HMDP) using genome-wide association (GWA). We replicated a locus previously identified in using linkage analysis in several genetic crosses for mean corpuscular volume (MCV) and a number of other red blood cell traits on distal chromosome 7. Our peak for SNP association to MCV occurred in a linkage disequilibrium (LD) block spanning from 109.38 to 111.75 Mb that includes Hbb-b1, the likely causal gene. Altogether, we identified five loci controlling red blood cell traits (on chromosomes 1, 7, 11, 12, and 16), and four of these correspond to loci for red blood cell traits reported in a recent human GWA study. For white blood cells, including granulocytes, monocytes, and lymphocytes, a total of six significant loci were identified on chromosomes 1, 6, 8, 11, 12, and 15. An average of ten candidate genes were found at each locus and those were prioritized by examining functional variants in the HMDP such as missense and expression variants. These results provide intermediate phenotypes and candidate loci for genetic studies of atherosclerosis and cancer as well as inflammatory and immune disorders in mice.     

Epigallocatechin-3-gallate prevents oxidative phosphorylation deficit and promotes mitochondrial biogenesis in human cells from subjects with Down's syndrome

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.     

Symptoms and Subjective Quality of Life in Post-Traumatic Stress Disorder: A Longitudinal Study

Background

Evidence suggests that post-traumatic stress disorder (PTSD) is associated with substantially reduced subjective quality of life (SQOL). This study aimed to explore whether and how changes in the levels of PTSD symptom clusters of intrusion, avoidance and hyperarousal are associated with changes in SQOL.

Methods

Two samples with PTSD following the war in former Yugoslavia were studied, i.e. a representative sample of 530 people in five Balkan countries and a non-representative sample of 215 refugees in three Western European countries. They were assessed on average eight years after the war and re-interviewed one year later. PTSD symptoms were assessed on the Impact of Event Scale - Revised and SQOL on the Manchester Short Assessment of Quality of Life. Linear regression and a two-wave cross lagged panel analysis were used to explore the association between PTSD symptom clusters and SQOL.

Results

The findings in the two samples were consistent. Symptom reduction over time was associated with improved SQOL. In multivariable analyses adjusted for the influence of all three clusters, gender and time since war exposure, only changes in hyperarousal symptoms were significantly associated with changes in SQOL. The two-wave cross-lagged panel analysis suggested that the link between hyperarousal symptoms and SQOL is bidirectional.

Conclusions

Low SQOL of patients with war-related PTSD is particularly associated with hyperarousal symptoms. The findings suggest a bidirectional influence: a reduction in hyperarousal symptoms may result in improved SQOL, and improvements in SQOL may lead to reduced hyperarousal symptoms.