The Translation Factor eIF6 Is a Notch-Dependent Regulator of Cell Migration and Invasion

A growing body of evidence indicates that protein factors controlling translation play an important role in tumorigenesis. The protein known as eIF6 is a ribosome anti-association factor that has been implicated in translational initiation and in ribosome synthesis. Over-expression of eIF6 is observed in many natural tumours, and causes developmental and differentiation defects in certain animal models. Here we show that the transcription of the gene encoding eIF6 is modulated by the receptor Notch-1, a protein involved in embryonic development and cell differentiation, as well as in many neoplasms. Inhibition of Notch-1 signalling by γ-secretase inhibitors slowed down cell-cycle progression and reduced the amount of eIF6 in lymphoblastoid and ovarian cancer cell lines. Cultured ovarian cancer cell lines engineered to stably over-expressing eIF6 did not show significant changes in proliferation rate, but displayed an enhanced motility and invasive capacity. Inhibition of Notch-1 signalling in the cells over-expressing eIF6 was effective in slowing down the cell cycle, but did not reduce cell migration and invasion. On the whole, the results suggest that eIF6 is one of the downstream effectors of Notch-1 in the pathway that controls cell motility and invasiveness

Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue

<p>Abstract</p> <p>Background</p> <p>The mucosae of the oral cavity are different at the histological level but appear all equally exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia may develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs) in the OPMLs from different oral anatomical subsites.</p> <p>Methods</p> <p>Samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on DNA obtained from diploid nuclei suspensions directly. When aneuploid nuclei were detected, these were physically separated from diploid nuclei on the base of their DI values by means of a DNA-FCM-Sorter in order to improve the a-CGH analysis.</p> <p>Results</p> <p>Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites.</p> <p>Conclusions</p> <p>We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this hypothesis should be validated in a prospective clinical study.</p

D-dimer testing, with gender-specific cutoff levels, is of value to assess the individual risk of venous thromboembolic recurrence in non-elderly patients of both genders: a post hoc analysis of the DULCIS study

Male patients, especially the young, are at a higher risk of recurrent venous thromboembolism (RVTE) than females. Recent scientific reports show the use of D-dimer does not help predict RVTE risk in males. In the present report, we reviewed the data obtained in the DULCIS study (main report published in Blood 2014), focusing on D-dimer results recorded in non-elderly patients of both genders included in the study, and their relationship with RVTE events occurring during follow-up. Using specifically designed cutoff values for positive/negative interpretation, serial D-dimer measurements (performed during warfarin treatment and up to 3&nbsp;months after discontinuation of anticoagulation) in 475 patients (males 57.3%) aged 64 65&nbsp;years were obtained. D-dimer resulted positive in 46.3% and 30.5% of males and females, respectively (p = 0.001). Following management procedure, anticoagulation was stopped in 53.7% of males and 69.5% of females, who had persistently negative D-dimer results. The rate of subsequent recurrent events was 1.7% (95% CI 0.5\u20134.5%) and 0.4% (95% CI 0\u20132.5%) patient-years in males and females, respectively, with upper limits of confidence intervals always below the level of risk considered acceptable by international scientific societies for stopping anticoagulation (&lt; 5%). In conclusion, using sensitive quantitative assays with specifically designed cutoff values and serial measurements during and after discontinuation of anticoagulation, D-dimer testing is useful to predict the risk of RVTE and is of help in deciding the duration of anticoagulation in both male and female adult patients aged up to 65&nbsp;years

A comparison of Thellier-type and multispecimen paleointensity determinations on Pleistocene and historical lava flows from Lanzarote (Canary Islands, Spain)

Sixteen Miocene, Pleistocene, and historic lava flows have been sampled in Lanzarote (Canary Islands) for paleointensity analysis with both the Coe and multispecimen methods. Besides obtaining new data, the main goal of the study was the comparison of paleointensity results determined with two different techniques. Characteristic Remanent Magnetization (ChRM) directions were obtained in 15 flows, and 12 were chosen for paleointensity determination. In Thellier-type experiments, a selection of reliable paleointensity determinations (43 of 78 studied samples) was performed using sets of criteria of different stringency, trying to relate the quality of results to the strictness of the chosen criteria. Uncorrected and fraction and domain-state corrected multispecimen paleointensity results were obtained in all flows. Results with the Coe method on historical flows either agree with the expected values or show moderately lower ones, but multispecimen determinations display a large deviation from the expected result in one case. No relation can be detected between correct or anomalous results and paleointensity determination quality or rock-magnetic properties. However, results on historical flows suggest that agreement between both methods could be a good indicator of correct determinations. Comparison of results obtained with both methods on seven Pleistocene flows yields an excellent agreement in four and disagreements in three cases. Pleistocene determinations were only accepted if either results from both methods agreed or a result was based on a sufficiently large number (n>4) of individual Thellier-type determinations. In most Pleistocene flows, a VADM around 5 31022 Am2 was observed, although two flows displayed higher values around 931022 Am2.project CGL2012-32149 (Ministerio de Econom ıa y Competitividad, Spain), project 320/2011 (Ministerio de Medio Ambiente y Medio Rural y Marino, Spain) and the European Regional Development Fund (ERDF)

Prediction Scores Do Not Correlate with Clinically Adjudicated Categories of Pulmonary Embolism in Critically Ill Patients

Copyright © 2014 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU).OBJECTIVE: To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients.METHODS: In a randomized trial of thromboprophylaxis, patients with suspected PE were adjudicated as possible, probable or definite PE. Data were then retrospectively abstracted for the Geneva Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic scores. The chance-corrected agreement between adjudicated categories and each score was calculated. ANOVA was used to compare values across the three adjudicated PE categories.RESULTS: Among 70 patients with suspected PE, agreement was poor between adjudicated categories and Geneva pretest probabilities (kappa 0.01 [95% CI −0.0643 to 0.0941]) or Wells pretest probabilities (kappa −0.03 [95% CI −0.1462 to 0.0914]). Among four possible, 16 probable and 50 definite PEs, there were no significant differences in Geneva scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30).CONCLUSIONS: Pretest probability scores developed outside the ICU do not correlate with adjudicated PE categories in critically ill patients. Research is needed to develop prediction scores for this population

Transesterification of Bis(2-Ethylhexyl) Phthalate for the Recycling of Flexible Polyvinyl Chloride Scraps in the Circular Economy Framework

The identification of suitable process solutions for the recycling of plastics is nowadays one of the main challenges to reduce their environmental impact and promote their sustainability. In this context, the recycling of flexible polyvinyl chloride (PVC) has severe limitations because this material can contain bis(2-ethylhexyl) phthalate (DEHP), a plasticizing additive recently banned by the European Chemicals Agency (ECHA) due to its endocrine disruptor effect. In this study, we investigated a transesterification process for the possible conversion of DEHP to other less toxic phthalates applicable in the context of PVC mechanical recycling using a selective dissolution process. Different catalytic routes have been tested to find optimal concentrations for pure DEHP conversion and applied under real process conditions. Best results have been obtained at 80 °C with tetrabutyl titanate [Ti(OBu)4], using alcohol/DEHP molar ratios from 10:1 to 5:1, with conversions of more than 90% for pure DEHP in 15 min. However, limitations are related to the final conversion of DEHP in the presence of the PVC phthalate mixture, ranging between 57 and 60% after 90 min for the Ti(OBu)4catalyst. Such results are ascribed to dilution for complete PVC dissolution and the preferential formation of monosubstituted phthalates