The transcription factor, nuclear factor erythroid 2 p45-related factor 2 (Nrf2), acts as a sensor of oxidative or electrophilic stresses and plays a pivotal role in redox homeostasis. Oxidative or ...electrophilic agents cause a conformational change in the Nrf2 inhibitory protein Keap1 inducing the nuclear translocation of the transcription factor which, through its binding to the antioxidant/electrophilic response element (ARE/EpRE), regulates the expression of antioxidant and detoxifying genes such as heme oxygenase 1 (HO-1). Nrf2 and HO-1 are frequently upregulated in different types of tumours and correlate with tumour progression, aggressiveness, resistance to therapy, and poor prognosis. This review focuses on the Nrf2/HO-1 stress response mechanism as a promising target for anticancer treatment which is able to overcome resistance to therapies.
The activation of Nrf2 has been demonstrated to play a crucial role in cancer cell resistance to different anticancer therapies. The inhibition of proteasome activity has been proposed as a ...chemosensitizing therapy but the activation of Nrf2 could reduce its efficacy. Using the highly chemoresistant neuroblastoma cells HTLA-230, here we show that the strong reduction in proteasome activity, obtained by using low concentration of bortezomib (BTZ, 2.5 nM), fails in reducing cell viability. BTZ treatment favours the binding of Nrf2 to the ARE sequences in the promoter regions of target genes such as heme oxygenase 1 (HO-1), the modulatory subunit of γ-glutamylcysteine ligase (GCLM) and the transporter for cysteine (x-CT), enabling their transcription. GSH level is also increased after BTZ treatment. The up-regulation of Nrf2 target genes is responsible for cell resistance since HO-1 silencing and GSH depletion synergistically decrease BTZ-treated cell viability. Moreover, cell exposure to all-trans-Retinoic acid (ATRA, 3 μM) reduces the binding of Nrf2 to the ARE sequences, decreases HO-1 induction and lowers GSH level increasing the efficacy of bortezomib. These data suggest the role of Nrf2, HO-1 and GSH as molecular targets to improve the efficacy of low doses of bortezomib in the treatment of malignant neuroblastoma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
RAGE is a multiligand receptor able to bind advanced glycation end-products (AGEs), amphoterin, calgranulins, and amyloid-beta peptides, identified in many tissues and cells, including neurons. RAGE ...stimulation induces the generation of reactive oxygen species (ROS) mainly through the activity of NADPH oxidases. In neuronal cells, RAGE-induced ROS generation is able to favor cell survival and differentiation or to induce death through the imbalance of redox state. The dual nature of RAGE signaling in neurons depends not only on the intensity of RAGE activation but also on the ability of RAGE-bearing cells to adapt to ROS generation. In this review we highlight these aspects of RAGE signaling regulation in neuronal cells.
•Photo- and thermionic emission of MWPECVD NCD films was compared.•The amount of incorporated hydrogen in the film was tuned by changing the grain size.•Higher emission was found in NCD film with BL ...grown at higher deposition temperature.
Nanocrystalline diamond (NCD) films with and without a diamond buffer layer (BL) have been grown on p-type silicon substrates by microwave plasma enhanced chemical vapor deposition technique at different values of deposition temperature (652–884°C). The photo- and thermionic electron emission properties of NCD films have been investigated, illustrated and explained by analyzing the surface morphology and the grain shape determined by atomic force microscopy, the chemical-structural properties by Raman spectroscopy and nanocrystallites size by X-ray diffraction. The NCD films with BL grown at the highest deposition temperature have shown the highest photo- and thermionic emission currents.
In this paper a study of Multi Wall Carbon Nanotube films deposited at low temperature by means of a spray technique on different substrates is presented. Nanodispersion of nanotube powder in a ...non-polar 1,2-dichloroethane solvent was used as starting solution. Electron Microscopy in Scanning and Transmission modes were used in order to verify the morphological properties of the deposited films.
Visible light detectors were prepared spraying Multi Wall Carbon Nanotubes on silicon substrates with different layouts. In some detectors the nanotubes were covered by an Indium Tin Oxide (ITO) layer. Electrical measurements, both in dark and under light irradiation, were performed and Current-Voltage characteristics are reported. The Indium Tin Oxide coating effect on the photoconductivity yield is presented and discussed along with device ageing test, resulting in a very good photoconduction and stability over four months.
•Carbon nanotubes were deposited at low temperature using a spray technique.•Visible photodetectors based on carbon nanotubes films were produced.•Contribution of carbon nanotubes to the quantum efficiency is shown.•Charge collection from the devices increases with an indium tin oxide contact.•Time stability of photodetectors based on carbon nanotubes is demonstrated.
Background
The Italian Research Group for Gastric Cancer supports the practice of follow-up after radical surgery for gastric cancer.
Methods
This multicenter, retrospective study (1998–2009) ...included patients with T1-4N0-3M0 gastric cancer who had undergone D2 gastrectomy and lymphadenectomy, with at least 15 lymph nodes examined, and who had developed recurrent disease. Timing and site of recurrence were correlated to the actual scheduled follow-up timing and modalities.
Results
From eight centers, 814 patients with recurrent cancer and over 1,754 (46.4 %) patients undergoing gastrectomy were investigated (median follow-up 31 months). The most frequent sites of recurrence were local/regional lymph nodes (35.4 %), liver (24.3 %), peritoneum (30.3 %), lung (10.4 %) and intraluminal (7.5 %). Ninety-four percent of the recurrences were diagnosed within 2 years and 98 % within 3 years. Thoracoabdominal computed tomography (CT) scan and (18)F-fluoro-2-deoxy-
d
-glucose positron emission tomography (18-FDG-PET) detected more than 90 % of recurrences, abdominal ultrasound detected 70 % and tumor markers detected 40 %, while <10 % were identified by physical examination, chest X-ray, and upper gastrointestinal endoscopy. Twenty-six percent of patients with recurrence were treated, but only 3.2 % were treated with potentially radical intent.
Conclusion
Oncological follow-up after radical surgery for gastric cancer should be focused in the first 3 years, and based mainly on thoracoabdominal CT scan and 18-FDG-PET.
We report on two different series of conjugated push–pull compounds bearing dimethylamino donor and 1,3-dicarbonyl acceptor functionalities with a “bent” or“cruciform” shape, exhibit striking ...differences in their supramolecular recognition of lanthanide cations. Both series of compounds are effective to coordinate lanthanide cations (Sc
3+
and Eu
3+
) in MeCN, CHCl
3
or MeOH solutions to the 1,3-dicarbonyl acceptor end. The stoichiometry of the complexes are largely dependent on the nature of the lanthanide cation, with Sc
3+
forming preferentially 1 : 3 metal : ligand complexes, and Eu
3+
forming 1 : 1 metal : ligand complexes. The coordination of the lanthanide cation results in an overall supramolecular polarization of the system and the redshifting of the intramolecular charge transfer band. The polarization of the “cruciform” systems is greatly enhanced with respect to the “bent” chromophores, reaching outstanding values for the red shift (238 nm, corresponding to an energy difference of 1.23 eV) with high binding constants (Log
K
a
>5.5).
Mammography and fecal occult blood testing (FOBT) improve the detection, management, and prognosis of breast and colorectal cancer, respectively, but are underperformed in the recent immigrant and ...refugee population. We aimed to identify barriers to screening and potential solutions in this population. A mixed-methods study involving a retrospective chart review and focus group interviews was conducted, with data analyzed using univariate logistic regression and thematic analysis, respectively. Mammography completion was associated with greater time in Canada (p = 0.01) and region of origin (p = 0.04), while FOBT completion was associated with region of origin (p = 0.03). Barriers included time constraints, language and cultural differences, and poor interprofessional communication. This study of recent immigrants and refugees identifies barriers to screening and supports potential solutions including culturally-congruent peer workers, targeted screening workshops, and visual screening aids. Further work is needed to address the unique healthcare needs of this diverse and growing population.
Objective
The consumption of potatoes is increasing worldwide, but few studies have assessed the association between potato consumption and mortality, particularly in Mediterranean countries. We ...therefore investigated whether potato consumption is associated with higher risk of death in a large cohort of people living in South Italy.
Design
Longitudinal.
Setting
Community-dwelling.
Measurements
2,442 participants coming from MICOL and NUTRIHEP studies aged more than 50 years at baseline were followed-up for 11 years. Dietary intake was assessed by means of a Food Frequency Questionnaire. Potato consumption was categorized in quintiles according to their daily consumption (< 3.95, 3.96-8.55, 8.56-15.67, 15.68-22.0, and > 22.0 g/day). Mortality was ascertained through validated cases of death. The association between potato consumption and mortality was assessed through Cox’s regression models, adjusted for potential confounders, and reporting the data as hazard ratios (HRs) with 95% confidence intervals (CIs).
Results
The 2,442 eligible participants were prevalently males (54.6%) and aged a mean of 64.3±9.3 years. During the 11-year follow-up, 396 (=16.2%) participants died. After adjusting for 12 potential baseline confounders, and taking those with the lowest consumption of potatoes as the reference group, participants with the highest consumption of potatoes did not have an increased overall mortality risk (HR=0.75; 95%CI: 0.53-1.07). Modelling the potato consumption as continuous (i.e. as increase in 10 g/day) did not substantially change our findings (fully-adjusted HR=0.93; 95%CI: 0.84-1.02).
Conclusion
Overall potato consumption was not associated with higher risk of death in older people living in a Mediterranean area. Future studies are warranted to elucidate the role of potato consumption on all-cause and cause-specific mortality.
A
bstract
The OPERA neutrino experiment at the underground Gran Sasso Laboratory has measured the velocity of neutrinos from the CERN CNGS beam over a baseline of about 730 km. The measurement is ...based on data taken by OPERA in the years 2009, 2010 and 2011. Dedicated upgrades of the CNGS timing system and of the OPERA detector, as well as a high precision geodesy campaign for the measurement of the neutrino baseline, allowed reaching comparable systematic and statistical accuracies.
An arrival time of CNGS muon neutrinos with respect to the one computed assuming the speed of light in vacuum of
was measured corresponding to a relative difference of the muon neutrino velocity with respect to the speed of light
. The above result, obtained by comparing the time distributions of neutrino interactions and of protons hitting the CNGS target in 10.5
μ
s long extractions, was confirmed by a test performed at the end of 2011 using a short bunch beam allowing to measure the neutrino time of flight at the single interaction level.
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