Emerging roles of purinergic signaling in anti-cancer therapy resistance

Cancer is a complex disease with a rapid growing incidence and often characterized by a poor prognosis. Although impressive advances have been made in cancer treatments, resistance to therapy remains a critical obstacle for the improvement of patients outcome. Current treatment approaches as chemo-, radio-, and immuno-therapy deeply affect the tumor microenvironment (TME), inducing an extensive selective pressure on cancer cells through the activation of the immune system, the induction of cell death and the release of inflammatory and damage-associated molecular patterns (DAMPS), including nucleosides (adenosine) and nucleotides (ATP and ADP). To survive in this hostile environment, resistant cells engage a variety of mitigation pathways related to metabolism, DNA repair, stemness, inflammation and resistance to apoptosis. In this context, purinergic signaling exerts a pivotal role being involved in mitochondrial function, stemness, inflammation and cancer development. The activity of ATP and adenosine released in the TME depend upon the repertoire of purinergic P2 and adenosine receptors engaged, as well as, by the expression of ectonucleotidases (CD39 and CD73) on tumor, immune and stromal cells. Besides its well established role in the pathogenesis of several tumors and in host–tumor interaction, purinergic signaling has been recently shown to be profoundly involved in the development of therapy resistance. In this review we summarize the current advances on the role of purinergic signaling in response and resistance to anti-cancer therapies, also describing the translational applications of combining conventional anticancer interventions with therapies targeting purinergic signaling

Impact of sidewall etching on the dynamic performance of GaN-on-Si E-mode transistors

Abstract The aim of this paper is to investigate the role of the etching of the sidewalls of p-GaN on the dynamic performance of normally-off GaN HEMTs with p-type gate. We analyze two wafers having identical epitaxy but with different recipes for the sidewall etching, referred to as "Etch A" (non-optimized) and "Etch B" (optimized). We demonstrate the following relevant results: (i) the devices with non-optimized etching (Etch A), when submitted to positive gate bias, show a negative threshold voltage shift and a decrease in Ron, which are ascribed to hole injection under the gate and/or in the access regions; (ii) transient characterization indicates the existence of two trap states, with activation energies of 0.84 eV (CN defects) and 0.30 eV. The latter (with time-constants in the ms range) is indicative of the hole de-trapping process, possibly related to trap states in the AlGaN barrier or at the passivation/AlGaN interface; (iii) by optimizing the p-GaN sidewall etching (for the same epitaxy) it is possible to completely eliminate the threshold voltage shift. This indicates that hole injection mostly takes place along the sidewalls

Identification of the safe(r) by design alternatives for nanosilver-enabled wound dressings

The use of silver nanoparticles (NPs) in medical devices is constantly increasing due to their excellent antimicrobial properties. In wound dressings, Ag NPs are commonly added in large excess to exert a long-term and constant antimicrobial effect, provoking an instantaneous release of Ag ions during their use or the persistence of unused NPs in the wound dressing that can cause a release of Ag during the end-of-life of the product. For this reason, a Safe-by-Design procedure has been developed to reduce potential environmental risks while optimizing functionality and costs of wound dressings containing Ag NPs. The SbD procedure is based on ad-hoc criteria (e.g., mechanical strength, antibacterial effect, leaching of Ag from the product immersed in environmental media) and permits to identify the best one among five pre-market alternatives. A ranking of the SbD alternatives was obtained and the safer solution was selected based on the selected SbD criteria. The SbD framework was also applied to commercial wound dressings to compare the SbD alternatives with products already on the market. The iterative procedure permitted to exclude one of the alternatives (based on its low mechanical strength) and proved to be an effective approach that can be replicated to support the ranking, prioritisation, and selection of the most promising options early in the innovation process of nano-enabled medical devices as well as to encourage the production of medical devices safer for the environment

Impact of 18F-FDG PET/CT on Clinical Management of Suspected Radio-Iodine Refractory Differentiated Thyroid Cancer (RAI-R-DTC).

Background: As reported in the literature, [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) provides useful qualitative and semi-quantitative data for the prognosis of advanced differentiated thyroid cancer. Instead, there is a lack of data about the real clinical impact of 18F-FDG PET/CT on the choice of the more effective therapeutic approach for advanced differentiated thyroid cancer (DTC) that starts to lose iodine avidity. The primary aim of this retrospective study was to assess how 18F-FDG PET/CT can guide the choice of the best therapeutic approach to RAI-refractory DTC (RAI-R-DTC) in patients with a doubtful iodine uptake/negative 18F-FDG PET/CT I whole-body scan after several radioactive iodine therapies (RAIT). The secondary aim was to assess the prognostic role of clinical and semi-quantitative metabolic 18F-FDG PET/CT parameters in comparison to published data. Materials and methods: A monocentric retrospective observational study was performed, reviewing the medical records of 53 patients recruited from a database of 208 patients treated at our Institution between 2011 and 2019, with advanced DTC that underwent FDG PET/CT scan for a suspected RAI-R-DTC. Selected patients had to perform a 18F-FDG PET/CT scan after the second RAIT based on a doubtful iodine uptake/negative 131 I whole-body scan and/or persistent elevated thyroglobulin levels. Metabolic response was defined according to positron emission tomography response criteria in solid tumors (PERCIST) guidelines. Standardized uptake value (SUV)max, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The association between metabolic features, clinical parameters and progression free survival (PFS) was assessed applying Kruskal-Wallis, chi-square-Pearson correlation tests, and Cox regression analyses when appropriate. Results: Among our sample of 53 patients (mean age 52.0 ± 19.9 years; 31 women and 22 men), 27 (51.0%) presented a positive 18F-FDG PET/CT scan: 16 (59.0%) underwent watchful waiting, 4 (15.0%) received external-beam radiation therapy (EBRT), 4 (15.0%) underwent surgery, 2 (7.4%) received another course of RAI therapy, and 1 underwent surgery + EBRT. PERCIST response was evaluated in 14/27 patients. Median follow-up was 5.8 ± 3.9 years and median PFS was 38.0 ± 21.8 months. At the last follow-up assessment, 14/53 (26.4%) demonstrated disease progression, 13/53 (24.5) persistence of structural disease, 25/53 (47%) persistence of biochemical disease, and 15/53 (28%) had an excellent response. A significant association was found between therapeutic approach, metabolic response, and final disease response evaluation, as well as a linear correlation between MTV and TLG with thyroglobulin level. Conclusions: Our Institutional experience confirmed the role of 18F-FDG PET/CT as a useful guide in the clinical management of RAI-R-DTC and obviated further unnecessary RAIT

ESA Voyage 2050 white paper: Unveiling the faint ultraviolet Universe

New and unique science opportunities in several different fields of astrophysics are offered by conducting spectroscopic studies of the Universe in the ultraviolet (UV), a wavelength regime that is not accessible from the ground. We present some of the scientific challenges that can be addressed with a space-based mission in 2035 - 2050. (1) By detecting the intergalactic medium in emission it will be possible to unveil the cosmic web, whose existence is predicted by current theories of structure formation, but it has not been probed yet. (2) Observations of the neutral gas distribution (by mapping the Lyman-alpha emission) in low-redshift galaxy cluster members will clarify the efficiency with which ram-pressure stripping removes the gas from galaxies and the role of the environment in quenching star formation. (3) By observing statistical samples of supernovae in the UV it will be possible to characterize the progenitor population of core-collapse supernovae, providing the initial conditions for any forward-modeling simulation and allowing the community to progress in the understanding of the explosion mechanism of stars and the final stages of stellar evolution. (4) Targeting populations of accreting white dwarfs in globular clusters it will be possible to constrain the evolution and fate of these stars and investigate the properties of the most compact systems with the shortest orbital periods which are expected to be the brightest low frequency gravitational wave sources. A UV-optimized telescope (wavelength range ~ 90 - 350 nm), equipped with a panoramic integral field spectrograph with a large field of view (FoV ~ 1 x 1 arcmin^2), with medium spectral (R = 4000) and spatial (~ 1" - 3") resolution will allow the community to simultaneously obtain spectral and photometric information of the targets, and tackle the science questions presented in this paper

Sensory and chemical profile of a phenolic extract from olive mill waste waters in plant-base food with varied macro-composition

Phenols from olive mill waste water (OMWW) represent valuable functional ingredients. The negative impact on sensory quality limits their use in functional food formulations. Chemical interactions phenols/biopolymers and their consequences on bioactivity in plant-base foods have been widely investigated, but no studies to date have explored the variation of bitterness, astringency and pungency induced by OMWW phenols as a function of the food composition. The aim of the paper was to profile the sensory and chemical properties of phenols from OMWW in plant-base foods varied in their macro-composition. Four phenol concentrations were selected (0.44, 1.00, 2.25, 5.06 g/kg) to induce significant variations of bitterness, sourness, astringency and pungency in three plant-base food: proteins/neutral pH \u2013 bean pur\ue9e (BP), starch/neutral pH \u2013 potato pur\ue9e (PP), fiber/low pH \u2013 tomato juice (TJ). The macro-composition affected the amount of the phenols recovered from functionalized food. The highest recovery was from TJ and the lowest from BP. Two groups of 29 and 27 subjects, trained to general Labelled Magnitude Scale and target sensations, participated in the evaluation of psychophysical curves of OMWW phenols and of functionalized plant-base foods, respectively. Target sensations were affected by the food macro-composition. Bitterness increased with phenol concentration in all foods. Astringency and sourness slightly increased with concentration, reaching the weak-moderate intensity at the highest phenol concentration in PP and TJ only. Pungency was suppressed in BP and perceived at weak-moderate intensity in PP and TJ sample at the highest phenol concentration. Proteins/neutral pH plant-food (BP) resulted more appropriate to counteract the impact of added phenol on negative sensory properties thus allowing to optimize the balance between health and sensory properties

Sensory and chemical profile of a phenolic extract from olive mill waste waters in plant-base food with varied macro-composition

Phenols from olive mill waste water (OMWW) represent valuable functional ingredients. The negative impact on sensory quality limits their use in functional food formulations. Chemical interactions phenols/biopolymers and their consequences on bioactivity in plant-base foods have been widely investigated, but no studies to date have explored the variation of bitterness, astringency and pungency induced by OMWW phenols as a function of the food composition. The aim of the paper was to profile the sensory and chemical properties of phenols from OMWW in plant-base foods varied in their macro-composition. Four phenol concentrations were selected (0.44, 1.00, 2.25, 5.06 g/kg) to induce significant variations of bitterness, sourness, astringency and pungency in three plant-base food: proteins/neutral pH \u2013 bean pur\ue9e (BP), starch/neutral pH \u2013 potato pur\ue9e (PP), fiber/low pH \u2013 tomato juice (TJ). The macro-composition affected the amount of the phenols recovered from functionalized food. The highest recovery was from TJ and the lowest from BP. Two groups of 29 and 27 subjects, trained to general Labelled Magnitude Scale and target sensations, participated in the evaluation of psychophysical curves of OMWW phenols and of functionalized plant-base foods, respectively. Target sensations were affected by the food macro-composition. Bitterness increased with phenol concentration in all foods. Astringency and sourness slightly increased with concentration, reaching the weak-moderate intensity at the highest phenol concentration in PP and TJ only. Pungency was suppressed in BP and perceived at weak-moderate intensity in PP and TJ sample at the highest phenol concentration. Proteins/neutral pH plant-food (BP) resulted more appropriate to counteract the impact of added phenol on negative sensory properties thus allowing to optimize the balance between health and sensory properties