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The joint ESA/NASA Mass-change And Geosciences International Constellation (MAGIC) has the objective to extend time-series from previous gravity missions, including an improvement of accuracy and spatio-temporal resolution. The long-term monitoring of Earth's gravity field carries information on mass change induced by water cycle, climate change and mass transport processes between atmosphere, cryosphere, oceans and solid Earth. MAGIC will be composed of two satellite pairs flying in different orbit planes. The NASA/DLR-led first pair (P1) is expected to be in a near-polar orbit around 500 km of altitude; while the second ESA-led pair (P2) is expected to be in an inclined orbit of 65°–70° at approximately 400 km altitude. The ESA-led pair P2 Next Generation Gravity Mission shall be launched after P1 in a staggered manner to form the MAGIC constellation. The addition of an inclined pair shall lead to reduction of temporal aliasing effects and consequently of reliance on de-aliasing models and post-processing. The main novelty of the MAGIC constellation is the delivery of mass-change products at higher spatial resolution, temporal (i.e. subweekly) resolution, shorter latency and higher accuracy than the Gravity Recovery and Climate Experiment (GRACE) and Gravity Recovery and Climate Experiment Follow-On (GRACE-FO). This will pave the way to new science applications and operational services. In this paper, an overview of various fields of science and service applications for hydrology, cryosphere, oceanography, solid Earth, climate change and geodesy is provided. These thematic fields and newly enabled applications and services were analysed in the frame of the initial ESA Science Support activities for MAGIC. The analyses of MAGIC scenarios for different application areas in the field of geosciences confirmed that the double-pair configuration will significantly enlarge the number of observable mass-change phenomena by resolving smaller spatial scales with an uncertainty that satisfies evolved user requirements expressed by international bodies such as IUGG. The required uncertainty levels of dedicated thematic fields met by MAGIC unfiltered Level-2 products will benefit hydrological applications by recovering more than 90 per cent of the major river basins worldwide at 260 km spatial resolution, cryosphere applications by enabling mass change signal separation in the interior of Greenland from those in the coastal zones and by resolving small-scale mass variability in challenging regions such as the Antarctic Peninsula, oceanography applications by monitoring meridional overturning circulation changes on timescales of years and decades, climate applications by detecting amplitude and phase changes of Terrestrial Water Storage after 30 yr in 64 and 56 per cent of the global land areas and solid Earth applications by lowering the Earthquake detection threshold from magnitude 8.8 to magnitude 7.4 with spatial resolution increased to 333 km. [ABSTRACT FROM AUTHOR]

We report on about 20 yr of relative gravity measurements, acquired on Mt. Somma–Vesuvius volcano in order to investigate the hydrological and volcano-tectonic processes controlling the present-day activity of the volcano. The retrieved long-term field of time gravity change (2003–2022) shows a pattern essentially related to the subsidence, which have affected the central part of the volcano, as detected by the permanent GNSS network and InSAR data. After reducing the observations for the effect of vertical deformation, no significant residuals are found, indicating no significant mass accumulation or loss within the volcanic system. In the north-western sector of the study area, at the border of the volcano edifice, however, significant residual positive gravity changes are detected which are associated to ground-water rebound after years of intense exploitation of the aquifers. On the seasonal timescale, we find that stations within the caldera rim are affected by the seasonal hydrological effects, while the gravity stations at the base of the Vesuvius show a less clear correlation. Furthermore, within the caldera rim a multiyear gravity transient is detected with an increase phase lasting about 4 yr followed by a slower decrease phase. Analysis of rain data seem to exclude a hydrological origin, hence, we hypothesize a deeper source related to the geothermal activity, which can be present even if the volcano is in a quiescent state. We infer the depth and volume of the source by inverting the spatial pattern of the gravity field at the peak of the transient. A volume of fluids of 9.5 × 107 m3 with density of 1000 kg m−3 at 2.3 km depth is capable to fit reasonably well the observations. To explain the gravity transient, simple synthetic models are produced, that simulate the ascent of fluids from a deep reservoir up to the depth of 2.3 km and a successive diffusion within the carbonate aquifer hosting the geothermal system. The whole process appears to not significantly affect the seismicity rate and the deformation of the volcano. This study demonstrates the importance of a 4-D gravity monitoring of a volcano to understand its complex gravity signals that cover different spatial and temporal scales. Discriminating the different contributions that mix up in the observed gravity changes, in particular those due to hydrologic/anthropogenic activities form those due to the geothermal dynamics, is fundamental for a complete and reliable evaluation of the volcano state. [ABSTRACT FROM AUTHOR]

Stems, leaves, buds and flowers of Laurus nobilis L. growing wild in Tunisia were analysed for their essential oil composition. The essential oil of Laurus nobilis L. gathered from different stations were isolated by hydrodistillation and analysed by GC/MS. The oil yields on a dry weight basis ranged between 0.4% and 1.1%. The major component identified was 1,8-cineole, other predominant components were α-terpinyl acetate, methyl eugenol, eugenol and linalool. Although the same compounds were present in all plant organs, the leaves differed from the stems in the concentration of 1,8-cineole and methyl eugenol, buds and flowers in the concentration of 1,8-cineole and the stem's oil composition differs from the others in content of methyl eugenol. The results obtained from GC/MS analysis of the volatile oils from individual plant organs were submitted to principal component analysis. Chemometric investigations led to differentiation of stems, leaves and buds-flowers with the respect to the content of 1,8-cineole, metyhyl eugenol and α-terpynil acetate; flowers and buds were non-differentiated. Finally, the antibacterial activity of the leaves' essential oils has been assayed. [ABSTRACT FROM AUTHOR]

Background: High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype of epithelial ovarian carcinoma. It is primarily diagnosed at stage III or IV when the 5-year survival rate ranges between 20% and 40%. Here, we aimed to validate the hypothesis, based on HGSOC cell lines, that proposed the existence of two distinct groups of HGSOC cells with high and low oxidative phosphorylation (OXPHOS) metabolism, respectively, which are associated with their responses to glucose and glutamine withdrawal., Methods: We isolated and cultivated primary cancer cell cultures from HGSOC and nontransformed ovarian fibroblasts from the surrounding ovarium of 45 HGSOC patients. We tested the metabolic flexibility of the primary cells, particularly in response to glucose and glutamine depletion, analyzed and modulated endoplasmic reticulum stress, and searched for indices of the existence of previously reported groups of HGSOC cells with high and low OXPHOS metabolism., Results: The primary HGSOC cells did not form two groups with high and low OXPHOS that responded differently to glucose and glutamine availabilities in the cell culture medium. Instead, they exhibited a continuum of OXPHOS phenotypes. In most tumor cell isolates, the responses to glucose or glutamine withdrawal were mild and surprisingly correlated with those of nontransformed ovarian fibroblasts from the same patients. The growth of tumor-derived cells in the absence of glucose was positively correlated with the lipid trafficking regulator FABP4 and was negatively correlated with the expression levels of HK2 and HK1. The correlations between the expression of electron transport chain (ETC) proteins and the oxygen consumption rates or extracellular acidification rates were weak. ER stress markers were strongly expressed in all the analyzed tumors. ER stress was further potentiated by tunicamycin but not by the recently proposed ER stress inducers based on copper(II)-phenanthroline complexes. ER stress modulation increased autophagy in tumor cell isolates but not in nontransformed ovarian fibroblasts., Conclusions: Analysis of the metabolism of primary HGSOC cells rejects the previously proposed hypothesis that there are distinct groups of HGSOC cells with high and low OXPHOS metabolism that respond differently to glutamine or glucose withdrawal and are characterized by ETC protein levels., (© 2024. The Author(s).)

Intact (whole) cell MALDI TOF mass spectrometry is a commonly used tool in clinical microbiology for several decades. Recently it was introduced to analysis of eukaryotic cells, including cancer and stem cells. Besides targeted metabolomic and proteomic applications, the intact cell MALDI TOF mass spectrometry provides a sufficient sensitivity and specificity to discriminate cell types, isogenous cell lines or even the metabolic states. This makes the intact cell MALDI TOF mass spectrometry a promising tool for quality control in advanced cell cultures with a potential to reveal batch-to-batch variation, aberrant clones, or unwanted shifts in cell phenotype. However, cellular alterations induced by change in expression of a single gene has not been addressed by intact cell mass spectrometry yet. In this work we used a well-characterized human ovarian cancer cell line SKOV3 with silenced expression of a tumor suppressor candidate 3 gene (TUSC3). TUSC3 is involved in co-translational N-glycosylation of proteins with well-known global impact on cell phenotype. Altogether, this experimental design represents a highly suitable model for optimization of intact cell mass spectrometry and analysis of spectral data. Here we investigated five machine learning algorithms (k-nearest neighbors, decision tree, random forest, partial least squares discrimination, and artificial neural network) and optimized their performance either in pure populations or in two-component mixtures composed of cells with normal or silenced expression of TUSC3. All five algorithms reached accuracy over 90 % and were able to reveal even subtle changes in mass spectra corresponding to alterations of TUSC3 expression. In summary, we demonstrate that spectral fingerprints generated by intact cell MALDI-TOF mass spectrometry coupled to a machine learning classifier can reveal minute changes induced by alteration of a single gene, and therefore contribute to the portfolio of quality control applications in routine cell and tissue cultures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

A new heteroleptic copper(II) compound named C0-UDCA was prepared by reaction of [Cu(phen) 2 (OH 2 )](ClO 4 ) 2 (C0) with the bile ursodeoxycholic acid (UDCA). The resulting compound is able to inhibit the lipoxygenase enzyme showing more efficacy than the precursors C0 and UDCA. Molecular docking simulations clarified the interactions with the enzyme as due to allosteric modulation. The new complex shows antitumoral effect on ovarian (SKOV-3) and pancreatic (PANC-1) cancer cells at the Endoplasmic Reticulum (ER) level by activating the Unfolded Protein Response. In particular, the chaperone BiP, the pro-apoptotic protein CHOP and the transcription factor ATF6 are upregulated in the presence of C0-UDCA. The combination of Intact Cell MALDI-MS and statistical analysis have allowed us to discriminate between untreated and treated cells based on their mass spectrometry fingerprints., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: As the continuation beyond progression (BP) of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) is becoming increasingly attractive for the treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), the definition of resistance factors is crucial. The aim of the study was to investigate the impact of CDK 4/6i BP and to explore potential genomic stratification factors., Materials and Methods: We retrospectively analyzed a multi-institutional cohort of patients with HR-positive HER2-negative MBC characterized for circulating tumor DNA through next-generation sequencing before treatment start. Differences across subgroups were analyzed by chi-square test, and survival was tested by univariable and multivariable Cox regression. Further correction was applied by propensity score matching., Results: Among the 214 patients previously exposed to CDK4/6i, 172 were treated with non-CDK4/6i-based treatment (non-CDK) and 42 with CDK4/6i BP. Multivariable analysis showed a significant impact of CDK4/6i BP, TP53 single-nucleotide variants, liver involvement, and treatment line on both progression-free survival (PFS) and overall survival (OS). Propensity score matching confirmed the prognostic role of CDK4/6i BP both for PFS and OS. The favorable impact of CDK4/6i BP was consistent across all subgroups, and a differential benefit was suggested for ESR1 -mutated patients. ESR1 and RB1 mutations were more represented in the CDK4/6i BP subgroup with respect to CDK4/6i upfront., Conclusion: The study highlighted a significant prognostic impact of the CDK4/6i BP strategy with a potential added benefit in patients with ESR1 mutations suggesting the need for an extensive biomarker characterization.

The design of novel antityrosinase agents appears extremely important in medical and industrial sectors because an irregular production of melanin is related to the insurgence of several skin-related disorders (e.g., melanoma) and the browning process of fruits and vegetables. Because melanogenesis also involves a nonenzymatic oxidative process, developing dual antioxidant and antityrosinase agents is advantageous. In this work, we evaluated the antioxidant and tyrosinase inhibition ability of two new bishydroxylated and two new monohydroxylated derivatives of (1 E )-2-(1-(2-oxo-2 H -chromen-3-yl)ethylidene)hydrazine-1-carbothioamide ( T1 ) using different experimental and computational approaches. The study was also carried out on another monohydroxylated derivative of T1 for comparison. Interestingly, these molecules have more potent tyrosinase-inhibitory properties than the reference compound, kojic acid. Moreover, the antioxidant activity appears to be influenced according to the number and substitution pattern of the hydroxyl groups. The safety of the compounds without ( T1 ), with one ( T3 ), and with two ( T6 ) hydroxyl groups, has also been assessed by studying their cytotoxicity on melanocytes. These results indicate that (1 E )-2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazine-1-carbothioamide and its hydroxylated derivatives are promising molecules for further drug development studies.

The reactivity of 1,1'-bis(3-methyl-4-imidazolin-2-selone)methane ( L1 ) and 1,2-bis(3-methyl-4-imidazolin-2-selone)ethane ( L2 ) toward I 2 has been explored in MeCN under different experimental conditions and compared with that in CH 2 Cl 2 . The compounds [ L1' ](I) 2 ( I ), [ L1 I] n (I) n ( II ), [ L1 (μ-Se)](I) 2 ·1/2H 2 O ( III ), [ L1 I](I 3 )·2I 2 ( IV ), and [ L2 ](I) 2 ·MeCN ( V ) were obtained and characterized. X-ray diffraction analyses point out an ionic nature for these compounds, which is presumably favored by the polarity of the solvent used. In particular, [ L1 I] n (I) n ( II ) represents the first example of an iodonium complex of imidazoline-2-selone derivatives, while [ L1 (μ-Se)](I) 2 ·1/2H 2 O ( III ) represents a unique example of a dicationic [RSeSeSeR] triselane. Density functional theory calculations have allowed us to better understand the nature of the obtained compounds and to justify their formations in polarizing reaction conditions rather than in low polar solvents.

Biointerfaces are significantly affected by electrolytes according to the Hofmeister series. This work reports a systematic investigation on the effect of different metal chlorides, sodium and potassium bromides, iodides and thiocyanates, on the ESI/MS spectra of bovine serum albumin (BSA) in aqueous solution at pH = 2.7. The concentration of each salt was varied to maximize the quality of the ESI/MS spectrum, in terms of peak intensity and bell-shaped profile. The ESI/MS spectra of BSA in the absence and in the presence of salts showed a main protein pattern characterized by the expected mass of 66.5 kDa, except the case of BSA/RbCl (mass 65.3 kDa). In all systems we observed an additional pattern, characterized by at least three peaks with low intensity, whose deconvolution led to suggest the formation of a BSA fragment with a mass of 19.2 kDa. Only NaCl increased the intensity of the peaks of the main BSA pattern, while minimizing that of the fragment. NaCl addition seems to play a crucial role in stabilizing the BSA ionized interface against hydrolysis of peptide bonds, through different synergistic mechanisms. To quantify the observed specific electrolyte effects, two "Hofmeister" parameters (H s and P s ) are proposed. They are obtained using the ratio of (BSA-Salt)/BSA peak intensities for both the BSA main pattern and for its fragment. SYNOPSIS: NaCl stabilizes BSA ion and almost prevents fragmentation due to denaturing pH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We examine Hofmeister specific ion effects of electrolytes added to protein solution under conditions minimizing electrostatic attraction between cations and positively charged protein. Hemoglobin (Hb) in aqueous solution at the denaturing pH = 2.7 is investigated in the presence of several metal chlorides, along with sodium and potassium bromides, iodides and thiocyanates, using electrospray ionization mass spectrometry (ESI-MS). Salt concentration was varied to maximize peak intensity and bell-shaped profile in the ESI-MS spectrum. The α-chain of myoglobin is identified as the main pattern of the ESI-MS spectra in all Hb-salt systems. Both peak intensity and quality of the bell-shaped profile of the protein spectrum decrease in the cation order: K + > > Mg 2+  > Li + > > Na +  > Ca 2+  ≈ Cs +  > Rb + for Hb-Metal Chloride systems, and decrease in the anion order: Cl -  > Br -  > I -  > SCN - for systems of both Hb-NaX and Hb-KX salts. To quantify salt addition effects two Hofmeister specific electrolyte parameters H S , and P S are proposed. H S is the mean (Hb-salt)/Hb peak intensity ratio, measured for the nine peaks used for ESI-MS spectra deconvolution, taken at the same m/z values of the Hb profile. P S is the ratio between H S standard deviation and H S , and provides a specific perturbation parameter measuring the loss of protein structure. These two Hofmeister parameters give clear evidence of the effects induced either by KCl, MgCl 2 and LiCl that enhance protein peak intensity, or by NaBr, NaI, NaSCN and KSCN that induce the protein fragmentation, due to electrolyte-mediated dissociation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Copper is an endogenous metal ion that has been studied to prepare a new antitumoral agent with less side-effects. Copper is involved as a cofactor in several enzymes, in ROS production, in the promotion of tumor progression, metastasis, and angiogenesis, and has been found at high levels in serum and tissues of several types of human cancers. Under these circumstances, two strategies are commonly followed in the development of novel anticancer Copper-based drugs: the sequestration of free Copper ions and the synthesis of Copper complexes that trigger cell death. The latter strategy has been followed in the last 40 years and many reviews have covered the anticancer properties of a broad spectrum of Copper complexes, showing that the activity of these compounds is often multi factored. In this work, we would like to focus on the anticancer properties of mixed Cu(II) complexes bearing substituted or unsubstituted 1,10-phenanthroline based ligands and different classes of inorganic and organic auxiliary ligands. For each metal complex, information regarding the tested cell lines and the mechanistic studies will be reported and discussed. The exerted action mechanisms were presented according to the auxiliary ligand/s, the metallic centers, and the increasing complexity of the compound structures.

The novel copper complex [Cu(phen)2(salubrinal)](ClO4)2 (C0SAL) has been synthesised and characterised. Copper(ii) is coordinated by salubrinal through the thionic group, as shown by the UV-Vis, IR, ESI-MS and tandem mass results, together with the theoretical calculations. The formed complex showed a DPPH radical scavenging ability higher than that of salubrinal alone. Studies on lipid oxidation inhibition showed that the C0SAL concentration, required to inhibit the enzyme, was lower than that of salubrinal. The inhibition of the enzyme could take place via allosteric modulation, as suggested by docking calculations. C0SAL showed a good cytotoxic activity on A2780 cells, 82 fold higher than that of the precursor salubrinal and 1.4 fold higher than that of [Cu(phen)2(H2O)](ClO4)2. Treatment with C0SAL in SKOV3 ovarian cancer cells induced expression of GRP-78 and DDIT3 regulators of ER-stress response. The cytotoxic effect of C0SAL was reverted in the presence of TUDCA, suggesting that C0SAL induces cell death through ER-stress. In A2780 cells treated with C0SAL γ-H2AX was accumulated, suggesting that DNA damage was also involved.

Unfortunately in the online published article, the name of compound "L-salicylidenealanine" was published with incorrect spelling in the section "Synthesis of L‑salicylideneaniline (1a)". The section should correctly read as "Synthesis of L-salicylidenealanine".

Schiff bases represent a class of molecules widely studied for their importance in organic and coordination chemistry. Despite the large amount of studies on the chemical and biological properties of the Schiff bases, the different experimental conditions prevent a useful comparison to search for a correlation structure-activity. Moreover, literature is lacking in comprehensive data on the spectroscopic characterization of these compounds. For this reason, six Schiff bases, derived from salicylaldehyde and natural amino acids were fully characterized by nuclear magnetic resonance and infrared spectroscopy, and their aqueous solution equilibria, antiproliferative activity and DNA-binding activity were examined. All experimental conditions were kept constants to achieve comparable information and useful insights about their structure-activity correlation. The synthesized compounds showed DNA binding constants in the 10 1 -10 2  M -1 range, depending on the substituent present in the amino acid side-chain, and resulted devoid of significant cytotoxic activity against the different human tumor cell lines showing IC50 values higher than 100 µM.

There is an ongoing need for the development of new cancer therapeutics that combine high cytotoxic efficiency with low side effects, and also override resistance to the first-line chemotherapeutics. Copper(ii)-phenanthroline complexes are promising compounds that were shown previously to induce an immediate cytotoxic response over a panel of tumor cell lines in vitro. The molecular mechanism, however, remained unresolved. In this work we performed a thorough study of the copper(ii)-phenanthroline complexes containing different imidazolidine-2-thione ligands in ovarian cancer cells, and revealed that these complexes induce endoplasmic reticulum (ER) stress and subsequently cell death mediated by the unfolded protein response. Alleviation of the ER-stress by tauroursodeoxycholic acid (TUDCA) attenuated the cytotoxic effects. In summary, we have identified a novel, ER-dependent, molecular mechanism mediating cytotoxic effects of copper(ii)-phenanthroline complexes.

Water supply from karst sources is a worldwide natural resource and the exploitation is tied to the knowledge of the positions of the hydrologic channels. We show that surface deformation induced by flood events in karst conduits is observable, and consists in uplift and outward movement from the hydraulic channel. Precipitation events produce the natural occurrence of subsurface hydraulic overpressure up to 1 MPa. Numerical modeling shows that the stresses are so strong to uplift and dislocate the surface by several mm and induce tilts in the order of microradians. The naturally induced deformation is compatible with a transient internal pressure loading of a channel. The results can be used to find new channels with dense GNSS networks. Sea water incursion and channels accessed for tourism could be monitored. Seismicity has been shown to have a seasonal variation in some areas, which could be explained by the subsurface stresses induced by the natural subsurface overpressure. The pressure induced deformation is expected to be observed in all karstic systems worldwide.

The antagonistic effect of glutathione (GSH) against the cytotoxicity of cisplatin was observed in both wild type and cisplatin-resistant human leukaemia and ovarian carcinoma cell lines. The simultaneous presence of the cytotoxic copper complex [Cu(phen) 2 (OH 2 )](ClO 4 ) 2 (C0) restored the sensitivity of the cells to cisplatin, and, at selected concentrations, led to strong synergistic effects. The C0-cisplatin-glutathione system showed a synergistic toxic effect even in the presence of 1000 μM GSH. The three-drug cocktail exerted a higher potency against leukemic cells than against freshly isolated lymphocytes from healthy donors. Compared to actively proliferating normal lymphocytes, leukaemia cells were much more susceptible to the cytocide effect of the three-drug combination and underwent the dying process(es) much faster. When the ovarian carcinoma cells were treated with cisplatin, alone or in combination with C0, late apoptotic effects were mainly observed, suggesting that DNA interactions with the C0-cisplatin complex trigger a process of programmed cell death. In contrast, the ternary combination induced apoptotic effects similar to that shown by C0 in single treatment, that is, early apoptosis. One possible explanation is that C0 and cisplatin compete for GSH-binding in the culture medium. GSH in combination with C0 and cisplatin caused a significant induction of the apoptotic process(es), through a pathway which does not compromise the integrity of the plasma membrane of cells., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Rationale: Development of therapy-resistant cancer is a major problem in clinical oncology, and there is an urgent need for novel markers identifying development of the resistant phenotype. Lipidomics represents a promising approach to discriminate lipid profiles of malignant phenotype cells. Alterations in phospholipid distribution or chemical composition have been reported in various pathologies including cancer. Here we were curious whether quantitative differences in phospholipid composition between cisplatin-resistant and -sensitive model cancer cell lines could be revealed by mass spectrometric means., Methods: The phospholipid contents of cell membranes of the cancer cell lines CCRF-CEM and A2780, both responsive and resistant to cisplatin, were analyzed by solid-phase extraction (SPE) and electrospray ionization mass spectrometry (ESI-MS and tandem mass spectrometry (MS/MS)). Extracts were obtained by disruption of cells with a dounce tissue grinder set followed by centrifugation. To minimize the enzymatic activity, phospholipids were extracted from cell extracts by SPE immediately after the cell lysis and analyzed by MS. Both supernatant and pellet fractions of cell extracts were analyzed., Results: A phospholipid profile specific for cell lines and their phenotypes was revealed. We have documented by quantitative analysis that phosphocholines PC P-34:0, PC 34:1, PC 20:2_16:0, LPC 18:1 and LPC 16:0 PLs were present in the 200-400 μM concentration range in CCRF-CEM cisplatin-responsive cells, but absent in their cisplatin-resistant cells. Similarly, PC 34:1, LPC 18:1 and LPC 16:0 were increased in cisplatin-responsive A2780 cells, and PC 20:2_16:0 was downregulated in cisplatin-resistant A2780 cells., Conclusions: In this work we showed that the ESI-MS analysis of the lipid content of the therapy-resistant and -sensitive cells can clearly distinguish the phenotypic pattern and determine the potential tumor response to cytotoxic therapy. Lipid entities revealed by mass spectrometry and associated with development of therapy resistance can thus support molecular diagnosis and provide a potential complementary cancer biomarker., (© 2018 John Wiley & Sons, Ltd.)

Coumarins show biological activity and are widely exploited for their therapeutic effects. Although a great number of coumarins substituted by heterocyclic moieties have been prepared, few studies have been carried out on coumarins containing pyridine heterocycle, which is known to modulate their physiological activities. We prepared and characterized three novel 3-(pyridin-2-yl)coumarins and their corresponding copper(II) complexes. We extended our investigations also to three known similar coumarins, since no data about their biochemical activity was previously been reported. The antiproliferative activity of the studied compounds was tested against human derived tumor cell lines and one human normal cell line. The DNA binding constants were determined and docking studies with DNA carried out. Selected Quantitative Structure-Activity Relationship (QSAR) descriptors were calculated in order to relate a set of structural and topological descriptors of the studied compounds to their DNA interaction and cytotoxic activity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Malignant mesothelioma is a rare and aggressive form of cancer affecting the mesothelium. This mainly occupational disease is becoming more common in those countries where asbestos has been used for industrial applications. Notwithstanding the progress made in the field, patients do not survive more than 12 months on average with standard treatment. With the advent of next generation sequencing, it is now possible to study the mutational landscape of each tumor with the aim of identifying the genetic aberrations driving tumorigenesis. This review encompasses the latest research in the field, with particular attention to new chemotherapy combinatorial regimens, molecular targets and immunotherapies, providing a comprehensive picture of the current and future treatment options for malignant mesothelioma patients.