This study focuses on the deposition of plasma polymer films (PPFs) on hydrogels that could act as permeation barriers for aqueous species. The deposited PPFs on hydrogels were studied in terms of ...their ability to resist the permeation of an aqueous dye molecule after 24‐h exposure to an aqueous solution and mechanical stress. Permeation of the dye toluidine blue O through the hydrogels after plasma polymerisation was at least 75% less than that through an untreated hydrogel. The X‐ray photoelectron spectroscopy analysis showed introduction of O‐ and N‐rich chemical functionalities in the surface chemical composition of the hydrogel after plasma polymerisation. Scanning electron microscope imaging pointed out that milder plasma conditions result in uniform films that do not degrade upon exposure to water or mechanical stress.
Water‐stable and flexible plasma polymer films have been deposited on hydrogels.
Lower energy plasma conditions lead to deposition of more uniform films.
These films can be used as a base layer on hydrogels to carry out ligand attachment.
Further functionalisation of these base layer films can be done to impart anti‐fouling or cell adherence enhancing properties.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hydrogels are surfaces suitable for use as biomedical devices. Contact lenses are commonly used biomedical devices made from hydrogels. To enhance the application of contact lenses as cell delivery ...options, surface modification using low-pressure plasma enhanced chemical vapor deposition. The study investigated cell attachment on a few types of plasma deposited organic films: two types each of pure ethylene plasma polymer films, O-rich, N-rich and S-rich films on top of the hydrogels. The films led to changes in wettability, protein adsorption and the mechanical properties of the hydrogel surfaces, which are factors affecting cell proliferation. These films were also investigated for stability towards steam sterilisation Finally, these films stable towards water exposure and steam sterilisation were used to immobilize laminin in order to improve cell proliferation. The study investigated the possibility of using surface modified contact lenses could to deliver cell therapies to the eye environment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Increased expression of zinc finger E-box binding homeobox 1 (ZEB1) is associated with tumor grade and metastasis in lung cancer, likely due to its role as a transcription factor in ...epithelial-to-mesenchymal transition (EMT). Here, we modeled malignant transformation in human bronchial epithelial cells (HBECs) and determined that EMT and ZEB1 expression are early, critical events in lung cancer pathogenesis. Specific oncogenic mutations in TP53 and KRAS were required for HBECs to engage EMT machinery in response to microenvironmental (serum/TGF-β) or oncogenetic (MYC) factors. Both TGF-β- and MYC-induced EMT required ZEB1, but engaged distinct TGF-β-dependent and vitamin D receptor-dependent (VDR-dependent) pathways, respectively. Functionally, we found that ZEB1 causally promotes malignant progression of HBECs and tumorigenicity, invasion, and metastases in non-small cell lung cancer (NSCLC) lines. Mechanistically, ZEB1 expression in HBECs directly repressed epithelial splicing regulatory protein 1 (ESRP1), leading to increased expression of a mesenchymal splice variant of CD44 and a more invasive phenotype. In addition, ZEB1 expression in early stage IB primary NSCLC correlated with tumor-node-metastasis stage. These findings indicate that ZEB1-induced EMT and associated molecular changes in ESRP1 and CD44 contribute to early pathogenesis and metastatic potential in established lung cancer. Moreover, TGF-β and VDR signaling and CD44 splicing pathways associated with ZEB1 are potential EMT chemoprevention and therapeutic targets in NSCLC.
•Selectivity coefficients between ions have been evaluated from ion flotation results using a polyethoxy-carboxylate surfactant.•Ion selectivity in the foam correlates with the ion selectivity at the ...micelle surface.•A depletion effect of lithium ions from the foam was observed in the presence of neodymium (III) ions.
Separation of metal cations of different charges, Na+, Li+, Ca2+, Sr2+, Cu2+, Nd3+ and Eu3+ was investigated through ion foam flotation using a pH sensitive surfactant, nonaoxyethylene oleyl ether carboxylic acid. We propose here a method to evaluate ion selectivity coefficients using mass and volume balances. This method yields selectivity coefficients in agreement with those obtained with the classical slope method. The ion selectivity obtained by the flotation experiments was found to correlate well with the apparent charge of the surfactant micelles (zeta potential values) in the presence of different salts and is therefore not influenced by the surface curvature. Consequently the ion specificity order has been established according to the surfactant–ion affinity at the air–water and micelle–water interfaces as Na+<Li+<Sr2+<Ca2+<Cu2+<Nd3+<Eu3+. It has been noticed that the selectivity coefficients between the different metal ions, obtained by ion flotation, differ from the ones predicted by using metal ion complexation constants of acetate, which is considered here as the non-surface active complexing part of the surfactant. This discrepancy was attributed to the surface complexation effects at the air–water interface in flotation experiments and at the micelle–water interface. For the separation of lithium and neodymium, a depletion phenomenon of lithium ions from the interface, hence from the foam, has been observed, i.e. once the flotation experiment was finished, the lithium concentration in the remaining foaming solution was indeed higher compared to the initial one. This phenomenon was explained by the strong adsorption of Nd3+ that leads Li+ to be repelled from the foam.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
ABSTRACT
Tumor‐derived cell lines play an important role in the investigation of tumor biology and genetics. Across a wide array of studies, they have been tools of choice for the discovery of ...important genes involved in cancer and for the analysis of the cellular pathways that are impaired by diverse oncogenic events. They are also invaluable for screening novel anticancer drugs. The TP53 protein is a major component of multiple pathways that regulate cellular response to various types of stress. Therefore, TP53 status affects the phenotype of tumor cell lines profoundly and must be carefully ascertained for any experimental project. In the present review, we use the 2014 release of the UMD TP53 database to show that TP53 status is still controversial for numerous cell lines, including some widely used lines from the NCI‐60 panel. Our analysis clearly confirms that, despite numerous warnings, the misidentification of cell lines is still present as a silent and neglected issue, and that extreme care must be taken when determining the status of p53, because errors may lead to disastrous experimental interpretations. A novel compendium gathering the TP53 status of 2,500 cell lines has been made available (http://p53.fr). A stand‐alone application can be used to browse the database and extract pertinent information on cell lines and associated TP53 mutations. It will be updated regularly to minimize any scientific issues associated with the use of misidentified cell lines (http://p53.fr).
We have used the 2014 release of the UMD TP53 database to show that TP53 status is still controversial for numerous cell lines, including some widely used lines from the NCI‐60 panel. Our analysis clearly confirms that, despite numerous warnings, the misidentification of cell lines is still present as a silent and neglected issue, and that extreme care must be taken when determining the status of p53, because errors may lead to disastrous experimental interpretations. A novel compendium gathering the TP53 status of 2,500 cell lines has been made available (http://p53.fr).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Intermediary metabolism in cancer cells is regulated by diverse cell-autonomous processes, including signal transduction and gene expression patterns, arising from specific oncogenotypes and cell ...lineages. Although it is well established that metabolic reprogramming is a hallmark of cancer, we lack a full view of the diversity of metabolic programs in cancer cells and an unbiased assessment of the associations between metabolic pathway preferences and other cell-autonomous processes. Here, we quantified metabolic features, mostly from the 13C enrichment of molecules from central carbon metabolism, in over 80 non-small cell lung cancer (NSCLC) cell lines cultured under identical conditions. Because these cell lines were extensively annotated for oncogenotype, gene expression, protein expression, and therapeutic sensitivity, the resulting database enables the user to uncover new relationships between metabolism and these orthogonal processes.
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•Cell-autonomous metabolic diversity is reported in over 80 lung cancer cell lines•Heterogeneous metabolic phenotypes support lung cancer cell growth•Relating metabolic and molecular data uncovers new aspects of metabolic regulation•Some metabolic features predict sensitivity to chemotherapy and targeted agents
Metabolic reprogramming influences therapeutic sensitivity in cancer, but the scope of metabolic diversity among cancer cells is unknown. Chen et al. characterized metabolic phenotypes in over 80 non-small cell lung cancer cell lines and then used genomics, transcriptomics, proteomics, and therapeutic sensitivities to uncover relationships between metabolism and orthogonal processes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We constructed a lung cancer-specific database housing expression data and clinical data from over 6700 patients in 56 studies. Expression data from 23 genome-wide platforms were carefully processed ...and quality controlled, whereas clinical data were standardized and rigorously curated. Empowered by this lung cancer database, we created an open access web resource-the Lung Cancer Explorer (LCE), which enables researchers and clinicians to explore these data and perform analyses. Users can perform meta-analyses on LCE to gain a quick overview of the results on tumor vs non-malignant tissue (normal) differential gene expression and expression-survival association. Individual dataset-based survival analysis, comparative analysis, and correlation analysis are also provided with flexible options to allow for customized analyses from the user.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Low‐pressure plasma‐deposited C2H4 and C4H6 films containing N‐ and O‐groups, are used to regulate fibrinogen (Fg) adsorption in the presence of human serum albumin (HSA), with the long‐term ...intention of achieving control over platelet activation. This work includes a study of the effect of pressure on the films’ surface chemistry, stability in phosphate buffer solution (PBS), and Fg adsorption. Tribometry tests against a polyethylene surface, in PBS, indicated that N‐rich films were more susceptible to wear than the O‐rich coating. Adsorption kinetics showed a distinct peak which suggested a multilayer formation of HSA owing to adsorption from a highly concentrated solution. Results conclude that Fg adsorption in the presence of a high concentration of HSA can still be regulated by the careful choice of film surface chemistry.
Properties of C2H4 and C4H6 based plasma polymer films with N and O groups, geared toward the long‐term goal of designing plasma polymer coated aneurysm coils, are studied. Films with different chemistries enabled the regulation of fibrinogen adsorption with and without the presence of albumin. Adsorption kinetics suggested the initial formation of an albumin multilayer. O‐based film is more resistant to wear against a polyethylene surface than the N‐based films.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The material class of skutterudites is believed to have strong potential for thermoelectric application due to the very low thermal conductivity of the filled structures. It is generally assumed that ...the atoms filling the skutterudite cages act as 'rattlers' and essentially induce a disordered lattice dynamics referred to as 'phonon glass'. Here, we present neutron spectroscopy experiments and ab initio computational work on phonons in LaFe(4)Sb(12) and CeFe(4)Sb(12). Our results give unequivocal evidence of essentially temperature-independent lattice dynamics with well-defined phase relations between guest and host dynamics, indicative of a quasi-harmonic coupling between the guests and the host lattice. These conclusions are in disagreement with the 'phonon glass' paradigm based on individual 'rattling' of the guest atoms. These findings should have an essential impact on the design and improvement of thermoelectric materials and on the development of microscopic models needed for these efforts.
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IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are ...frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal. Transcription of CPS1 is suppressed by LKB1 through AMPK, and CPS1 expression correlates inversely with LKB1 in human NSCLC. Silencing CPS1 in KL cells induces cell death and reduces tumour growth. Notably, cell death results from pyrimidine depletion rather than ammonia toxicity, as CPS1 enables an unconventional pathway of nitrogen flow from ammonia into pyrimidines. CPS1 loss reduces the pyrimidine to purine ratio, compromises S-phase progression and induces DNA-polymerase stalling and DNA damage. Exogenous pyrimidines reverse DNA damage and rescue growth. The data indicate that the KL oncological genotype imposes a metabolic vulnerability related to a dependence on a cross-compartmental pathway of pyrimidine metabolism in an aggressive subset of NSCLC.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK