- Liège, Liege, Belgium
The effects of cis-dichloro-diammino-platinum(II) (cis-Pt) bound to DNA have been compared to those of free cis-Pt in mouse Ehrlich tumour cells, in peritoneal macrophages and in chick embryo fibroblasts cultivated in vitro. Cis-Pt has no... more
The effects of cis-dichloro-diammino-platinum(II) (cis-Pt) bound to DNA have been compared to those of free cis-Pt in mouse Ehrlich tumour cells, in peritoneal macrophages and in chick embryo fibroblasts cultivated in vitro. Cis-Pt has no antimitotic activity anymore when linked to DNA. This would be due to the fact that free cis-Pt is not released from cis-Pt-DNA complex inside lysosomes.
Research Interests: Chemistry, Biology, Macrophages, Medicine, Cell Division, and 10 moreEmbryo, Biological Sciences, DNA, In Vitro, Mice, Animals, Platinum, Cisplatin, Lysosomes, and fibroblasts
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Additional file 2: Table S2. The 121 proteins found as most discriminant in the DH versus DI versus pT1N0M0 versus pT2N0M0 comparison and common to the list of proteins found significant in the pT1N0M0 versus pT2N0M0 analysis are reported... more
Additional file 2: Table S2. The 121 proteins found as most discriminant in the DH versus DI versus pT1N0M0 versus pT2N0M0 comparison and common to the list of proteins found significant in the pT1N0M0 versus pT2N0M0 analysis are reported with p value, Fc and with the results of the analysis on GEXC. Abbreviations: DH: diverticulitis (adjacent normal tissue), DI: diverticulitis inflammatory (diverticulitis zone itself), ADK: adenocarcinome, GEXC: Gene Expression Commons, NR: Not relevant, Absent: Not available in the Data set, yes: the distribution of the gene expression between groups showed a similar tendency to the protein distribution obtained by proteomics, no: the distribution of the gene expression between groups did not showed a similar tendency to the protein distribution obtained by proteomics, The proteins previously associated with cancer development or CRC [19–22, 45] are in bold. Protein selected and validated in this paper are in red. Proteins found significant betwee...
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Human exhaled breath contains several hundreds of volatile organic compounds (VOCs) [1] that can be seen as a fingerprint that could possibly be used to differentiate between individuals exhibiting various health statuses. Breath analysis... more
Human exhaled breath contains several hundreds of volatile organic compounds (VOCs) [1] that can be seen as a fingerprint that could possibly be used to differentiate between individuals exhibiting various health statuses. Breath analysis has shown to be usable to highlight possible markers of specific diseases in these individuals [2]. Such an approach is particularly adapted to potential early diagnostic of cancer because its low level of invasiveness and relative ease of implementation on a large scale basis. This is of added value when considering diseases that suffer from poor prognosis as patients are often diagnosed at an advanced stage [3]. The implementation of an early diagnostic procedure for cancer screening by means of breath analysis could thus contribute to increase the survival rate of diagnosed patients. GC×GC-TOFMS has been reported to be able to isolate more than a thousand VOCs from one single human breath [4]. Such an approach is however still far from clinical ...
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INTRODUCTION: Sessile serrated adenoma/polyp (SSA/p) is a precancerous lesion, mostly located in the right side of the colon (cecum, ascending and transverse colon). The difficulty is to visualize this lesion during colonoscopy because of... more
INTRODUCTION: Sessile serrated adenoma/polyp (SSA/p) is a precancerous lesion, mostly located in the right side of the colon (cecum, ascending and transverse colon). The difficulty is to visualize this lesion during colonoscopy because of its subtle appearance. MATERIAL AND METHOD: We compared proteomes of serrated polyps (SSA/p) and conventional adenomas using residual human formalin fixed paraffin embedded (FFPE) samples. FFPE-FASP method was applied on samples before label free proteomic analysis. Immunohistochemistry (IHC) characterisation of one candidate marker was performed for tissue validation on an independent set of samples including: conventional adenomas (low and high-grade dysplasia), serrated polyps (hyperplastic polyps, SSA/p and traditional serrated adenoma) and finally normal colon (taken at the margin of colorectal cancer (CRC) or of diverticular disease). RESULTS: Proteomics provided 765 proteins (out of 5992 proteins identified) significantly discriminating conventional adenomas from serrated lesions. We selected 53BP1 (Tumor suppressor p53-binding protein 1) among these for IHC validation, because of its tumor suppressor gene function and role as a mediator of DNA damage checkpoint. 53BP1 appeared significantly up-regulated in proteomes of low and high grade adenomas compared to these of normal tissue and SSA/p. 53BP1 IHC signal was located in the nucleus and the percentage of positive nucleus decreased in serrated polyps, especially in crypts and in the border epithelium, confirming part of the proteomic results. CONCLUSION: This study highlights potential marker proteins, including 53BP1 from which IHC signal was strongly decreased in some serrated polyps. The loss of 53BP1 has been associated with tumour progression and poor prognosis, while little is currently known about its involvement in precancerous CRC lesions. 53BP1 decrease of expression in the nucleus and therefore possible loss of function in some epithelial cells could reflect important changes occurring during dysplasia to neoplasia progression in serrated lesions.Peer reviewe
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Introduction and objectives: Colorectal cancer (CRC) is the second most frequent cancer in women and the third in men. Identification of the mechanisms of progression in these early CRC stages is important to develop new diagnostic and... more
Introduction and objectives: Colorectal cancer (CRC) is the second most frequent cancer in women and the third in men. Identification of the mechanisms of progression in these early CRC stages is important to develop new diagnostic and therapeutic tools. Formalin-Fixed Paraffin-Embedded (FFPE) specimens are materials that enable proteomic clinical research. Hence our aim was to address the comparison of FFPE samples from early CRC stages patients using shotgun proteomic analysis. Methods: We performed a retrospective study on 36 CRC tissue samples (pT1N0M0, n=16 and pT2N0M0, n=20) compared together and with 40 control tissue samples (20 patients with diverticulitis, using paired inflamed (DI) and healthy tissue (DH)). Each tissue slice was macrodissected to enrich in epithelial cells. We used FFPE-FASP kit (Expedeon) for sample preparation and protein digests were analyzed using 2D-nanoAquity UPLC separation online with Q-Tof Synapt HDMSTM G2 using ion mobility as additional separation. We performed protein identification and differential analysis using Progenesis QI for proteomics (Nonlinear Dynamics). Results and discussion: We selected 149 proteins differentially distributed between T1 and T2 CRC stages which were not significantly different between CRC and DH or DI. Only 30 proteins were significantly more abundant in T1 versus T2 and 119 were distributed inversely, with a minimum fold ratio of 2. Among those, ATP synthase subunit beta, Aspartate-tRNA ligase, Haptoglobin and Kininogen were identified. . Moreover, we validated Kininogen and 3 others proteins with a significant differential distribution between pT1N0M0 and pT2N0M0 stages by immunohistochemistry. Conclusion: This FFPE retrospective study comparing T1 and T2 CRC highlighted proteins already previously identified as potential CRC biomarkers. These proteins may reflect important early changes in cancer development and may help understanding early tumor progression.Peer reviewe
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Despite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the identification of patients with preneoplastic lesions or with early CRC stages remains challenging and is important for reducing CRC... more
Despite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the identification of patients with preneoplastic lesions or with early CRC stages remains challenging and is important for reducing CRC incidence and increasing patient's survival. We analysed 76 colorectal tissue samples originated from early CRC stages, normal or inflamed mucosa by label-free proteomics. The characterisation of three selected biomarker candidates was performed by immunohistochemistry on an independent set of precancerous and cancerous lesions harbouring increasing CRC stages. Out of 5258 proteins identified, we obtained 561 proteins with a significant differential distribution among groups of patients and controls. KNG1, OLFM4 and Sec24C distributions were validated in tissues and showed different expression levels especially in the two early CRC stages compared to normal and preneoplastic tissues. We highlighted three proteins that require further investigations t...
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Magnetic nanoparticles (MNPs) of magnetite (Fe3O4) were prepared using a polystyrene-graft-poly(2-vinylpyridine) copolymer (denoted G0PS-g-P2VP or G1) as template. These MNPs were subjected to self-assembly with a poly(acrylic... more
Magnetic nanoparticles (MNPs) of magnetite (Fe3O4) were prepared using a polystyrene-graft-poly(2-vinylpyridine) copolymer (denoted G0PS-g-P2VP or G1) as template. These MNPs were subjected to self-assembly with a poly(acrylic acid)-block-poly(2-hydroxyethyl acrylate) double-hydrophilic block copolymer (DHBC), PAA-b-PHEA, to form water-dispersible magnetic polyion complex (MPIC) micelles. Large Fe3O4 crystallites were visualized by transmission electron microscopy (TEM) and magnetic suspensions of MPIC micelles exhibited improved colloidal stability in aqueous environments over a wide pH and ionic strength range. Biological cells incubated for 48 h with MPIC micelles at the highest concentration (1250 µg of Fe3O4 per mL) had a cell viability of 91%, as compared with 51% when incubated with bare (unprotected) MNPs. Cell internalization, visualized by confocal laser scanning microscopy (CLSM) and TEM, exhibited strong dependence on the MPIC micelle concentration and incubation time, a...
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Polydimethylsiloxane (PDMS) constitutes an interesting material for a variety of biomedical applications, especially as intraocular lenses (IOLs), for its excellent transparency. In this work, a photoreversible PDMS-coumarin network,... more
Polydimethylsiloxane (PDMS) constitutes an interesting material for a variety of biomedical applications, especially as intraocular lenses (IOLs), for its excellent transparency. In this work, a photoreversible PDMS-coumarin network, whose shape and properties can be adjusted postoperatively in a noninvasive manner, is developed. The synthesis of PDMS-coumarin is achieved by amidation of a coumarin acid chloride derivative with amine-functionalized PDMSs. Under exposure of λ > 300 nm, these polymers can be cured by dimerization of coumarin. The cured polymers can be uncrosslinked via photocleavage of cyclobutane dimers upon illumination at λ < 290 nm. The diffusion of linear PDMSs in a crosslinked network and the controlled shape modification are studied, which demonstrate that these polymers are good candidates for adjustable IOL application. IOL disks prepared from these materials show high hydrophobicity and good transparency. In vitro cytotoxicity, lens epithelial cell adh...
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Polymer-infiltrated-ceramic-network (PICN) materials constitute an innovative class of CAD-CAM materials offering promising perspectives in prosthodontics, but no data are available in the literature regarding their biological properties.... more
Polymer-infiltrated-ceramic-network (PICN) materials constitute an innovative class of CAD-CAM materials offering promising perspectives in prosthodontics, but no data are available in the literature regarding their biological properties. The objective of the present study was to evaluate the in vitro biocompatibility of PICNs with human gingival fibroblasts (HGFs) in comparison with materials typically used for implant prostheses and abutments. HGF attachment, proliferation and spreading on discs made of PICN, grade V titanium (Ti), yttrium zirconia (Zi), lithium disilicate glass-ceramic (eM) and polytetrafluoroethylene (negative control), were evaluated using a specific insert-based culture system (IBS-R). Sample surface properties were characterized by XPS, contact angle measurement, profilometry and SEM. Ti and Zi gave the best results regarding HGF viability, morphology, number and coverage increase with time in comparison with the negative control, while PICN and eM gave intermediate results, cell spreading being comparable for PICN, Ti, Zi and eM. Despite the presence of polymers and their related hydrophobicity, PICN exhibited comparable results to glass-ceramic materials, which could be explained by the mode of polymerization of the monomers. The results of the present study confirm that the currently employed materials, i.e. Ti and Zi, can be considered to be the gold standard of materials in terms of HGF behavior, while PICN gave intermediate results comparable to eM. The impact of the present in vitro results needs to be further investigated clinically, particularly in the view of the utilization of PICNs for prostheses on bone-level implants.
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Methylmercury (MeHg) is highly immunotoxic and can alter the health status of the harbour seal, Phoca vitulina, from the North Sea. To investigate the mechanism of MeHg-induced toxicity in harbour seal lymphocytes, Concanavalin A... more
Methylmercury (MeHg) is highly immunotoxic and can alter the health status of the harbour seal, Phoca vitulina, from the North Sea. To investigate the mechanism of MeHg-induced toxicity in harbour seal lymphocytes, Concanavalin A (ConA)-stimulated peripheral blood leucocytes were exposed in vitro to sublethal concentrations of MeHgCl (0.2, 1, and 2 µM) for 72 h and then analysed for their viability and ultrastructure. After 72 h of incubation, cells were counted with a propidium iodide staining technique, a metabolic MTS assay was performed, and cells exposed to 1 µM of MeHgCl were observed by transmission electron microscopy (TEM). Alive cell numbers decreased with increased MeHgCl concentrations. In presence of ConA and 1 µM of MeHgCl, TEM images revealed a higher frequency of apoptotic cells. Exposed cells displayed condensation of the chromatin at the nuclear membrane and mitochondrial damages. The results suggest that in vitro MeHgCl-induced apoptosis in harbour seal lymphocyte...
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In this study, we report the synthesis of a nanoscaled drug delivery system, which is composed of a gold nanorod-like core and a mesoporous silica shell (GNR@MSNP) and partially uploaded with phase-changing molecules (1-tetradecanol, TD,... more
In this study, we report the synthesis of a nanoscaled drug delivery system, which is composed of a gold nanorod-like core and a mesoporous silica shell (GNR@MSNP) and partially uploaded with phase-changing molecules (1-tetradecanol, TD, Tm 39 °C) as gatekeepers, as well as its ability to regulate the release of doxorubicin (DOX). Indeed, a nearly zero premature release is evidenced at physiological temperature (37 °C), whereas the DOX release is efficiently achieved at higher temperature not only upon external heating, but also via internal heating generated by the GNR core under near infrared irradiation. When tagged with folate moieties, GNR@MSNPs target specifically to KB cells, which are known to overexpress the folate receptors. Such a precise control over drug release, combining with the photothermal effect of GNR cores, provides promising opportunity for localized synergistic photothermal ablation and chemotherapy. Moreover, the performance in killing the targeted cancer cel...
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The viability, cytolysis and apoptosis-mediated cellular death induced by giganteosides D and E (Gig-D and Gig-E) and hederacolchisides A and A1 (Hcol-A and Hcol-A1) were analysed in HL-60 cells. The end-point metabolic (WST1) and lactate... more
The viability, cytolysis and apoptosis-mediated cellular death induced by giganteosides D and E (Gig-D and Gig-E) and hederacolchisides A and A1 (Hcol-A and Hcol-A1) were analysed in HL-60 cells. The end-point metabolic (WST1) and lactate dehydrogenase (LDH) assays were used. Cell cycle analysis and apoptosis were measured by flow cytometry, DNA laddering and caspase-3 analyses. the HL-60 cell line was more sensitive to Hcol-A1 and Gig-D (IC50 3-5 microM) than to Gig-E and Hcol-A (IC50 8-13 microM; WST1 assay). This was related to LDH release. The induction of apoptosis could be detected without caspase-3 activation after 24 h of treatment. DNA fragmentation could be detected only with Gig-D. With Hcol-A1 and Gig-D, an accumulation of cells in the S-phase and an increase of cells in sub-G1 peak were observed. By the annexinV-fluorescein isothiocyanate (FITC)/7-amino-actinomycin D (AAD) assay, the majority of cells were in late apoptosis with Gig-D, and in necrosis with Hcol-A1. Hcol...
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Ophthalmic lenses are medical devices with considerable requirements in terms of optical, biomechanical and biological performance. There is limited number of materials used for their manufacturing, comprising mainly silicones and... more
Ophthalmic lenses are medical devices with considerable requirements in terms of optical, biomechanical and biological performance. There is limited number of materials used for their manufacturing, comprising mainly silicones and poly(meth)acrylates. This series of publications aims at investigating the applicability of thermoplastic polyurethane elastomers (TPU) for the manufacturing of ophthalmic lenses and examining the properties of the respective devices. This study is related to the synthesis of TPUs with chemical compositions that comprise chemically grafted filters for the hazardous-light. GC-MS, attenuated total reflectance Fourier transform infrared spectroscopy, and UV-vis spectroscopies confirmed the reaction completion and the beneficial effect of the filters on the light transmittance, respectively. Relatively high refractive index of the material was measured and allows for the manufacturing of thinner lenses. The contrast sensitivity determined for a model intraocular lens (IOL) was satisfactory. Few optical defects were, however, present on the model lens prepared by thermoplastic injection molding. The elasticity of the materials was evaluated in view to their potential applicability as foldable IOLs by determining their glass transition temperature and their Young modulus and measuring their shore A. The TPU materials demonstrated more bioadhesive character compared with a benchmark hydrophilic acrylic reference material, which is already used for IOL manufacturing. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2014.
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Formalin-fixed paraffin-embedded (FFPE) specimens of patients are useful sources of materials for clinical research and have recently gained interest for use in the discovery of clinical proteomic biomarkers. However, the critical step in... more
Formalin-fixed paraffin-embedded (FFPE) specimens of patients are useful sources of materials for clinical research and have recently gained interest for use in the discovery of clinical proteomic biomarkers. However, the critical step in this field is the ability to obtain an efficient and repeatable extraction using the limited quantities of material available for research in hospital biobanks. This work describes the evaluation of the peptide/protein extraction using FFPE sections treated by the following two methods before shotgun proteomic analysis: a commercial solution (FFPE-FASP) (filter aided sample preparation) and an antigen retrieval-derived protocol (On Slice AR). Their efficiencies and repeatabilities are compared using data-independent differential quantitative label-free analysis. FFPE-FASP was shown to be globally better both qualitatively and quantitatively than On Slice AR. FFPE-FASP was tested on several samples, and differential analysis was used to compare the tissues of diverticulitis patients (healthy and inflammatory tissues). In this differential proteomic analysis using retrospective clinical FFPE material, FFPE-FASP was reproducible and provided a high number of confident protein identifications, highlighting potential protein biomarkers. In clinical proteomics, FFPE is an important resource for retrospective analysis and for the discovery of biomarkers. The challenge for FFPE shotgun proteomic analysis is preparation by an efficient and reproducible protocol, which includes protein extraction and digestion. In this study, we analyzed two different methods and evaluated their repeatabilities and efficiencies. We illustrated the reproducibility of the most efficient method, FFPE-FASP, by a pilot study on diverticulitis tissue and on FFPE samples amount accessible in hospital biobanks. These data showed that FFPE is suitable for use in clinical proteomics, especially when the FFPE-FASP method is combined with label-free shotgun proteomics as described in the workflow presented in this work.
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To compare hydrophilic and hydrophobic acrylic materials designed for intraocular lenses in a multiparametric investigation in a liquid environment to highlight their properties in terms of adhesion forces, lens epithelial cell (LEC)... more
To compare hydrophilic and hydrophobic acrylic materials designed for intraocular lenses in a multiparametric investigation in a liquid environment to highlight their properties in terms of adhesion forces, lens epithelial cell (LEC) adhesion, and tissue response as indicators of the risk for posterior capsule opacification (PCO) development. University of Liège, Liège, Belgium. Experimental study. The hydrophobicity and surface adhesion force were assessed using contact-angle and atomic force microscopy measurements. The bioadhesiveness of the disks and the tissue response were determined by in vitro experiments using bovine serum albumin and porcine LECs and by in vivo rabbit subcutaneous implantation, respectively. Increasing surface hydrophobicity led to a greater surface-adhesion force and greater LEC adhesion. After 1 month, the rabbit subcutaneous implants showed a similar thin layer of fibrous capsule surrounding the disks without extensive inflammation. A layer of rounded cells in contact with disks was detected on the hydrophobic samples only. Hydrophobic acrylic disks that have been associated with a reduced risk for PCO in clinical studies showed increased tackiness. Proprietary or commercial disclosures are listed after the references.
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Hydrophilic nanogels based on partially hydrolyzed poly(2-ethyl-2-oxazoline) were synthesized in dilute aqueous media in the presence of 1,6-hexanediol diglycidyl ether as a cross-linker. Nanogel formation was monitored by DLS and HSQC... more
Hydrophilic nanogels based on partially hydrolyzed poly(2-ethyl-2-oxazoline) were synthesized in dilute aqueous media in the presence of 1,6-hexanediol diglycidyl ether as a cross-linker. Nanogel formation was monitored by DLS and HSQC NMR spectroscopy, and the final nano-objects were characterized by DLS, TEM, AFM, and NanoSight analyses. Nanogels with a hydrodynamic radius of 78 nm exhibiting a slight positive surface charge were obtained. MTS assays (cell metabolic activity test) evidenced that nanogels were nontoxic in the investigated concentration range (i.e., 0.1 to 400 μg/mL) and that no specific interaction with bovine serum albumin was observed.
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Plasma enhanced chemical vapor deposition has been tested for the formation of hydrophobic perfluorinated coating on the surface of hydrophilic poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) [poly(HEMA-co-MMA)] substrates, used... more
Plasma enhanced chemical vapor deposition has been tested for the formation of hydrophobic perfluorinated coating on the surface of hydrophilic poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) [poly(HEMA-co-MMA)] substrates, used for the fabrication of intraocular lenses (IOLs). The properties of the dry and hydrated surface modified by two plasma techniques, Radio-frequency (RF) and Microwave (MW), were investigated in parallel by contact angle measurements in
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... c, Christine Jérômea, Catherine Passiranid, Nolwenn Lautramd, Jean-F. Desreuxe, Mike Collodorof, Marie-Claire De Pauw-Gilletf and Christophe Detrembleur*a. a Center for Education and Research on Macromolecules (CERM), University of... more
... c, Christine Jérômea, Catherine Passiranid, Nolwenn Lautramd, Jean-F. Desreuxe, Mike Collodorof, Marie-Claire De Pauw-Gilletf and Christophe Detrembleur*a. a Center for Education and Research on Macromolecules (CERM), University of Liège, B6 Sart-Tilman, B-4000 ...
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Preparation of thermo-responsive poly(vinyl alcohol)-b-poly(N-vinylcaprolactam) copolymer-stabilized gold nanoparticles for drug delivery.
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Research Interests: Phytochemistry, Cytotoxicity, Macromolecular X-Ray Crystallography, Biological Sciences, X Rays, and 15 moreCell line, Humans, CHEMICAL SCIENCES, Isolation, Croton, Diterpenes, HeLa cells, Biological activity, Human Fibroblasts, Molecular Structure, Plant Leaves, Terpenoid, fibroblasts, Plant Leaf, and Medical and Health Sciences
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The antifouling properties of poly(2-hydroxyethyl methacrylate- co-methyl methacrylate) hydrogels were improved by the surface grafting of a brush of poly(oligoethylene glycol methyl ether acrylate) [poly(OEGA)]. The atom-transfer radical... more
The antifouling properties of poly(2-hydroxyethyl methacrylate- co-methyl methacrylate) hydrogels were improved by the surface grafting of a brush of poly(oligoethylene glycol methyl ether acrylate) [poly(OEGA)]. The atom-transfer radical polymerization (ATRP) of OEGA (degree of polymerization = 8) was initiated from the preactivated surface of the hydrogel under mild conditions, thus in water at 25 degrees C. The catalytic system was optimized on the basis of two ligands [1,1,4,7,10,10-hexamethyl-triethylenetetramine (HMTETA) or tris[2-(dimethylamino)ethyl]amine (Me6TREN)] and two copper salts (CuIBr or CuICl). Faster polymerization was observed for the Me 6TREN/CuIBr combination. The chemical composition and morphology of the coated surface were analyzed by X-ray photoelectron spectroscopy, attenuated total reflectance Fourier transform infrared spectroscopy, contact angle measurements by the water droplet and captive bubble methods, scanning electron microscopy, and environmental scanning electron microscopy. The hydrophilicity of the surface increased with the molar mass of the grafted poly(OEGA) chains, and the surface modifications were reported in parallel. The antifouling properties of the coatings were tested by in vitro protein adsorption and cell adhesion tests, with green fluorescent protein, beta-lactamase, and lens epithelial cells, as model proteins and model cells, respectively. The grafted poly(OEGA) brush decreased the nonspecific protein adsorption and imparted high cell repellency to the hydrogel surface.
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This paper reports the identification of biomarkers resulting from the exposure of MCF-7/BOS cells to 17β-estradiol (E(2)). The biomarkers were identified using 2 independent and complementary techniques, 2-D DIGE/MALDI-TOF peptide mass... more
This paper reports the identification of biomarkers resulting from the exposure of MCF-7/BOS cells to 17β-estradiol (E(2)). The biomarkers were identified using 2 independent and complementary techniques, 2-D DIGE/MALDI-TOF peptide mass fingerprint, and 2-D UPLC-ESI MS/MS. They were identified from the cytosolic fractions of cells treated for 24h with mitogenic concentrations of 1, 30 and 500 pM of 17β-estradiol. Five biomarkers were up-regulated proteins, namely HSP 74, EF2, FKBP4, EF1 and GDIB and one was a down-regulated protein, namely K2C8. Three of these proteins, EF2, FKBP4 and K2C8 are implicated in a network centered on the estrogen receptors ESR1 and ESR2 as well as on AKT1. After the discovery phase, three biomarkers were selected to test the presence of estrogens using selected reaction monitoring (SRM). They were monitored using SRM after incubation of MCF-7/BOS in the presence of E(2) for confirmation or selected xenoestrogens. Daidzein, coumestrol and enterolactone induced an up-regulation of EF2 and FKPB4 proteins, while tamoxifen and resveratrol induced a down-regulation. The exposure of all phytoestrogens induced the down-regulation of K2C8. These markers form a preliminary molecular signature that can be used when testing the estrogenic activity of xenobiotics, either pure or in mixtures.
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On the basis of the original lead neocryptolepine or 5-methyl-5H-indolo[2,3-b]quinoline, an alkaloid from Cryptolepis sanguinolenta, derivatives were prepared using a biradical cyclization methodology. Starting from easily accessible... more
On the basis of the original lead neocryptolepine or 5-methyl-5H-indolo[2,3-b]quinoline, an alkaloid from Cryptolepis sanguinolenta, derivatives were prepared using a biradical cyclization methodology. Starting from easily accessible educts, this approach allowed the synthesis of hitherto unknown compounds with a varied substitution pattern. As a result of steric hindrance, preferential formation of the 3-substituted isomers over the 1-substituted isomers was observed when cyclizing N-(3-substituted-phenyl)-N&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-[2-(2-trimethylsilylethynyl)phenyl]carbodiimides. All compounds were evaluated for their activity against chloroquine-sensitive as well as chloroquine-resistant Plasmodium falciparum strains, for their activity against Trypanosoma brucei and T. cruzi, and for their cytotoxicity on human MRC-5 cells. Mechanisms of action were investigated by testing heme complexation using ESI-MS, inhibition of beta-hematin formation, DNA interactions (DNA-methyl green assay and linear dichroism), and inhibition of human topoisomerase II. Neocryptolepine derivatives with a higher antiplasmodial activity and a lower cytotoxicity than the original lead have been obtained. This selective antiplasmodial activity was associated with inhibition of beta-hematin formation. 2-Bromoneocryptolepine was the most selective compound with an IC(50) value against chloroquine-resistant P. falciparum of 4.0 microM in the absence of cytotoxicity (IC(50) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 32 microM). Although cryptolepine, a known lead for antimalarials also originally isolated from Cryptolepis sanguinolenta, was more active (IC(50) = 2.0 microM), 2-bromoneocryptolepine showed a low affinity for DNA and no inhibition of human topoisomerase II, in contrast to cryptolepine. Although some neocryptolepine derivatives showed a higher antiplasmodial activity than 2-bromocryptolepine, these compounds also showed a higher affinity for DNA and/or a more pronounced cytotoxicity. Therefore, 2-bromoneocryptolepine is considered as the most promising lead from the present work for new antimalarial agents. In addition, 2-bromo-, 2-nitro-, and 2-methoxy-9-cyanoneocryptolepine exhibited antitrypanosomal activity in the micromolar range in the absence of obvious cytotoxicity.
Research Interests: Organic Chemistry, Medicinal Chemistry, Polymers, DNA, Cell line, and 15 moreHumans, Animals, Alkaloids, Heme, Liquid Chromatography / Electrospray Ionization Mass Spectrometry, Trypanosoma Cruzi, Trypanosoma brucei brucei, Plasmodium falciparum, Antimalarials, Trypanocidal Agents, Quinolines, Structure activity Relationship, Hemin, "Intercalating Agents", and Pharmacology and pharmaceutical sciences
Herein, we report a new drug-delivery system (DDS) that is comprised of a near-infrared (NIR)-light-sensitive gold-nanorod (GNR) core and a phase-changing poly(ε-caprolactone)-b-poly(ethylene glycol) polymer corona (GNR@PCL-b-PEG). The... more
Herein, we report a new drug-delivery system (DDS) that is comprised of a near-infrared (NIR)-light-sensitive gold-nanorod (GNR) core and a phase-changing poly(ε-caprolactone)-b-poly(ethylene glycol) polymer corona (GNR@PCL-b-PEG). The underlying mechanism of the drug-loading and triggered-release behaviors involves the entrapment of drug payloads among the PCL crystallites and a heat-induced phase change, respectively. A low premature release of the pre-loaded doxorubicin was observed in PBS buffer (pH 7.4) at 37 °C (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10% of the entire payload after 48 h). However, release could be activated within 30 min by conventional heating at 50 °C, above the Tm of the crystalline PCL domain (43.5 °C), with about 60% release over the subsequent 42 h at 37 °C. The NIR-induced heating of an aqueous suspension of GNR@PCL-b-PEG under NIR irradiation (802 nm) was investigated in terms of the irradiation period, power, and concentration-dependent heating behavior, as well as the NIR-induced shape-transformation of the GNR cores. Remotely NIR-triggered release was also explored upon NIR irradiation for 30 min and about 70% release was achieved in the following 42 h at 37 °C, with a mild warming (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;4 °C) of the surroundings. The cytotoxicity of GNR@PCL-b-PEG against the mouse fibroblastic-like L929 cell-line was assessed by MTS assay and good compatibility was confirmed with a cell viability of over 90% after incubation for 72 h. The cellular uptake of GNR@PCL-b-PEG by melanoma MEL-5 cells was also confirmed, with an averaged uptake of 1250(±110) particles cell(-1) after incubation for 12 h (50 μg mL(-1)). This GNR@PCL-b-PEG DDS is aimed at addressing the different requirements for therapeutic treatments and is envisaged to provide new insights into DDS targeting for remotely triggered release by NIR activation.
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The appropriate experimental conditions for the preparation of complexes of cis-dichlorodiammineplatinum(II) with DNA and with purine nucleosides have been determined which leave negligible amounts of free drug in the solution. Important... more
The appropriate experimental conditions for the preparation of complexes of cis-dichlorodiammineplatinum(II) with DNA and with purine nucleosides have been determined which leave negligible amounts of free drug in the solution. Important conformational changes of DNA upon binding to cis-Pt(NH3)2-Cl2 have been evidenced through viscosity, electric birefringence and thermal denaturation experiments. The antimitotic and antitumor activity of the drug was found to be totally inhibited by its binding to DNA and to the purine nucleosides. Enzymic degradation observations on the DNA-cis-Pt(NH3)2Cl2 complexes indicated an important inhibition of the degradation and the absence of release of free drug. The implications of the results in relation with the mode of binding of this compound to DNA, with the choice of carriers for drugs and the mechanism of action of lysosomotropic agents are discussed.
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Cataract surgery is a routine ophthalmologic intervention resulting in replacement of the opacified natural lens by a polymeric intraocular lens (IOL). A main postoperative complication, as a result of protein adsorption and lens... more
Cataract surgery is a routine ophthalmologic intervention resulting in replacement of the opacified natural lens by a polymeric intraocular lens (IOL). A main postoperative complication, as a result of protein adsorption and lens epithelial cell (LEC) adhesion, growth, and proliferation, is the secondary cataract, referred to as posterior capsular opacification (PCO). To avoid PCO formation, a poly(ethylene glycol) (PEG) chemical coating was created on the surface of hydrogel IOLs. Attenuated total reflectance Fourier transform infrared spectroscopy, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;captive bubble&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;water droplet&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; contact angle measurements, and atomic force microscopy analyses proved the covalent grafting of the PEG chains on the IOL surface while keeping unchanged the optical properties of the initial material. A strong decrease of protein adsorption and cell adhesion depending on the molar mass of the grafted PEG (1100, 2000, and 5000 g/mol) was observed by performing the relevant in vitro tests with green fluorescent protein and LECs, respectively. Thus, the study provides a facile method for developing materials with nonfouling properties, particularly IOLs.
Research Interests: Engineering, Atomic Force Microscopy, Adhesion, Biological Sciences, In Vitro, and 13 moreTransparency, Animals, Wettability, Surface topography, Eye, CHEMICAL SCIENCES, Epithelial cells, Poly Ethylene Glycol, Fourier transform infrared spectroscopy, Materials Testing, Biomacromolecules, Chemical Modification, and Polyethylene Glycols
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Research Interests: Biochemistry, Electrochemistry, Enzyme Inhibitors, Cytotoxicity, DNA, and 15 moreBeta decay, Animals, Cell Death, Alkaloids, Analog, Enzyme, Cattle, Enzyme activity, BIOCHEMICAL PHARMACOLOGY, Base Sequence, Catalytic Activity, Biochemistry and cell biology, DNA sequence, binding sites, and DNA Restriction Enzymes
The effects of selenium compounds such as sodium selenite, sodium selenate, seleno-DL-cystine and seleno-DL-methionine (100 microM and 10 microM) on B16 and pigmented cloned pB16 murine melanoma cells were investigated in vitro. At the... more
The effects of selenium compounds such as sodium selenite, sodium selenate, seleno-DL-cystine and seleno-DL-methionine (100 microM and 10 microM) on B16 and pigmented cloned pB16 murine melanoma cells were investigated in vitro. At the tested concentrations, B16 cells showed a greater sensitivity to the toxic effects of sodium selenite and seleno-DL-cystine than pB16 cells, whereas no decrease of B16 and pB16 cell number was observed after incubation with sodium selenate or seleno-DL-methionine. Glutathione (GSH) percentages were strongly decreased only by selenite and seleno-DL-cystine; it was marked more in B16 than in pB16 cells. The pretreatment of B16 cells with a GSH depleting agent (10 microM buthionine-[S,R]-sulfoximine) did not significantly influence the cytotoxic effects of selenite and seleno-DL-cystine. On both cell populations, GSH preincubation (50 microM) enhanced the cytotoxicity of selenite whereas the survival of seleno-DL-cystine treated cells was increased. Glutathione peroxidase (GSH-Px) activity in B16 cells was more sensitive than in pB16 cells to the activating effect of selenite, and particularly of seleno-DL-cystine: however, cell-free controls indicated that activation was mainly due to glutathione reductase. The rate of 75Se (as sodium selenite) uptake in both cell populations was maximal within the first hour of incubation, with a preferential accumulation in the cytosol; after 24 h of incubation, the amount of 75Se in cytosol and pellet was approximately the same.(ABSTRACT TRUNCATED AT 250 WORDS)
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Research Interests:
Research Interests:
Abstract:[en] Despite 30 years of international regulations, Hg levels in marine mammals have not decreased. Various environmental models even suggest a rise of mercury in the biota during the next decades, linked to climate change. The... more
Abstract:[en] Despite 30 years of international regulations, Hg levels in marine mammals have not decreased. Various environmental models even suggest a rise of mercury in the biota during the next decades, linked to climate change. The objective of this study is (1) to assess Hg levels in blood samples of free-ranging pinnipeds,(2) to understand level variation during different periods of life (gestation, lactation, fasting) and potential impact on lymphocytes using a preliminary in vitro model (peripheral blood mononuclear cells, ...