Marie -Claire Gillet | Université de Liège (original) (raw)
Papers by Marie -Claire Gillet
Comptes rendus des séances de la Société de biologie et de ses filiales, 1976
The effects of cis-dichloro-diammino-platinum(II) (cis-Pt) bound to DNA have been compared to tho... 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.
Journal of Biomedical Materials Research Part A, 2019
Stereolithography (SLA) is an interesting manufacturing technology to overcome limitations of com... more Stereolithography (SLA) is an interesting manufacturing technology to overcome limitations of commercially available particulated biomaterials dedicated to intra-oral bone regeneration applications. The purpose of this study was to evaluate the in vitro and in vivo biocompatibility and osteoinductive properties of two CaP-based scaffolds manufactured by SLA 3D printing. Pellets and macro-porous scaffolds were manufactured in pure hydroxyapatite (HA) and in biphasic CaP (HA:60-TCP:40). Physicochemical characterization was performed using Micro X-ray Fluorescence (µXRF), Scanning Electron Microscopy (SEM), optical interferometry and microtomography (µCT) analyses. Osteoblast-like MG-63 cells were used to evaluate the biocompatibility of the pellets in vitro with MTS assay and the cell morphology and growth characterized by SEM and DAPI-actin staining showed similar early behavior. For in vivo biocompatibility, newly formed bone and biodegradability of the experimental scaffolds were evaluated in a subperiosteal cranial rat model using µCT and descriptive histology. The histological analysis has not indicated evidences of inflammation but highlighted close contacts between newly formed bone and the experimental biomaterials revealing an excellent scaffold osseointegration. This study emphasizes the relevance of SLA 3D printing of CaP-based biomaterials for intra-oral bone regeneration even if manufacturing accuracy has to be improved and further experiments using biomimetic scaffolds should be conducted.
Advanced Healthcare Materials, 2018
Dental Materials, 2013
Infiltration of cracks in glass with resins is a widespread concept in glass industry and is used... more Infiltration of cracks in glass with resins is a widespread concept in glass industry and is used successfully, for example, to reinforce cracked automotive windshields. This study had the purpose to evaluate the potential of a low-viscosity resin to infiltrate surface cracks in glass and feldspathic ceramic substrates and its effects on flexural strength as a potential prophylactic measure for contactinduced damage. Methods and materials: Discs (d = 12.5 mm and 1.2 mm in thickness) were produced using a glass-ceramic powder material (VM9, Vita Zahnfabrik) by condensation and sintering. The sintered discs were reduced to the final thickness by grinding with a diamond wheel and subsequently mirror polished (up to 4000 SiC paper Grit) on the side subjected to tension. Sodalime glass discs (d = 15 mm and 1.9 mm in thickness; Schott, Germany) were used for comparison. A Vickers indent (Zwick, Germany) was produced on the tensile side of the discs (1 kg during 15 s for VM9 and 500 g during 15 s for glass), which was subsequently coated with an experimental photo-cured lowviscosity resin (DMG, Germany). After 24 h of water storage, the discs were tested in flexure using the piston-on-three-balls setup. Weibull parameters m and sigma0 were calculated (n = 15 for VM9 and n = 10 for glass) and mathematically corrected according to the n number. The infiltration depth into the Vickers indent was measured in samples infiltrated with a fluorescent dyed-infiltrant using a confocal laser scanning microscope (TCS SL, Leica, Germany). Results: Shape and scale parameters for the Glass samples were as follows: m = 7.0 and sigma0 = 335.9 MPa for polished; m = 5.9 and sigma0 = 106.8 MPa for indented; m = 8.2 and sigma0 = 223.2 MPa for infiltrated. Shape and scale parameters for the Ceramic VM9 samples were as follows m = 10.3 and sigma0 = 101.2 MPa for polished; m = 11.4 and sigma0 = 63.52 MPa for indented; m = 5.1 and sigma0 = 83.9 MPa for infiltrated. The increase in sigma0 after infiltration was significant at a 95% level for both glass and ceramic. Infiltration depth in glass samples were recorded up to 18 m in depth, while in ceramis the infiltration depth was limited to the 2-4 m subsurface zone. Conclusion: As in glass, the infiltration of surface cracks with low-viscosity resin infiltrants is able to strengthen veneering ceramics and potentially prevent chipping events. The infiltration depth in ceramics is limited but does not seem to hinder its reinforcing effect.
Additional file 2: Table S2. The 121 proteins found as most discriminant in the DH versus DI vers... 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...
TD-GCxGC-HRTOFMS in biological applications Efficient trapping, separation, and identification of... more TD-GCxGC-HRTOFMS in biological applications Efficient trapping, separation, and identification of volatile organic compounds (VOCs) produced during complex biological processes require the use of multi-dimensional techniques such as TD-GCxGC-(HR)TOFMS. We currently use it to create large matrices of data that are further processed to statistically differentiate between classes of samples in several medical and forensic applications.
Human exhaled breath contains several hundreds of volatile organic compounds (VOCs) [1] that can ... 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 ...
INTRODUCTION: Sessile serrated adenoma/polyp (SSA/p) is a precancerous lesion, mostly located in ... 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
Introduction and objectives: Colorectal cancer (CRC) is the second most frequent cancer in women ... 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
Clinical proteomics, 2017
Despite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, t... 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...
Nanomaterials
Magnetic nanoparticles (MNPs) of magnetite (Fe3O4) were prepared using a polystyrene-graft-poly(2... 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...
Macromolecular bioscience, Jan 15, 2017
Polydimethylsiloxane (PDMS) constitutes an interesting material for a variety of biomedical appli... 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...
Dental Materials, 2016
Polymer-infiltrated-ceramic-network (PICN) materials constitute an innovative class of CAD-CAM ma... 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.
European Respiratory Journal, 2015
Archives of environmental contamination and toxicology, Jan 12, 2015
Methylmercury (MeHg) is highly immunotoxic and can alter the health status of the harbour seal, P... 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...
Small (Weinheim an der Bergstrasse, Germany), Jan 12, 2015
In this study, we report the synthesis of a nanoscaled drug delivery system, which is composed of... 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...
Comptes rendus des séances de la Société de biologie et de ses filiales, 1976
The effects of cis-dichloro-diammino-platinum(II) (cis-Pt) bound to DNA have been compared to tho... 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.
Journal of Biomedical Materials Research Part A, 2019
Stereolithography (SLA) is an interesting manufacturing technology to overcome limitations of com... more Stereolithography (SLA) is an interesting manufacturing technology to overcome limitations of commercially available particulated biomaterials dedicated to intra-oral bone regeneration applications. The purpose of this study was to evaluate the in vitro and in vivo biocompatibility and osteoinductive properties of two CaP-based scaffolds manufactured by SLA 3D printing. Pellets and macro-porous scaffolds were manufactured in pure hydroxyapatite (HA) and in biphasic CaP (HA:60-TCP:40). Physicochemical characterization was performed using Micro X-ray Fluorescence (µXRF), Scanning Electron Microscopy (SEM), optical interferometry and microtomography (µCT) analyses. Osteoblast-like MG-63 cells were used to evaluate the biocompatibility of the pellets in vitro with MTS assay and the cell morphology and growth characterized by SEM and DAPI-actin staining showed similar early behavior. For in vivo biocompatibility, newly formed bone and biodegradability of the experimental scaffolds were evaluated in a subperiosteal cranial rat model using µCT and descriptive histology. The histological analysis has not indicated evidences of inflammation but highlighted close contacts between newly formed bone and the experimental biomaterials revealing an excellent scaffold osseointegration. This study emphasizes the relevance of SLA 3D printing of CaP-based biomaterials for intra-oral bone regeneration even if manufacturing accuracy has to be improved and further experiments using biomimetic scaffolds should be conducted.
Advanced Healthcare Materials, 2018
Dental Materials, 2013
Infiltration of cracks in glass with resins is a widespread concept in glass industry and is used... more Infiltration of cracks in glass with resins is a widespread concept in glass industry and is used successfully, for example, to reinforce cracked automotive windshields. This study had the purpose to evaluate the potential of a low-viscosity resin to infiltrate surface cracks in glass and feldspathic ceramic substrates and its effects on flexural strength as a potential prophylactic measure for contactinduced damage. Methods and materials: Discs (d = 12.5 mm and 1.2 mm in thickness) were produced using a glass-ceramic powder material (VM9, Vita Zahnfabrik) by condensation and sintering. The sintered discs were reduced to the final thickness by grinding with a diamond wheel and subsequently mirror polished (up to 4000 SiC paper Grit) on the side subjected to tension. Sodalime glass discs (d = 15 mm and 1.9 mm in thickness; Schott, Germany) were used for comparison. A Vickers indent (Zwick, Germany) was produced on the tensile side of the discs (1 kg during 15 s for VM9 and 500 g during 15 s for glass), which was subsequently coated with an experimental photo-cured lowviscosity resin (DMG, Germany). After 24 h of water storage, the discs were tested in flexure using the piston-on-three-balls setup. Weibull parameters m and sigma0 were calculated (n = 15 for VM9 and n = 10 for glass) and mathematically corrected according to the n number. The infiltration depth into the Vickers indent was measured in samples infiltrated with a fluorescent dyed-infiltrant using a confocal laser scanning microscope (TCS SL, Leica, Germany). Results: Shape and scale parameters for the Glass samples were as follows: m = 7.0 and sigma0 = 335.9 MPa for polished; m = 5.9 and sigma0 = 106.8 MPa for indented; m = 8.2 and sigma0 = 223.2 MPa for infiltrated. Shape and scale parameters for the Ceramic VM9 samples were as follows m = 10.3 and sigma0 = 101.2 MPa for polished; m = 11.4 and sigma0 = 63.52 MPa for indented; m = 5.1 and sigma0 = 83.9 MPa for infiltrated. The increase in sigma0 after infiltration was significant at a 95% level for both glass and ceramic. Infiltration depth in glass samples were recorded up to 18 m in depth, while in ceramis the infiltration depth was limited to the 2-4 m subsurface zone. Conclusion: As in glass, the infiltration of surface cracks with low-viscosity resin infiltrants is able to strengthen veneering ceramics and potentially prevent chipping events. The infiltration depth in ceramics is limited but does not seem to hinder its reinforcing effect.
Additional file 2: Table S2. The 121 proteins found as most discriminant in the DH versus DI vers... 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...
TD-GCxGC-HRTOFMS in biological applications Efficient trapping, separation, and identification of... more TD-GCxGC-HRTOFMS in biological applications Efficient trapping, separation, and identification of volatile organic compounds (VOCs) produced during complex biological processes require the use of multi-dimensional techniques such as TD-GCxGC-(HR)TOFMS. We currently use it to create large matrices of data that are further processed to statistically differentiate between classes of samples in several medical and forensic applications.
Human exhaled breath contains several hundreds of volatile organic compounds (VOCs) [1] that can ... 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 ...
INTRODUCTION: Sessile serrated adenoma/polyp (SSA/p) is a precancerous lesion, mostly located in ... 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
Introduction and objectives: Colorectal cancer (CRC) is the second most frequent cancer in women ... 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
Clinical proteomics, 2017
Despite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, t... 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...
Nanomaterials
Magnetic nanoparticles (MNPs) of magnetite (Fe3O4) were prepared using a polystyrene-graft-poly(2... 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...
Macromolecular bioscience, Jan 15, 2017
Polydimethylsiloxane (PDMS) constitutes an interesting material for a variety of biomedical appli... 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...
Dental Materials, 2016
Polymer-infiltrated-ceramic-network (PICN) materials constitute an innovative class of CAD-CAM ma... 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.
European Respiratory Journal, 2015
Archives of environmental contamination and toxicology, Jan 12, 2015
Methylmercury (MeHg) is highly immunotoxic and can alter the health status of the harbour seal, P... 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...
Small (Weinheim an der Bergstrasse, Germany), Jan 12, 2015
In this study, we report the synthesis of a nanoscaled drug delivery system, which is composed of... 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...