Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 41
Filter
1.
Chemosphere ; 350: 141062, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38159734

ABSTRACT

It is now widely recognized that the sampling rate of Polar Organic Chemical Integrative Samplers (POCIS) is significantly affected by flow velocity, which can cause a consequent bias when determining time-weighted average concentrations (TWAC). We already observed the desorption of deisopropylatrazine (DIA) over time when added to the receiving phase of a POCIS. This desorption rate was particularly influenced by flow velocity, in an agitated water environment in situ. In the method presented here, we calibrated 30 pesticides under controlled laboratory conditions, varying the flow velocity over four levels. We simultaneously studied the desorption rate of DIA-d5 (a deuterated form of DIA) over time. An empirical model based on a power law involving flow velocity was used to process the information from the accumulation kinetics of the compounds of interest and elimination of DIA-d5. This type of model makes it possible to consider the effect of this crucial factor on exchange kinetics, and then to obtain more accurate TWACs with reduced bias and more acceptable dispersion of results.


Subject(s)
Pesticides , Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Environmental Monitoring/methods , Pesticides/analysis , Organic Chemicals/chemistry , Calibration
3.
J Agric Food Chem ; 2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36749916

ABSTRACT

This paper presents a multi-step methodology to identify relationships between integrative pesticide quantifications and land uses on a given watershed of the Adour-Garonne Basin (Southwestern France). In fact, a large amount of pesticide concentration data was collected from 51 sites located in the Adour-Garonne Basin for a 1 year monitoring period in 2016. The sampling devices used here were polar organic chemical integrative samplers (POCIS), which provided time-weighted average concentration estimates. For each study site, its associated watershed and land cover distribution were determined using Corine Land Cover 2012 (CLC 2012) and Geographic Information System (GIS). The large-scale data were analyzed using multivariate statistical analyses, such as hierarchical cluster analysis (HCA) and principal component analysis (PCA). HCA grouped the 51 sites into five clusters with similar primary land uses. Next, the integrated pesticide concentration and land use distribution data sets were analyzed in a PCA. The key variables responsible for discriminating the sample sites showed distribution patterns consistent with specific land uses. To confirm these observations, pesticide fingerprints from sites with contrasting land uses were compared using a waffle method. The overall multivariate approach allowed for the identification of contamination sources related to their likely initial use, at the watershed level, that could be useful for preventing or containing pesticide pollution beyond simply acting on areas at risk.

4.
Sci Rep ; 12(1): 15985, 2022 09 26.
Article in English | MEDLINE | ID: mdl-36163442

ABSTRACT

Alizarin detection in fish fins is extensively employed because it is easy to use. However, in eels, the eelGFP fluorescent protein may impede the detection of the fluorescent markers in the eel tissues. The study tests the effectiveness of three of the most up-to-date alizarin-detecting technologies on the living body and fins of European glass eels (Anguilla anguilla L.). The findings demonstrated that the control group had a high autofluorescence at alizarin and eelGFP maxima bands. With fluorescence reflectance imaging (FRI), the eel living body autofluorescence impeded the detection of the marked eels. In contrast with experimental excitation-emission-matrix (EEM) fluorescence analyses, 99% of the marked eels were correctly assigned to their group from fluorescence analyses of their fin cellular contents. With epifluorometry (EPI), 100% of the marked eels were detected with the caudal fin tips when excited at 450-490 nm wavelengths due to a weaker autofluorescence signal. EEM and FRI assays unveiled an average fluorescence quenching 60% and 44% of the marked group respectively, in the alizarin and eelGFP maxima bands. The fluorescence quenching observed is discussed. Results will benefit experimental design by examining autofluorescence effects on mark detection and the development of non-invasive detection methods in this critically endangered species.


Subject(s)
Anguilla , Anguilla/metabolism , Animals , Anthraquinones/metabolism , Coloring Agents/metabolism
6.
Science ; 375(6582): eabm4459, 2022 02 18.
Article in English | MEDLINE | ID: mdl-35175798

ABSTRACT

The blood-brain barrier (BBB) protects the central nervous system (CNS) from harmful blood-borne factors. Although BBB dysfunction is a hallmark of several neurological disorders, therapies to restore BBB function are lacking. An attractive strategy is to repurpose developmental BBB regulators, such as Wnt7a, into BBB-protective agents. However, safe therapeutic use of Wnt ligands is complicated by their pleiotropic Frizzled signaling activities. Taking advantage of the Wnt7a/b-specific Gpr124/Reck co-receptor complex, we genetically engineered Wnt7a ligands into BBB-specific Wnt activators. In a "hit-and-run" adeno-associated virus-assisted CNS gene delivery setting, these new Gpr124/Reck-specific agonists protected BBB function, thereby mitigating glioblastoma expansion and ischemic stroke infarction. This work reveals that the signaling specificity of Wnt ligands is adjustable and defines a modality to treat CNS disorders by normalizing the BBB.


Subject(s)
Blood-Brain Barrier/physiology , GPI-Linked Proteins/agonists , Glioblastoma/therapy , Receptors, G-Protein-Coupled/agonists , Stroke/therapy , Wnt Proteins/genetics , Wnt Signaling Pathway , Animals , Brain/metabolism , Endothelial Cells/metabolism , Frizzled Receptors/metabolism , Glioblastoma/metabolism , Ligands , Mice , Mice, Inbred C57BL , Mutagenesis , Nervous System/embryology , Protein Engineering , Proto-Oncogene Proteins/chemistry , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Stroke/metabolism , Wnt Proteins/chemistry , Wnt Proteins/metabolism , Xenopus laevis , Zebrafish
7.
Environ Sci Pollut Res Int ; 29(1): 40-50, 2022 Jan.
Article in English | MEDLINE | ID: mdl-30350144

ABSTRACT

In this lab-scale study, the POCIS capacity to integrate short contamination peaks of variable intensity and duration was evaluated. POCIS were immersed for 14 days in tanks filled with tap water and spiked at different concentrations with 12 pesticides of various polarities (log Kow = 1.1-4.7) and classes (herbicides, fungicides, and insecticides). Concentrations were kept relatively constant at 1 µg L-1 and 5 µg L-1, respectively, in two "background" exposure tanks. Three contamination peaks of increasing intensity and decreasing duration were simulated (10 µg L-1 for 24 h, 40 µg L-1 for 6 h, and 60 µg L-1 for 1 h). This lab-scale study demonstrated that ten moderately polar compounds (2 < log Kow < 4) showed a linear uptake, as observed in previous studies, while a non-linear model fits the data of the two most polar pesticides (log Kow < 2). Depending on chemical polarity, some compounds exhibited a "burst effect" or "lag effect" during the first 3 days of exposure. After 14 days of exposure, contamination peaks appeared integrated for seven compounds, showing the ability of POCIS to catch very short pollution events and to provide acceptable time-weighted average concentration estimates under laboratory-controlled conditions.


Subject(s)
Pesticides , Water Pollutants, Chemical , Environmental Monitoring , Laboratories , Organic Chemicals , Pesticides/analysis , Water Pollutants, Chemical/analysis
8.
Biomater Sci ; 9(22): 7575-7590, 2021 Nov 09.
Article in English | MEDLINE | ID: mdl-34665185

ABSTRACT

This work describes the preparation, characterization and functionalization with magnetic nanoparticles of a bone tissue-mimetic scaffold composed of collagen and hydroxyapatite obtained through a biomineralization process. Bone remodeling takes place over several weeks and the possibility to follow it in vivo in a quick and reliable way is still an outstanding issue. Therefore, this work aims to produce an implantable material that can be followed in vivo during bone regeneration by using the existing non-invasive imaging techniques (MRI). To this aim, suitably designed biocompatible SPIONs were linked to the hybrid scaffold using two different strategies, one involving naked SPIONs (nMNPs) and the other using coated and activated SPIONs (MNPs) exposing carboxylic acid functions allowing a covalent attachment between MNPs and collagen molecules. Physico-chemical characterization was carried out to investigate the morphology, crystallinity and stability of the functionalized materials followed by MRI analyses and evaluation of a radiotracer uptake ([99mTc]Tc-MDP). Cell proliferation assays in vitro were carried out to check the cytotoxicity and demonstrated no side effects due to the SPIONs. The achieved results demonstrated that the naked and coated SPIONs are more homogeneously distributed in the scaffold when incorporated during the synthesis process. This work demonstrated a suitable approach to develop a biomaterial for bone regeneration that allows the monitoring of the healing progress even for long-term follow-up studies.


Subject(s)
Bone Regeneration , Tissue Scaffolds , Bone and Bones/diagnostic imaging , Collagen , Durapatite
9.
Nanoscale ; 13(39): 16509-16524, 2021 Oct 14.
Article in English | MEDLINE | ID: mdl-34590110

ABSTRACT

The preparation of an efficient bimodal single probe for magnetic resonance (MRI) and optical imaging (OI) is reported. Paramagnetic properties have been obtained by the non-covalent encapsulation of the clinically used Gd3+ chelate (i.e., Gd-HP-DO3A) within silica nanoparticles through a water-in-oil microemulsion process. To ensure colloidal stability, the surface of the particles was modified by means of treatment using PEG-silane, and further functionalized photochemically using a diazirine linker bearing carboxylic functions. Optical properties were obtained by the covalent grafting of a near-infrared emitting probe (NIR) on the resulting surface. The confinement of Gd complexes within the permeable matrix resulted in a significant increase in longitudinal relaxivities (>500% at 20 MHz) in comparison with the relaxivities of free chelate, while the post-functionalization process of PEG with fluorescent compounds appeared promising for the derivatization procedure. Several physico-chemical properties attested to the efficient surface modification and confirmed covalent grafting. Preliminary imaging experiments complete this study and confirm the potential of the presented system for preclinical imaging experiments.


Subject(s)
Contrast Media , Silicon Dioxide , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Optical Imaging
10.
J Mater Chem B ; 9(25): 5055-5068, 2021 07 07.
Article in English | MEDLINE | ID: mdl-34132320

ABSTRACT

Bimodal sub-5 nm superparamagnetic iron oxide nanoparticles (SPIO-5) coated with polyethylene glycol of different chain lengths (i.e. PEG-800, -2000 and -5000) have been prepared and characterized. Fluorescence properties have been obtained by mean of the grafting of a near-infrared-emitting dye (NIR-dye) onto the surface of the oxide, thanks to the carboxylic acid functions introduced towards an organosilane coating. Such modification allowed us to follow in vivo their biodistribution and elimination pathways by T1-w and T2-w high-field magnetic resonance imaging (MRI), as well as by optical and optoacoustic imaging. Interestingly, it has been highlighted that for a given composition, the thickness of the coating strongly influences the pharmacokinetic properties of the administrated SPIO-5.


Subject(s)
Magnetic Iron Oxide Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Animals , Female , Mice , Mice, Hairless , Molecular Structure , Optical Imaging , Tissue Distribution
11.
Mol Imaging ; 2021: 6677847, 2021.
Article in English | MEDLINE | ID: mdl-33746630

ABSTRACT

Molecular imaging holds great promise in the noninvasive monitoring of several diseases with nanoparticles (NPs) being considered an efficient imaging tool for cancer, central nervous system, and heart- or bone-related diseases and for disorders of the mononuclear phagocytic system (MPS). In the present study, we used an iron-based nanoformulation, already established as an MRI/SPECT probe, as well as to load different biomolecules, to investigate its potential for nuclear planar and tomographic imaging of several target tissues following its distribution via different administration routes. Iron-doped hydroxyapatite NPs (FeHA) were radiolabeled with the single photon γ-emitting imaging agent [99mTc]TcMDP. Administration of the radioactive NPs was performed via the following four delivery methods: (1) standard intravenous (iv) tail vein, (2) iv retro-orbital injection, (3) intratracheal (it) instillation, and (4) intrarectal installation (pr). Real-time, live, fast dynamic screening studies were performed on a dedicated bench top, mouse-sized, planar SPECT system from t = 0 to 1 hour postinjection (p.i.), and consequently, tomographic SPECT/CT imaging was performed, for up to 24 hours p.i. The administration routes that have been studied provide a wide range of possible target tissues, for various diseases. Studies can be optimized following this workflow, as it is possible to quickly assess more parameters in a small number of animals (injection route, dosage, and fasting conditions). Thus, such an imaging protocol combines the strengths of both dynamic planar and tomographic imaging, and by using iron-based NPs of high biocompatibility along with the appropriate administration route, a potential diagnostic or therapeutic effect could be attained.


Subject(s)
Nanoparticles , Animals , Magnetic Iron Oxide Nanoparticles , Mice , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Workflow
12.
Inorg Chem ; 60(6): 3604-3619, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33625836

ABSTRACT

Magnetic resonance imaging (MRI) has a leading place in medicine as an imaging tool of high resolution for anatomical studies and diagnosis of diseases, in particular for soft tissues that cannot be accessible by other modalities. Many research works are thus focused on improving the images obtained with MRI. This technique has indeed poor sensitivity, which can be compensated by using a contrast agent (CA). Today, the clinically approved CAs on market are solely based on gadolinium complexes that may induce nephrogenic systemic fibrosis for patients with kidney failure, whereas more recent studies on healthy rats also showed Gd retention in the brain. Consequently, researchers try to elaborate other types of safer MRI CAs like manganese-based complexes. In this context, the synthesis of Mn2+ complexes of four 12-membered pyridine-containing macrocyclic ligands based on the pyclen core was accomplished and described herein. Then, the properties of these Mn(II) complexes were studied by two relaxometric methods, 17O NMR spectroscopy and 1H NMR dispersion profiles. The time of residence (τM) and the number of water molecules (q) present in the inner sphere of coordination were determined by these two experiments. The efficacy of the pyclen-based Mn(II) complexes as MRI CAs was evaluated by proton relaxometry at a magnetic field intensity of 1.41 T near those of most medical MRI scanners (1.5 T). Both the 17O NMR and the nuclear magnetic relaxation dispersion profiles indicated that the four hexadentate ligands prepared herein left one vacant coordination site to accommodate one water molecule, rapidly exchanging, in around 6 ns. Furthermore, it has been shown that the presence of an additional amide bond formed when the paramagnetic complex is conjugated to a molecule of interest does not alter the inner sphere of coordination of Mn, which remains monohydrated. These complexes exhibit r1 relaxivities, large enough to be used as clinical MRI CAs (1.7-3.4 mM-1·s-1, at 1.41 T and 37 °C).


Subject(s)
Azabicyclo Compounds/chemistry , Contrast Media/chemistry , Coordination Complexes/chemistry , Azabicyclo Compounds/chemical synthesis , Contrast Media/chemical synthesis , Coordination Complexes/chemical synthesis , Ligands , Magnetic Resonance Imaging , Manganese/chemistry , Oxygen Isotopes/chemistry , Proof of Concept Study , Proton Magnetic Resonance Spectroscopy , Water/chemistry
13.
Molecules ; 24(24)2019 Dec 17.
Article in English | MEDLINE | ID: mdl-31861222

ABSTRACT

The growing concern over the toxicity of Gd-based contrast agents used in magnetic resonance imaging (MRI) motivates the search for less toxic and more effective alternatives. Among these alternatives, iron-iron oxide (Fe@FeOx) core-shell architectures have been long recognized as promising MRI contrast agents while limited information on their engineering is available. Here we report the synthesis of 10 nm large Fe@FeOx nanoparticles, their coating with a 11 nm thick layer of dense silica and functionalization by 5 kDa PEG chains to improve their biocompatibility. The nanomaterials obtained have been characterized by a set of complementary techniques such as infra-red and nuclear magnetic resonance spectroscopies, transmission electron microscopy, dynamic light scattering and zetametry, and magnetometry. They display hydrodynamic diameters in the 100 nm range, zetapotential values around -30 mV, and magnetization values higher than the reference contrast agent RESOVIST®. They display no cytotoxicity against 1BR3G and HCT116 cell lines and no hemolytic activity against human red blood cells. Their nuclear magnetic relaxation dispersion (NMRD) profiles are typical for nanomaterials of this size and magnetization. They display high r2 relaxivity values and low r1 leading to enhanced r2/r1 ratios in comparison with RESOVIST®. All these data make them promising contrast agents to detect early stage tumors.


Subject(s)
Dextrans/chemistry , Ferric Compounds/chemistry , Iron/chemistry , Magnetic Resonance Imaging , Magnetite Nanoparticles/chemistry , Silicon Dioxide , Cell Line, Tumor , Coated Materials, Biocompatible , Humans , Magnetite Nanoparticles/ultrastructure , Models, Theoretical , Silicon Dioxide/chemistry , Spectroscopy, Fourier Transform Infrared
14.
Chem Biodivers ; 16(11): e1900322, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31544357

ABSTRACT

The synthesis of poly[N,N-bis(3-aminopropyl)glycine] (PAPGly) dendrons Gd-based contrast agents (GdCAs) via an orthogonal protection of the different functional groups and an activation/coupling strategy wherein a specific number of synthetic steps add a generation to the existing dendron has been described. The aim of this protocol is to build up two different generations of dendrons (G-0 or dendron's core, and G-1) with peripheral NH2 groups to conjugate a 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) derivative and afterwards to chelate with Gd3+ paramagnetic ions. These complexes, which have a well-defined molecular weight, are of relevance to MRI as an attempt to gain higher 1 H relaxivity by slowing down the rotation of molecule compared to monomeric Gd(III) complexes used as contrast agents and to increase the number of paramagnetic centers present in one molecular structure. From the study of their water 1 H longitudinal relaxation rate at different magnetic fields (NMRD, Nuclear Magnetic Relaxation Dispersion) and by evaluating the variable temperature 17 O-NMR data we determined the parameters characterizing the water exchange rate and the rotational correlation time of each complex, both affecting 1 H relaxivity. Furthermore, these two novel PAPGly GdCAs were objects of i) an in vivo study to determine their biodistributions in healthy C57 mice at several time points, and ii) the Dynamic Contrast-Enhanced MRI (DCE-MRI) approach to assess their contrast efficiency measured in the tumor region of C57BL/6 mice transplanted subcutaneously with B16-F10 melanoma cells. The aim of the comparison of these two dendrons GdCAs, having different molecular weights (MW), is to understand how MW and relaxivity may influence the contrast enhancement capabilities in vivo at low magnetic field (1 T). Significant contrast enhancement was observed in several organs (vessel, spleen and liver), already at 5 min post-injection, for the investigated CAs. Moreover, these CAs induced a marked contrast enhancement in the tumor region, thanks to the enhanced permeability retention effect of those macromolecular structures.


Subject(s)
Contrast Media/chemistry , Gadolinium/chemistry , Melanoma/chemistry , Organometallic Compounds/chemistry , Animals , Contrast Media/chemical synthesis , Contrast Media/pharmacokinetics , Gadolinium/pharmacokinetics , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Melanoma/diagnostic imaging , Mice , Mice, Inbred C57BL , Molecular Structure , Neoplasms, Experimental/chemistry , Neoplasms, Experimental/diagnostic imaging , Organometallic Compounds/chemical synthesis , Organometallic Compounds/pharmacokinetics , Tissue Distribution
15.
Inorg Chem ; 58(19): 12798-12808, 2019 Oct 07.
Article in English | MEDLINE | ID: mdl-31496230

ABSTRACT

The inherent lack of sensitivity of MRI needs the development of new Gd contrast agents in order to extend the application of this technique to cellular imaging. For this purpose, two multimeric MR contrast agents obtained by peptidic coupling between an amido amine dendron and GdDOTAGA chelates (premetalation strategy, G1-4GdDOTAGA) or DO3A derivatives which then were postmetalated (G1-4GdDO3A) have been prepared. By comparison to the monomers, an increase of longitudinal relaxivity has been observed for both structures. Especially for G1-4GdDO3A, a marked increase is observed between 20 and 60 MHz. This structure differs from G1-4GdDOTAGA by an increased rigidity due to the aromatic linker between each chelate and the organic framework. This has the effect of limiting local rotational movements, which has a positive impact on relaxivity.

16.
Sci Total Environ ; 651(Pt 1): 684-695, 2019 Feb 15.
Article in English | MEDLINE | ID: mdl-30245424

ABSTRACT

Fifty-one monitoring stations from the Water Framework Directive network (2000/60/CE) were selected in the Adour-Garonne basin (117,650 km2, SW France). These stations were characterized by a diversity of land use, implying different water pesticide contamination profiles. In each, Polar Organic Chemical Integrative Sampler (POCIS) deployment (14 days) and grab water samples (1 per period) were performed 6 times in 2016 in order to obtain contamination levels (29 pesticides monitored). The large amount of data collected during this 1-year monitoring required specific graphical and map processing to compare the information provided by POCIS and grab samples. Graphical projections demonstrated that with POCIS the number of quantified pesticides and the quantification frequencies were higher than with grab samples. Additionally, projections showed that POCIS provided better temporal representativeness of monthly contamination levels. Indeed, the POCIS data showed seasonal trends which were directly linked with the use of each pesticide (application period) and the land use of each sampling site, that was not visible with the grab samples data. Map projections of the measured concentrations, using a common scale for the two sampling strategies, clearly showed the strengths of the POCIS deployment and the link between measured contamination levels, quantified pesticides and land use. Finally, this study shows that the combination of grab sample data (magnitude of contamination peaks) and POCIS data (average concentration over a given period) provided more complete and reliable knowledge of the contamination levels in the Basin than either method alone.

17.
Sci Total Environ ; 651(Pt 1): 1219-1225, 2019 Feb 15.
Article in English | MEDLINE | ID: mdl-30360253

ABSTRACT

Biofilms are excellent bioindicators for water quality assessment because of their ability to integrate contamination, and their position at the base of the trophic chain in aquatic environments. Pesticides are ubiquitous in aquatic environments and can constantly interact with aquatic organisms, including those that make up biofilms, at fluctuating concentrations. The aim of this study was to describe pesticide behaviour in biofilms. Previous research highlighted that contaminant sorption was not always linear, but no study considered organic bioaccumulation isotherms and toxic impacts to biofilms concurrently. In order to characterize pesticide sorption isotherms in biofilms and the mechanisms involved in the uptake process, we simultaneously assessed bioaccumulation and toxic impact of diuron (a photosynthesis inhibiting herbicide) at the water-biofilm concentrations equilibrium. Mature biofilms grown on glass slides during one month were subsequently exposed in channels to 7 increasing concentrations of diuron from 1 to 500 µg·L-1, plus a control condition, for 2 h with a flow velocity of 2 cm·s-1. Then, a Langmuir isotherm equation was fitted to the bioaccumulation data, and an Emax model to toxic impact results. This study established that diuron bioaccumulation in biofilm is nonlinear, and allowed to calculate the Langmuir constant and maximal concentration of diuron potentially accumulated in biofilm (up to 17,771 µg·g-1). In turn, we found that photosynthetic inhibition followed classical dose-response patterns with diuron concentrations in the water, and that EC50 could be established at 75 µg·L-1. A continuous diffusion phenomenon was thus demonstrated but it was not linearly correlated to bioaccumulation, highlighting complex uptake mechanisms operating within the matrix. The coupling of toxicokinetic and toxicodynamic approaches provided original information about pesticide behaviour and impact in periphytic microorganisms.


Subject(s)
Bacterial Physiological Phenomena , Biofilms , Diuron/metabolism , Water Pollutants, Chemical/metabolism , Adsorption , Fresh Water , Herbicides/metabolism
18.
Int Orthop ; 42(7): 1755-1767, 2018 07.
Article in English | MEDLINE | ID: mdl-29882123

ABSTRACT

INTRODUCTION: Human spontaneous osteonecrosis of the knee (SPONK) is still challenging as the current treatments do not allow the production of hyaline cartilage tissue. The aim of the present study was to explore the therapeutic potential of cartilage regeneration using a new biphasic scaffold (type I collagen/hydroxyapatite) previously loaded or not with concentrated bone marrow cells. MATERIAL AND METHODS: Female rabbits were operated of one knee to create articular lesions of the trochlea (three holes of 4 × 4mm). The holes were left empty in the control group or were filled with the scaffold alone or the scaffold previously loaded with concentrated bone marrow cells. After two months, rabbits were sacrificed and the structure of the newly formed tissues were evaluated by macroscopic, MRI, and immunohistochemistry analyses. RESULTS: Macroscopic and MRI evaluation of the knees did not show differences between the three groups (p > 0.05). However, histological analysis demonstrated that a higher O'Driscoll score was obtained in the two groups treated with the scaffold, as compared to the control group (p < 0.05). The number of cells in treated area was higher in scaffold groups compared to the control group (p < 0.05). There was no difference for intensity of collagen type II between the groups (p > 0.05) but subchondral bone repair was significantly thicker in scaffold-treated groups than in the control group (1 mm for the control group vs 2.1 and 2.6 mm for scaffold groups). Furthermore, we observed that scaffolds previously loaded with concentrated bone marrow were more reabsorbed (p < 0.05). CONCLUSION: The use of a biphasic scaffold previously loaded with concentrated bone marrow significantly improves cartilage lesion healing.


Subject(s)
Cartilage, Articular/surgery , Knee Joint/physiopathology , Mesenchymal Stem Cell Transplantation/methods , Tissue Scaffolds , Animals , Bone Regeneration/physiology , Cartilage, Articular/metabolism , Cartilage, Articular/physiopathology , Collagen Type I/pharmacology , Collagen Type II/metabolism , Durapatite/pharmacology , Female , Immunohistochemistry , Knee Joint/metabolism , Knee Joint/surgery , Magnetic Resonance Imaging , Rabbits
19.
Oncogene ; 37(9): 1237-1250, 2018 03.
Article in English | MEDLINE | ID: mdl-29242606

ABSTRACT

Cancer research is increasingly dependent of patient-derived xenograft model (PDX). However, a major point of concern regarding the PDX model remains the replacement of the human stroma with murine counterpart. In the present work we aimed at clarifying the significance of the human-to-murine stromal replacement for the fidelity of colorectal cancer (CRC) and liver metastasis (CRC-LM) PDX model. We have conducted a comparative metabolic analysis between 6 patient tumors and corresponding PDX across 4 generations. Metabolic signatures of cancer cells and stroma were measured separately by MALDI-imaging, while metabolite changes in entire tumors were quantified using mass spectrometry approach. Measurement of glucose metabolism was also conducted in vivo using [18F]-fluorodeoxyglucose (FDG) and positron emission tomography (PET). In CRC/CRC-LM PDX model, human stroma was entirely replaced at the second generation. Despite this change, MALDI-imaging demonstrated that the metabolic profiles of both stromal and cancer cells remained stable for at least four generations in comparison to the original patient material. On the tumor level, profiles of 86 water-soluble metabolites as well as 93 lipid mediators underlined the functional stability of the PDX model. In vivo PET measurement of glucose uptake (reflecting tumor glucose metabolism) supported the ex vivo observations. Our data show for the first time that CRC/CRC-LM PDX model maintains the functional stability at the metabolic level despite the early replacement of the human stroma by murine cells. The findings demonstrate that human cancer cells actively educate murine stromal cells during PDX development to adopt the human-like phenotype.


Subject(s)
Cancer-Associated Fibroblasts/metabolism , Colorectal Neoplasms/metabolism , Disease Models, Animal , Glucose/metabolism , Liver Neoplasms/metabolism , Metabolome , Stromal Cells/metabolism , Animals , Cancer-Associated Fibroblasts/pathology , Cohort Studies , Colorectal Neoplasms/pathology , Female , Humans , Liver Neoplasms/secondary , Male , Mice , Mice, Inbred NOD , Mice, SCID , Phenotype , Stromal Cells/pathology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
20.
Int J Oncol ; 51(3): 760-770, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28677745

ABSTRACT

Fine-needle aspiration (FNA) is the most commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. Based on multifunctionality of the endogenous galectin-1, we aimed to assess its status for early diagnosis of thyroid cancer. Immunohistochemistry for galectin-1 and -3 was performed on a clinical series of 69 cases of thyroid lesions. Galectin-1 expression was further examined in two additional tissue microarrays (TMA) composed of 66 follicular adenomas and 66 papillary carcinomas in comparison to galectin-3 and cytokeratin-19 (CK19). In addition, a knockdown of galectin-1 in papillary (TPC-1) and anaplastic (8505C) thyroid cancer cell lines was achieved by lentiviral transduction for in vitro experiments. A murine orthotopic thyroid cancer model was used to investigate tumor growth and metastatic ability. Immunohistochemical analyses of galectin-1 and -3 in the series of 69 cases of thyroid lesions revealed that galectin-1 was completely absent in the epithelial compartment of all benign thyroid lesions. Levels of both galectins significantly increased in the cytoplasmic compartment of malignant thyroid cells. Galectin-1 expression in the TMA yielded an excellent specificity (97%), while galectin-3 and CK19 presented a higher sensitivity (>97%) in discriminating benign from malignant thyroid lesions. In vitro experiments revealed that migration was negatively affected in TPC-1 galectin-1 knockdown (KD) cells, and that proliferation and invasion capacity of 8505C cells decreased after galectin-1 KD. Moreover, an orthotopic mouse model displayed a lower rate of tumor development with galectin-1 KD thyroid anaplastic cancer cells than in the control. Our findings support the introduction of galectin-1 as a reliable diagnostic marker for thyroid carcinomas. Its involvement in cell proliferation, migration, invasion and tumor growth also intimate functional involvement of galectin-1 in the progression of thyroid carcinoma, suggesting its potential as a therapeutic target.


Subject(s)
Adenoma/diagnosis , Carcinoma, Papillary/diagnosis , Galectin 1/genetics , Neoplasms/diagnosis , Thyroid Neoplasms/diagnosis , Adenoma/genetics , Adenoma/pathology , Adult , Animals , Biomarkers, Tumor/genetics , Biopsy, Fine-Needle , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Cell Line, Tumor , Diagnosis, Differential , Disease Progression , Early Detection of Cancer , Female , Galectin 3/genetics , Gene Expression Regulation, Neoplastic , Humans , Keratin-19/genetics , Male , Mice , Middle Aged , Neoplasms/genetics , Neoplasms/pathology , Thyroid Cancer, Papillary , Thyroid Gland/pathology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Xenograft Model Antitumor Assays
SELECTION OF CITATIONS
SEARCH DETAIL
...