L'adénocarcinome canalaire pancréatique (ACP) est le type de cancer le plus fréquent touchant le pancréas exocrine. Il est caractérisé par un phénotype métastatique et chimio-résistant pour lequel il n'existe aucun marqueur diagnostic, ni de traitement efficace. Les projections pour 2030 montrent que ce cancer pourrait devenir la deuxième cause de mortalité. Il y a un besoin urgent de mieux comprendre comment progresse l'ACP. La dissémination métastatique dépend de plusieurs mécanismes cellulaires dont l'invasion du stroma par les cellules cancéreuses. Nous avons montré récemment que le canal transmembranaire TRPM7 est surexprimé dans l'ACP et régule la migration cellulaire. Le but de ce travail est d'évaluer le rôle de TRPM7 dans l'invasion et de mettre en évidence les mécanismes moléculaires impliqués dans les cellules cancéreuses d'ACP et également dans les cellules non-cancéreuses. TRPM7 régule l'invasion basale dans les cellules cancéreuses pancréatiques via l'entrée constitutive de magnésium et la régulation de la sécrétion de MMP-2, uPA et Hsp90α. TRPM7 interagit directement avec Hsp90α et sa kinase participe à la phosphorylation des résidus sérines. De plus, l'expression de TRPM7 dans les métastases est corrélée à celle dans la tumeur primaire. Dans les cellules non cancéreuses, TRPM7 n'est pas impliqué dans l'invasion basale mais sa surexpression (par transfections de plasmides ou induite par une exposition au cadmium, un polluant probablement carcinogène) entraine la transformation des cellules vers un phénotype invasif. TRPM7 est impliqué dans la modification de l'homéostasie magnésique majoritairement, dans la modification de morphologie cellulaire et la transition épithélio-mésenchymateuse. Pour conclure, nos résultats apportent de nouvelles connaissances sur le rôle TRPM7 en tant que régulateur de l'invasion basale dans l'ACP et initiateur dans l'acquisition du phénotype invasif des cellules non-cancéreuses / Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. It is characterized by a metastatic and chemoresistant phenotype for which there is no diagnostic marker or effective treatment. It may become the second leading cause of cancer-related death by 2030. There is an urgent need to better understand PDAC progression. Metastatic spread depends on several cellular mechanisms, including the invasion of stroma by cancer cells. We have recently shown that the transmembrane channel TRPM7 (Transient Receptor Potential Melastatin related 7) is overexpressed in PDAC and regulates cell migration. The aim of this work is to evaluate TRPM7 implication in invasion and to highlight the molecular mechanisms in PDAC and non-cancer pancreatic cells. TRPM7 channel regulates basal cell invasion, MMP-2, uPA and Hsp90α secretion in human pancreatic cancer cell lines through constitutive magnesium entry. TRPM7 interacts directly with Hsp90α and it contributes to the phosphorylation of serine residues. Magnesium could participate by activating TRPM7 kinase or by modifying Hsp90α conformation. Moreover, TRPM7 expression in metastatic lymph nodes is correlated to its expressionin primary tumor. In non-cancer cells, TRPM7 is not implicated in basal cell invasion but its overexpression (through plasmid orchronic treatment with cadmium, known as probable carcinogen pollutant) induces invasive phenotype transition. TRPM7 is mainly involved in magnesium homeostasis variation, in cellular morphology modification and mesenchymal transition. In conclusion, our results provide new insights into the key role of TRPM7 in both regulation of basal cell invasion in ACP and initiation of invasive phenotype acquisition in non-cancer epithelial cells

Thin layer deposits of cadmium sulfide (CdS) for photovoltaic purposes can be made by cathodic deposition from a nonaqueous solution. There were numerous parameters that were controlled in this electro-deposition. Several of these parameters, including temperature, current density, reactant concentrations and impurity level doping, were studied and optimized. The mechanism of this deposition process is not fully understood, mainly due to the complex chemistry of sulfur. Part of this complexity is the presence of S(,6) and S(,7) along with the major component of S(,8) in sulfur solutions. At 90(DEGREES), these minor species constitute 2% of the total sulfur. Electrochemical studies were made on these species with gold, porous carbon and CdS single crystal electrodes. These showed that S(,6) and S(,7) are electrochemically more reactive than S(,8). Furthermore, they may be the main reacting species in CdS formation, even though they are present at such low levels. Adsorption of all species of sulfur was noted at room temperature and this adsorption may be causing excess sulfur to be incorporated into the CdS deposits. There has been an important development in the measurement of impurity levels of semiconductors called electrochemical photocapacitance spectroscopy. It can be used to analyze impurity levels in a wide variety of semiconductors by shining subband gap light on the semiconductor in a photoelectrochemical cell while measuring the capacitance on the surface. Interpretation of these spectra has previously been qualitative. A quantitative model was developed here along with a computer program utilizing this interpretation. Several types of semiconductors were analyzed by this technique, including these CdS deposits which showed impurity levels that may be due to excess sulfur. Other types of compound semiconductors can also be made by this cathodic deposition. It is hoped that the information gathered here can be used to improve these other semiconductor depositions as well as CdS.

Probing the surface chemistry of thiol ligand binding to cadmium chalcogenide nanoparticles is important to clarify factors involved in quantum dot stability and surface functionalisation. This research is a spectroscopic investigation aimed at gaining a better understanding of the interaction/bonding of various ligands to CdS, with respect to the use of CdS in biological imaging. The findings of this research are important to the more general field of cadmium chalcogenide materials as biological imaging agents. Deposited CdS nanoparticle films were used in this work as model quantum dot surfaces for ligand adsorption studies. The adsorption of the monothiol-containing ligands, mercaptoacetic acid, mercaptopropionic acid, and mercaptoethanol, to CdS thin films were studied in situ using attenuated total reflectance infrared spectroscopy. The absence of an S-H stretch absorption for the adsorbed species showed that adsorption occurred via the deprotonated thiol group. The adsorption of the dithiol-containing ligands α-lipoic acid, dihydrolipoic acid, and dithiothreitol to CdS nanoparticle films was investigated. The adsorption of dihydrolipoic acid and dithiothreitol was found to occur via both thiol functional groups and an additional interaction between the carboxylate group and the CdS surface. The adsorption of α-lipoic acid to CdS in the presence of light proceeded with photo-oxidation of the CdS surface and reductive cleavage of the disulfide bond of α-lipoic acid to produce some adsorbed dihydrolipoic acid and thiosulfate. The adsorption of α-lipoic acid to CdS in the absence of visible light showed no photo-oxidation, and suggested adsorption occurred via retention of the disulfide bond. The kinetics of adsorption and desorption of oxalic acid on deposited anatase TiO₂ films were studied to investigate the feasibility of extracting molecular information from attenuated total reflectance infrared spectroscopic kinetic data of ligand processes on deposited particle films. Oxalic acid adsorbed on anatase TiO₂ is a well-studied example and is reported to result in three different surface species. The profile of the desorption data indicated contributions from three different components. Different component contributions were unable to be obtained from the adsorption data which is attributed to adsorption occurring much faster than desorption and thus being relatively insensitive to the presence of different adsorbed species. The kinetics of adsorption and desorption of mercaptoacetic acid on CdS were investigated. The desorption data profile indicated the presence of two adsorbed species with different affinities for the CdS surface, the exact chemical nature of which can only be speculated upon given the absence of distinguishing IR spectral features. Ligand exchange reactions at the surface of oleate and trioctylphosphine oxide-capped CdS quantum dot films were investigated. Adsorbed oleate was coordinated to the CdS in a chelating bidentate manner through the carboxylate functional group, while adsorbed trioctylphosphine oxide was coordinated though the P=O functional group. Ligand exchange reactions on the oleate and trioctylphosphine-capped CdS films were studied, and exchange with monothiol-containing ligands was observed only at solution pH where the exchanging ligand was uncharged. Avidin-biotin bioconjugation reactions were carried out on CdS films, which involved the sequential adsorption of mercaptoacetic acid, the protein avidin, and the subsequent binding of the ligand biotin. The spectral data suggested that avidin underwent a conformational change upon adsorption to the CdS surface. This conformation appeared to be perturbed again upon binding of biotin, and it is speculated that the conformation partially reverted back to the native solution conformation.

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Introduction. Le métabolisme osseux se résume à l'action des ostéoclastes résorbant le tissu osseux et des ostéoblastes formant l'os. Des études épidémiologiques associent l'exposition au Cd à un risque accru de développer l'ostéoporose. En plus des effets néphrotoxiques perturbant le métabolisme de la vitamine D et altérant indirectement le métabolisme osseux, le Cd semble exercer une toxicité sur les cellules osseuses, altérant donc le squelette par des mécanismes directs. Objectifs. Les buts de cette étude étaient de caractériser la cytotoxicité et l'accumulation cellulaire du Cd dans un modèle in vitro de différenciation ostéoblastique, ainsi que de comparer la sensibilité au Cd de plusieurs lignées cellulaires au phénotype ostéoblastique. Méthodologie. Des essais de cytotoxicité et d'accumulation cellulaire ont été effectués sur la lignée ostéoblastique murine MC3T3-E1, ainsi que sur les lignées ostéoblastiques humaines MG 63 et U2 OS. Un modèle de différenciation a été obtenu en traitant les MC3T3 avec de l'acide ascorbique et du glycérol-2-phosphate. Une approche pharmacologique a été utilisée afin de cerner les voies d'entrée du Cd dans ces cellules. L'expression des canaux membranaires de type TRPM et TRPV, des candidats comme voie d'entrée du Cd dans les ostéoblastes, a été vérifiée dans les 3 lignées par RT-PCR. Résultats. Sur 3 minutes, les cellules MC3T3 accumulent plus de Cd que les cellules MG 63 et D2 OS. Par contre, l'accumulation sur 24h est supérieure dans les lignées humaines. La hausse du Ca extracellulaire diminue la cytotoxicité et le transport du Cd dans les MC3T3 immatures et les MG 63; le Mg a un impact semblable sur les 3 lignées. Un modulateur de canaux TRP, le 2-APB, protège significativement les MG 63 et les U2 OS contre le Cd, surtout en absence de Mg, mais demeure sans effet dans les MC3T3. La différenciation des MC3T3-E1 diminue la cytotoxicité et le transport du Cd. Conclusion. La maturité ostéoblastique est un facteur important dans la sensibilité de ces cellules au Cd. L'effet différent du Ca et du Mg sur les 3 lignées suggère des mécanismes de transport calciques et magnésiques distincts perméables au Cd. Le 2-APB offrant une protection efficace dans les lignées humaines, certains canaux de la classe des TRPM sont soupçonnés d'être des voies d'entrée importantes pour le Cd dans les ostéoblastes humains, ainsi que des TRPV dans les ostéoblastes murins. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Ostéoblaste, Cadmium, Cytotoxicité, Accumulation cellulaire, Calcium, Magnésium.

We have successfully synthesized the zinc and cadmium complexes containing bis(3-trimethylsilyl-2-thiophenyl)phenylphosphine (SiPS2): [NEt4][(SiPS2)Cd(SC6H5)] (1) , [NEt4][(SiPS2)Cd(SC6H11)] (2) , [NEt4][(SiPS2)Cd(SCH2C6H5)] (3) , [NEt4][(SiPS2)Zn(SC6H5)] (4) , [NEt4][(SiPS2)Zn(SC6H11)] (5) and [NEt4][(SiPS2)Zn(SCH2C6H5)] (6) , and characterized them using 31P NMR and mass spectrum.1 and 2 were also characterized by X-ray diffraction methods. In the attemprs to get crystals of 4 and 6, we got the oxidized dimer complex 4* and 6* instead. In these complexes the two oxygen atoms of the oxidized ligands and the sulfur atom of the monodentate thiolate ligand bridge both the cadmium centers. Zinc complexes exhibit distorted tetrahedral structure. However, the cadmium ion tends to form five coordination oxidation dimeric complexes.

Thèse de docteur-ingénieur : Sciences et Techniques du déchet : Villeurbanne, INSA : 2001. / Thèse : 2001ISAL0071. Titre provenant de l'écran-titre. Bibliogr. p.205-225.

Reproduction de : Thèse de 3e cycle : Physique du solide : Metz : 1973. / Titre provenant de l'écran-titre. Notes bibliogr.

Reproduction de : Thèse de doctorat : Toxicologie : Metz : 1978. / Titre provenant de l'écran-titre. Notes bibliographiques. Index.

Thesis (Ph. D.)--University of Hong Kong, 1988.