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Chaouki, Ghita. "Etude du rôle de la voie de signalisation eIF2αATF4 au cours des états inflammatoires, dans le cadre du stress mitochondrial et de l’anorexie associée à la pathologie." Electronic Thesis or Diss., Université Clermont Auvergne (2021-...), 2022. http://www.theses.fr/2022UCFAC109.
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La voie de signalisation eIF2α-ATF4 est activée dans les cellules en réponse à un large éventail de stress cellulaires. Son activation conduit à une inhibition de la synthèse protéique globale et la régulation de l’expression de gènes cibles du facteur de transcription ATF4. Cette voie est sollicitée en réponse au déficit en acides aminés indispensables, au stress mitochondrial, au stress du réticulum endoplasmique ou encore aux infections virales. Elle déclenche des mécanismes adaptatifs, à l’échelle cellulaire (tels que l’inhibition de la synthèse protéique et l’augmentation du niveau d’autophagie) et de l’organisme entier (comme la régulation du métabolisme, l’inflammation, l’immunité et la prise alimentaire). Les résultats précédents générés par notre laboratoire ainsi que les données de la littérature nous ont amenés à étudier le rôle de la signalisation eIF2α-ATF4 dans deux contextes différents. Dans une première partie, nous avons exploré le rôle de la signalisation eIF2α-ATF4 dans l’anorexie associée aux pathologies cataboliques inflammatoires (sepsis et cancer). Nous avons émis l’hypothèse que cette voie de signalisation pourrait contribuer à l’inhibition de prise alimentaire par une action directe au niveau central et/ou en stimulant l’expression de cytokines anorexigènes, dont GDF15, en périphérie (foie, intestin). Nous avons utilisé deux modèles expérimentaux reproduisant une anorexie associée à la pathologie chez la souris : un modèle d’inflammation systémique aigue de type sepsis (administration unique de lipopolysaccharide bactérien) et un modèle de souris porteuses d’une tumeur de cellules de carcinome de colon C26. Ces deux modèles ont été caractérisés en phase précoce de l’anorexie, par une inflammation aux niveaux périphérique et central (hypothalamus), une augmentation des niveaux circulants d’IL-6 et de GDF15, une profonde modification du métabolisme des acides aminés, et une activation de la voie de signalisation eIF2α-ATF4 dans l’hypothalamus et dans le foie. Ensuite, la réponse de modèles inductibles de perte de fonction d’ATF4 a été testée dans le modèle de sepsis. L’invalidation d’ATF4 au niveau du foie et de l’intestin n’a pas eu d’impact ni sur l’anorexie, ni sur l’induction de la production de GDF15. L’invalidation constitutive de GDF15 a également été sans effet sur l’inhibition de prise alimentaire induite par l’administration de LPS. Le rôle de la fonction ATF4 au niveau central n’a pas pu être testée et devra faire l’objet d’expérimentations futures. L’analyse des échantillons des souris invalidées pour la fonction d’ATF4 au niveau hépatique nous permettra d’évaluer son implication dans les réorientations du métabolisme des AA (transport, biosynthèse, autophagie). Dans le modèle de cancer C26, le passage du stade de pré-anorexie au stade de début d’anorexie a été associé à une activation de la voie signalisation eIF2αATF4 aux niveaux hépatique et hypothalamique, et une approche fonctionnelle pharmacologique sera prochainement mise en place à l’aide de l’ISRIB (ISR Inhibitor) pour étudier son implication dans la régulation de l’appétit et du métabolisme des AA (dans ce modèle les invalidations géniques ne sont pas possibles). Dans une deuxième partie, nous nous sommes intéressés au dysfonctionnement mitochondrial, qui représente une menace majeure pour l'homéostasie cellulaire, favorise l'apparition de nombreux troubles métaboliques et joue un rôle crucial dans la pathogenèse du sepsis. Compte-tenu du rôle joué par la voie de signalisation eIF2α-ATF4 dans la réponse adaptative au stress mitochondrial, nous avons cherché à savoir si un prétraitement activateur de cette voie pourrait être un moyen d'augmenter la résilience du pool mitochondrial lors d'événements stressants ultérieurs. (...)The eIF2α-ATF4 signaling pathway is activated in cells in response to a wide range of cellular stresses. Its activation leads to the inhibition of the global protein synthesis and the regulation of the transcription factor ATF4 target genes expression. This pathway is activated in response to essential amino acid deficiency, mitochondrial stress, endoplasmic reticulum stress or viral infections. Its activation triggers adaptive mechanisms, both at the cellular level (such as inhibition of protein synthesis and increased autophagy) and at the whole organism level (such as regulation of metabolism, inflammation, immunity and food intake). Previous results generated by our laboratory as well as data from the scientific literature led us to investigate the role of eIF2α-ATF4 signaling in two different contexts. Firstly, we explored the role of eIF2α-ATF4 signaling in anorexia associated with catabolic inflammatory pathologies (sepsis and cancer). We hypothesized that this signaling pathway could contribute to the inhibition of food intake by its direct action at the central level and/or by stimulating the expression of anorectic cytokines, including GDF15, in the periphery (liver, intestine). We used two experimental models reproducing pathology-associated anorexia in mice: a sepsis model of acute and systemic inflammation (single administration of bacterial lipopolysaccharide) and a model of mice carrying a C26 colon carcinoma cell tumor. Both models were characterized in the early phase of anorexia by inflammation at the peripheral and central (hypothalamus) levels, increased circulating levels of IL-6 and GDF15, profound alterations in amino acid metabolism, and activation of the eIF2αATF4 signaling pathway in the hypothalamus and liver. Afterwards, the response of inducible models of ATF4 loss-of-function was tested in the sepsis model. ATF4 knock-out in the liver and intestine had no impact on either anorexia or the induction of GDF15 production. Constitutive invalidation of GDF15 also had no effect on the inhibition of food intake induced by LPS administration. The role of ATF4 function at the central level could not be tested and should be the subject of future experiments. The analysis of samples from mice knocked-out for ATF4 at the hepatic level, will allow us to evaluate ATF4 involvement in the reorientation of AA metabolism (transport, biosynthesis, autophagy). In the C26 cancer model, the transition from pre-anorexia to early anorexia was associated with an activation of the eIF2α-ATF4 signaling pathway at the hepatic and hypothalamic levels, and a pharmacological approach using ISRIB (ISR Inhibitor) will soon be implemented to study the involvement of the ISR in the regulation of appetite and AA metabolism (in this model, genes knock-out is not possible) Secondly, we focused on mitochondrial dysfunction, which represents a major threat to cellular homeostasis, promotes the development of many metabolic disorders and plays a crucial role in the pathogenesis of sepsis. Given the role played by the eIF2α-ATF4 signaling pathway in the adaptive response to mitochondrial stress, we investigated whether a pretreatment activating this pathway could be a way to increase the resilience of the mitochondrial pool during subsequent stressful events. We demonstrated in mice that a pretreatment activating the GCN2-eIF2α-ATF4 pathway upstream of inflammatory stress (LPS administration) counteracted some of the effects of this stress on mitochondrial homeostasis in the liver, an organ playing a major role in the metabolic and immune response to endotoxic stress. These results are presented as an article that will be submitted soon for publication
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Enyindah-Asonye, Gospel. "PATHOPHYSIOLOGICAL ROLE OF CD6 AND ITS NEW LIGAND IN DISEASES." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1491389112552353.
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Falkenberg, Christiane. "Optimizing Organic Solar Cells." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-89214.
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This thesis deals with the characterization and implementation of transparent electron transport materials (ETM) in vacuum deposited p-i-n type organic solar cells (OSC) for substituting the parasitically absorbing standard ETM composed of n-doped C60. In addition to transparency in the visible range of the sun spectrum, the desired material properties include high electron mobility and conductivity, thermal and morphological stability, as well as good energy level alignment relative to the adjacent acceptor layer which is commonly composed of intrinsic C60. In this work, representatives of three different material classes are evaluated with regard to the above mentioned criteria.
HATCN (hexaazatriphenylene hexacarbonitrile) is a small discoid molecule with six electron withdrawing nitrile groups at its periphery. It forms smooth thin films with an optical energy gap of 3.3eV, thus being transparent in the visible range of the sun spectrum. Doping with either 5wt% of the cationic n-dopant AOB or 7wt% of the proprietary material NDN1 effectively increases the conductivity to 7.6*10^-6 S/cm or 2.2*10^-4 S/cm, respectively. However, the fabrication of efficient OSC is impeded by the exceptionally high electron affinity (EA ) of approximately 4.8eV that causes the formation of an electron injection barrier between n-HATCN and intrinsic C60 (EA=4.0eV). This work presents a strategy to remove the barrier by introducing doped and undoped C60 intermediate layers, thus demonstrating the importance of energy level matching in a multi-layer structure and the advantages of Fermi level control by doping.
Next, a series of six Bis-Fl-NTCDI (N,N-bis(fluorene-2-yl)-naphthalenetetracarboxylic diimide) compounds, which only differ by the length of the alkyl chains attached to the C9 positions of the fluorene side groups, is examined. When increasing the chain length from 0 to 6 carbon atoms, the energy levels remain nearly unchanged: We find EA=3.5eV as estimated from cyclic voltammetry, an ionization potential (IP ) in the range between 6.45eV and 6.63eV, and Eg,opt=3.1eV which means that all compounds form transparent thin films. Concerning thin film morphology, the addition of side chains results in the formation of amorphous layers with a surface roughness <1nm on room temperature glass substrates, and (1.5+/-0.5)nm for deposition onto glass substrates heated to 100°C. In contrast, films composed of the side chain free compound Bis-HFl-NTCDI exhibit a larger surface roughness of (2.5+/-0.5)nm and 9nm, respectively, and are nanocrystalline already at room temperature. Moreover, the conductivity achievable by n-doping is very sensitive to the side chain length: Whereas doping of Bis-HFl-NTCDI with 7wt% NDN1 results in a conductivity in the range of 10^-4 S/cm, the attachment of alkyl chains causes a conductivity which is more than three orders of magnitude smaller despite equal or slightly higher doping concentrations. The insufficient transport properties of the alkylated derivatives lead to the formation of pronounced s-kinks in the jV -characteristics of p-i-n type OSC while the use of n-Bis-HFl-NTCDI results in well performing devices.
The last material, HATNA-Cl6 (2,3,8,9,14,15- hexachloro-5,6,11,12,17,18-hexaazatrinaphthylene), exhibits Eg,opt=2.7eV and is therefore not completely transparent in the visible range of the sun spectrum. However, its energy level positions of EA=4.1eV and IP=7.3eV are well suited for the application as ETM in combination with i-C60 as acceptor. The compound is dopable with all available n-dopants, resulting in maximum conductivities of sigma=1.6*10^-6, 3.5*10^-3, and 7.5*10^-3 S/cm at 7.5wt% AOB, Cr2(hpp)4, and NDN1, respectively. Applying n-HATNA-Cl6 instead of the reference ETM n-C60 results in a comparable or improved photocurrent density at an ETM thickness d(ETM)=40nm or 120nm, respectively. At d(ETM)=120nm, the efficiency eta is more than doubled as it increases from eta(n-C60)=0.4% to eta(n-HATNA-Cl6)=0.9% .
Optical simulations show that the replacement of n-C60 by n-Bis-HFl-NTCDI, n-HATNA-Cl6, or the previously studied n-NTCDA (naphthalenetretracarboxylic dianhydride) in p-i-n or n-i-p type device architectures is expected to result in an increased photocurrent due to reduced parasitic absorption. For quantifying the gain, the performance of p-i-n type OSC with varying ETM type and thickness is evaluated. Special care has to be taken when analyzing devices comprising the reference ETM n-C60 as its conductivity is sufficiently large to extend the area of the aluminum cathode and thus the effective device area which may lead to distorted results. Overall, the experiment is able to confirm the trends predicted by the optical simulation. At large ETM thickness in the range between 60 and 120nm, the window layer effect of the ETM is most pronounced. For instance, at d(ETM)=120nm, eta(C60) is more than doubled using n-HATNA-Cl6 and even more than tripled using n-Bis-HFl-NTCDI or n-NTCDA. At optimized device geometry the photocurrent gain is slightly less than expected but nonetheless, the efficiency is improved from eta(max)=2.1% for n-C60 and n-HATNA-Cl6 solar cells to eta(max)=2.3, and 2.4% for n-Bis-HFl-NTCDI and n-NTCDA devices, respectively. This development is supported by generally higher Voc and FF in solar cells with transparent ETM.
Finally, p-i-n type solar cells with varying ETM are aged at a temperature of 50°C and an illumination intensity of approximately 2 suns. Having extrapolated lifetimes t(80) of 36, 500, and 14000h and nearly unchanged jV-characteristics after 2000h, n-C60 and n-Bis-HFl-NTCDI devices exhibit the best stability. In contrast, n-NTCDA devices suffer from a constant decrease in Isc while n-HATNA-Cl6 solar cells show a rapid dscegradation of both Isc and FF associated with a decomposition of the material or a complete de-doping of the ETM. Here, lifetimes of only 4500h and 445hare achieved.
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Chang, Shang-wen. "Cu₂S/ZnCdS thin film heterojunction solar cell studies." Diss., Virginia Polytechnic Institute and State University, 1985. http://hdl.handle.net/10919/54740.
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Cu₂S/CdS solar cells have been studied extensively for the past two decades due to their potentially high efficiencies per unit cost. The operation and characteristics of Cu₂S/CdS solar cells are fairly well understood. However, the properties of the newer Cu₂S/ZnCdS cell type are not well understood.
The main goals of this thesis were to compare Cu₂S/CdS and Cu₂S/ZnCdS cells using Cu₂S/CdS cells as a reference, and to understand the operation and properties of Cu₂S/ZnCdS cells in order to improve cell performance. Four different measurements were used in this research to achieve these goals. They were; electrical, spectral, capacitance and deep trap measurements.
I-V measurements give important electrical parameters of the cells; cell efficiency, fill factor, short circuit current, open circuit voltage, shunt resistance and series resistance are reported. From a In(ISC) versus VOC measurement, the diode factor, A, was found to be about 1 for Cu₂S/CdS, Cu₂S/Zn0.11Cd0.89S, and about 1.2 for Cu₂S/Zn0.25Cd0.75S cells. The relation between In(Joo) (current density) and ϕ (potential barrier height) is linear for both types of cells. The slope of this linear relationship increases as the content of Zn increases in ZnxCd1-xS. Under air mass 1 (100 mW/cm²) illumination, it was found that VOC decays and capacitance increases for Cu₂S/ZnCdS cells. This is attributed to electron relaxation from deep traps near the junction.
Spectral response with and without bias light were measured for both Cu₂S/CdS and Cu₂S/ZnCdS cells. White and blue bias light enhance the spectral response, while red bias light quenches the response. This is attributed to ionization and filling of deep traps near the junction.
Capacitance measurements on both cell types show that 1/C² versus voltage is quite flat, which indicates the existence of an i-layer (insulation layer) in the CdS or ZnCdS near the junction.
Three methods–photocapacitance, space-charge-limited current, and thermally stimulated. current techniques–were used for deep trap measurements. Photocapacitance measurements indicate one deep donor energy and two deep acceptor energy levels. These trap energies become larger as the content of Zn in ZnCdS increases. Space-charge-limited current measurements give a trap density of the order of 10¹⁶ cm³ for both cell types. The shallow energy trap is found to be 0.26 eV below the conduction band edge of CdS. The occurrence of a current-saturated region for Cu₂S/ZnCdS is attributed to the filling of the interface traps near the junction. Thermally stimulated current measurements give two energy levels below the conduction band of CdS; 0.05 eV and 0.26 eV.
From the above results, several differences between the Cu₂S/CdS and the Cu₂S/ZnCdS cells can be seen. The Cu₂S/ZnCdS cells show stronger red quenching, smaller electron lifetime at the interface near the junction, and deeper traps than the Cu₂S/CdS cells. These differences can account for the decline of ISC and the VOC decay. The smaller ISC for the Cu₂S/ZnCdS cells can also possibly result from smaller electron lifetime at the interface, larger interface recombination velocity, different deep trap levels, and enhanced Zn concentration near the junction. The VOC decay for the Cu₂S/ZnCdS cells is mostly due to long decay of charge. Longer decay could be attributed to deeper traps.Ph. D.
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Allen, Frederick Jr. "CCL3 Augments Antitumor Responses in CT26 by Enhancing Cellular Trafficking and Interferon-Gamma Expression." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1513124234665339.
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Hassan, Namir. "Interactions of the leukocyte cell-surface proteins CD5 and CD6." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398158.
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Yeh, Ming-Hsin. "Identification of CD8+ T cell-stimulating shared antigens that are uncovered in CT26 vaccinated mice in the absence of CD25+ regulatory T cells." Thesis, University of Southampton, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431953.
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Liu, Gin-Yun. "Analysis of the effects of Leptomycin B on Cells Exiting Mitosis." The Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1153488860.
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Alam, Israt Shamima. "Imaging tumour cell death using the C2A domain of Synaptotagmin-I." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609494.
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Lau, Mike Rudi. "Characterisation of the class II phosphoinositide 3-kinase, PI 3K-C2β." Thesis, Institute of Cancer Research (University Of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342221.
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Wong, Kit-man Sunny, and 王傑民. "Identification of the regulatory mechanism for conferring metastasis of CD26-expressing colorectal cancer stem cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/209489.
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Cancer stem cells are a subpopulation of cells needed for cancer initiation and progression. Previous works have revealed CD26-expressing colorectal cancer (CRC) stem cells are not only endowed with tumor-initiating properties, but also capable of conferring metastasis. However, whether the CD26 molecule plays role in metastasis and the underlying mechanism by which CD26 may mediate metastasis remain unclear. This study aims to reveal the biology and the molecular characteristics of the CD26-expressing CRC stem cells.
Here, by the gene manipulation experiment, we showed that CD26 molecule is a functional marker that confers metastasis as transient and stable knock-down of the CD26 molecule in the CRC stem cells resulted in reduced wound healing, migration and invasion abilities in vitro and the capability to generate metastatic liver nodules in vivo, respectively. With the use of genome-wide expression array and immuno-blotting analysis, Smad-dependent TGF-β signaling, orchestrated by the SMAD2, SMAD3 and SMAD4 molecules, was up-regulated and activated in the CD26 expressing colorectal CSCs. In addition, expressions of the SMAD2 and SMAD3 molecules were found to be positively correlated with the CD26 molecule in clinical samples by qPCR and immunohistochemistry studies. Furthermore, no metastasis through EMT could be achieved once the Smad-dependent TGF-β signaling was down-regulated in the CD26 expressing CRC stem cells, which suggested that Smad-dependent TGF-β signaling was necessary for CD26-expressing CRC stem cells to induce metastasis. Finally, our result showed that the Smad-dependent TGF-β signaling was regulated by the CD26 molecule possibly through the down-regulation of CAV1 protein.
To conclude, our findings have not only revealed the functional role of CD26 molecule, but have also unveiled a linkage between the CD26 molecule and Smad-dependent TGF-β signaling. Further study of this connection may introduce a novel mechanism, through which CRC metastasis can be induced by this functional CD26 marker of CRC stem cells.published_or_final_version
Surgery
Doctoral
Doctor of Philosophy
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Mei, Hong. "NB1-C16-Insulin incorporated liposomal anticancer agents : formulation, cell uptake and cytotoxicity /." The Ohio State University, 1999. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488187049541811.
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Osorio, Fernández Lyda María. "Regulation of T-cell proliferation and B-CLL apoptosis by CD6 and FAS/FASL /." Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980605osor.
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Mazza, Simona. "Role of Class II phosphoinositide 3-kinase PI3K-C2α in pancreatic β cell function." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8759.
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Phosphoinositide 3-kinases (PI3Ks) are a family of enzymes that catalyse the synthesis of different lipid second messengers, regulating a plethora of intracellular functions. Deregulation of their signalling pathway has different functional consequences, and it has been associated with a variety of human diseases. The existence of eight distinct isoforms, divided into three classes, has raised in the past many questions on whether and to which extent their role was redundant or overlapping. The study of their intracellular signalling pathways and cellular functions is crucial, because some of these isoforms have been identified as important therapeutic targets. The most investigated PI3Ks belong to the class I subfamily, and they have a well established role in the regulation of cell growth, survival and proliferation. In the past years, attention and research efforts focussed on class I isoforms and alteration of their signalling pathways, one of the most common causes of cancer. More recently, evidence indicated that the least investigated class II PI3Ks have different intracellular roles. This work focussed on the class II isoform PI3K-C2α, the study of its intracellular function(s) in pancreatic β cells and the implications of its inhibition through downregulation in pancreatic β cells homeostasis. It was reported that PI3K-C2α has a crucial role insulin granules exocytosis. This study has demonstrated that this enzyme synthesises the lipid product PtdIns3P specifically at the plasma membrane of pancreatic β cells upon depolarisation of the plasma membrane and stimulation of insulin secretion. Moreover, the data herein presented indicated for the first time that glucose-induced activation of PI3K-C2α is able to protect β cells from cell death induced by nutrients deprivation. Analysis of the intracellular pathways stimulated by glucose indicated that PI3K-C2α is able to modulate the activity of mTOR and its downstream effectors, key regulators of cell proliferation and growth. Importantly, the activation of mTOR pathway upon glucose does not seem to involve the activation of the upstream regulator Akt or class I PI3K, suggesting a novel intracellular pathway stimulated by glucose.
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Sampaio, Raquel João Santos Ferreira Nunes. "The signaling role of the accessory receptors CD2 and CD6 in T cell activation." Doctoral thesis, Instituto de Ciências Biomédicas Abel Salazar, 2007. http://hdl.handle.net/10216/7167.
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Sampaio, Raquel João Santos Ferreira Nunes. "The signaling role of the accessory receptors CD2 and CD6 in T cell activation." Tese, Instituto de Ciências Biomédicas Abel Salazar, 2007. http://hdl.handle.net/10216/7167.
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Fawcett, Sarah Louise. "Detection of cell death using fluorescent and radiolabelled derivatives of the C2A domain of Synaptotagmin-I." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608000.
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Zhao, Xiangli [Verfasser]. "Investigation on the role of CD26 in Th1 and Th17 cell differentiation and allogeneic graft rejection / Xiangli Zhao." Berlin : Freie Universität Berlin, 2018. http://d-nb.info/1158597665/34.
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Orta, Mascaró Marc. "Implicacions funcionals i terapèutiques de les interaccions moleculars mitjançades per CD5 i CD6 en les respostes immunitàries." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/399678.
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Els receptors de superfície CD5 i CD6 són receptors altament homòlegs amb dominis tipus scavenger, expressats principalment als timòcits i cèl·lules T madures. Els dos es troben associats al receptor de cèl·lules T (TCR) actuant com a moduladors de les senyals transmeses a nivell intracel·lular. Pel que fa a CD5, s’ha pogut determinar en diferents estudis la seva funció com a modulador negatiu de la senyal del TCR en timòcits i cèl·lules T madures a través del seu domini citoplasmàtic. En canvi, la manca de models animals ha fet que el rol biològic de CD6 encara sigui una incògnita, tot i que sí s’ha demostrat que esta implicat en la formació i estabilització de la sinapsi immunològica a través de la unió al seu lligand CD166/ALCAM. Estudis del nostre laboratori van demostrar que curiosament les regions extracel·lular de CD5 i CD6 son capaces d’unir-se a fongs i bactèries, respectivament, tot i que la rellevància biològica d’aquesta interacció encara esta per determinar. Per tal d’aprofundir en el paper que juguen aquests dos receptors limfocitaris, el nostre laboratori ha adquirit recentment dos ratolins transgènics knock-out per CD5 i CD6 (CD5-/- i CD6-/-) amb la finalitat de caracteritzar fenotípica i funcionalment la nova línia de ratolins deficients per a CD6-/- tant en condicions normals como d’agressió biològica, i establir analogies fenotípiques i funcionals entre els nous ratolins CD6-/- i els prèviament descrits CD5-/-. L’anàlisi de les poblacions limfocitàries va revelar que els ratolins CD6-/- presentaven una disminució al timus de les poblacions CD4+ i CD8+SP (single positive), i que les cèl·lules doble positives CD4+CD8+ (DP) presentaven augmentada l’alliberació de calci intracel·lular en resposta a l’estimulació via TCR. Es van realitzar experiments amb quimeres mixtes de medul·la òssia que van demostrar una desavantatge selectiva de les cèl·lules T CD6-/- durant el desenvolupament, fet confirmat al observar que ratolins transgènics pel TCR (OT-I i Marilyn) presentaven una selecció de cèl·lules T anormal en absència de CD6. L’estudi de les cèl·lules T perifèriques CD6-/- va revelar que aquestes proliferaven menys in vivo però més in vitro davant l’estimulació del TCR amb anticossos anti-CD3, així com que els ratolins CD6-/- tenien més cèl·lules de tipus memòria/efectores i T reguladores. De manera rellevant, es va veure que els ratolins CD6-/- eren més sensibles a patir fenòmens d’autoimmunitat, degut a una artritis induïda per col·lagen més severa en aquests animals relacionada amb una patró de citocines pro-inflamatòries més elevat. Pel que fa a la resposta davant un xoc sèptic en la seva funció com a receptors de patòngens, els ratolins CD6-/- van presentar una major sensibilitat a la mort per peritonitis polimicrobiana, però no en canvi els ratolins CD5-/- a una peritonitis induïda per derivats fúngics. Un estudi més detallat va revelar que la soca de ratolins C57BL/6 era deficient en la secreció d’IFN-γ comparat amb la soca CD1, i que l’administració d’IFN-γ recombinant juntament amb la proteïna CD5 soluble augmentava la supervivència dels animals de manera estadísticament significativa. En conclusió, en aquesta tesi doctoral s’ha demostrat que CD6 regula el llindar d’activació dels timòcits i de les cèl·lules T perifèriques, i que l’expressió d’aquest receptor dóna resistència a fenòmens autoimmunitaris i a la mort per peritonitis polimicrobiana. Per altra banda, també s’ha vist que l’administració d’IFN-γ recombinant soluble juntament amb la proteïna CD5 protegeix de la mort induïda per un xoc sèptic induït per derivats fúngics.The CD6 glycoprotein, as its related receptor CD5, is a lymphocyte surface receptor putatively involved in T-cell development and activation. CD6 facilitates adhesion between T-cells and APC through its interaction with CD166/ALCAM, and physically associates with the TCR at the centre of the immunological synapse. However, its precise role during thymocyte development and peripheral T-cell immune responses remains to be defined. Interestingly, a report published by our group showed that both CD6 and CD5 can bind bacteria and fungi, respectively, although so far the biologic relevance of this interaction has not been defined. Here, we analyze the in vivo consequences of CD6-deficiency. CD6-/- thymi showed a reduction in both CD4+ and CD8+ single-positive subsets, and double-positive thymocytes exhibited increased Ca2+ mobilization to TCR-crosslinking in vitro. Bone marrow chimera experiments revealed a T-cell autonomous selective disadvantage of CD6-/- T cells during development. The analysis of TCR-transgenic mice (OT-I and Marilyn) confirmed that abnormal T-cell selection events occur in the absence of CD6. CD6-/- mice displayed increased frequencies of antigen-experienced peripheral T-cells generated under certain level of TCR signal strength and/or co-stimulation such as effector/memory (CD4+TEM, CD8+TCM) and regulatory (Treg) T-cells. Furthermore, CD6-/- mice presented an exacerbated autoimmune response to collagen as well as higher mortality in a polimicrobian induced septic shock. In contrast, CD5-/- mice responded equally to WT in a fungi induced septic shock. However, a detailed analysis revealed that C57BL/6 mice were deficient in the secretion of IFN-γ, and that the administration of soluble IFN-γ in combination with soluble CD5 protects mice from the septic shock like syndrome. Taken together these data indicate that CD6 modulates the threshold for thymocyte selection and the generation and/or function of several peripheral T-cell subpopulations including Treg cells.
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Dareini, Ali. "Prediction and analysis of model’s parameters of Li-ion battery cells." Thesis, Blekinge Tekniska Högskola, Institutionen för tillämpad signalbehandling, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-11799.
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Lithium-ion batteries are complex systems and making a simulation model of them is always challenging. A method for producing an accurate model with high capabilities for predicting the behavior of the battery in a time and cost efficient way is desired in this field of work. The aim of this thesis has been to develop a method to be close to the desired method as much as possible, especially in two important aspects, time and cost. The method which is the goal of this thesis should fulfill the below five requirements: 1. Able to produce a generic battery model for different types of lithium-ion batteries 2. No or low cost for the development of the model 3. A time span around one week for obtaining the model 4. Able to predict the most aspects of the battery’s behavior like the voltage, SOC, temperature and, preferably, simulate the degradation effects, safety and thermal aspects 5. Accuracy with less than 15% error The start point of this thesis was the study of current methods for cell modeling. Based on their approach, they are divided into three categories, abstract, black box and white box methods. Each of these methods has its own advantages and disadvantages, but none of them are able to fulfill the above requirements. This thesis presents a method, called “gray box”, which is, partially, a mix of the black and white boxes’ concepts. The gray box method uses values for model’s parameters from different sources. Firstly, some chemical/physical measurements like in the case of the white box method, secondly, some of the physical tests/experiments used in the case of the black box method and thirdly, information provided by cell datasheets, books, papers, journals and scientific databases. As practical part of this thesis, a prismatic cell, EIG C20 with 20Ah capacity was selected as the sample cell and its electrochemical model was produced with the proposed method. Some of the model’s parameters are measured and some others are estimated. Also, the abilities of AutoLion, a specialized software for lithium-ion battery modeling were used to accelerate the modeling process. Finally, the physical tests were used as part of the references for calculating the accuracy of the produced model. The results show that the gray box method can produce a model with nearly no cost, in less than one week and with error around 30% for the HPPC tests and, less than this, for the OCV and voltage tests. The proposed method could, largely, fulfill the five mentioned requirements. These results were achieved even without using any physical tests/experimental data for tuning the parameters, which is expected to reduce the error considerably. These are promising results for the idea of the gray box which is in its nascent stages and needs time to develop and be useful for commercial purposes.
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Chu, Hin Lun. "Intracellular delivery of radioimmunoconjugates that target the cancer testis antigen, NY-ESO-1." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:84c830c4-c216-4b2c-8383-e1119d77c295.
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Cancer testis antigens (CTA) represent attractive targets for targeted radiotherapy and imaging as their expression is restricted to cancer and germ cells. NY-ESO-1, a member of the CTA family, is highly immunogenic and expressed in multiple tumor types including carcinoma of bladder, liver lung. The aim of this study was to develop radioimmunoconjugates (RIC) to target NY-ESO-1 protein in cancer cells. Anti-NY-ESO-1 antibodies were modified by addition of DTPA for 111In-labelling or, in the presence of Iodogen, were 123I-labelled. Delivery of radiolabeled immunoconjugates across the cell membrane was achieved using a protein transfection (PT) reagent (SAINT-PhD) and by chemical linkage with the cell-penetrating and nuclear-localizing peptide, TAT (YGRKKRRQRRR). Cellular internalization, distribution and efflux of 111In-DTPA-anti-NY-ESO-1-TAT-PT and 123I-anti-NY-ESO-1-TAT-PT were investigated in cell fractionation and retention assays. It was shown that protein transfection reagent has promoted the cellular uptake of RICs into SK-MEL-37 and both of 111In-DTPA-anti-NY-ESO-1-TAT-PT and 123I-anti-NY-ESO-1-TAT-PT was retained longer in SK-MEL-37 cells in comparison to their isotope control RIC. In clonogenic assays, 111In-DTPA-anti-NY-ESO-1-TAT-PT significantly reduced surviving fraction of SK-MEL-37 cells. Cytotoxicity was inversely proportional to specific activity and the concentration of cells exposed to 111In-DTPA-anti-NY-ESO-1-TAT-PT. siRNA knock down of NY-ESO-1 resulted in partial reversal of 111In-DTPA-anti-NY-ESO-1-TAT-PT associated cytotoxicity. These promising results obtained from the in vitro study has brought the probe further into in vivo study. In preliminary biodistribution studies in SK-MEL-37 xenograft-bearing mice, tumour:muscle ratio for 111In-DTPA-anti-NY-ESO-1-TAT-PT was statistically significant compared to the control RIC 48 h post injection. This clearly indicated that the probe can be delivered into tumour in in vivo model and the successful uptake of radioactivity increased the chance of causing cytotoxicity to tumour cells through DNA damage. All of these findings have suggested that intracellular cancer associated antigen NY-ESO-1 can be reached by protein transfection reagent and cell penetrating peptide and initiates DNA damage through radio-isotope mediated cytotoxicity. Therefore, it represents a novel approach to the treatment of CTA-expressing cancers.
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Beckenkamp, Aline. "Relação da expressão da DPPIV/CD26 com a progressão tumoral do carcinoma cervical humano e proteínas oncogênicas do HPV." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/170657.
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O câncer cervical é uma neoplasia muito prevalente na população feminina e está associado à infecção pelo papilomavírus humano (HPV). As oncoproteínas E6 e E7 de HPV de alto risco são as principais responsáveis pelas alterações celulares que levam ao desenvolvimento deste tipo tumoral. A dipeptidil peptidase IV (DPPIV/CD26) é uma enzima que exerce importantes funções relacionadas à progressão tumoral. Diversos estudos demonstram alterações na expressão e atividade desta proteína em diferentes tipos de câncer. Tendo em vista a relação entre a DPPIV/CD26 e o câncer, e que ainda não existem estudos relacionando esta proteína ao câncer cervical, neste estudo inicialmente investigamos a expressão e atividade da DPPIV/CD26 em linhagens celulares de carcinoma cervical humano (SiHa, HeLa e C33A) e em queratinócitos imortalizados (HaCaT). Nossos resultados demonstram uma baixa expressão da DPPIV/CD26 nas linhagens celulares estudadas, sendo praticamente indetectável na linhagem HeLa. Foi verificada a atividade enzimática dipeptidilpeptidásica tanto ligada à membrana quanto solúvel em todas as linhagens. Na presença do inibidor de DPPIV/CD26 (fosfato de sitagliptina) observamos que a linhagem SiHa apresentou um aumento na migração celular, e assim sugerimos que ao menos em parte a migração nesta linhagem é regulada pela atividade enzimática da DPPIV/CD26. A fim de investigar a relação da expressão da DPPIV/CD26 com as oncoproteínas E6 e E7 do HPV, avaliamos sua expressão em queratinócitos normais e transduzidos com estas oncoproteínas. Verificamos que queratinócitos expressando E6 de HPV de alto risco apresentam uma redução na expressão da DPPIV/CD26, e esta regulação parece ser dependente da degradação da p53. Considerando que as linhagens celulares estudadas apresentam baixa expressão e atividade da DPPIV/CD26, para melhor compreender a importância da expressão desta proteína, nós induzimos a superexpressão da DPPIV/CD26 em linhagem de câncer cervical (HeLa) para posterior avaliação dos efeitos em diferentes mecanismos tumorais. Os resultados demonstram uma redução no crescimento de células expressando DPPIV/CD26, sendo este efeito independente da atividade enzimática. Além disso, foi demonstrado que a indução da expressão de DPPIV/CD26 não afeta os mecanismos de migração e adesão celular na linhagem HeLa. Sendo assim, acreditamos que o esclarecimento do papel da DPPIV/CD26 no contexto do câncer cervical possibilita que novas abordagens diagnósticas e terapêuticas sejam implementadas no futuro.Cervical cancer is a very prevalent neoplasm in female population and is associated with human papillomavirus (HPV) infection. The high risk HPV E6 and E7 oncoproteins are responsible for cellular alterations that lead to the development of this tumor type. The dipeptidyl peptidase IV (DPPIV/CD26) is an enzyme that exerts important functions related to tumor progression. Several studies have shown changes in the expression and activity of this protein in different types of cancer. Considering the relationship between DPPIV/CD26 and cancer, and that there are still no studies relating this protein to cervical cancer, in the present study we first investigated the DPPIV/CD26 expression and activity in human cervical carcinoma cell lines (SiHa, HeLa and C33A) and in immortalized keratinocytes (HaCaT). Our results demonstrate a low DPPIV/CD26 expression in the studied cell lines, being almost undetectable in HeLa cell line. The dipeptidylpeptidasic enzymatic activity was verified both membrane bound and in the soluble form in all cell lines. In the presence of the DPPIV/CD26 inhibitor (sitagliptin phosphate) we observed that SiHa cell line showed an increase in cell migration, thus we suggest that at least in part cell migration in this cell line is regulated by DPPIV/CD26 enzymatic activity. In order to investigate the relationship between DPPIV/CD26 expression and HPV E6 and E7 oncoproteins, we evaluated the expression of this protein in normal keratinocytes or transduced with these oncoproteins. We have found that keratinocytes expressing high-risk HPV E6 present a reduction in DPPIV/CD26 expression, and this regulation appears to be dependent on p53 degradation. Considering that the cell lines studied have low DPPIV/CD26 expression and activity, in order to better understand the importance of the expression of this protein, we induced the DPPIV/CD26 overexpression in a cervical cancer cell line (HeLa) for further evaluation of the effects on different tumor mechanisms. The results demonstrate a reduction in cell growth of DPPIV/CD26 expressing cells, being this effect independent of the enzymatic activity. In addition, it has been demonstrated that the induction of DPPIV/CD26 expression does not affect the cell migration and adhesion mechanisms in the HeLa cell line. Thus, we believe that the elucidation of the DPPIV/CD26 role in the context of cervical cancer enables new diagnostic and therapeutic approaches to be implemented in the future.
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Siqueira, Adriane Sousa de. "Peptídeo C16, derivado da laminina, regula invasão, dinâmica de formação e atividade de invadopódios em linhagens celulares de carcinoma epidermóide e fibrossarcoma." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-24092014-154312/.
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A laminina contém peptídeos que podem ser liberados por proteólise. Nosso laboratório estuda os efeitos de peptídeos da laminina em biologia tumoral. Neste trabalho, verificamos se C16 (cadeia g1) estimularia invasão e atividade de invadopódios em células de carcinoma epidermóide (CAL27) e fibrossarcoma (HT1080). C16 promoveu aumento na taxa de invasão e atividade de invadopódios em ambas às linhagens celulares, comparado ao peptídeo controle C16SX. Microscopia em time-lapse demonstrou que C16 induz aumento na atividade de invadopódios em função do tempo. C16 estimula fosforilação de Src e ERK 1/2, e inibição da via ERK reduz invasão e atividade de invadopódios relacionados ao peptídeo. C16 conjugado à rodamina foi encontrando decorando a membrana de células CAL27, sugerindo possível interação com receptores. Diminuição dos níveis de integrina b1 reduzem atividade de invadopódios em amostras tratadas com C16. Nossos dados sugerem que C16 regula invasão e atividade de invadopódios em células CAL27 e HT1080, provavelmente por meio de Src, ERK e integrina b1.Laminin harbors bioactive peptides released upon tumor-induced proteolysis. Our Laboratory has been studying laminin peptides effects in tumor biology. Here we addressed whether C16 (g1 chain) would regulate invasion and invadopodia activity in cell lines from squamous cell carcinoma (CAL27) and fibrosarcoma (HT1080). C16 increased invasion rate and invadopodia activity compared to control peptide (C16SX). Through time-lapse microscopy, we observed that C16 stimulated invadopodia activity overtime. We searched for signaling pathways related to peptide effects. C16 stimulated Src and ERK 1/2 phosphorylation, and ERK signaling cascade inhibition decreased C16-induced invasion and invadopodia. Next, we addressed how C16 would interact with tumor cells. Rhodamine-conjugated C16 was found decorating CAL27 cell membrane, suggesting an interaction with receptors. Knockdown of b1 integrin reduced invadopodia activity of C16-treated cells. We propose that C16 regulates invasion and invadopodia activity of CAL27 and HT1080 cells through Src, ERK and b1 integrin.
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Minchin, James. "Pax3 genes drive cell fate choice in tissue-restricted progenitors." Thesis, King's College London (University of London), 2009. https://kclpure.kcl.ac.uk/portal/en/theses/pax3-genes-drive-cell-fate-choice-in-tissuerestricted-progenitors(746b8b18-c26e-49ac-aac4-835074e198fa).html.
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Bernardi, Maria Auxiliadora. "Expressão de CD44 e CD24 em carcinomas mamários ductais invasivos de acordo com análise dos subtipos moleculares e sua relação com fatores prognósticos." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-27102011-172419/.
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Carcinomas de mama são heterogêneos e consistem de diversos tipos celulares. Perfis de expressão gênica usando DNA microarrays identificaram quatro subtipos moleculares fundamentais baseados na expressão de receptores hormonais (estrógeno e progesterona) e de fator de crescimento epidérmico (HER2) (luminal tipo A, luminal tipo B, tumores expressando somente HER2 e triplos negativos) refletindo a heterogeneidade molecular dos carcinomas. Sugeriu-se que esta heterogeneidade advém da presença de células tronco tumorais com a capacidade de se diferenciar ao longo de vias divergentes e outros estudos sugeriram que a presença destas células tronco tumorais pode ser evidenciada pela análise fenotípica de CD44 e CD24. Nosso objetivo foi detectar a freqüência de CD24 e CD44 isolados ou combinados, analisados por imunoistoquímica e sua associação com os subtipos moleculares e com diversos marcadores biológicos em 95 casos de carcinoma ductal infiltrativo organizados em um microarranjo tissular (TMA). Realizamos determinações imunoistoquímicas de CD44, CD24, citoqueratinas (CK5, CK6, CK18), claudina 7 e Ki67. Subgrupos moleculares foram definidos pela expressão imunoistoquímica de RE, RP e HER2. Resultados: Os tumores apresentaram uma maior freqüência dos grupos luminais (49,5%) atribuído à alta expressão de RP ou RE (47,4%), e freqüência menor de tumores triplo negativos (21,5%) e HER2 (9,5%). Os fenótipos CD44+CD24- e CD44-/CD24+ estavam respectivamente presentes em 8,4% e 16,8% dos tumores e o fenótipo duplamente positivo foi predominante (45,3%). Ausência de ambas as proteínas foi evidente em 6,3% dos tumores. Tumores com fenótipo CD44+CD24- (definido como um marcador de células tronco tumorais por estudos in vitro) foram mais comuns em tumores triplos negativos mas não demonstraram nenhum tipo de associação com características clinico-patológicas e demais marcadores. Este fenótipo não foi expresso nos tumores HER2 positivos. O fenótipo duplamente positivo CD44+CD24+ mostrou-se mais freqüente nos subtipos luminais ou com alta expressão de HER2. Os fenótipos (CD44-CD24+ e CD44-CD24-) não mostraram associação com os subgrupos. Tumores expressando CD24+ isolado, com grande freqüência deste marcador (74,7%), mostraram significativa associação com positividade do RE, RP e Ki67 e uma significância marginal com marcadores de diferenciação luminal (CK18 e claudina 7, p = 0,14). Nenhuma associação foi observada com tumores CD44+ quando analisado isoladamente. A expressão de claudina 7 e Ki67 não mostrou associação com os subgrupos e a expressão de CK5 apresentou uma tendência a uma maior negatividade nos subtipos luminais e uma freqüência maior de positividade nos tumores HER2 e triplo negativos. De outro lado, associação da freqüência da expressão positiva de CK18 nos subgrupos luminais foi estatisticamente significativa (p = 0,003). Para se determinar se CD24+ e CD44+ e seus subtipos combinados poderiam afetar a sobrevida global e o intervalo livre da doença preparamos curvas de sobrevida de acordo com Kaplan-Meier que foram analisadas estatisticamente (log rank test). A mediana do período de seguimento das pacientes do nosso estudo foi de 4,8 anos (0,36 10,9 anos). Estas análises não demostraram influência dos fenótipos CD44+CD24- ou CD44+ sobre a sobrevida global ou intervalo livre de doença, mas observamos uma tendência a um prognóstico mais favorável. Interessantemente tumores HER2 positivos não expressaram este fenótipo, sugerindo que outros marcadores de células tronco caracterizam estes tumores. O fenótipo CD44-CD24+ mostrou-se mais freqüente nos tumores luminais, mas não apresentou correlação com marcadores clínico-patológicos ou biológicos analisados. Não houve diferenças significativas com respeito a sobrevida global ou intervalo livre de doença . A expressão de CD24+ isolado associou-se a expressão dos marcadores de diferenciação celular e a uma diminuição do intervalo livre de doença. A sobrevida livre de doença (10 anos) indicou uma percentagem de 94,1% para CD24- e 72,1% para os pacientes CD24+ enquanto a sobrevida global foi de 84,2% para os pacientes CD24- e 72,1% para os pacientes CD24+. Citoqueratinas (CK5, CK18) e Ki67 não influenciaram a sobrevida e o intervalo livre de doença. No entanto a expressão positiva de claudina 7, embora não associada à sobrevida global, foi estatisticamente associada ao decréscimo do intervalo livre da doença (p = 0,05). Conclusão: As características dos tumores CD44+CD24- e sua tendência a associação um prognóstico mais favorável parecem não estar de acordo com as propriedades descritas na literatura para células tronco e enfatizam a necessidade de outros marcadores. A determinação da freqüência de CD44+ e claudina 7 positiva pode contribuir para a análise do prognóstico em carcinoma de mamaBackground: Breast carcinomas consist phenotypically of diverse cells and exhibit intra tumoral heterogeneity being stratified in several subgroups based in gene expression profiles or histochemical biomarkers. It was suggested that this heterogeneity is derived in part from the transformation of different subsets of cancer stem cells (CSC) in each intrinsic subgroup. The presence of CSC can be evidenced by phenotypic analysis of CD44 e CD24. This study aimed to identify the CD24 and CD44 immunophenotype within invasive ductal breast carcinoma (IDC) subtypes and determine its influence on prognosis as well as its association with the expression of Ki67, citokeratins (CK5, CK6 and CK18) and claudin-7. Methods: Immuno expression of CD44 and CD24 alone or in combination was investigated in 95 IDC cases arranged in a tissue microarray (TMA). The association with intrinsic subgroups defined as luminal A (ER+, PR+, HER2-), luminal B (ER and or PR+, HER2+), HER2 subtype (ER-, PR-, HER2+) and triple negative (ER-, PR-, HER2-), and the other markers and prognosis was analyzed. Results: CD44+CD24- and CD44-CD24+ were respectively presents in 8.4% and 16.8% of the tumors, a lack of both proteins was detected in 6.3%, while CD44+CD24+ was determined in 45.3% of the tumors. Although there was no significant correlation between subgroups and different phenotypes, the CD44+CD24- phenotype was more common in the basal subgroups but the frequency of this subtype has not been associated with clinical characteristic or biological markers. The phenotype was absent in HER2 tumors whereas luminal tumors are enriched in CD44-CD24+ and CD44+CD24+ cells which did not show associations with clinical/biological markers features. There was also no significant association of the subtypes with the event free (DFS) and overall survival (OS) but the CD44+CD24- phenotype showed a more favorable prognostic as compared to CD44-CD44+ phenotype that showed a worse prognosis (p = 0.26) (median follow up, 4.8 years) CD44+ alone was evident in 57.9%, while CD24+ was positive in 74.7% of the tumors, the latter showing a significant association with ER, PR and Ki67 and a marginal association with CK18 and claudin-7. Expression of claudin-7 and Ki67 did not associate with the cancer subgroups, while a positive association between CK18 and the luminal subgroups was found. CD44+ was not significantly associated with OS (p = 0.684) and DFS (p = 0.386) whereas CD24+ expression was also no significantly associated with OS (p = 0.32) but was associated with a decrease in DFS (p = 0.07). CK5, CK18 and Ki67 expression had no influence in OS or DFS, however claudin-7 positive although not statistically associated with OS, was associated with reduced DFS (p = 0.05). Conclusions: The heterogeneity of cells with several CD44CD24 expression may indicate the presence of different stem cell populations. Ocurrence of CD44+CD24- phenotype is more common in triple negative tumors and lower in tumors of luminal type and absent in HER2 tumors. Although not associated significantly with patho-biological markers or OS and DFS, the CD44+CD24- phenotype has a tendency to be a favorable prognostic marker in breast cancer raising the possibilty that the putative tumorigenic ability may no be restricted to cells of this phenotype. The presence of CD44-CD24+ may indicat a worse prognosis. CD24+ was associated with ER, PR, Ki67and showed a marginal association with CK18 and claudin-7. CD24 and Claudin-7 positivity were the only biological markers associated with reduced DFS. These two investigated markers can be used to improve the assessement of prognosis in breast cancer
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Bezine, Maryem. "Implication du canal potassium Kv3.1 dans la lipotoxicité du 7-cétocholestérol, 24S-hydroxycholestérol et de l’acide tétracosanoïque sur des cellules nerveuses 158N et BV-2 : Etude des relations entre Kv3.1, homéostasie potassique et métabolisme peroxysomal dans la maladie d’Alzheimer." Thesis, Bourgogne Franche-Comté, 2017. http://www.theses.fr/2017UBFCI010/document.
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Le potassium (K+) est impliqué dans la régulation de l’excitabilité cellulaire, la régulation du cycle cellulaire, la viabilité cellulaire, la neuroprotection et le maintien des fonctions microgliales et oligodendrocytaires. Le dysfonctionnement des canaux potassiques, décrit dans plusieurs maladies neurodégénératives comme la Maladie d’Alzheimer (MA), la sclérose en plaques (SEP), la maladie de Parkinson et la maladie de Huntington, pourrait être une potentiel cible thérapeutique. Les mécanismes toxiques sous-jacents de ces pathologies neurodégénératives impliquent des oxystérols, dérivés oxydés du cholestérol, et des acides gras en relation avec le métabolisme peroxysomal. Le 7-cétocholestérol (7KC), le 24S-hydroxycholestérol (24S-OHC) et l'acide tétracosanoïque (C24: 0), souvent trouvés à des taux élevés au niveau du cerveau et dans le plasma de patients atteints de maladies neurodégénératives (MA, maladie de Nieman-Pick, SEP, maladie de Parkinson, maladie de Huntington et X-ALD conduisent une rupture de l’équilibre Redox qui aboutirait à la neurodégénérescence. Dans ce contexte, il est intéressant de déterminer l’éventuelle connexion entre environnement lipidique et homéostasie potassique. L’étude in vitro a été réalisée sur des olygodendrocytes murins 158N et les cellules microgliale BV-2. Nous avons montré que la lipotoxicité du 7KC, 24S-OHC et C24:0 implique une rétention du K+ faisant intervenir les canaux potassium voltage dépendant (Kv). Ces résultats ont montré que l'inhibition des canaux Kv conduisant à une augmentation la [K+]i contribue à la cytotoxicité du 7KC, 24S-OHC et C24:0. Nous nous sommes focalisés sur le canal Kv3.1b. La retention du K+ induite par les oxystérols (7KC et 24S-OHC) serait sous le contrôle de Kv3.1b. L’étude clinique réalisée sur du plasma de MA a révélé une corrélation négative entre le taux d’acide docosahexaénoïque (DHA) et la concentration de K+. Chez les souris transgéniques J20, modèle de la MA, l’étude de la topographie d’expression de Kv3.1b et d’Abcd3, au niveau de l’hippocampe et du cortex, a montré une baisse de l’expression de ces deux marqueurs. Dans leur ensemble, les résultats obtenus ont établi des relations entre lipotoxicité, métabolisme peroxysomal et altération de l’homéostasie potassique dans la neurodégénérescence et suggèrent une possible modulation de l’expression et de l’activité de kv3.1b dans la physiopathologie des maladies neurodégénérativesPotassium (K+) is involved in the regulation of cellular excitability, cell cycle regulation, cell viability, neuroprotection and maintenance of microglial and oligodendrocytic functions. Potassium dysfunction, described in several neurodegenerative diseases such as Alzheimer's Disease (AD), multiple sclerosis (MS), Parkinson's disease and Huntington's disease, may be a potential therapeutic target. The underlying toxic mechanisms of these neurodegenerative pathologies involve oxysterols, which are oxidized cholesterol derivatives, and fatty acids including those associated with peroxisomal metabolism. 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC) and tetracosanoic acid (C24:0), often found at increased levels in the brain and plasma of patients with neurodegenerative diseases (Nieman-Pick disease, MS, Parkinson's disease, Huntington's disease and X-ALD) lead to a breakdown of the redox equilibrium leading to neurodegeneration. In this context, it is interesting to determine the possible connection between the lipid environment and potassium homeostasis The in vitro study was carried out on 158N murine oligodendrocytes and microglial BV-2 cells. We have shown that the lipotoxicity of 7KC, 24S-OHC and C24:0 implies retention of K+ involving the voltage dependent potassium channels (Kv). These results have shown that inhibition of Kv channels lead to an increase in [K +] i contributing to the cytotoxicity of 7KC, 24S-OHC and C24:0. The retention of K+ induced by oxysterols (7KC and 24S-OHC) would be under the control of Kv3.1b. A clinical study, on plasma of patients with Alzheimer’s disease, revealed a negative correlation between docosahexaenoic acid (DHA) and K+ concentration. In the J20 mice, a transgenic model of Alzheimer’s disease, the expression of Kv3.1b and Abcd3 was decreased in the hippocampus and cortex. Overall, the results obtained established relationships between lipotoxicity, peroxisomal metabolism and potassium homeostasis in neurodegeneration and suggest a possible modulation of the expression and activity of kv3.1b in the pathophysiology of neurodegenerative diseases. So, modulation of Kv3.1 could constitute a new therapeuthic approach against some neurodegenerative diseases
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Zi-WeiGuo and 郭子瑋. "Studies of the Mechanism for Metastatic Tumor Cell-induced CD26 Upregulation in Innate Immune Cells that involves Endothelial Cells." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/83z8t5.
Full textAbstract:
碩士國立成功大學
生物化學暨分子生物學研究所
101
In our previous data, we demonstratedthat metastatic cancer cells binded to CD26, which is an adhesison molecule on lung endothelail cells. CD26 not only expressed in lung endothelial cells but also in immune cells. CD26 overexpressed in immune cells plays a role of negative regulating in host immunity against microbes.In clinical investigation,CD26 overexpressed in immune cellsof cancer patients consider revising bad prognosis.In our previous data, we demostrated metastastic tumor cell-induced CD26 upregulation in innate immune cells resulting in cytotoxic suppression.Ex vivo, we demostrated metastatic cancer cells can’t directly induce CD26 overexpress in immune cells.This data suggesting us that another factors to participate in the inhibited mechanism. Metastatic cancer cells recruitedmyeloid-derived suppressor cellsto bloodstream resulte in suppression of immune cells. But in our experiment,CD26 upregulation of innate immune cells can’t be induce by metastatic cancer cells via myeloid-derived suppressor cells. In blood stream, whole blood cells and endothelail cells exist in vivo no in vitro. We demostrated that endothelial cells are required for metastatic cancer cell-induced CD26 upregulation of innate immune cells, not via whole blood cells. Furthermore, we observed that metastatic cancer cells stimulated endothelial cells secreting conditioned medium to induce CD26 upregulation and cytotoxic suppression of innate immune cells. Innate immune cells activated via several of cytokine and chemokine. Therefore, we used the flowcytomix bead-based protein detection system to analyse the condition medium and observed that IL-6 upregualtion in C.M..
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Campbell, Timothy Brandon. "IN VIVO HEMATOPOIETIC CELL ENGRAFTMENT IS MODULATED BY DPPIV/CD26 INHIBITION AND RHEB2 OVEREXPRESSION." Thesis, 2009. http://hdl.handle.net/1805/1854.
Full textAbstract:
Indiana University-Purdue University Indianapolis (IUPUI)Hematopoietic cell transplantation (HCT) is an important modality used to treat patients with hematologic diseases and malignancies. A better understanding of the biological processes controlling hematopoietic cell functions such as migration/homing, proliferation and self-renewal is required for improving HCT therapies. This study focused on the role of two biologically relevant proteins, dipeptidylpeptidase IV (DPPIV/CD26) and Ras homologue enriched in brain 2 (Rheb2), in modulating hematopoietic cell engraftment. The first goal of this study was to determine the role of the protein DPPIV/CD26 in modulating the engraftment of human umbilical cord blood (hUCB) CD34+ stem/progenitor cells using a NOD/SCID mouse xenograft model, and based upon previous work demonstrating a role for this enzyme in Stromal-Derived Factor-1/CXCL12 mediated migration and homing. Related to this first goal, pretreatment with an inhibitor of DPPIV/CD26 peptidase activity increased engraftment of hUCB CD34+ cells in vivo in recipient Non Obese Diabetic/Severe Combined Immunodeficiency (NOD/SCID) mice while not disturbing their differentiation potential following transplantation. These results support using DPPIV/CD26 inhibition as a strategy for enhancing the efficacy of cord blood transplantation. The second goal was to determine, by overexpression, the role of the Rheb2 in affecting the balance between proliferation and in vivo repopulating activity of mouse hematopoietic cells. Rheb2 is known to activate the mammalian target of rapamycin (mTOR) pathway, a pathway important in hematopoiesis. Rheb2 overexpression increased the proliferation and mTOR signaling of two hematopoietic cell lines, 32D and BaF3, in response to delayed IL-3 addition. In primary mouse hematopoietic cells, Rheb2 overexpression enhanced the proliferation and expansion of hematopoietic progenitor cells (HPCs) and phenotypic hematopoietic stem cells (HSCs) in vitro. In addition, HPC survival was enhanced by Rheb2 overexpression. Using in vivo competitive repopulation assays, Rheb2 overexpression transiently expanded immature HPC/HSC populations shortly after transplantation, but reduced the engraftment of total transduced cells. These findings support previous work showing that signaling proteins able to enhance the proliferative status of hematopoietic stem cells often cause exhaustion of self-renewal and repopulating ability. These studies of hematopoietic engraftment modulated by both of these molecules provide information which may be important to future work on HCT.
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Kuo, Hui-Shan, and 郭惠珊. "The Anti-tumor Effect of AICAR on CT26.CL25 Cells." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/64248346575102073433.
Full textAbstract:
碩士慈濟大學
生命科學系碩士班
99
Colorectal cancer, also called colon cancer or large bowel cancer, includes cancerous growths in the colon, rectum and appendix. Fluorouracil (5-FU or f5U) is a drug that is a pyrimidine analog which is used in the treatment of colon cancer. To increase the anti-tumor effects of 5-FU,the in vitro anti-tumor activities of AICAR evaluated in this study in mouse colon carcinoma cell lines. MTT assay was used to compare the cytotoxicity of cells treated with compound C, AICAR, cisplatin and 5-FU. AICA ribonucleotide or AICAR is an intermediate in the generation of inosine monophosphate, which acts as an AMP-activated protein kinase agonist. AICAR at 2 mM and 5-FU showed significant growth inhibition in CT26.CL25. AICAR treated CT26.CL25 cells showed S-phase arrest, and S- phase related genes - cyclin A expression level has also been affected. The effect of AICAR provides the molecular evidence for the growth inhibition on cancer cells and further develop as the tumor therapy.
30
McIntyre, Patrick. "The Effects of a Pyk2 Kinase Inhibitor on the Proliferation and Differentiation of Human Dental Pulp Stem Cells." Thesis, 2021. http://dx.doi.org/10.7912/C2/24.
Full textAbstract:
Indiana University-Purdue University Indianapolis (IUPUI)Introduction: Regenerative endodontic procedures are an effective treatment option for immature teeth with infected necrotic pulps to allow for healing and potential continued root development, yet challenges to ideal treatment outcomes remain. Consistent development of root length and width of dentin remains a challenge, as does development of the pulp-dentin complex. Previous in vitro studies have assessed the role of different growth factors and bioactive molecules in combination with scaffolds to potentially facilitate continued development of the pulp-dentin complex using dental pulp stem cells (DPSCs). The proline-rich tyrosine kinase 2 (Pyk2) is linked with osteoblast activity and the regulation of bone mass. Further, the Pyk2 inhibitor PF-4618433 (PF-46) has been shown in previous studies to enhance osteoblast activity and mineral deposition in vitro. However, whether Pyk2 targeting promotes the osteogenic differentiation of DPSCs remains unknown. Objective: The purpose of this study was to investigate the effect of a Pyk2 inhibitor, PF-46, on the proliferation, differentiation, and mineralization of human DPSCs. Materials and Methods: Human DPSCs were cultured in 24-well plates with α-MEM with 10% FBS, and containing 0 μM (vehicle control) or 0.1 μM, 0.3 μM, or 0.6 μM PF-46. Fresh media and treatments were replaced every 2-3 days. After 1 day incubation, cytotoxic effects were evaluated by using an MTS proliferation assay. After 4 days of treatment, direct cell counting was performed. To induce osteogenic differentiation, ascorbic acid and β-glycerol phosphate were added to the culture media and the DPSCs were cultured with PF-46 for 14 days. Then, an alkaline phosphatase (ALP) assay and mineral deposition assay were performed. Differences between treatment groups were analyzed by a one-way ANOVA followed by pair-wise tests conducted using Tukey’s multiple comparisons procedure with a 5% significance level. Results: The 0.6 μM PF-46 group had a significantly higher cell count, ALP activity and mineral deposition when compared to 0 μM PF-46. The 0.1 and 0.3 μM PF-46 groups also had significantly higher ALP activity compared to the 0 μM PF-46 group after 14 days of incubation. There was a general trend of increased differentiation and mineral deposition as the concentration of PF-46 increased from 0.1 μM to 0.6 μM. Conclusion: There was a general concentration-dependent increase in cell count, differentiation, and mineral deposition by human DPSCs as the concentration of PF-46 increased from 0 μM up to 0.6 μM, with the highest activity observed with 0.6 μM PF-46. Although further research is needed, these results suggest that strategies that target Pyk2 may potentially be used to improve the osteogenic differentiation of DPSCs to aid endodontic regeneration.
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"A study on bilayer and dye-doped polymer solar cells." 2015. http://repository.lib.cuhk.edu.hk/en/item/cuhk-1291486.
Full textAbstract:
Polymer solar cells (PSCs) are one of the cost-effective alternatives to the traditional silicon-based solar cell. To be commercially viable, a number of its shortfalls have to be addressed. First, the charge mobility and life time of the organic materials used in PSCs are low and results in a large series resistance and inefficient charge separation. Second, the range of absorption of light in PSCs is not wide enough to cover the whole solar spectrum. Hence, the highest power conversion efficiency (PCE) achieved by PSCs is still low compare to other types of solar cells. In this thesis, several methods were investigated to improve the PCE of PSCs base on the donor polymer Poly(3-hexylthiophene-2,5-diyl) (P3HT) and acceptor fullerene Phenyl-C61-butyric acid methyl ester (PCBM). It was found to be essential to control the drying rate of the solvent after spin-coating the polymer solution on a piece of glass as it would affect the ordering and crystallinity of the polymer chains. Besides, instead of a bulk heterojuction (BHJ) structure, a bilayer device can also give a comparable PCE by spin-coating P3HT and PCBM separately using orthogonal solvents. Factors that could affect the performance of bilayer devices, such as the drying rate and thermal annealing, were investigated. It was found that thermal annealing is essential since it would facilitate the interdiffusion of the two layers. In order to improve the range of spectral absorption of light, a squaraine dye was introduced. Squaraine has a high absorbance in the near-infrared range where the absorption is poor for P3HT. The PCE was found to increase by about 5 % by incorporating 0.5 wt % of squaraine into the BHJ system. In addition, squaraine was introduced to the bilayer system. It was found that the performance was slightly improved when squaraine was blended with PCBM in the upper layer. Various parameters were tuned to optimize the performance of this bilayer system.聚合物太陽能電池是其中一個比傳統晶體矽太陽能電池有更高成本效益的代替品。然而，聚合物太陽能電池仍然有若干缺點需要解決才能夠成為商業市場上流通的產品。首先，聚合物太陽能電池所使用的有機材料的電荷遷移率和壽命低，造成較大的串聯電阻和低效率的電荷分離。其次，聚合物太陽能電池的吸收光譜範圍較窄，不足以覆蓋整個太陽光譜。因此，相比起其他類型的太陽能電池，聚合物太陽能電池的最高能量轉換效率仍然偏低。在本論文中，我們建基於供體P3HT和受體PCBM' 進行了多分面的研究。我們發現旋塗聚合物溶液後，控制溶劑的乾燥速度是很重要的，因為這會影響聚合物鏈的排序和結晶度。另外，除了體異質接面結構外，利用正交溶劑來分別旋塗P3HT和PCBM的雙層結構亦可得到可比的最高能量轉換效率。我們研究了數個可能影響雙層結構聚合物太陽能電池效能的因素，例如乾燥速度和熱退火處理，並發現熱退火處理是非常重要，因為熱退火可以有利於兩層聚合物的相互擴散。為了擴闊電池的吸收光譜範圍，我們引入了方酸染料。方酸在近紅外線範圍內具有高的吸光率，而在此範圍內P3HT的吸光率都欠佳。在慘雜0.5重量百分比的方酸到原有的體異質接面結構後，最高能量轉換效率提升了大約百分之五。此外，方酸也才參雜到雙層結構系統內，結果發現，當方酸慘雜在上層中的PCBM後，電池的效能稍有改善。我們調整了各種參數，以完善該雙層系統的效能。
Chow, Chun Yin = 雙層及摻雜染料聚合物太陽能電池研究 / 周俊然.
Thesis M.Phil. Chinese University of Hong Kong 2015.
Includes bibliographical references (leaves 90-92).
Abstracts also in Chinese.
Title from PDF title page (viewed on 07, October, 2016).
Chow, Chun Yin = Shuang ceng ji shan za ran liao ju he wu tai yang neng dian chi yan jiu / Zhou Junran.
Detailed summary in vernacular field only.
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Pai, Li-Wen, and 白利文. "Effect of Mouse Bone Marrow Dendritic Cell-Stimulated Lymphocytes on Mouse CT26 Cells in the Present of Pleurotus ostreatus Water Extracts." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/72472803061781585880.
Full textAbstract:
碩士國立臺灣大學
食品科技研究所
92
Malignant tumor is ranked top among the ten major causes of death with an increasing mortality year by year. Dendritic cell (DC) is a potent antigen presenting cell (APC) and is capable of uptake and processing foreign antigens, such as bacteria and tumor cells, and presents specific peptides of antigen to major histocompability complex (MHC). As a consequence, activation of T cells occurs and leads to strong adaptive immune response. Such characteristics of DC enable it to be focused recently on cancer therapy. In this study, to study the growth inhibition of activated mixed lymphocytes in presence with various levels of cold water extracts from PO on CT26 cells. Mouse DCs were cultured from bone marrow and then activated and matured by incubation for 1 day with LPS or CT26 cell lysates, which were prepared by repeated freezing and thawing. The mature DCs were then co-cultured with mixed lymphocytes from mouse splenocytes at a ratio of 1/10 to enhance the proliferation and specific cytotoxicity of mixed lymphocytes (containing T-cells). Subsequently, the activated mixed lymphocytes were co-cultured with CT26 cells (at a ratio of 1/20), in the presence or absence of PO water extracts, to observe the inhibition on CT26 cells. Results showed that mature DCs were effective in proliferating and enhancing the cytotoxic specificity of mixed lymphocytes. PO cold water extracts exhibited CT26 cell inhibition on growth, while stimulating the proliferation of mixed lymphocytes, as detected by a MTT assay. However, PO cold water extracts showed anti-proliferation on activated mixed lymphocytes by about 20 %. The activated mixed lymphocytes displayed remarkable inhibition of CT26 cells by about 80 %; however, in the presence (200 - 600 μg/mL) of PO cold water extracts, they showed much stronger inhibition on CT26 cells by about 90 %, revealing the activation of DCs and activated mixed lymophocytes by PO cold water extracts. On the other hands, PO hot water extracts proliferated both CT26 cells and activated mixed lymphocytes. Although PO cold water extracts showed adverse results on CT26 cells and mixed lymphocytes, they were effective in inhibiting CT26 cell growth by increased cytotoxity of T cells as a result of the co-cultivation with PO extracts. Reasons for proliferating or anti-proliferating the activated mixed lymphocytes could be due to the difference in compositions between PO cold and hot water extracts.
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"Pathological mechanisms of systemic lupus erythematosus: toll-like receptors, intracellular signaling molecules, CD26, T helper 17 cells and B cell chemokine." 2008. http://library.cuhk.edu.hk/record=b5893555.
Full textAbstract:
Wong, Tsz Yan.Thesis (M.Phil.)--Chinese University of Hong Kong, 2008.
Includes bibliographical references (leaves 140-159).
Abstracts in English and Chinese.
Acknowledgements --- p.I
Abbreviations --- p.III
Abstract --- p.V
摘要 --- p.VIII
Publications --- p.XI
Table of Contents --- p.XII
Chapter Chapter 1: --- General Information
Chapter 1.1 --- Characteristics and Prevalence of SLE --- p.1
Chapter 1.2 --- Diagnosis of SLE --- p.2
Chapter 1.3 --- Assessment of Disease Activity --- p.4
Chapter 1.4 --- Causes of SLE --- p.4
Chapter 1.4.1 --- Genetic Factors --- p.4
Chapter 1.4.2 --- Hormonal Factors --- p.6
Chapter 1.4.3 --- Environment Factors --- p.7
Chapter 1.5 --- Drug Treatments of SLE --- p.8
Chapter 1.6 --- Immunological Dysregulation in SLE --- p.9
Chapter 1.6.1 --- Types and Properties of Lymphocytes --- p.9
Chapter 1.6.2 --- Cytokines and Chemokines --- p.14
Chapter 1.6.3 --- Toll-like Receptors --- p.17
Chapter 1.6.4 --- Intracellular Signal Transduction Pathways --- p.21
Chapter 1.7 --- Objectives of Our study --- p.25
Chapter Chapter 2: --- Material and Methods
Chapter 2.1 --- Materials --- p.27
Chapter 2.1.1 --- SLE Patients and Control Subjects --- p.27
Chapter 2.1.2 --- Reagents for cell culture --- p.28
Chapter 2.1.3 --- Reagents for Flow Cytometry --- p.30
Chapter 2.1.4 --- Reagents for Phosphorylation State Analysis --- p.33
Chapter 2.1.5 --- Reagents for Total RNA Extraction --- p.35
Chapter 2.1.6 --- Reagents for Polymerase Chain Reaction (PCR) --- p.36
Chapter 2.1.7 --- Reagents for Gel Electrophoresis --- p.38
Chapter 2.1.8 --- Reagents for Real-Time Polymerase Chain Reaction --- p.39
Chapter 2.1.9 --- Other Reagents --- p.40
Chapter 2.2 --- Methods --- p.41
Chapter 2.2.1 --- Preparation of Plasma and Purification of Peripheral Blood Mononuclear Cells (PBMC) from EDTA-Blood --- p.41
Chapter 2.2.2 --- Immunophenotyping of Cell Surface Molecules by Flow Cytometry --- p.42
Chapter 2.2.3 --- Immunophenotyping of Intracellular Molecules by Flow Cytometry --- p.43
Chapter 2.2.4 --- Phosphorylation State Analysis of Intracellular Signaling Molecules --- p.43
Chapter 2.2.5 --- Cytometric Bead Array of Cytokines and Chemokines --- p.44
Chapter 2.2.6 --- Total RNA Extraction from PBMC --- p.46
Chapter 2.2.7 --- Reverse Transcription of the Extracted Total RNA --- p.46
Chapter 2.2.8 --- Real-time Polymerase Chain Reaction --- p.46
Chapter 2.2.9 --- Enzyme-Linked Immunosorbent Assay (ELISA) --- p.48
Chapter 2.2.10 --- Enzyme-Linked Immunosorbent Spot (ELISPOT) --- p.48
Chapter 2.2.11 --- Statistical Analysis --- p.49
Chapter Chapter 3: --- B Cell Chemokine CXCL13 in SLE
Chapter 3.1 --- Introduction --- p.49
Chapter 3.2 --- Methods --- p.52
Chapter 3.3 --- Results --- p.52
Chapter 3.3.1 --- Characteristics of SLE Patients and Control Subjects --- p.52
Chapter 3.3.2 --- Expression of Plasma CXCL13 --- p.53
Chapter 3.3.3 --- Gene Expression of TNF-α in PBMC --- p.53
Chapter 3.3.4 --- Expression of sTNFRl in Plasma --- p.53
Chapter 3.4 --- Discussion --- p.57
Chapter Chapter 4: --- T lymphocyte Co-stimulatory Molecule CD26 in SLE
Chapter 4.1 --- Introduction --- p.61
Chapter 4.2 --- Methods --- p.64
Chapter 4.3 --- Results --- p.66
Chapter 4.3.1 --- Characteristic of SLE Patients and Control Subjects --- p.66
Chapter 4.3.2 --- Expression of Human CD26 in Plasma --- p.66
Chapter 4.3.3 --- "Cell Surface Expression of CD26 on Monocytes, Th, Tc plus Ts, B and iNKT Lymphocytes" --- p.66
Chapter 4.3.4 --- Circulating Number of iNKT Lymphocytes --- p.67
Chapter 4.4 --- Discussion --- p.71
Chapter Chapter 5: --- Thl7 Lymphocytes and Expression of IL-17 in SLE
Chapter 5.1 --- Introduction --- p.76
Chapter 5.2 --- Methods --- p.78
Chapter 5.3 --- Results --- p.79
Chapter 5.3.1 --- Characteristics of SLE Patients and Control Subjects --- p.79
Chapter 5.3.2 --- Ex vivo production of IL-17A from PBMC --- p.79
Chapter 5.3.3 --- Circulating Number of Thl7 Lymphocytes --- p.79
Chapter 5.4 --- Discussion --- p.82
Chapter Chapter 6: --- Intracellular Mitogen Activated Protein Kinases in SLE
Chapter 6.1 --- Introduction --- p.87
Chapter 6.2 --- Methods --- p.89
Chapter 6.3 --- Results --- p.91
Chapter 6.3.1 --- Characteristics of SLE Patients and Control Subjects --- p.91
Chapter 6.3.2 --- Expression of Phospho-p38 MAPK in PBMC --- p.91
Chapter 6.3.3 --- Expression of Phospho-ERK in PBMC --- p.92
Chapter 6.3.4 --- Expression of Phospho-JNK in PBMC --- p.92
Chapter 6.3.5 --- "Relative Percentage Increase of Phosphorylated p38 MAPK, ERK and JNK upon IL-18 Activation" --- p.93
Chapter 6.4 --- Discussion --- p.104
Chapter Chapter 7: --- Toll-like Receptors in SLE
Chapter 7.1 --- Introduction --- p.111
Chapter 7.2 --- Methods --- p.113
Chapter 7.3 --- Results --- p.115
Chapter 7.3.1 --- Characteristics of SLE Patients and Control Subjects --- p.115
Chapter 7.3.2 --- Expression of TLRl to TLR9 of PBMC --- p.115
Chapter 7.3.3 --- Preliminary Results of Cytokine and Chemokine Expression Upon TLR Lignad Activation --- p.116
Chapter 7.4 --- Discussion --- p.126
Chapter Chapter 8: --- Conclusion and Future Perspectives --- p.133
Appendix --- p.138
References --- p.140
34
Chen, Shiuan-Yu, and 陳宣諭. "Inhibitory Effects of Agaricus blazei on U937 Cells and on Metastasis in Mice Injected with CT26 Cells." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/77867595348573063411.
Full textAbstract:
碩士國立臺灣大學
食品科技研究所
92
Agaricus blazei (AB) is a dietary mushrooms and known for its immunoenhancing, antitumor, antioxidation, antiviral, and anti- mutagenesis actions. In the present study, furiting body of AB was used to investigate the immunoenhancing and antitumor activities in vitro and in vivo. First, 4℃ cold-water extracts, boiled-water extracts, and ethanol (75%) precipitates of both cold- and boiled-water extracts from AB were incubated with human leukemic U937 cells to observe the changes in growth inhibition (%) and differentiation-inducing effect by conditioned medium (CM) method or co-cultivation method, followed by the cell cycle arrest test by a flow cytometry. Results showed that remarkable growth inhibition (about 78 %) was observed when U937 cells were incubated with 400 mg/mL of ethanol precipitates of boiled-water extracts from AB, while cell cycle of U937 cells were arrested at G0/G1 phase when were incubated for 5 days with ethanol precipitates of boiled-water extracts from AB without apoptosis occurrence (< 0.2 %). On the other hand, in vivo, male Balb/c mice, orally administrated with different amounts (200~600 mg/kg/day) of ethanol precipitates of boiled-water extracts from AB, were injected with 2 × 105 CT26 (colon tumor) cells intraveneously via a tail vein to establish pulmonary metastases and then sacrificed after 12 days of inoculation. Metastatic lung nodules in control group were counted to be 121/mouse and experimental group fed with 200, 400, and 600 mg/kg/day were counted to show 36/mouse, 36/mouse, and 55/mouse, respectively, revealing significantly (p < 0.05) the anti-metastatic effect of AB. Histopathologic results in lungs was also consistent with the finding in vivo. Insignificant changes in renal functions and immunohistograph were observed in mice fed with Agaricus blazei at those three dosages.
35
Liu, Hsien-Ta, and 劉顯達. "Protein Interaction of Nucleophosmin/B23 with Nucleolin/C23 in Cell Proliferation and Cell Cycle." Thesis, 1997. http://ndltd.ncl.edu.tw/handle/94784220798883938947.
Full textAbstract:
碩士長庚醫學暨工程學院
基礎醫學研究所
85
Nucleophosmin/B23, is a major nucleolar phosphoprotein which is more abundant in tumor cells as compared to normal resting cells. When cells are treatment with an anti-tumor drug, such as actinomycin D, that inhibits cell growth or during the stationary phase of growth, nucleophosmin/B23 translocates from nucleolus to nucleoplasm. Nucleophosmin/B23 has been proposed to be involved in the preribosomal particle assembly and nucleolin/ C23 has been proposed to be involved in rRNA processing. In this report, cross-linking reagent, dithiobis succinimidyl propionate (DSP), was used to detect nucleophosmin/B23-nucleolin/C23 complex in HeLa cells. By using immunoprecipitation, immunofluorescence and confocal microscopy, I have found that nucleophosmin/B23 interacts with nucleolin/C23 in interphase as well as in cytokinesis, but not in prometaphase nor in metaphase of cell cycle. In actinomycin D-induced inhibition of cell growth, the interaction of nucleophosmin/B23 and nucleolin/C23 is found not only in cells in which both proteins are localized in nucleolus but also in cells in which they have translocated from nucleolus to nucleoplasm. In cell free kinase and immunoprecipitation assays, the nucleophosmin/B23-nucleolin/C23 interaction is not related to the cell cycle dependent phosphorylation states of nucleophosmin/B23. These results indicate: (1) The associated complex of nucleophosmin/B23 and nucleolin/C23 during cytokinesis and interphase may be a part of the assembly line responsible for the synthesis and processing of pre-ribosomal particles and rRNA. (2) Factors other than phosphorylations of nucleophosmin/B23 to interact with nucleolin/C23, resulting in the cease of nucleolar activities and mitotically structural dissolution of the nucleolus.
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Cunha, Ana Margarida Delindro Ferreira da. "Study of CDC5 and CDC6 expression on human iNKT cells." Master's thesis, 2018. http://hdl.handle.net/10773/25182.
Full textAbstract:
Invariant Natural Killer (iNKT) cells are T lymphocytes that recognize lipid antigens presented by CD1d molecules and have a semi-invariant T cell receptor. iNKT cells produce high quantities of cytokines after antigen recognition or activation. The regulation of iNKT cell activation is crucial for its role in infection and tumor control. CD5 and CD6 are transmembrane surface glycoproteins expressed by conventional T cells that regulate the activation of these cells, but their expression on human iNKTs has not been investigated yet. Here, we studied the basal expression of both CD5 and CD6 on human iNKTs and also their modulation after activation. The involvement of CD6 in antigen induced iNKT cell activation was also addressed. Our results show that human peripheral blood iNKT cells express both CD5 and CD6, at similar and higher levels, respectively, than conventional T cells. Activation of a human iNKT cell line with the non-specific stimulus Phytohaemagglutinin (PHA) down-regulated the expression of both CD5 and CD6, whereas when the prototypic antigen α-Galactosylceramide (α-GalCer) was used only a decrease in CD6 expression was observed. The use of Raji B cells, expressing or not CD166, a ligand for CD6, as antigen presenting cells did not disclose a major role for CD6 in α-GalCer induced iNKT cell activationAs células Invariant Natural killer T (iNKT) são um subtipo de linfócitos T que reconhecem antigénios lipídicos através da molecula de CD1d e têm um recetor de células T semi-invariante. Estas células produzem grandes quantidades de citocinas após serem ativadas. A regulação das iNKTs é crucial para controlar o seu efeito na infeção e no cancro. CD5 e CD6 são glicoproteínas transmembranares expressas na superfície das células T e que regulam a sua activação, sendo que a sua expressão em células iNKTs humanas ainda não tinha sido estudada. Neste trabalho estudou-se a expressão basal destas moléculas em iNKTs humanas e também a sua modelação após activação. O envolvimento do CD6 na indução de ativação das iNKTs pelo antigénio α-Galactosylceramide (α-GalCer) também foi estudada. Os resultados mostraram que as iNKTs presentes no sangue humano periférico expressam CD5 e CD6, sendo que em comparação com as células T convencionais, o CD5 é expresso a níveis semelhantes e o CD6 é expresso em níveis superiores. A activação de iNKTs humanas pela Phytohaemagglutinin (PHA) (estímulo não específico) diminuiu a expressão das moléculas CD5 e CD6 enquanto que com o antigénio prototípico α-GalCer só se verificou uma descida na expressão de CD6. O uso de células Raji expressando ou não o CD166, um ligando do CD6, como células apresentadoras de antigénio, não revelou ter um papel importante na indução de activação da iNKTs pelo antigénio α-GalCer
Mestrado em Biomedicina Molecular
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Freitas, Raquel Filipa Reis de. "The impact of CD6 targeting in T cell function and immunopathology." Doctoral thesis, 2018. http://hdl.handle.net/10451/44166.
Full textAbstract:
In the last few decades, monoclonal antibodies have become one of the most widely used classes of therapeutic agents, representing a billion-dollar industry with more than 30 monoclonal antibodies approved for human therapeutics and many others under clinical evaluation.1
Their main advantages regarding other therapeutic agents consist of high specificity and high flexibility, which applied against targets involved in immune synapse will enhance its immunomodulatory therapeutic benefits. CD6 an immune synapse transmembrane glycoprotein, important for the stability of antigen presentation, maturation of immunological synapse and optimal T-cell proliferation, has been revived as a therapeutic target since the creation of a nondepleting anti-CD6 mAb in the early '90s. Despite CD6 has been extensively studied, understanding its biology has been difficult due to paradoxical results. Still, one thing is for sure, which is its role in autoimmune pathologies, as it is the case of Multiple Sclerosis, Rheumatoid Arthritis, and Psoriasis. And an example of CD6 paradoxical impact is, while in experimental autoimmune encephalomyelitis (EAE) and imiquimod-induced psoriasis CD6-deficient mice show disease protection or attenuation, in collagen-induced arthritis (CIA) the absence of CD6 made it even worst.
So, we have decided to take advantage of this new non-depleting mAb against CD6 d1, developed by our collaborators in Cuba and try to understand how targeting CD6 would impact T cell functional properties and how it would interfere in immune pathologies. Here, I show how both murine and human antibodies targeting CD6 domain 1 influenced exactly that.
First, we have investigated how targeting CD6 with our mAb would affect the normal development of a mouse model of MS, to do so we used a well-established EAE model, which had already been used in the lab.
Treatment with anti-CD6 was intriguing, since the outcome was heavily related to the dose being used, meaning while a low dose was protective, high doses showed a level of disease severity equivalent or even worse than the control group. However, our mice results do resemble the reports on RA clinical trials, where lower doses were the ones giving longer-term responses. To uncover the mechanisms behind it, we investigated how CD6 targeting was affecting CD4+ T cell functional specialization. And accordingly, to our in-vitro results, we verified that once more, in a dose-dependent manner, while increasing doses were compromising Tregs polarization, in the case of Th1's it was favoring it. To try to exclude a possible steric hindrance effect due to the mAb size, we used a soluble CD166 (CD6 d3 ligand) as a means to disrupt T cell's CD6 interactions with APC's CD166. However, this did not mimic CD6 targeting with our anti-CD6 d1 mAb, suggesting a steric hindrance independent effect. More, targeting CD6 with our mAb suggests a direct effect over signaling itself, since its modulatory properties are only detectable if under activating physiologic conditions. Under supra-physiologic stimulation like with anti-CD3/anti-CD28, the impact over polarization is lost.
We expected the impact of anti-CD6 d1 to be a fine-tuned one since no major alterations were seen on either T cell survival or proliferation.
Following the rationale of this dose-dependent effect caused by CD6 targeting, we decided to explore its therapeutic potential on other disease models with opposite kinetics to autoimmune diseases. So, we investigated if in a model of breast cancer, high doses of anti-CD6, given under different delivery strategies, would result in total tumor clearance or reduced tumor growth. Our results ended up showing a reduced growth tumor ability if given in in-situ cumulative doses. However, the way CD6 targeting specifically impacted the CD4+ T cell population was not very conclusive due to the lack of statistical significance. But once more the data suggested a negative impact over CD25+Foxp3+ regulatory T cells, specifically tumor-infiltrating ones. Another observation was a potential increase of IL-17 expression by these very same infiltrating Tregs which has been associated with MAPK activation pathways also associated with CD6 activation. Under these same conditions our data also suggests, a negative impact of CD6 targeting over CD4+ T cell activation as measured by CD25 MFI levels, a relation previously reported on human cells by literature.
To validate the mice anti-CD6 d1 mab as an adequate proxy of itolizumab, we have also investigated how Itolizumab would impact CD4+ T cell's functional properties in-vitro. And as expected, when treated with anti-CD6 d1, human cells also displayed a dose-dependent negative impact over Treg polarization while on the other side favoring Th1's. But contrary to mice, and despite no impact on survival, targeting CD6 did significantly impact. Besides that, human data also suggested a steric hindrance independent effect and dependence on physiological activation conditions so that an impact on T-cell functional properties could be perceived. Activation strategies like anti-CD3/anti-CD28 or SAg mix and APCs, precisely because did not allow an impact of anti-CD6 d1 on CD4+ T cells, shed some light into which signaling pathways anti-CD6 d1 was affecting.
Overall our data show a dose-dependent impact of anti-CD6 d1 over T cell functional specialization, meaning while increasingly high doses reduce T cell's polarization ability towards Tregs also favors Th1 induction, something true for both murine and human cells. A potential explanation for such observations is the relation between activation levels and polarization sensitivity, so different activation levels caused by CD6 targeting might favor specific polarization phenotypes.
Our data highlights the importance of dosage and how the same drug might be beneficial for different disease conditions.
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Allehaibi, Hanaa S. "Role of CD26/DPPIV in the Homing and Engraftment of Long-Term CD34- Negative Hematopoietic Stem Cells." Thesis, 2021. http://hdl.handle.net/10754/668873.
Full textAbstract:
CD26/DPPIV is a dipeptidyl peptidase that cleaves and destroys a variety of substrates
such as the chemokine SDF-1α, a chemokine expressed along bone marrow endothelium,
which is essential for the recruitment of hematopoietic stem cells (HSCs) via binding with
its receptor CXCR4 to the bone marrow. Thus, CD26 is thought to interfere with the second
step, chemokine/chemokine receptor interactions, of the cellular migration paradigm. To
further study the role of CD26 in the migration of HSCs, we screened several human
leukemic cell lines to find a model cell line that expresses active CD26 and discovered that
the pro-monocytic cell line, U937 was optimal for this purpose. U937 cells were used to
optimize a variety of assays including an CD26 activity assay and transwell migration assay
with and without the use of a CD26 inhibitor, Diprotin A. Then, we isolated short-term and
long-term HSCs from the bone marrow of C57BL/6N mice using a combination of surface
markers and a fluorescence-activated cell sorter. The expression levels of Step 2’s homing
molecules were measured by FACS in both fractions of HSCs. Interestingly, we detected
differences in the expression of CD26 between these two populations that may help explain
the inability of long-term HSCs to migrate to the bone marrow. Thus, through the use of a
CD26 inhibitor the long-term HSCS migration to the bone marrow could be enhanced,
leading to a prolonged and efficient stem cell engraftment activity. Such studies are could
help develop protocols to improve stem cell engraftment for patients suffering from
hematological diseases such as leukemia.
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Ahandoust, Sina. "Osteocyte signaling and its effects on the activities of osteoblasts and breast cancer cells." Thesis, 2021. http://dx.doi.org/10.7912/C2/9.
Full textAbstract:
Indiana University-Purdue University Indianapolis (IUPUI)Bone is a common location for breast cancer cell metastasis, and progression of tumor in bone can lead to bone loss and affect human health. Osteocytes have important roles in bone homeostasis and osteogenesis, and their interaction with metastasized cancer cells are known to affect progression of metastasized tumor. However, the potential role of metabolic signaling and actin- cytoskeleton-associated moesin in the interaction of osteocytes and tumor cells remain poorly understood. In this study, we first examined the roles of metabolic signaling, specifically global AMPK modulators and mitochondria-specific AMPK inhibitor (Mito-AIP), as well as mechanical force in beta catenin signaling through interaction between osteocytes and precursor osteoblasts as well as osteocytes and breast cancer cells. We also evaluated the role of metabolic signaling in Rho GTPases including RhoA, Rac1 and Cdc42. We observed that AMPK activator (A769662) and Mito-AMPK stimulated beta catenin translocation to the nucleus, indicating the activation of Wnt signaling, while Mito-AIP did not significantly affect beta catenin activation in osteoblasts. We also observed that osteocyte conditioned medium (CM) treated with Mito-AIP substantially increased beta catenin signaling in osteoblasts, while decreasing beta catenin signaling in breast cancer cells. CM of osteocytes treated with fluid flow increased beta catenin signaling in breast cancer cells. A769662 and Mito-AIP also decreased the activities of RhoA, Rac1, and Cdc42 in cancer cells which are known to regulate cancer cell migration. Additionally, we evaluated the roles of intracellular and extracellular moesin (MSN) protein in well-established oncogenic signaling proteins, such as FAK, Src, and RhoA as well beta catenin signaling. Constitutively active MSN (MSN+) significantly increased FAK and Src activities in cancer cells, but decreased the activity of RhoA. Surprisingly, CM of mesenchymal stem cells treated with MSN+ decreased the activities of FAK, Src, and RhoA, suggesting the inhibitory role of extracellular MSN in tumor-promoting signaling. Our results suggest the distinct role of AMPK signaling, specifically at mitochondria of osteocytes, in the activities of beta-catenin signaling in osteoblasts and breast cancer cells and the distinct role of intracellular and extracellular MSN in these two types of cell.
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Tweel, Kristin. "Competing Influences Of The Tumor Microenvironment On CD26 And The Cancer Phenotype Of Colorectal Carcinoma Cells." Thesis, 2011. http://hdl.handle.net/10222/21904.
Full textAbstract:
In Canada, colorectal cancer is the second leading cause of cancer death for both men and women. There are many different factors that contribute to the progression and spread of the disease. However, increasing evidence now suggests that the tumor microenvironment plays a paramount role in these processes.
CD26 is a multifunctional, cell-surface glycoprotein that has intrinsic enzyme activity, binds adenosine deaminase and interacts with the extracellular matrix. Through its various functions it serves to constrain cancer progression. For example, it is known to cleave CXCL12, the ligand for CXCR4. The CXCL12:CXCR4 axis is normally involved in cancer metastasis by promoting cancer cell migration, invasion and proliferation. Down-regulation of CD26 is observed in certain cancers - this has been shown in vitro to occur in response to certain soluble mediators.
The first part of this study looked at the effects of glucose and its metabolic product lactate on CD26 expression in colorectal carcinoma cells. Our study showed that CD26 expression is lower in cancer cells that are grown in low-glucose, high-lactate conditions, which replicates the situation within a tumor.
The second part of this study examined the effect of adenosine, a purine nucleoside, on colorectal carcinoma cells and supportive stromal cells - cancer-associated HS675.T fibroblasts (CAFs) and Met-5a mesothelial cells. Adenosine increased the proliferation of CAFs and increased CXCL12 mRNA in both stromal cell lines. It also increased MMP-13 mRNA in stromal cells as well as colorectal cancer cells, suggesting that adenosine may promote progression and metastasis through various mechanisms.
The last section focused on the ability of cellular products and 3-dimensional tissue topology to coordinate and affect the behaviour of the different cell populations. Here we show that secretory products from colorectal cancer cells promote CAF proliferation but inhibit mesothelial cell proliferation, and are also able to modulate MMP-13 expression. Finally, certain responses are enhanced in multicellular spheroids.
In conclusion, the tumor microenvironment represents a major consideration in the treatment of solid tumors. Our data suggest that various soluble mediators, such as adenosine, may have therapeutic implications in cancer treatment and might represent novel targets for future research.
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Santos, Ana Rita Faria dos. "DISSECTING T CELL SIGNALING: A DUAL FUNCTION OF CD6 THAT IMPACTS ON T CELL RESPONSES AND AUTOIMMUNITY." Doctoral thesis, 2020. https://hdl.handle.net/10216/129030.
Full text
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Santos, Ana Rita Faria dos. "DISSECTING T CELL SIGNALING: A DUAL FUNCTION OF CD6 THAT IMPACTS ON T CELL RESPONSES AND AUTOIMMUNITY." Tese, 2020. https://hdl.handle.net/10216/129030.
Full text
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Falkenberg, Christiane. "Optimizing Organic Solar Cells: Transparent Electron Transport Materials for Improving the Device Performance." Doctoral thesis, 2011. https://tud.qucosa.de/id/qucosa%3A26053.
Full textAbstract:
This thesis deals with the characterization and implementation of transparent electron transport materials (ETM) in vacuum deposited p-i-n type organic solar cells (OSC) for substituting the parasitically absorbing standard ETM composed of n-doped C60. In addition to transparency in the visible range of the sun spectrum, the desired material properties include high electron mobility and conductivity, thermal and morphological stability, as well as good energy level alignment relative to the adjacent acceptor layer which is commonly composed of intrinsic C60. In this work, representatives of three different material classes are evaluated with regard to the above mentioned criteria.
HATCN (hexaazatriphenylene hexacarbonitrile) is a small discoid molecule with six electron withdrawing nitrile groups at its periphery. It forms smooth thin films with an optical energy gap of 3.3eV, thus being transparent in the visible range of the sun spectrum. Doping with either 5wt% of the cationic n-dopant AOB or 7wt% of the proprietary material NDN1 effectively increases the conductivity to 7.6*10^-6 S/cm or 2.2*10^-4 S/cm, respectively. However, the fabrication of efficient OSC is impeded by the exceptionally high electron affinity (EA ) of approximately 4.8eV that causes the formation of an electron injection barrier between n-HATCN and intrinsic C60 (EA=4.0eV). This work presents a strategy to remove the barrier by introducing doped and undoped C60 intermediate layers, thus demonstrating the importance of energy level matching in a multi-layer structure and the advantages of Fermi level control by doping.
Next, a series of six Bis-Fl-NTCDI (N,N-bis(fluorene-2-yl)-naphthalenetetracarboxylic diimide) compounds, which only differ by the length of the alkyl chains attached to the C9 positions of the fluorene side groups, is examined. When increasing the chain length from 0 to 6 carbon atoms, the energy levels remain nearly unchanged: We find EA=3.5eV as estimated from cyclic voltammetry, an ionization potential (IP ) in the range between 6.45eV and 6.63eV, and Eg,opt=3.1eV which means that all compounds form transparent thin films. Concerning thin film morphology, the addition of side chains results in the formation of amorphous layers with a surface roughness <1nm on room temperature glass substrates, and (1.5+/-0.5)nm for deposition onto glass substrates heated to 100°C. In contrast, films composed of the side chain free compound Bis-HFl-NTCDI exhibit a larger surface roughness of (2.5+/-0.5)nm and 9nm, respectively, and are nanocrystalline already at room temperature. Moreover, the conductivity achievable by n-doping is very sensitive to the side chain length: Whereas doping of Bis-HFl-NTCDI with 7wt% NDN1 results in a conductivity in the range of 10^-4 S/cm, the attachment of alkyl chains causes a conductivity which is more than three orders of magnitude smaller despite equal or slightly higher doping concentrations. The insufficient transport properties of the alkylated derivatives lead to the formation of pronounced s-kinks in the jV -characteristics of p-i-n type OSC while the use of n-Bis-HFl-NTCDI results in well performing devices.
The last material, HATNA-Cl6 (2,3,8,9,14,15- hexachloro-5,6,11,12,17,18-hexaazatrinaphthylene), exhibits Eg,opt=2.7eV and is therefore not completely transparent in the visible range of the sun spectrum. However, its energy level positions of EA=4.1eV and IP=7.3eV are well suited for the application as ETM in combination with i-C60 as acceptor. The compound is dopable with all available n-dopants, resulting in maximum conductivities of sigma=1.6*10^-6, 3.5*10^-3, and 7.5*10^-3 S/cm at 7.5wt% AOB, Cr2(hpp)4, and NDN1, respectively. Applying n-HATNA-Cl6 instead of the reference ETM n-C60 results in a comparable or improved photocurrent density at an ETM thickness d(ETM)=40nm or 120nm, respectively. At d(ETM)=120nm, the efficiency eta is more than doubled as it increases from eta(n-C60)=0.4% to eta(n-HATNA-Cl6)=0.9% .
Optical simulations show that the replacement of n-C60 by n-Bis-HFl-NTCDI, n-HATNA-Cl6, or the previously studied n-NTCDA (naphthalenetretracarboxylic dianhydride) in p-i-n or n-i-p type device architectures is expected to result in an increased photocurrent due to reduced parasitic absorption. For quantifying the gain, the performance of p-i-n type OSC with varying ETM type and thickness is evaluated. Special care has to be taken when analyzing devices comprising the reference ETM n-C60 as its conductivity is sufficiently large to extend the area of the aluminum cathode and thus the effective device area which may lead to distorted results. Overall, the experiment is able to confirm the trends predicted by the optical simulation. At large ETM thickness in the range between 60 and 120nm, the window layer effect of the ETM is most pronounced. For instance, at d(ETM)=120nm, eta(C60) is more than doubled using n-HATNA-Cl6 and even more than tripled using n-Bis-HFl-NTCDI or n-NTCDA. At optimized device geometry the photocurrent gain is slightly less than expected but nonetheless, the efficiency is improved from eta(max)=2.1% for n-C60 and n-HATNA-Cl6 solar cells to eta(max)=2.3, and 2.4% for n-Bis-HFl-NTCDI and n-NTCDA devices, respectively. This development is supported by generally higher Voc and FF in solar cells with transparent ETM.
Finally, p-i-n type solar cells with varying ETM are aged at a temperature of 50°C and an illumination intensity of approximately 2 suns. Having extrapolated lifetimes t(80) of 36, 500, and 14000h and nearly unchanged jV-characteristics after 2000h, n-C60 and n-Bis-HFl-NTCDI devices exhibit the best stability. In contrast, n-NTCDA devices suffer from a constant decrease in Isc while n-HATNA-Cl6 solar cells show a rapid dscegradation of both Isc and FF associated with a decomposition of the material or a complete de-doping of the ETM. Here, lifetimes of only 4500h and 445hare achieved.
44
Li, Yan-Qing, and 李彥慶. "The synergistic anticancer effect of Lipo-Dox and perforin on colon cancer cell, CT26." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/59998506349437875104.
Full textAbstract:
碩士國立暨南國際大學
生物醫學科技研究所
97
Perforin, a secreted protein, is synthesized by activated cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. It is a key component of the lytic machinery, being able to insert into the plasma membrane of targeted cells to form pores which lead to cell destruction. In the present study, we investigated the possibility of tumor eradication through the effect of perforin and its synergistic effect with antitumor drug, doxorubicin (Dox). Several perforin plasmids, driven by CMV promoter, were constructed and were transfected to murine colon cancer cell line, CT26. The cytotoxicity of perforin was evaluated by MTT assay. The flanking of mouse VEGF signal sequence and the deletion of C-terminus sequence on perforin at DNA level were performed to enhance the cytotoxicity against cancer cells. This synergistic effect of perforin and Dox suggested a potential strategy for cancer therapy and to reduce antitumor drugs caused side effects.
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Wang, Ｙa-Ling, and 翁雅玲. "Anti-metastatic effect achieved by oral administration of resveratrol on BALB/c mice challenged with CT26 tumor cells." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/27605823301766634752.
Full textAbstract:
碩士國立嘉義大學
食品科學系研究所
95
Multiple bioactivities of resveratrol such as prevention of cardiovascular disease, anti-cancer and extension of lifespan have been demonstrated. Among its anti-cancer activities, anti-metastasis has been meagerly studied. In this study, pulmonary metastasis of BALB/c mice challenged with CT26 of colorectal adenocarcinoma cells as affected by oral administration with different doses of resveratrol was examined. Tail intravenous injection with CT26 cells was conducted. The oral administration doses included low dose group (5 mg/kg/day, n=10), middle dose group (15 mg/kg/day, n=26), high dose group (30 mg/kg/day, n=10), and control group (without oral administration of resveratrol, n=27). When young mice (5-wk-old) were raised 1 wk for adaptation, resveatrol was given by oral administration once every two days. After continuous administration of resveratrol for 8 or 12 times, injection of CT26 cells (3x105 cells/mouse) was conducted and oral administration of resveratrol was continued until the end of each experiment. As observed in a preliminary test, the control mice died at the 20th day after injection of CT26 cells due to pulmonary tumor metastasis. Therefore, sacrifice was carried on the 20th day after injection of CT26 cells to examine pulmonary metastasis by enumerating tumor nodules on lungs. Histopathological examination, blood cells and biochemical analyses were investigated. As resulted, effectiveness in suppression of cancer cell metastasis by resveratrol administration was observed. The most effective suppression was observed in the middle dose group, in which above 60% of the test mice did not bear any tumor nodule observed by visual examination nor tumor tissue detected by histopathological section examination. Significant anti-metastasis effect was also observed in the low dose and the high dose groups of mice. Based on analyses of serum GOT, GPT, BUN and creatinine, there was no significant difference observed among the test groups, indicating that the applied doses of resveratrol did not result in liver or kidney toxicity. When the control, low and middle groups were subjected to survival curve experiment for 100 days, one of the control mice died at the 20th day after injection of CT26 cancer cells mainly due to pulmonary metastasis. After 100 days, the survival rates of the control, low and middle groups were 0, 40 and 50%, respectively. After dissection and inspection of the lungs from all died mice, some lungs festered and all other lungs were seriously occupied with tumor nodules. When the survival mice were further challenged with hypodermic injection of CT26 cancer cells and oral administration of resveratrol was ceased for 30 days, both lungs and the injection parts of the sacrificed mice did not bear any tumor. This reveals that those mice might have created potency against metastasis. As concluded, oral administration with different doses of resveratrol applied for the tests of tumor metastasis and the survival curve, administration levels ranged from 5 to 30 mg/kg/day were observed being effective in suppression of tumor metastasis. These doses were not toxic to liver and kidney.
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Chein, Chia-Yi, and 簡佳怡. "Inhibitory Effect of proteins from Hypsizigus marmoreus on CT26 Colon Adenocarcinoma Cells and Metastasis in Balb/c Mice." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/89761337724577504075.
Full textAbstract:
碩士國立臺灣大學
食品科技研究所
93
Hypsizigus marmoreus (HM), one of popular dietary mushrooms, contains high protein, low calorie, and low fat and has long been consumed in Japan. Several researches indicate that HM has antitumor and antifungal activities. In the present study, HM was used to study its antitumor activity in vitro and in vivo. First, 40~80% ammonium sulfate precipitates of cold-salt water extracts from HM were prepared and incubated with mouse colon CT26 cells to observe the changes in growth inhibition (%) for 24, 48 and 72 hr by MTT assay, followed by the cell cycle arrest by a Flow Cytometry. Results showed that remarkable growth inhibition, higher than 68 %, was observed when CT26 cells were incubated with 600 μg/mL of 40~80 % ammonium sulfate precipitates of cold-salt water extracts from HM. In addition, cell cycle arrest of CT26 cells at G2/M phase and apoptosis were induced. In vivo, pulmonary metastasis of CT26 tumor on male Balb/c mice orally administrated for 13 days with doses (200, 400 and 600 mg/kg bw/day) of ammonium sulfate precipitates of cold-salt water extracts from HM and injected (iv) with 1×105 CT26 cells via a tail vein was established to observe the results. Metastasic lung nodules in experimental group fed with 200, 400 or 600 mg/kg bw/day decreased in a dose-dependent manner, revealing the significant (p<0.05) anti-metastatic effect of HM proteins. Histopathologic results in lung was consistent with the finding in vivo. Insignificant changes in renal and immunohistograph were observed in mice at those three dosages.
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"Drug Delivery And Homing Function Of Mesenchymal Stem Cells In Hiv Therapy." Tulane University, 2014.
Find full textAbstract:
Human Immunodeficiency Virus -1 infects CD4+ cells, and the subsequent loss of these cells cause Acquired Immune Deficiency Syndrome. Highly active antiretroviral therapy (HAART) is crucial to control viremia in the clinical management of AIDS/HIV infection; however, drug regimens are complex, expensive, and require life-long intervention with potential side effects. Current conventional anti-HIV drugs target different phases of the HIV life cycle and can be categorized as nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, entry inhibitors (co-receptor antagonists and fusion inhibitors), and integrase inhibitors(II). Enfuvirtide (Fuzeon, or T-20) is the first fusion inhibitor approved by the FDA and has substantial side effects and drug delivery issues with most patients developing some local injection site reaction. The subcutaneous application of enfuvirtide and its short half-life, which requires twice daily administration, has disadvantages in patients who are already burdened by complex oral therapy. To overcome these drug issues, we propose an alternative method to administer the HIV-1 peptide fusion inhibitor C46. Stem cells can be a vehicle for delivering genes to specific tissues in the body and their therapeutic delivery systems are extensively used in cancer research. For many years, restoration of blood and immune system function has been used as a component in the care of cancer patients who have been treated with chemotherapeutic agents. Mesenchymal Stem Cells (MSCs) have been demonstrated as a delivery vehicle for gene therapy applications based on their ability to engraft and home to inflamed tissues. MSCs are multi-potent and have immunological function in several human diseases. To investigate MSCs immune suppressive ability in HIV infection system, we will evaluate the crosstalk between MSCs and HIV infection immune-modulatory network.acase@tulane.edu
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Yang, Shih-Cheng, and 楊仕丞. "Analyzing the role of interleukin-7 in regulating innate lymphoid cells and tumor immunity by using CT26 tumor model." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/cx3432.
Full textAbstract:
碩士國立陽明大學
微生物及免疫學研究所
106
Tumor microenvironment (TME) is constructed by the tumor and tumor infiltrated cells, and is crucial for establishing host immune system against tumor. In tumor microenvironment, many infiltrating immune cells and tumor infiltrating lymphocytes could be observed. CD4+, CD8+ T-cells and regulatory T-cells (Treg) are the major type infiltrating lymphocytes in tumor microenvironment. Recently, a newly identified cell population called innate lymphoid cell (ILC) have been reported that also involve in tumor progression. Innate lymphoid cells play the key roles in mucus environment to against many infections. Dysregulation of these cell usually leads to chronic inflammation which is believed to be an essential condition in tumorigenesis. Although innate lymphoid cell had pro-tumor effect due to IL-13, IL-17 and IL-22, anti-tumor effect was established under IFN-γ condition. Interleukin-7 (IL-7) is a critical cytokine for lymphoid cell development. Furthermore, IL-7 could be a tumor promotor or inhibitor according to different cancer. It is interesting to study whether IL-7 would regulate ILC and modulate tumor immunity in CT26 tumor model.
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McCue, Rachel A. "Effects of Hydrocephalus on Rodent Optic Nerve and Optic Disc." Thesis, 2021. http://dx.doi.org/10.7912/C2/59.
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Indiana University-Purdue University Indianapolis (IUPUI)Hydrocephalus affects 1 in 1,000 newborns and nearly 1,000,000 Americans, leading to an increase in intercranial pressure due to the build-up of cerebrospinal fluid. There are numerous complications that arise as a result of hydrocephalus, but this study focuses on optic disc edema. The subarachnoid space surrounding the optic nerve contains cerebrospinal fluid. The cerebrospinal fluid increases in hydrocephalus, putting pressure on the optic nerve. The additional intracranial pressure has been proposed to cause axoplasmic stasis within the retinal ganglion cell axons, leading to axonal damage and retinal ischemia. The purpose of this study was to determine the effects of hydrocephalus on the optic disc and retina in several animal models of hydrocephalus. This study uses two genetic and two injury-induced models of hydrocephalus in addition to immunohistochemistry and histological stains to examine the optic disc, thickness of retinal layers, and numbers of retinal cells. This study serves as preliminary work to help build the case that hydrocephalus causes cell loss in the retina, as well as swelling of the retinal ganglion cell axons, leading to axoplasmic stasis and cell death.
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Glória, Vânia Raquel Gomes. "When chromatin structure meets CD6 exon 5 Alternative Splicing: an encounter triggered by T cell activation." Doctoral thesis, 2014. https://repositorio-aberto.up.pt/handle/10216/76795.
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