Dissertations / Theses on the topic 'Cell membranes Effect of drugs on'
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1
Englund, Marita. "Effects of hypoxia and antiepileptic drugs on electrophysiological properties of CA1 neurons in hippocampus /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-237-8/.
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Dricu, Anica. "Role of dolichyl phosphate, N-linked glycosylation and cell membrane expression of insulin-like growth factor-1 receptor in maintenance of malignant cell growth /." Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2751-0.
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Boyd, Nolan Lee. "The effect of shear stress on caveolae formation and function in endothelial cells." Diss., Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04082004-180030/unrestricted/boyd%5Fnolan%5Fl%5F200312%5Fphd.pdf.
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Meza, Benjamin. "The Effect of Cell Type on the Efficacy of CMV Antiviral Drugs." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1567.
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Until recently, all in vitro drug susceptibility assays of cytomegalovirus (CMV) were performed in clinically irrelevant fibroblast cells. This study sought to test if drug susceptibility was affected by cell type. MRC-5 embryonic lung fibroblasts and ARPE-19 retinal pigmented epithelial cells were infected with BADrUL131-Y4 epithelial/fibroblast tropic virus under serial concentrations of ganciclovir (GCV) or maribavir (MBV). Virus was quantified using plaque reduction, GFP fluorescence, and yield reduction. Both drugs performed less efficiently in ARPE-19 cells. A cell type effect was observed for both plaque reduction and yield reduction assays with implications for the treatment of CMV retinitis as well as other manifestations of CMV Disease that involve non-fibroblast cell types.
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Chapman, Dail. "The Effect of Cholesterol on Small-Molecule Diffusion Through Liver Cell Membranes." Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/scripps_theses/269.
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Cholesterol is an important component in maintaining the structure and dynamics of cell membranes. Dysregulation of cholesterol results in detrimental changes including decreased fluidity of the membrane and changes in membrane permeability. Because cholesterol is synthesized and regulated in the liver, many liver diseases are accompanied by dysregulation of cholesterol. And this dysregulation could alter transportation of small molecules through the cell membrane of such diseased cells. This study will focus on the diffusion of three small-molecule drugs through liver cell membranes with varying cholesterol concentration using a molecular dynamics approach. Results from this study could provide more detail about cholesterol’s effect on liver cell membrane permeability.
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Hartsel, Scott Clifton. "Effect of membrane supramolecular structure on the photoresponse and structural stability of bacteriorhodopsin /." The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487260531954914.
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Almaawi, Abdulaziz. "Effect of acetaminophen and nonsteroidal anti-inflammatory drugs on gene expression of human mesenchymal stem cells." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114405.
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A major drawback of cartilage tissue engineering is that human mesenchymalStem cells (MSCs) from patients with osteoarthritis (OA) express high levels of type X collagen. Type X collagen is a marker of late stage chondrocyte hypertrophy, linked with endochondral ossification. Also, MSCs from OA patients express osteogenic marker genes such as alkaline phosphatase (ALK), bone sialoprotein (BSP), and osteocalcin (OC) as well as aggrecan (ACAN), a marker of chondrogenesis, but not type II collagen. OA patients, in an attempt to relieve pain and other symptoms, often take NSAIDs and pain relievers like acetaminophen. The aim of this present study was to determine how these drugs influence human MSC gene expression of different chondrogenic and osteogenic markers. MSCs isolated from the bone marrow of osteoarthritic patients or from normal donors were cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) without or with Acetaminophen (Acet) or non-steroidal anti-inflammatory drugs (NSAIDs), Ibuprofen (Ibu), Diclofenac (Dic), Naproxen (Npx) and Celecoxib (Cele). After 3 days of culture, the cells were collected and gene expression was measured using quantitative PCR for type X collagen (COL10A1), aggrecan (ACAN) and type 1 collagen，as well as osteogenic marker genes such as alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OC) and Runt-related transcription factor 2 (RUNX2). Acet and Npx supplementation led to a significant increase in COL10A1 & RUNX2 expression when compared to control. Furthermore, with Ibu, Acet and Npx supplementation, aggrecan message levels were decreased. In contrast, addition of Cele significantly increased aggrecan gene expression. Finally, Ibu, Acet and Npx decreased type I collagen expression while Cele had a tendency to increase type I collagen expression. The present study showed that NSAIDs and Acet could affect Osteogenic and chondrogenic differentiation of human MSCs. These are features that could interfere with intervertebral disc (IVD) or cartilage repair. Thus, caution must be exercised when using MSCs from OA patients in biological repair of articular cartilage or disc.Un des principaux problèmes de l'ingénierie tissulaire du cartilage réside dans le fait que les cellules souches mésenchymateuses humaines (hCSMs) de patients osteoarthritiques (OA) expriment fortement le collagène de type X (Col X) qui est un marqueur de l'hypertrophie des chondrocvytes, hypertrophie qui est associée à l'ossification. Les hCSMs de patients OA expriment également des marqueurs de l'ostéogénèse tels que la phosphatase alcaline (ALK), une sialoprotéine de l'os (BSP) et l'ostéocalcine (OC), ainsi que l'aggrécane (AGG), un marqueur de la chondrogenèse. Dans le but de diminuer la douleur et autres symptômes reliés à leur maladie, les patients OA consomment des drogues anti-inflammatoires non-stéroïdiennes (NSAIDs). Le but de la présente étude était de déterminer si ces drogues pouvaient influencer l'expression de gènes associés à la chondrogenèse ou à l'ostéogénèse dans les hCSMs. Les CSMs isolées de la moelle osseuse de patients OA ou de donneurs normaux ont été cultivées dans du milieu Eagle modifié selon Dulbecco (DMEM) supplémenté avec 10% de sérum de veau fétal (SVF), sans ou avec Acétominophène (Acét), Ibuprofène (Ibu), Dichlorofenac (Dic), Naproxen (Npx) et Célécoxib (célé). L'expression des marqueurs ostéogéniques et du Col X a été mesurée par PCR quantitatif après 3 jours en culture. Les résultats montrent que l'Acét et le Npx induisaient significativement l'expression du Col X et diminuaient, tout comme l'Ibu, l'expression de l'AGG et du Col de type I (Col I). Cependant, Célé stimulait de façon significative l'expression de l'AGG et inhibait, mais de façon non significative, l'expression du Col I. En résumé, la présente étude montre que les NSAIDs peuvent moduler l'expression de gènes associés à l'ostéogénèse et à la chondrogenèse dans les hCSMs, indiquant qu'ils pourraient interférer dans la réparation du cartilage. L'utilisation de hCSMs de patients OA devrait donc être faite avec prudence pour la réparation biologique du cartilage articulaire et même du disque intervertébral.
8
Wu, Diana. "Effect of membrane thickness and unsaturation on dye efflux rates induced by [delta]-Lysin from phosphatidylcholine vesicles /." Electronic version (PDF), 2005. http://dl.uncw.edu/etd/2005/wud/dianawu.pdf.
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Porter, Tyrone M. "An investigation of the synergy between ultrasound and membrane-disruptive polymers and its effect on cell membranes /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/8126.
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Liao, Ximan, and 廖喜漫. "A study of proteoglycan production during suppressed cell proliferation of a human colon carcinoma cell line." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B3123897X.
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Ho, Yee-wa Eva, and 何綺華. "Effects of Ganoderma lucidum on rheumatoid synovial fibroblasts." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29489933.
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Zhu, Weiwei. "Effects of Membrane Lateral Organization on the Anticancer Activity of Liposomal CA4P against MCF-7 Breast Cancer Cells." Master's thesis, Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/87353.
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BiochemistryM.S.
The goal of this research is to study how the cholesterol content in liposomal formulations affects the anticancer activity (e.g., cell growth suppression) of combretastatin A4 phosphate (CA4P). CA4P is a powerful antivascular agent currently under clinical trials for treating solid tumors. Liposomal CA4P has several advantages over free CA4P, including the reduced toxicities and the increased overall drug efficacy. In this thesis work, I have demonstrated that the proliferation of breast cancer MCF-7 cells varies with the cholesterol mole fraction in the formulation of liposomal CA4P in a biphasic manner, displaying a local minimum at the critical sterol mole fractions (Cr) for maximal superlattice formation. Cell proliferation was monitored using a fluorescence-based assay. Since cholesterol content determines membrane lateral organization, my results imply that membrane lateral organization plays an important role in regulating the anti-cancer activity of liposomal CA4P. This finding provides a new concept in the rational design of liposomal anti-cancer drugs. More than 20 anticancer drug formulations are in the market or under clinical trials. Most of them include cholesterol as a major component. My present study indicates that cholesterol is not just serving as a vesicle stabilizing agent, but also modulates the activity of liposomal drugs. The principle learned from CA4P can be extended to other liposomal anti-cancer drugs. This study is also significant from the membrane biophysics point of view. The data provide additional support for the sterol superlattice model and illustrate that the concept of sterol superlattice can be applied to biotechnology development.
Temple University--Theses
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Chan, Sze-yin, and 陳詩妍. "The effects of ganoderma extracts on immune cell subsets." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43781494.
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Lau, Ping-woi Echo, and 劉頻迴. "The anti-cancer effect of berberine in a human nasopharyngeal carcinoma cell line HONE 1." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40687697.
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Langham, Jennifer. "Effects of aspirin and its derivatives in combination with electroporation for drug delivery in cultured cells." [Tampa, Fla.] : University of South Florida, 2004. http://purl.fcla.edu/fcla/etd/SFE0000614.
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Bradbury, Emma L. "Uptake and transport of orally-deliverable drugs across caco-2 cell monolayers: the effect of lipid formulations." Thesis, Aston University, 2005. http://publications.aston.ac.uk/11031/.
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The aim of this thesis is to investigate the physicochemical parameters which can influence drug loading within liposomes and to characterise the effect such formulations have on drug uptake and transport across in vitro epithelial barrier models. Liposomes composed of phosphatidylcholine (PC) or distearoyl phosphatidylcholine (DSPC) and cholesterol (0, 4, 8, 16 µM) were prepared and optimised in terms of drug loading using the hand-shaking method (Bangham et al., 1965). Subsequently, liposomes composed of 16 µM PC or DSPC and cholesterol (4 µM) were used to monitor hydroxybenzoate release and transport from Iiposomes. The MIT (3[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and crystal violet assays were employed to determine toxicity of the Iiposome. formulations towards the Caco-2 cell line, employed to model the epithelial barrier in vitro. Uptake and transport of mannitol, propranolol, glutamine and digoxin was measured in the presence and absence of Iiposome formulations to establish changes in absorption resulting from the presence of lipid formulations. Incorporation of the four hydroxybenzoates was shown to be influenced by a number of factors, including liposome composition and drug conformation. Methyl hydroxybenzo.ate (MP) was incorporated into the bilayer most effectively with percentage incorporation of 68% compared to 45% for butyl hydroxybenzoate (BP), despite its increased Iipophilicity. This was attributed to the decreased packing ability of BP within the hydrocarbon core of the lipid bilayer compared to MP. Release studies also suggested that the smaller MP was more strongly incorporated within the lipid bilayer with only 8% of the incorporated solute being released after 48-hours compared to 17% in the case of BP. Model transport studies were seen to reflect drug release profiles from the liposome bilayers with significantly (p < 0.01) higher amounts of BP partitioning from the liposome compared to MP, Caco-2 cell viability was maintained above 86% in the presence of all Iiposome formulations tested indicating the liposome formulations are non-toxic towards Caco-2 cells. Paracellular (apical-to-basolateral) transport of mannitol was significantly increased in the presence of DSPC, PC / DSPC:Cholesterol (16:4 µM; 1000 µg). Glutamine uptake and transport via the carrier-mediated route was Significantly (p < 0.01) increased in the presence of PC I DSPC:Cholesterol (16:0; 16:4 µM). Digoxin apical-to-basolateral transport was significantly increased (p < 0,01) in the presence of PC / DSPC:Cholesterol (16:0; 16:4 µM); thus reducing digoxin efflux via P-glycoprotein. In contrast, PC:ChoJesterol (16:0; 16:4 µM) significantly (p < 0.01) decreased propranolol uptake via the passive transcellular route. Bi-directional transport of propranolol was significantly (p < 0,01) decreased in the presence of PC/DSPC:Cholesterol (16:0; 16:4 µM). The structure of a solute is an important determinant for the incorporation and release of a solute from liposome formulations. PC, DSPC and cholesterol liposome formulations are nontoxic towards Caco-2 cell monolayers and improved uptake and transport of mannitol, glutamine. and digoxin across Caco-2 cell monolayers; thus providing a potential alternative delivery vehicle.
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Ikeda, Masahiro. "Effect of the drugs used perioperatively on activity of proopiomelanocortin gene promotor in a pituitary cell line." Kyoto University, 2009. http://hdl.handle.net/2433/126444.
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Forster, Trevor Henry. "Effect of inhibitors of platelet function in haemostasis." Thesis, Queensland University of Technology, 1986. https://eprints.qut.edu.au/36709/1/36709_Forster_1986.pdf.
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Investigation of the role of platelets in the haemostatic
process has been a high priority for many years. In
spite of this the mechanisms by which platelets help to
maintain vascular integrity in undamaged blood vessels
have not been clearly defined. The concept of
endothelial support suggested by the work of Wojcik, Van
Horn, Webber and Johnson (6) has been controversial as it
implies a direct interaction between platelets and
endothelium. An alternate theory offered has been that
of platelet support by attachment to sub-endothelium
following damage to the endothelial cell layer.
To investigate the proposition that platelets and
endothelial cells were capable of direct interaction, a
reaction system using cultured human umbilical vein
endothelial cells was devised. As a result of
experiments using this model it has been shown that a
direct reaction between platelets and endothelial cells
does occur in vitro.
Experiments and techniques were devised to investigate
both the observed interaction and to assess the effect of
inhibitors of platelet function on the reaction.
Evidence gained by scanning electron microscopy and
transmission electron microscopy indicates that a
specific interaction actively involving endothelial cells
is responsible for the observed attachment of platelets
to these cells.
Studies using aspirin inhibited platelets indicate that a
two stage process is involved
first stage of which is
cyclo-oxygenase pathway. The
in this interaction,
independent of
second stage of
reaction appears to involve an active contribution
endothelial cells via their cyclo-oxygenase pathway.
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Ball, Lucy Margaret. "Antifungals and the trichophyton rubrum cell wall." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670146.
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VanDenBosch, Leah M. "Investigating the effect of fluid shear stress on the failure of cancer cell membranes: an experimental and computational analysis." Thesis, University of Iowa, 2018. https://ir.uiowa.edu/etd/6318.
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Cancer metastasis, or the formation of a secondary tumor at a site distant from the primary tumor, is known to be an inefficient process. Historically, it was believed that the shear stresses and forces experienced by cancer cells traveling through the circulatory system are major limiting factors to their metastatic potential and viability. High levels of fluid shear stress are known to be capable of destroying tumor cells. However, more recent research has shown that cancer cells survive migration through the circulatory system and extravasation into distant tissues with a high degree of efficiency, indicating that hemodynamic forces are not primarily responsible for metastatic cancer cell death. A current subject of investigation is the biomechanical effect of fluid shear stress on cancer cells – how do cancer cells react to the fluidic forces and stresses they experience in circulation? This study focused on quantifying the elastic modulus and rupture behavior of prostate cancer and prostate epithelial cells, with and without exposure to fluid shear stress. Micropipette aspiration was the means of inducing deformation and rupture of the cell membrane. Images obtained through micropipette aspiration were analyzed to calculate elastic modulus and to quantify local stresses along the aspirated cell membrane. An axisymmetric stress model of the aspirated cell membrane was solved using MATLAB; the trends for direction and relative magnitude of stresses were confirmed by an Abaqus finite element model.
Results of the micropipette aspiration included statistically significant differences in elastic modulus and rupture pressure between experimental groups. The elastic modulus of epithelial cells exposed to shear stress was significantly higher than that of the cancer cell groups, both exposed and unexposed to shear stress. There was no difference in elastic modulus between cancer cells exposed to shear stress and unexposed to shear stress. This is contrary to the findings of a previous study; prostate cancer cells have been observed to stiffen after exposure to shear stress. It has also been well documented that epithelial cells exhibit higher elastic moduli than cancer cells; however, no difference was observed in this study in the comparison of elastic moduli of cancer and epithelial cells that were unexposed to shear stress. The rupture pressure of the cancer cells unexposed to shear stress was significantly lower than any other group. This suggests a strengthening reaction of the cancer cell membrane in response to shear stress exposure. This effect was observed to be transient; the increase in rupture pressure disappeared by an hour after the shear stress exposure. The epithelial cells did not exhibit any change in rupture pressure after exposure to shear stress. There was no correlation between elastic modulus and rupture pressure; the stiffness of the cells did not indicate how likely they were to rupture.
The MATLAB and Abaqus models agreed well for trends of principal stresses and von Mises stress. The MATLAB model was quite sensitive to the curvature of the spline fitted to the membrane edge, resulting in irregular patterns and some extreme values of stress and making the results difficult to interpret. The maximum stress did tend to increase with increased aspiration pressure. The location of the maximum stress along the membrane did not reliably correspond to the location of rupture during micropipette aspiration. This model may be improved by automating the process of fitting a spline to the edge of the membrane to reduce user error in plotting individual points.
Further studies to characterize the effects of fluid shear stress on cancer cell mechanics will be useful to confirm differences in elastic modulus and rupture pressure and to investigate the effect of time, temperature, cancer cell line, culture medium, and other variables on cancer cell properties.
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Whittington, John. "Physiological effects of salinity on chara corallina /." Title page, contents and summary only, 1990. http://web4.library.adelaide.edu.au/theses/09PH/09phw6258.pdf.
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Sawant, Meera. "In Vitro Investigations of Antibiotic Influences on Nerve Cell Network Responses to Pharmacological Agents." Thesis, University of North Texas, 2014. https://digital.library.unt.edu/ark:/67531/metadc699991/.
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Neuronal networks, derived from mouse embryonic frontal cortex (FC) tissue grown on microelectrode arrays, were used to investigate effects of gentamicin pretreatment on pharmacological response to the L-type calcium channel blocker, verapamil. Gentamicin is a broad spectrum antibiotic used to control bacterial contamination in cell culture. The addition of gentamicin directly to medium affects the pharmacological and morphological properties of the cells in culture. A reproducible dose response curve to verapamil from untreated cultures was established and the mean EC50 was calculated to be 1.5 ± 0.5 μM (n=10). 40 μM bicuculline was added to some cell cultures to stabilize activity and verapamil dose response curves were performed in presence of bicuculline, EC50 1.4 ± 0.1 μM (n=9). Statistical analysis showed no significant difference in verapamil EC50s values obtained in presence of bicuculline and hence the data was combined and a standard verapamil EC50 was calculated as 1.4 ± 0.13 μM (n=19). This EC50 was then used to compare verapamil EC50s obtained from neuronal cell cultures with chronic and acute exposures to gentamicin. FC cultures (21- 38 days old) were found to be stable in presence of 2300 μM gentamicin. The recommended concentration of gentamicin for contamination control is 5uL /1 ml medium (108 μM). At this concentration, the verapamil EC50 shifted from 1.4 ± 0.13 μM to 0.9 ± 0.2 μM. Given the limited data points and only two complete CRCs, statistical comparison was not feasible. However, there is a definite trend that shows sensitization of cells to verapamil in presence of gentamicin. The cultures exposed to 108 μM gentamicin for 5 days after seeding showed loss of adhesion and no data could be collected for pharmacological analysis. To conclude, acute gentamicin exposure of neuronal cell cultures causes increased sensitivity to verapamil and chronic or long term exposure to gentamicin may cause loss of adhesion of the cell culture by affecting the glial growth. The effect of chronic exposure to gentamicin on pharmacological responses to verapamil remains inconclusive.
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Manrique, Blanco Thibaldo Javier. "The partial purification and characterization of a soluble activator for the sodium adenosinetriphosphatase from rat cerebral cortex and the effect of cholinergic agents." Scholarly Commons, 1986. https://scholarlycommons.pacific.edu/uop_etds/2117.
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Arikatla, Swetha. "Effect of Tumor Microenvironmental Conditions on Non Small Cell Lung Cancer." Scholarly Commons, 2017. https://scholarlycommons.pacific.edu/uop_etds/126.
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Tumor microenvironmental conditions play a vital role in promoting metastasis and tumor recurrence. Due to inefficient vasculature, cancer cells experience hypoxia, glucose deprivation and low pH even during the early stages of tumor growth. Tumor cells are proposed to adapt to these microenvironmental conditions by acquiring increased migratory and invasion potential and tumor initiating ability. Our research addresses the effect of these biochemical factors of the tumor microenvironment (TME) on motility, epithelial to mesenchymal transition (EMT) and stemness of non-small cell lung cancer (NSCLC). NCI-H292 and NCI-H1650 NSCLC cell lines were used to measure the effect of the above mentioned TME conditions. Apart from acidic pH, low glucose and hypoxia, the effect of high glucose conditions was also measured on H292 and H1650 cell lines. Acidic pH, high and low glucose conditions were observed to have no effect on the motility, EMT and stemness of H1650 cell line. Hence, use of this cell line was discontinued and no further treatment conditions were tested on this cell line. In H292 cell line, acidic pH, low glucose and tumor like conditions combined together (acidic pH + low glucose + hypoxia) [AP+LG+HYP] significantly decreased motility whereas hypoxia significantly increased the motility of H292 cells. High glucose did not affect the motility of H292 cells. Although N-cadherin, a mesenchymal marker, expression was significantly upregulated by acidic pH, high and low glucose conditions, no direct correlation was observed between N-cadherin expression and motility. E-cadherin expression was not affected by acidic pH, high and low glucose conditions. An increase in N-cadherin expression and no change in E-cadherin expression under these conditions might be an indication of partial EMT. Hypoxia and AP+LG+HYP did not alter the expression of E-cadherin and N-cadherin. Although expression of vimentin, another mesenchymal marker, and Sox2, a cancer stem cell marker (CSC), was observed at the mRNA level, no expression of vimentin and Sox2 proteins was observed in H292 cells under any of these treatment conditions. The expression of OCT4, another CSC marker, was also not observed at the protein level in H292 cells. HIF-1α expression was observed in H292 cells under normoxic conditions and was unaffected by hypoxia and AP+LG+HYP. Therefore our research indicates that the effect of these TME conditions might be different on different cancer cell lines or cancer types. Not all cancers may depend on EMT for metastasis. An increase in metastasis under hypoxia may be independent of HIF-1α.
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Li, Jing, and 李靜. "Effects of intrinsic & extrinsic factors on the growth and differentiation of human mesenchymal stem cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B37238310.
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Gridley, Shelly M. "The effect of dietary fatty acids on cholesterol/phospholipid ratios and fatty acids in plasma membranes of spontaneous mammary tumors from strain A/ST mice." Virtual Press, 1989. http://liblink.bsu.edu/uhtbin/catkey/722452.
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It has been suggested that plasma membranes play a role in tumor production. Changes in plasma membrane lipid composition may change membrane fluidity and disrupt cellular communication. These changes in membrane lipid composition appear to be related to the fatty acid content of the animal's diet. The purpose of this investigation was to compare the effect of dietary linoleic and stearic acids and tumor size on cholesterol/phospholipid ratios and fatty acids in membranes of mammary adenocarcinomas.Plasma membranes of mammary tumors from Strain A/St mice were isolated by centrifugation and the lipids extracted. Phospholipid content was assayed by the method of Bartlett (102); cholesterol and fatty acids by gas liquid chromatography.Plasma membranes of tumors from mice fed the high linoleic diet (SAFF) were found to have the highest cholesterol/phospholipid ratios (Mean=0.396); mice fed high stearic acid diets produced tumors with the lowest ratios (0.280). Membranes of tumors from mice fed SA-4 and Stock diets had intermediate ratios (0.0.341 and 0.0.346, respectively).Department of Biology
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廖寶韶 and Po-shiu Jackie Liu. "Effects of flavonoids on proliferation of breast cancer cells and vascular smooth muscle cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45011394.
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Nowacki, Laetitia. "Étude des effets antiprolifératifs de la bétanine extraite de betterave sur cellules cancéreuses humaines et de son mode d'action au niveau des membranes cellulaires." Thesis, Compiègne, 2014. http://www.theses.fr/2014COMP2024.
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Au cours de cette thèse nous avons étudié les propriétés anticancéreuses du pigment majoritaire de la betterave rouge : la bétanine, ainsi que son mode d’action. Nos travaux reposent sur une approche pluridisciplinaire. Nous avons tout d’abord mis au point un protocole d’extraction et de purification de la bétanine à partir de betteraves rouges fraîches. Plusieurs étapes de purification se terminant par la séparation des molécules d’intérêt sur HPLC semi-préparative sont nécessaires à l’obtention de la bétanine à un degré de pureté de 90 %, une qualité d’extrait jusqu’à présent inégalé. Nous avons ensuite évalué l’effet cytotoxique de notre extrait sur cellules cancéreuses. Nous avons pu démontrer son innocuité sur cellules non cancéreuses et identifier les voies de signalisation pouvant être impliquées. Nous avons ainsi pu avancer des pistes concernant le mode d’action de la bétanine sur les cellules, mais également soumettre pour la première fois l’idée d’une implication de l’autophagie dans la mort cellulaire induite par la bétanine. Enfin, nous avons montré, par des techniques d’analyse biophysique aux interfaces appliquées aux membranes cellulaires et biomimétiques, qu’indépendamment de son insertion jusqu’au cœur hydrophobe des membranes, la bétanine n’influait pas sur la fluidité et la perméabilité membranaire. Ce travail exploratoire confirme l’intérêt à porter à la bétanine qui, compte tenu de sa haute biodisponibilité, présente de nombreuses applications thérapeutiques potentiellesDuring this thesis we studied the anticancer properties of the major beetroot’s pigment: betanin. Our work is based on a multidisciplinary approach.First we developed a protocol for the extraction and the purification of betanin from fresh beetroots. Several purification steps ended by separation in semi-preparative HPLC are required to obtain a betanin at 90 % pure, which is the highest purity ever recorded. Then we assessed the cytotoxic effect of our extract on cancer cells and its safety on non-cancer cells. By identifying the signaling pathways that might be involved in these effects, we were thus able to suggest ways concerning the mode of action of betanin on cells, but also propose, for the first time, the idea of an involvement of autophagy in cell death induced by betanin. Finally, we have shown by interfacial biophysical techniques applied on cell and biomimetic membranes that, regarless to its deep insertion in the hydrophobic core of the lipid bilayer, betanin did not affect the physical properties of the membrane such as its fluidity or its permability.This scoping study confirms the interest to bring to betanin which, given its high bioavailability, has many potential therapeutic applications
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Ngandu, Jean Pierre Kabue. "Coreceptor expression and T lymphocyte subset distribution in HIV-infected and TB co-infected South African patients on anti-retroviral therapy." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/2219.
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Thesis (MScMedSc (Pathology. Medical Virology))--University of Stellenbosch, 2009.ENGLISH ABSTRACT: In 2007, AIDS caused an estimated 2.1 millions deaths worldwide; about 70% in sub-Saharan Africa. HIV preferentially targets activated CD4 T cells, expressing the major HIV receptor CD4, as well as the major chemokine coreceptors CCR5 and CXCR4. These coreceptors play a prominent role during HIV cell entrance phase, HIV transmission and also disease progression. They have been found to be differentially expressed by CD4 T cell subsets. Tuberculosis coinfection may enhance immune activation in vivo thus accelerating HIV disease progression and has become a major challenge in the control of TB in Africa. Introduction of HAART has reduced disease progression to AIDS, as well as risk of further morbidity and mortality. HAART results in a rapid decline of viral load and an initial increase of peripheral CD4 count, however little is known on the effect of HAART in regulation of coreceptor expression, immune activation status and CD4 T cell subset distribution in HIV infection and HIV/TB coinfection. This study is a cross-sectional analysis of coreceptor expression, immune activation status and CD4 T cell subpopulation distribution in South African HIV and HIV/TB coinfected patients before and after ARV. A total of 137 South African individuals were investigated, comprising 15 healthy normal donors (healthy subgroup), 10 patients with active pulmonary tuberculosis (PTB subgroup), 33 HIV-1 positive patients without active PTB (HIV subgroup), 23 positive patients with active PTB (HIV/PTB subgroup), 36 HIV-1 positive patients on ARV (HIV on ARV subgroup) and 20 HIV-1 positive patients with active PTB on ARV (HIV/PTB on ARV subgroup). CD4 absolute count and plasma viral load were determined for all donors. Freshly isolated PBMC were classified by flow cytometry into the following CD4+ T lymphocyte subsets: naïve (CD45+, CD27+), effector memory (CD45-, CD27-), central memory (CD45-, CD27+), and effector (CD45+, CD27-). Coreceptor expression and activation status was assessed by CCR5, CXCR4 and CD38 expression on CD4 T cell subsets. HIV, TB and HIV/TB coinfection was associated with a decrease in percentage CCR5+ T cells as compared to healthy controls, with the HIV/TB group showing the most extensive decrease. In treatment naive patients, CD4 T cells showed elevated surface expression of CCR5 and CD38 as determined by mean fluorescence intensity in HIV/TB co-infection compared to HIV infection alone. The percentage of antigen-experienced cells was higher in the HIV/TB co-infected group compared to the HIV group. The percentage of naïve T cells was decreased in both the HIV infected and the HIV/TB co-infected groups compared to healthy controls. HIV patients with more than 6 months of ARV showed decreased CCR5 and CD38 surface level expression in the HIV and the HIV/ TB co-infected subgroups. An increased percentage of naïve T cells was observed in the HIV infected subgroup, but not in the HIV/TB subgroup, similarly, a decreased percentage of antigen-experienced cells was observed in the HIV subgroup, but not in the HIV/TB co-infected subgroup. A positive correlation was found between CCR5 and CD38 expression, and CXCR4 and CD38 expression (Spearman coefficient of correlation respectively: r=0.59, p<0.001 and r=0.55, p<0.001). Furthermore we found plasma viral load positively associated with CD38 expression (r=0.31, p<0.001) and percentage activated CCR5+ expressing CD4 T cells positively related to viral load (r=0.31, p<0.001). Percentage naïve CD4 T cells was positively associated with CD4 count (r=0.60, p<0.001) and negatively correlated to viral load (r=-0.42, p<0.001). These results indicate that TB coinfection exacerbates certain aspects of dysregulation of CD4 T cell homeostasis and activation caused by HIV infection. In addition, ARV-associated decrease in coreceptor expression, immune activation status and a normalisation of CD4 T cell subset distribution was observed in HIV infected individuals, but not in HIV/TB coinfection. Despite viral suppression after ARV treatment, the decline in the immune activation marker CD38 and coreceptor CCR5 expression, increase in percentage naïve CD4 T cells and decrease of antigen-experienced cells did not reach the levels displayed in the healthy control group. This may indicate that ongoing (albeit reduced) T cell immune activation may occur in the presence of ARV. Further longitudinal studies are needed to closely monitor immune activation during ARV treatment. This study highlighted an association of TB disease with immune activation in HIV infection, the importance of T-cell activation in HIV pathogenesis and its impact on ARV treatment. Further studies are needed to identify causative factors that may lead to a persistent immune activation status during ARV treatment, and how TB coinfection confounds normal responses to ARV.
AFRIKAANSE OPSOMMING: In 2007 was ongeveer 2.1 miljoen sterftes wêreldwyd veroorsaak deur VIGS; ongeveer 70% in Sub-Sahara Afrika. CD4 T selle is die hoof teiken van MIV, aangesien dit die primêre CD4 reseptor, sowel as een of beide van die vernaamste chemokien koreseptore CCR5 en CXCR4 vrystel. Hierdie koreseptore speel ‘n prominente rol wanneer die MIV die sel binnedring, asook tydens MIV oordrag en verloop van die siekte. Dit word ook deur verskillende fraksies van CD4 T selle vrygestel. Gelyktydige TB infeksie mag immuunaktivering in vivo verhoog en dus die siekeproses versnel. MIV het ‘n groot uitdaging geword in die beheer van TB in Afrika. Bekendstelling van HAART het die ontwikkeling van VIGS vertraag, asook die risiko van verdere morbiditeit en mortaliteit. HAART veroorsaak ‘n vinnige afname in virale lading ‘n toename in CD4 telling, hoewel die spesifieke invloed van HAART op die regulering van koreseptor vrystelling, immuunaktivering en verspreiding van CD4 fraksies in MIV en MIV/TB infeksies nog onduidelik is. Hierdie studie het gepoog om koreseptor vrystelling, immuunaktiveringstatus en die verspreiding van CD4 subpopulasies in pasiënte met MIV en MIV/TB voor en na ARV behandeling te ondersoek. ‘n Totaal van 137 Suid-Afrikaanse individue is ondersoek en die studiegroep het bestaan uit 15 normale persone (gesonde subgroep), 10 pasiënte met aktiewe pulmonale TB (PTB subgroup), 33 MIV positiewe pasiënte sonder PTB (MIV subgroep), 23 MIV positiewe pasiënte met aktiewe PTB (MIV/PTB subgroep), 36 MIV positiewe pasiënte op ARV (MIV op ARV subgroep) en 20 MIV positiewe pasiënte met aktiewe PTB op ARV (MIV/PTB op ARV subgroep). Absolute CD4 telling en virale ladings was bepaal vir alle deelnemers. Vars geïsoleerde perifere bloed mononukleêre selle is geklassifiseer deur middel van vloeisitometrie as die volgende CD4 T limfosiet subgroepe: naïewe selle (CD45+, CD27+), effektor geheueselle (CD45-, CD27-), sentrale geheueselle (CD45-, CD27+), en effektor selle (CD45+, CD27-). Koreseptor vrystelling en aktivering was beoordeel volgens CCR5, CXCR4 en CD38 vrystelling op CD4 T sel subgroepe. HIV, TB en MIV/TB ko-infeksie is geassosieer met ‘n afname in die persentasie CCR5+ T selle, vergeleke met gesonde kontroles, waar die MIV/TB subgroep die grootste afname getoon het. In onbehandelde pasiënte het die CD4 T selle verhoogde vrystelling van CCR5 en CD38 op die oppervlakte getoon en dit is bevestig deur die gemiddelde fluoresserende vii intensiteit in die MIV/TB subgroep vergeleke met die subgroep met slegs MIV. Die MIV/TB subgroep het verder ook ‘n verhoogde persentasie totale geheue T selle getoon vergeleke met die MIV subgroep. Die persentasie naïewe T selle was egter verlaag in beide die MIV en MIV/TB subgroepe vergeleke met normale kontroles. MIV pasiënte wat langer as 6 maande op ARV behandeling was in beide die MIV en MIV/TB subgroepe, het ‘n verlaagde vrystelling van CCR5 en CD38 op die oppervlakte van die CD4 selle getoon. ‘n Verhoogde persentasie naïewe T selle het in die MIV subgroep voorgekom, maar nie in die MIV/TB subgroup nie. ‘n Soortgelyke tendens is gevind waar die persentasie totale geheueselle verlaag was in die MIV subgroep, maar nie in die MIV/TB subgroep nie. ‘n Positiewe korrelasie is gevind tussen CCR5 en CD38 vrystelling, asook CXCR4 en CD38 vrystelling (Spearman korrelasie koëffisiënt: r=0.59, p<0.001 en r=0.55, p<0.001 onderskeidelik). Verder het die plasma virale lading ‘n positiewe assosiasie getoon met CD38 vrystelling (r=0.31, p<0.001) en die persentasie geaktiveerde CCR5+ vrystellende CD4 T selle met virale lading (r=0.31, p<0.001). Die persentasie naïewe CD4 T selle het ‘n positiewe assosiasie getoon met CD4 telling (r=0.60, p<0.001) en ‘n negatiewe korrelasie met virale lading (r=-0.42, p<0.001). Volgens hierdie resultate vererger TB ko-infeksie sekere aspekte van die disregulasie van CD4 T selhomeostase en aktivering as gevolg van MIV infeksie. Verder kon ‘n ARVgeassosieerde afname in koreseptor vrystelling, immuunaktivering en normalisering van CD4 T sel fraksies bespeur word in die MIV subgroep, maar nie in die MIV/TB subgroep nie. Ten spyte van virale onderdrukking veroorsaak deur ARV behandeling, het die afname in die immuunmerker CD38 en koreseptor CCR5, toename in die persentasie naïewe CD4 selle en afname in totale geheue CD4 T selle nie die vlakke van die normale kontrolegroep bereik nie. Dit is moontlik dat volgehoue verlaagde T sel immuunaktivering nog steeds mag plaasvind in die teenwoordigheid van ARV. Verdere longitudinale studies is nodig om immuunaktivering tydens ARV behandeling te monitor. Hierdie studie het die belangrikheid van T sel aktivering in MIV patogenese en dit impak daarvan op ARV behandeling beklemtoon. Verdere studies is nodig om moontlike oorsake of bydraende faktore te identifiseer wat tot volgehoue immuunaktivering tydens ARV behandeling kan lei, asook tot mate waartoe TB ko-infeksie kan inmeng met die normale werking van ARV behandeling.
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Allard, Antoine. "Studying in vitro the effect of actin dynamics on membrane tubes Mapping and modeling the nanomechanics of bare protein-coated lipid nanotubes Actin modulates shape and mechanics of tubular membranes Actin dynamics drive cell-like membrane deformation Fluctuations of a membrane nanotube revealed by high-resolution force measurements." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASE003.
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Les propriétés mécaniques des nanotubes membranaires (sans la présence du cytosquelette), en particulier la force nécessaire pour les former et les maintenir, sont maintenant bien comprises. Par contre, bien que dans la cellule les nanotubes soient souvent couplés à l’actine, son mécanisme d’action sur de telles structures est inconnu. L’objectif de cette thèse est donc de comprendre comment la dynamique de polymérisation de l’actine affecte la croissance et la stabilité des nanotubes de membrane et contribue à leur scission. Le projet consistera à adresser deux questions principales : - comment la force pour maintenir un nanotube de membrane évolue en présence du cytosquelette d’actine ? - comment la structure du réseau d’actine (taille de la maille, composition, dynamique) détermine les effets mécaniques observés ? La dynamique de l’actine stabilise-t-elle le nanotube ? Les forces générées par la polymérisation peuvent-elles provoquer une scission des nanotubes ? La structure du réseau d’actine permet-elle d’expliquer ces deux effets opposés ? Quel est l’effet de l’ajout de myosines, moteurs moléculaires capables de faire coulisser les filaments d’actine entre eux et de créer une contrainte mécanique supplémentaire dans le réseau ? Ces questions indissociables seront étudiées en collaboration entre les équipes de C. Sykes à l’Institut Curie (Paris), et de C. Campillo et S. Labdi au LAMBE (Evry)The mechanics of membrane nanotubes (without the presence of the cytoskeleton), especially the force needed to form and maintain a nanotube, are now well understood. But, although in the cell the nanotubes are often coupled with actin, its action mechanism on such structures is unknown. The objective of this thesis is to understand how actin polymerization dynamics affect the growth and stability of membrane nanotubes and may contribute to their scission. The project will address two main questions: - How the force to maintain a membrane nanotube evolves in presence of a reconstituted actin cytoskeleton? - How the structure of the actin network (mesh size, composition, dynamic) determines its mechanical effect on the nanotube? Does actin dynamics stabilize the nanotube? Are the forces generated by actin polymerization able to cut nanotubes? Does the structure of the actin network explain these two opposite effects? What is the effect of adding myosins, molecular motors able to create additional mechanical stress in the network? These inseparable issues will be studied in collaboration between the teams of C. Sykes at the Institut Curie (Paris), and C. Campillo and S. Labdi in LAMBE (Evry)
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Drbal, Abed Alnaser A. A. "Studies on Bioactive Lipid Mediators Involved in Brain Function and Neurodegenerative Disorders. The effect of ¿-3PUFA supplementation and lithium treatment on rat brain sphingomyelin species and endocannabinoids formation; changes in oxysterol profiles in blood of ALS patients and animal models of ALS." Thesis, University of Bradford, 2013. http://hdl.handle.net/10454/6285.
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Lipids are important for structural and physiological functions of neuronal cell membranes. They exhibit a range of biological effects many are bioactive lipid mediators derived from polyunsaturated fatty acids such as sphingolipids, fatty acid ethanolamides (FA-EA) and endocannabinoids (EC). These lipid mediators and oxysterols elicit potent bioactive functions in many physiological and pathological processes of the brain and neuronal tissues. They have been investigated for biomarker discovery of ageing, neuroinflammation and neurodegenerative disorders. The n-3 fatty acids EPA and DPA are thought to exhibit a range of neuroprotective effects many of which are mediated through production of such lipid mediators.
The aims of this study were to evaluate the effects of n-3 EPA and n-3 DPA supplementation on RBC membranes and in this way assess dietary compliance and to investigate brain sphingomyelin species of adult and aged rats supplemented with n-3 EPA and n-3 DPA to evaluate the effects and benefits on age-related changes in the brain. Furthermore, to study the effects of lithium on the brain FA-EAs and ECs to further understand the neuroprotective effects of lithium neuroprotective action on neuroinflammation as induced by LPS. Finally to examine if circulating oxysterols are linked to the prevalence of ALS and whether RBC fatty acids are markers of this action in relation to age and disease stages. These analytes were extracted from tissue samples and analysed with GC, LC/ESI-MS/MS and GC-MS.
It was found that aged rats exhibited a significant increase in brain AA and decrease in ¿n-3 and ¿n-6 PUFAs when compared to adult animals. The observed increase of brain AA was reversed following n-3 EPA and n-3 DPA supplementation. Sphingomyelin was significantly increased when aged animals were supplemented with n-3 DPA. LPS treatment following lithium supplementation increased LA-EA and ALA-EA, while it decreased DHA-EA. Both oxysterols 24-OH and 27-OH increased in ALS patients and SOD1-mice. Eicosadienoic acid was different in ASL-patients compared to aged SOD1-mice.
These studies demonstrated that dietary intake of n-3 EPA and n-3DPA significantly altered RBC fatty acids and sphingolipids in rat brain. They suggest that n-3 DPA can be a potential storage form for EPA, as shown by retro-conversion of n-3 DPA into EPA in erythrocyte membranes, ensuring supply of n-3 EPA. Also, n-3 EPA and n-3 DPA supplementation can contribute to an increase in brain sphingomyelin species with implications for age effects and regulation of brain development. Effects of lithium highlight novel anti-neuroinflammatory treatment pathways. Both 24-hydroxycholesterol and eicosadienoic acid may be used as biomarkers in ALS thereby possibly helping to manage the progressive stages of disease.Libyan Government
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Drbal, Abed Alnaser Anter Amer. "Studies on bioactive lipid mediators involved in brain function and neurodegenerative disorders : the effect of ω-3PUFA supplementation and lithium treatment on rat brain sphingomyelin species and endocannabinoids formation : changes in oxysterol profiles in blood of ALS patients and animal models of ALS." Thesis, University of Bradford, 2013. http://hdl.handle.net/10454/6285.
Full textAbstract:
Lipids are important for structural and physiological functions of neuronal cell membranes. They exhibit a range of biological effects many are bioactive lipid mediators derived from polyunsaturated fatty acids such as sphingolipids, fatty acid ethanolamides (FA-EA) and endocannabinoids (EC). These lipid mediators and oxysterols elicit potent bioactive functions in many physiological and pathological processes of the brain and neuronal tissues. They have been investigated for biomarker discovery of ageing, neuroinflammation and neurodegenerative disorders. The n-3 fatty acids EPA and DPA are thought to exhibit a range of neuroprotective effects many of which are mediated through production of such lipid mediators. The aims of this study were to evaluate the effects of n-3 EPA and n-3 DPA supplementation on RBC membranes and in this way assess dietary compliance and to investigate brain sphingomyelin species of adult and aged rats supplemented with n-3 EPA and n-3 DPA to evaluate the effects and benefits on age-related changes in the brain. Furthermore, to study the effects of lithium on the brain FA-EAs and ECs to further understand the neuroprotective effects of lithium neuroprotective action on neuroinflammation as induced by LPS. Finally to examine if circulating oxysterols are linked to the prevalence of ALS and whether RBC fatty acids are markers of this action in relation to age and disease stages. These analytes were extracted from tissue samples and analysed with GC, LC/ESI-MS/MS and GC-MS. It was found that aged rats exhibited a significant increase in brain AA and decrease in Σn-3 and Σn-6 PUFAs when compared to adult animals. The observed increase of brain AA was reversed following n-3 EPA and n-3 DPA supplementation. Sphingomyelin was significantly increased when aged animals were supplemented with n-3 DPA. LPS treatment following lithium supplementation increased LA-EA and ALA-EA, while it decreased DHA-EA. Both oxysterols 24-OH and 27-OH increased in ALS patients and SOD1-mice. Eicosadienoic acid was different in ASL-patients compared to aged SOD1-mice. These studies demonstrated that dietary intake of n-3 EPA and n-3DPA significantly altered RBC fatty acids and sphingolipids in rat brain. They suggest that n-3 DPA can be a potential storage form for EPA, as shown by retro-conversion of n-3 DPA into EPA in erythrocyte membranes, ensuring supply of n-3 EPA. Also, n-3 EPA and n-3 DPA supplementation can contribute to an increase in brain sphingomyelin species with implications for age effects and regulation of brain development. Effects of lithium highlight novel anti-neuroinflammatory treatment pathways. Both 24-hydroxycholesterol and eicosadienoic acid may be used as biomarkers in ALS thereby possibly helping to manage the progressive stages of disease.
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Morphet, Marilynn Norma. "Method for identification of effective first-line treatment for HAART naïve HIV/AIDS patients." Thesis, Queensland University of Technology, 2002.
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Zhou, Yong. "Effect of nonsteroidal anti-inflammatory drugs on the mechanical and electrical stability of phospholipid membranes." Thesis, 2007. http://hdl.handle.net/1911/20677.
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Non-steroidal anti-inflammatory drugs (NSAIDs) display powerful anti-inflammatory, analgesic and anti-pyretic activities. Serious side effects of NSAIDs, such as gastrointestinal (GI) bleeding and peptic ulcer disease, cause hospitalization and even death of many patients who take these drugs. This is thought to result from the ability of NSAIDs to induce a back-diffusion of luminal acids into GI tissues. NSAID-induced back-diffusion of luminal acids has both biochemical and biophysical aspects. The biochemical aspect of NSAID activity, i.e. the ability of NSAIDs to inhibit the enzyme cyclo-oxygenase, has been examined extensively. However, the biophysical aspect of NSAID cyto-toxicity, i.e. the ability of NSAIDs to directly induce proton permeation across a phospholipid layer covering the GI tract, is not well understood.
In order to gain a deeper understanding of the cyto-toxicity of NSAIDs, the biophysical effect of NSAIDs on lipid membranes must be examined. The proton permeability of a phospholipid membrane depends on several factors: the packing of lipids, the membrane rigidity and deformability, the tendency for a membrane to form pores and the electrostatic properties of the membrane.
We utilized a variety of experimental techniques, including micropipette aspiration of giant unilamellar vesicles, fluorescent spectroscopy and electrophoretic motility, to quantitatively characterize the effect of the sodium salt of salicylic acid, a classic anti-inflammatory agent, on mechanical and electrostatic properties of phospholipid membranes. We found that at near neutral pH, salicylate/salicylic acid decreases the bending stiffness of membranes composed of 1-stearoyl-2-oleoyl-phosphatidylcholine (SOPC) and induces pore formation. As the solution pH was lowered to simulate the condition in the GI tract, the packing stability of SOPC vesicles exposed to sodium salicylate was seriously disrupted and the membrane dipole potential was decreased significantly. Salicylate anions also alter the membrane interfacial charge distribution by partitioning into the membrane.
Thus, both salicylic acid and salicylate anion partition into membranes and affect membrane mesoscopic properties that determine membrane ion permeability. The ability of salicylate/salicylic acid to induce membrane pores suggests that this anti-inflammatory agent increases the probability of protons permeating across a phospholipid layer in the GI tract. The larger membrane damage caused by salicylate/salicylic acid at acidic pHs correlates well with clinical findings of higher toxicity of these drugs at low stomach pHs. It further confirms that the NSAID-lipid interaction is crucial the integrity of the mucosa. Moreover, since membranes are intimately involved in many important cell functions, effects of salicylate/salicylic acid on membranes observed in this thesis have relevance beyond the GI tract.
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DING, QING-XIONG, and 丁慶雄. "Effect of nosteroidal anti-inflammatory drugs on the generation of lymphokine-activated killer cell activity." Thesis, 1992. http://ndltd.ncl.edu.tw/handle/26870047853897962147.
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JIAN, HAN-SIOU, and 簡含修. "To Investigate the Effect of Disease Modifying Anti-Rheumatic Drugs (DMARDs) on the Foam Cell Formation." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/63908740329034123418.
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碩士國防醫學院
微生物及免疫學研究所
102
Atherosclerosis is a chronic inflammatory disease of the wall of large- and medium-sized arteries and is a major health concern in the world. The formation of foam cells is a crucial reason in the process of atherosclerosis which start from the uptake of oxidized low-density lipoprotein (ox-LDL) by macrophage via scavenger receptors (SRs). In addition to accumulate lipid and activate endothelial cells, these foam cells release pro-inflammatory cytokines which further enhance the severity of the disease. Interestingly, regulation of foam cells depends on ingestion of ox-LDL as well as efflux of excess cholesterol via reverse cholesterol transporters (RCTs). It has been showed that overall cardiovascular disease (CVD) had a lifetime prevalence (9.3%) among rheumatoid arthritis (RA) patients. The cumulative inflammation of RA, with the abundant synthesis of proinflammatory cytokines, may contributes directly to the early formation of the atheromatic plaque. Since disease modifying anti-rheumatic drugs (DMARDs) have strong anti-inflammatory effects, we planned to examine whether currently used DMARDs in RA patients are able to slow down the progression of foam cell formation. We evaluated six DMARDs, including Leflunomide, Azathioprine, Cyclosporine A, Hydroxychloroquine, Methotrexate and Sulfasalazine, and two steroidal anti-inflammatory drugs, Prednisolone and Dexamethasone in this study. We examined the effects of these drugs on SRs (SR-A and CD36) and RCTs (ABCA1and ABCG1) expression, ox-LDL uptake, and total cholesterol content in THP-1-macrophage. Our results showed that Leflunomide dose-dependently increased ABCA1 expression, which indicated Leflunomide might be able to enhance cholesterol efflux in macrophage. Meanwhile, we found SR-A expression, dii-oxLDL uptake as well as total cholesterol content were reduced in THP-1 macrophages after Cyclosporin A treatment. Moreover, HCQ increased both ABCA1 and ABCG1 protein expression. These findings suggested Leflunomide, Cyclosporine A and HCQ might modulate foam cell formation. Other tested DMARDs, including Azathioprine, Methotrexate and Sulfasalazine, had no apparent effect on SRs and RCTs levels. We further showed here that steroid drugs, including Prednisolone and Dexamethasone, reduced ABCA1 expression in THP-1-macrophage, which indicated that these two drugs might promote foam cell formation and increase risk of cardiovascular disease. Clinician should be aware of this when use these two drugs in the treatment of RA.
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Lin, Hsuan-Jen, and 林宣任. "Melatonin enhances the anticancer effect of the first line chemotherapeutic drugs in small cell lung cancer." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/z8xe4z.
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碩士國立交通大學
分子醫學與生物工程研究所
107
According to World Health Organization (WHO), cancer is the second leading death cause in the world. Furthermore, lung cancer ranks in the first place. Small cell lung cancer (SCLC) is one of the deadliest types of lung cancer due to its biological characteristics of rapid growth, early metastases. Melatonin, a natural hormone found in the body has exhibited an anticancer effect in SCLC in our preceding study. In addition, it has also shown positive anticancer effects in cancers such as breast, prostate, gastric, and colorectal cancers. However, it has not been tested with first-line therapy drugs, etoposide and cisplatin (EP) in SCLC. In this study, we hypothesize that melatonin may enhance the anticancer effect when treated along with lower concentrations of EP. First, through MTS assay, by comparing to the singular treatment of EP, melatonin and EP significantly reduced the cell viability at the highest concentration from 57% to 26% in H146, and 50% to 35% in H209. With western blotting, we assessed poly ADP-ribose polymerase (PARP) cleavage to see that triple combination favorably showed greater apoptotic effect. Moreover, we observed an inhibition in cell proliferation via the expressions of downstream proteins in MAPK/ERK pathway. Correspondingly, we conducted PI staining to examine the cell cycle distribution, and triple combination resulted in a G2/M arrest. Furthermore, with Hoechst 33342 staining, fluorescence microscopy demonstrated that melatonin and EP treatment exhibited a significantly larger amount of apoptotic bodies than any of singular treatment. In summary, triple combination decreased cell viability, increased expression of PARP cleavage, affecting cellular responses of downstream proteins in MAPK/ERK pathway, caused a G2/M cell cycle arrest, and produced large amount of apoptotic bodies. This study suggests that while melatonin exhibits novelty in singular treatment, it is also able to enhance the anticancer effects of first-line therapy drugs in SCLC cell lines. We are hopeful to see this promising result benefit in further researches.
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Chang, Su-i., and 張塑益. "Effect of various micro-porous layer preparations on the performance of proton exchange membranes fuel cell." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/03086981172440653194.
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碩士逢甲大學
材料科學所
98
Proton exchange membrane fuel cell（PEMFC）is nowadays widely studied and discussed in the field. The reason is not only the high electric discharge potency but also the zero pollution that draw attention to. The basic principle for PEMFC is to use the hydrogen to work as the fuel gas and then use the penetration proton exchange membrane to dissociate the hydrogen ions and the electron in order to discharge. The hydrogen ions link up to oxygen at the other end and produce the only by-product - liquid water. The design of the micro-porous layer（MPL）for PEMFC is not only to attain better cell performance, but also to achieve better water management for the PEMFC system. In this paper, the effects of two different MPL preparation methods, including spraying method and scraping method, on the performance of the PEMFC were researched.
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Chen, Che-Yi, and 陳哲毅. "Expressing Membrane Antibody Reporter in the Islet Cells of Nonobese Diabetic Mice to noninvasive assessthe therapeutic effects of drugs for autoimmune diabete." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/88z47y.
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Figueira, Tiago Nascimento. "Blocking HIV at cell entry: innovative exploitation of the interaction between membranes and next generation drugs: single domain antibodies, peptides and photoactivatable oxidants." Master's thesis, 2013. http://hdl.handle.net/10451/9621.
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Tese de mestrado em Bioquímica (Bioquímica Médica), apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2013Desde a sua descoberta, o Vírus da Imunodeficiência Humana (VIH) tornou-se uma das principais preocupações da comunidade médica e científica mundial. Mais de 34 milhões de pessoas encontram-se infectadas em todo o mundo, sob o risco de contrair o Síndrome da Imunodeficiência Adquirida (SIDA). Este estado imunocomprometido resulta de dois pontos críticos da patogenicidade lentiviral: a deplecção de linfócitos T CD4+ circulantes para níveis incapazes de combater infecções oportunistas e a persistência de reservatórios virais em macrófagos e células dendríticas.. O ciclo de vida do VIH revela alvos favoráveis no combate à progressão infecciosa. Ao entrar em contacto com as células do hospedeiro, o reconhecimento de receptores e co-receptores específicos desencadeia a fusão das membranas celular e viral com libertação do conteúdo para o citoplasma das células do hospedeiro. No interior da célula, o material genético é processado e integrado no genoma do indivíduo, a partir do qual poderão ser traduzidas novas proteínas virais. Da membrana do hospedeiro emergem novos viriões posteriormente activados por maturação proteolítica. Cada vírus apresenta um lipidoma sob a forma de bicamada lipídica que engloba e envolve o proteoma e genoma viral. Apesar de já se encontrarem disponíveis inibidores para as diversas fases do processo de infecção, as potencialidades terapeuticas destas drogas não permitem a eliminação total do vírus, mesmo sob a elevada carga farmacológica dos regimes de terapia antiretroviral (TARV). Os inibidores de entrada do VIH são uma classe de antiretrovirais direccionados para a fase primária da infecção, que guia o reconhecimento, acoplamento e entrada do vírus. Uma vez que inibem o avanço do ciclo viral antes da invasão celular, estes inibidores possuem claras vantagens perante outros antivirais que actuam em estágios tardios. Por não ser necessária a sua presença ao nível do citoplasma, possuem ainda vantagens farmacológicas que favoreceram a aposta no seu desenvolvimento para aplicação terapeutica. Devido à natureza do processo de entrada, a gama de potenciais alvos permite uma variedade de mecanismos inibitórios e espécies moleculares, o que dinamiza as estratégias de combate ao vírus e atrasam o fenómeno de resistência. As proteínas do complexo do envelope (Env), gp41 e gp120, são os mais comuns alvos de inibição. Devido à sua variabilidade conformacional, intimamente relacionada com as propriedades fusogénicas, estas proteínas tornam-se vulneráveis à acção de moléculas que estabilizem umaa estrutura tridimensional específica, competindo na dinâmica de infecção. Anticorpos monoclonais neutralizantes, fragmentos de anticorpo e pequenos péptidos foram já implicados neste tipo de mecanismo inibitório. O envelope viral é também um potencial alvo de inibidores de fusão. O processo de fusão membranar é sensível a variações nas propriedades físicas da bicamada lipídica como a fluidez e a curvatura, que podem ser modificadas pela acção de pequenas moléculas. Considerando que a membrana provém da célula do hospedeiro e não está sujeita a variabilidade genética, é um alvo conservado entre estirpes que não adquire resistência a fármacos. Apesar do interesse demonstrado na última década, suportado por ensaios clínicos promissores, a comercialização e aplicação terapeutica de inibidores de fusão em TARV encontra-se ainda atrasada relativamente a outros inibidores. Apenas um inibidor de fusão, o péptido Enfuvirtide, se encontra actualmente disponível no mercado o que ilustra a necessidade de apostar no melhoramento das propriedades farmacologicas e citotoxicidade. A aplicação de conceitos modernos de biodistribuição, biodisponibilidade aliados a sistemas de libertação controlada recentemente descritos são uma via estratégica no melhoramento da farmacoterapeutica destes inibidores. A versatilidade e diversidade dos inibidores de fusão compatibilizamnos com novas modalidades de direccionamento do fármaco. Independentemente do alvo molecular final, foi já sugerido que a interacção inespecífica com membranas lipídicas desempenha um papel activo no modo de acção de alguns inibidores de entrada Esta interacção gera um aumento de concentração favorável aos mecanismos inibitórios junto dos locais de acção, nomeadamente as membranas viral e da célula hospedeira. De igual forma, se esta interacção for explorada para o desenvolvimento de sistemas lipídicos de transportes de fármacos, as propriedades inibitórias bem como o próprio direccionamento dos inibidores de fusão para os locais de interesse serão consideravelmente aumentados. A possibilidade de promover direccionamento e transporte através do reconhecimento de ambientes membranares poderá ser uma resposta à baixa compatibilidade terapeutica dos inibidores de fusão. Seguindo esta premissa, o principal objectivo deste trabalho foi compreender de que forma diferentes inibidores de fusão, de pesos moleculares e propriedades químicas distintas, poderiam explorar a interacção inespecífica com membranas lipídicas de modo a melhorar o seu direccionamento para os locais de acção e as suas propriedades farmacológicas no geral. Recorremos a três inibidores de fusão: um fragmento de anticorpo, F63; um péptido, sifuvirtide; e uma pequena molécula oxidante, LJ001. Tanto o F63 como o sifuvirtide actuam sobre a proteína gp41, enquanto que o LJ001 inibe a entrada do VIH através da rigidificação do envelope viral. A nossa abordagem consiste em duas frentes com o mesmo princípio base. Por um lado, pretendemos determinar de que forma o fragmento de anticorpo F63 interage com membranas lipídicas que mimetizam a membrana viral (rica em colesterol) e da célula hospedeira (maioritariamente fosfolipídica), tentando correlacionar as observações experimentais com o seu modo de acção. Estudámos também a interacção de duas versões modificadas do F63, F63-MPR e F63-CRAC, nas quais se adicionaram motivos de reconhecimento de colesterol, com os mesmos modelos membranares. Numa outra linha de trabalho, avaliámos a compatibilidade de dois inibidores de fusão, com modo de acção e propriedades moleculares distintas, para o transporte simultâneo na membrana de um sistema de biodistribuição lipossomal catiónico. Através de composições simples com carga e fluidez variável, procurámos identificar a formulação lipídica ideal para uma interacção compatível de ambas as moléculas com a mesma membrana, idealizando um veículo/vector sinérgico não só no modo de acção consertado em diferentes alvos mas também no processo de transporte. Recorremos a técnicas de espectroscopia de fluorescências para analizar a interacção entre os inibidores e as membranas lipídicas. Seguimos a fluorescência intrínseca dos resíduos de triptofano, assim como a fluorescência intrínseca da molécula de LJ001, para traçar o perfil de partição dos três inibidores entre a fase aquosa e lipídica. Com o mesmo intuito, usou-se uma sonda potenciométrica sensível a alterações no potencial dipolar membranar para caracterizar a interacção com modelos membranares. As técnicas de anisotropia e a extinsão de emissão de fluorescência foram também utilizadas para, respectivamente, monitorizar a fluidez membranar e a acessibilidade do fluoróforo à molécula extintora aquando a adsorção/inserção do inibidor no ambiente membranar. O fragmento de anticorpo F63 particiona para membranas lipídicas, independentemente do seu conteúdo em colesterol, o que sugere uma interacção não selectiva com a superfície celular e viral in vivo. As versões modificadas F63-MPR e F63-CRAC não apresentaram aumento de afinidade na presença de colesterol apesar dos domínios de reconhecimento membranar. Pelo contrário, a alteração do F63 parece ter prejudicado ligeiramente a dinâmica de interacção, possivelmente por destabilização da sua estrutura ou pela introdução de um local adicional de ligação à membrana. As nossas observações sugerem que modificações conformacionais poderão explicar a estabilização na superfície membranar, suportadas pela flexibilidade estrutural deste tipo de domínios proteicos. Tanto o sifuvirtide como o LJ001 interagem com lipossomas catiónicos, exibindo preferência para bicamadas em fase ordenada ou fase fluida, respectivamente. Um aumento da carga catiónica traduz-se num aumento da partição do sifuvirtide, que apresenta carga aniónica, mas não parece afectar a partição da molécula de LJ001. Os vectores lipossomais catiónicos de fase ordenada e fluida tiveram sucesso no carregamento das duas moléculas à superfície tanto individual como simultaneamente. Apesar da necessidade de optimização, os resultados são uma prova primária da possibilidade de desenvolver lipossomas como vectores de biodistribuição duais, com modo de acção sinérgico. No entanto, as técnicas de fluorescência foram insuficientes para monitorização eficiente de ambas as moléculas no mesmo plano espacial e temporal, devido à sobreposição das suas propriedades espectrais. Será necessária uma abordagem biofísica de maior complexidade, recorrendo a técnicas capazes de resolver os perfis de interacção individuais, para um mesmo veículo lipossomal.
Since its discovery, the Human Immunodeficiency Virus (HIV) has become one of the major concerns of the scientific and medical community. More than 34 million infected people worldwide bear the risk of contracting the Acquired Immunodeficiency Syndrome (AIDS), due to limited access to therapy. The available antiretroviral drugs struggle to effectively deplete viral loads and require administration in heavy therapeutic regimens. Fusion inhibitors are a class of antivirals capable of blocking viral progression before cell invasion. Though the initial interest was reinforced by promising clinical results, their therapeutic relevance has fallen in recent years. Still, their versatile molecular properties enable the application of novel concepts of drug targeting and delivery. Following this premise, the aim of our study was to understand how HIV fusion inhibitors of different molecular weight could exploit lipid membrane interactions to enhance their antiviral potency and pharmacological properties. Through a biophysical approach, we analyzed the interaction of the inhibitory single-domain antibody (sdAb) F63 with host and viral model membranes, as well as two modified versions containing cholesterol-targeting domains. We used the same approach to characterize the loading profiles of two fusion inhibitors, sifuvirtide and LJ001, to cationic liposomal membranes, as a primary description of a combined delivery system. F63 has high affinity to lipid model membranes, regardless of cholesterol content, suggesting a potential interaction with both host and viral membranes in vivo. The modified versions of this sdAb failed to enhance the interaction with cholesterol-rich membranes. Sifuvirtide and LJ001 were successfully loaded to cationic membranes, supporting the concept of dual liposomal delivery.
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Zhu, Xiaoyi [Verfasser]. "Transfer of lipophilic drugs between liposomal membranes by using the ion-exchange micro-column technique and the fluorescence dequenching effect / von Xiaoyi Zhu." 2008. http://d-nb.info/993360122/34.
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"Anticancer effect of histone deacetylase inhibitors in gastric cancer cell line." 2006. http://library.cuhk.edu.hk/record=b5892753.
Full textAbstract:
Tang Angie.Thesis submitted in: November 2005.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2006.
Includes bibliographical references (leaves 151-172).
Abstracts in English and Chinese.
Acknowledgements --- p.i
Abstract --- p.iii
Abstract in Chinese --- p.vi
Table of Contents --- p.vii
List of Publications --- p.xi
Awards --- p.xii
List of Abbreviations --- p.xiii
List of Tables --- p.xv
List of Figures --- p.xvi
Chapter Chapter 1 --- Introduction --- p.1
Chapter Chapter 2 --- Literature Review --- p.3
Chapter 2.1 --- Gastric cancer-overview --- p.3
Chapter 2.1.1 --- Epidemology --- p.3
Chapter 2.1.2 --- Pathology --- p.3
Chapter 2.1.3 --- Etiologies and Risk Factors --- p.4
Chapter I. --- Environmental factors --- p.4
Chapter a. --- Helicobacter pylori infections --- p.4
Chapter b. --- Epstein-Barr virus (EBV) --- p.6
Chapter c. --- Dietary factors --- p.6
Chapter d. --- Smoking --- p.6
Chapter II. --- Genetic Factors --- p.7
Chapter a. --- Hereditary Gastric Cancer --- p.7
Chapter b. --- Genetic polymorphism --- p.8
Chapter III. --- Cyclooxygenases (COX) enzymes --- p.10
Chapter IV. --- Molecular carcinogenesis --- p.11
Chapter a. --- Activation of proto-oncogenes --- p.11
Chapter b. --- Candidate tumor suppressor genes --- p.12
Chapter 1. --- Gene mutation and deletion --- p.12
Chapter 2. --- Epigenetic Silencing --- p.13
Chapter 2.2 --- Epigenetics --- p.14
Chapter 2.2.1 --- DNA methylation --- p.15
Chapter 2.2.2 --- Histone modification --- p.28
Chapter I. --- Histone acetylation and deacetylation --- p.32
Chapter II. --- Histone methylation --- p.32
Chapter III. --- Histone phosphorylation --- p.34
Chapter IV. --- Histone ubiquitylation --- p.34
Chapter 2.3 --- "HAT, HDAC and HDAC inhibitors" --- p.36
Chapter 2.3.1 --- HAT --- p.38
Chapter 2.3.2 --- HDAC --- p.39
Chapter (a) --- Class I --- p.40
Chapter (b) --- Class II --- p.41
Chapter (c) --- Class III --- p.42
Chapter (d) --- Mammalian HDAC and their mechanism of deacetylation --- p.44
Chapter 2.3.3 --- HDAC inhibitors --- p.45
Chapter I. --- Class I/II natural inhibitors --- p.47
Chapter II. --- Class I/II synthetic inhibitors --- p.48
Chapter III. --- Sirtuins inhibitors --- p.49
Chapter IV. --- Activity of HDAC inhibitors in vitro --- p.50
Chapter a. --- Effect in the gene expression --- p.50
Chapter b. --- Non-transcriptional effects --- p.55
Chapter c. --- Activity of HDAC inhibitors with other agents --- p.57
Chapter d. --- Effects in xenograft tumor models --- p.57
Chapter V. --- Clinical trials of HDAC inhibitors --- p.59
Chapter Chapter 3 --- Aims of the study --- p.63
Chapter Chapter 4 --- Materials and Methods --- p.64
Chapter 4.1 --- Cell culture --- p.64
Chapter 4.2 --- Drug treatment --- p.64
Chapter 4.2.1 --- Suberoylanilide Hydroxamic Acid treatment --- p.64
Chapter 4.2.2 --- Trichostatin A treatment --- p.65
Chapter 4.3 --- Cell proliferation assay --- p.66
Chapter 4.4 --- Apoptotic assay --- p.67
Chapter 4.5 --- Flow cytometry --- p.67
Chapter 4.5.1 --- Cell preparation --- p.67
Chapter 4.5.2 --- Propidium Iodide staining --- p.68
Chapter 4.5.3 --- Annexin V-FITC staining --- p.68
Chapter 4.5.4 --- Flow cytometer analysis --- p.69
Chapter 4.6 --- Total RNA extraction --- p.70
Chapter 4.7 --- DNA extraction --- p.71
Chapter 4.8 --- Protein extraction --- p.72
Chapter 4.9 --- Western blottng --- p.72
Chapter 4.10 --- Microarray analysis --- p.74
Chapter 4.10.1 --- Sample preparation for microarray --- p.74
Chapter 4.10.2 --- Hybridization --- p.75
Chapter 4.10.3 --- Scanning and data processing --- p.75
Chapter 4.10.4 --- Data analysis --- p.76
Chapter 4.11 --- Primer design --- p.77
Chapter 4.12 --- RT-PCR --- p.77
Chapter 4.12.1 --- Reverse transcription --- p.77
Chapter 4.12.2 --- Quantitative RT-PCR --- p.78
Chapter 4.13 --- Methlyation study --- p.79
Chapter 4.13.1 --- Demethylation by 5-aza-2'deoxycytidine --- p.79
Chapter 4.13.2 --- Bisulfite modification --- p.79
Chapter 4.13.3 --- Methylation-specific PCR (MSP) --- p.79
Chapter Chapter 5 --- Results --- p.81
Chapter 5.1 --- Morphological changes in AGS cells --- p.81
Chapter 5.2 --- Anti-cancer effects of HDAC inhibitors --- p.81
Chapter 5.2.1 --- Effect of HDAC inhibitors on cell growth --- p.81
Chapter a. --- SAHA inhibits cell proliferation --- p.82
Chapter b. --- TSA inhibits cell proliferation --- p.82
Chapter 5.2.2 --- Cell cycle analysis --- p.87
Chapter a. --- Effect of SAHA on cell cycle --- p.87
Chapter b. --- Effect of TSA on cell cycle --- p.88
Chapter 5.2.3 --- Induction of apoptosis on AGS cells --- p.92
Chapter a. --- SAHA induces apoptotic cell death --- p.92
Chapter b. --- TSA induces apoptotic cell death --- p.94
Chapter 5.3 --- Induction of histone expression on AGS cells --- p.102
Chapter 5.3.1 --- HDAC inhibitors induced acetylation of histone H3 --- p.102
Chapter 5.3.2 --- HDAC inhibitors induced acetylation of histone H4 --- p.103
Chapter 5.4 --- SAHA- and TSA-induced gene expression profiles --- p.106
Chapter 5.5 --- Verification of gene expression by quantitative RT-PCR --- p.108
Chapter 5.6 --- Methylation study --- p.113
Chapter Chapter 6 --- Discussion --- p.116
Chapter 6.1 --- Improved treatment strategy is needed for gastric cancer. --- p.116
Chapter 6.2 --- HDAC inhibitors as potential anti-cancer agents --- p.117
Chapter 6.3 --- Potential anti-cancer effect of TSA and SAHA on AGS cells --- p.120
Chapter I. --- Morphological changes of AGS gastric cancer cells --- p.120
Chapter II. --- Inhibition of cell proliferation --- p.120
Chapter III. --- Induction of cell cycle arrest --- p.121
Chapter IV. --- Induction of apoptosis --- p.122
Chapter 6.4 --- Expression of acetylated histones upon treatment with TSA and SAHA --- p.124
Chapter 6.5 --- Identify potential target genes upon treatment with TSA and SAHA --- p.125
Chapter 6.5.1 --- Candidate genes involved in cell cycle --- p.126
Chapter a. --- P21WAF1 --- p.126
Chapter b. --- p27kip1. --- p.128
Chapter c. --- Cyclin E & Cyclin A --- p.128
Chapter d. --- Signal-induced proliferation-associated gene 1 (SIPA1) .… --- p.129
Chapter 6.5.2 --- Candidate genes involved in apoptosis and anti-proliferation --- p.130
Chapter a. --- BCL2-interacting killer (apoptosis-inducing) (BIK) (Pro-apoptotic gene) --- p.131
Chapter b. --- Thioredoxin interacting protein (TXNIP) (Proapoptotic gene)
Chapter c. --- Cell death-inducing DFFA-like effector b (CIDEB) (apoptosis induction) --- p.132
Chapter d. --- B-cell translocation gene 1 (BTG1) - (anti-proliferation) --- p.133
Chapter e. --- Quiescin 6 (QSCN6) (anti-proliferation) --- p.133
Chapter f. --- "Cysteine-rich, angiogenic inducer, 61 (CYR61) (anti-proliferative)" --- p.134
Chapter g. --- Metallothionein 2A (MT2A) (apoptosis induction and anti-proliferative) --- p.134
Chapter 6.5.3 --- Other genes reported to be up-regulated with HDAC inhibitors treatment --- p.135
Chapter a. --- Glia maturation factor-gamma (GMFG) --- p.135
Chapter b. --- v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS)
Chapter c. --- Interleukin 8 (IL-8) --- p.136
Chapter d. --- Insulin-like growth factor binding protein- 2 (IGFBP2) --- p.137
Chapter e. --- Integrin alpha chain 7 (ITGA7) --- p.138
Chapter 6.5.4 --- Selected highly up-regulated genes with HDAC inhibitors treatment --- p.139
Chapter a. --- Aldo-keto reductase family 1，member C3 (AKR1C3) --- p.139
Chapter b. --- GPI-anchored metastasis-associated protein homolog (C4.4A) --- p.139
Chapter c. --- "Serine (or cysteine) proteinase inhibitor，clade I (neuroserpin), member 1 (SERPINI1)" --- p.140
Chapter d. --- "Serine (or cysteine) proteinase inhibitor，clade E (nexin, plasminogen activator inhibitor type 1), member 1 (SERPINE1)" --- p.140
Chapter e. --- Adrenomedullin (ADM) --- p.141
Chapter f. --- Dehydrogenase/reductase (SDR family) member 2 (HEP27) --- p.142
Chapter g. --- Cholecystokinin (CCK) --- p.142
Chapter h. --- Silver homolog (mouse) (SILV) --- p.143
Chapter 6.6 --- Genes regulated by gene promoter hypermethylation in AGS cells --- p.143
Chapter Chapter 7 --- Conclusion --- p.147
Chapter Chapter 8 --- Further Studies --- p.150
References --- p.151
Appendix I --- p.151
Appendix II --- p.III
Appendix III --- p.IV
Appendix IV --- p.VI
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Wu, Yifei. "The effect of saturated and unsaturated fatty acids on HEPG2 cells and the trehalose protection of HEPG2 cells on palmitate induced toxicity." Diss., 2008.
Find full textAbstract:
Thesis (M.S.)--Michigan State University. Dept. of Chemical Engineering and Material Science, 2008.Title from PDF t.p. (viewed on July 29, 2009) Includes bibliographical references (p. 34-41). Also issued in print.
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Ying-Sui and 孫瑛穗. "Inhibitory effect of silibinin on the invasion and migration and enhancing effect of silibinin on the cytotoxicity of anticancer drugs, taxol, vinblastine, 5-fluorouracil of renal cell carcinoma." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/02969570407519748925.
Full textAbstract:
碩士中山醫學大學
醫學研究所
96
Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression VEGF and HIF-1α. The VEGF and HIF-1α has intervene in the renal cell carcinoma angiogenesis and metastasis. In this study, we assayed the cell viability, cell invasion/migration, matrix metalloproteinases(MMPs) activity, and urokinase-plasminogen activator (u-PA) activity of 786-O cells with silibinin treatments by MTT assays, invasion/motility assays, gelatin、casein zymography. We found that silibinin relevant to inhibite the cell invasion/migration capacities and the activities of MMP-2, MMP-9 and u-PA in VHL-null 786-O ccRCC cells. without affecting cell viability. Besides, we showed that silibinin downregulated the protein of MMP-2, MMP-9 and u-PA, and also enhanced expression of TIMP-2 and PAI-1. A treatment with silibinin also led to a dose-dependent inhibition on the activation of ERK1/2, p38, NF-κB, c-Jun and c-Fos. In vivo, an anti-tumor study using nude mice (ICR nu/nu) xenograft model by a subcutaneous inoculation of 786-O cells was performed. The average tumor volume of treatment groups was lower than that of control group, statistically. In conclusion, silibinin may be a powerful candidate for a preventive agent against kindey cancer development and metastasis. On the other hand, we investigated the activity and toxicity of a combination of taxol, vinorelbine(VBL) and 5-fluorouracil(5-FU) in metastatic renal cancer. We found that silibinin with low concentration of anticancer drugs have the similar death rate of the high concentration. Among these anticancer drugs, 5-fluorouracil had a best effect upon inhibit the cell viability. These results suggest silibinin in combination with anticancer drugs may be a beneficial chemotherapeutic strategy. This review focuses on the chemistry and analogues of silibinin, multiple possible molecular mechanisms, in vitro as well as in vivo anti-cancer activities, and studies on human clinical trials.
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Soni, Smita Pravin. "The Effect of Acyl Chain Unsaturation on Phospholipid Bilayer." 2010. http://hdl.handle.net/1805/2097.
Full textAbstract:
Indiana University-Purdue University Indianapolis (IUPUI)Each biological cell is surrounded by a membrane that consists of many different kinds of lipids. The lipids are mainly composed of phospholipids, which form a fluid bilayer that serves as the platform for the function of membrane bound proteins regulating cellular activity. In the research described in this thesis we employed solid state 2H NMR, complemented by DSC (differential scanning calorimetry) and MD (molecular dynamics) simulations, to study the effect of PUFA (polyunsaturated fatty acids) and TFA (trans fatty acids) on molecular organization in protein-free model membranes of controlled composition. These two classes of unsaturated fatty acid incorporate into membrane lipids and have, respectively, a beneficial and harmful impact on health. The aim is to gain insight into the molecular origin of this behavior. DHA (docosahexaenoic acid), which with 6 "natural" cis double bonds is the most highly unsaturated PUFA found in fish oils, and EA (elaidic acid), which with only a single "unnatural" trans double bond is the simplest manmade TFA often found in commercially produced food, were the focus. 2H NMR spectra for [2H31]-N-palmitoylsphingomyelin ([2H31]16:0SM) in SM/16:0-22:6PE (1-palmitoyl-2-docosahexaenoylphosphatidylethanolamine)/cholesterol (1:1:1 mol) mixed membranes were recorded. This system served as our PUFA-containing model. The spectra are consistent with lateral separation into nano-sized (< 20 nm) domains that are SM-rich/cholesterol-rich (raft), characterized by higher chain order, and DHA-rich/cholesterol-poor (non-raft), characterized by lower chain order. The aversion cholesterol has for DHA, as opposed to the affinity cholesterol has for predominantly saturated SM, excludes the sterol from DHA-containing PE-rich domains and DHA from SM-rich/cholesterol-rich domains. It is the formation of highly disordered membrane domains that we hypothesize is responsible, in part, for the diverse health benefits associated with dietary consumption of DHA. 2H NMR spectra for 1-elaidoyl-2-[2H35]stearoylphosphatidylcholine (t18:1-[2H35]18:0PC) and 1-oleoyl-2-[2H35]stearoylphosphatidylcholine (c18:1-[2H35]18:0PC) were recorded to compare membranes with respect to a trans vs. cis ("natural") double bond. The spectra indicate that while a trans double bond produces a smaller deviation from linear conformation than a cis double bond, membrane order is decreased by a comparable amount because the energy barrier to rotation about the C-C single bonds either side of a
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Wang, Shih Siou, and 王士修. "Development of high-throughput microfluidic 3-dimensional cell culture system and its application for the chemosensitivity assays of anti-cancer drugs- Effect of cell culture models on the results of chemosensitivity assays." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/28412281443175613220.
Full textAbstract:
碩士長庚大學
生化與生醫工程研究所
101
Microfluidic cell culture systems have been widely used in cell culture-based assays (e.g. drug testing). However, most of previous works can not provide a stable, well-defined, and more biologically-relevant culture environment for a high-throughput and high-precision cell-based assay. To tackle these issues, this research aims to develop a microfluidic cell culture system consisting of a microfluidic cell culture chip and a controller for micro-scale perfusion 3-D cell culture-based assays. Its advantages include the function for both efficient and high throughput micro-scale 3-D culture construct preparation and loading, the capability for multiplexed medium delivery, and the design of waste medium reservoir array facilitating the subsequent high throughput bioassay works. Furthermore, a chemosensitivity assay was successfully demonstrated using the proposed cell culture system. Comparnig with the chemosensitivity assays using other cell culture models, results showed that the different cell culture format could lead to different evaluation outcomes. In establishing in vitro cell-based assays, therefore, it might be necessary to investigate the fundamental physiological variations of the cultured cells in different culture models to avoid any misinterpretation of data. Overall, the proposed cell culture system not only can provide more stable, well-defined and biologically-relevant culture environments, but it also features in low consumption of research resources. All these features are found valuable for a high throughput and high precision cellular assays.
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Curtis, Marc James. "Evidence for the involvement of a mitochondrial permeability transistion in a victorin-Induced cell death." Thesis, 2003. http://hdl.handle.net/1957/31853.
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"The effect of danshen-gegen compound formula on in vitro foam cell formation and in vivo antioxidant level." 2007. http://library.cuhk.edu.hk/record=b5893290.
Full textAbstract:
Wong, Wai Yin.Thesis (M.Phil.)--Chinese University of Hong Kong, 2007.
Includes bibliographical references (leaves 92-108).
Abstracts in English and Chinese.
Chapter Chapter 1 --- Introduction --- p.1
Chapter 1.1 --- Atherosclerosis --- p.1
Chapter 1.1.1 --- Pathogenesis of Atherosclerosis --- p.2
Chapter 1.1.2 --- Atherosclerosis and Cardiovascular Disease --- p.4
Chapter 1.2 --- Cardiovascular Disease (CVD) --- p.5
Chapter 1.2.1 --- Term Definition --- p.5
Chapter 1.2.2 --- Risk Factors --- p.6
Chapter 1.2.3 --- Current Western Medications --- p.7
Chapter 1.3 --- Reactive Oxygen Species (ROS) --- p.8
Chapter 1.3.1 --- Impact of ROS --- p.8
Chapter 1.3.2 --- "Superoxide Anion Radical, Hydrogen Peroxide, Hydroxyl Radical, Nitric Oxide" --- p.9
Chapter 1.3.3 --- ROS Production by NAD(P)H Oxidases --- p.11
Chapter 1.3.4 --- ROS Production by Mitochondria --- p.12
Chapter 1.3.5 --- Lipid Peroxidation --- p.13
Chapter 1.3.6 --- Other Sources of ROS --- p.15
Chapter 1.4 --- Antioxidants --- p.16
Chapter 1.4.1 --- Superoxide Dismutase (SOD) --- p.16
Chapter 1.4.2 --- Catalase (CAT) --- p.17
Chapter 1.4.3 --- Glutathinoe Peroxidase (GPx) --- p.17
Chapter 1.4.4 --- Glutathione-S-Transferase (GST) --- p.18
Chapter 1.4.5 --- Vitamin E --- p.18
Chapter 1.4.6 --- Vitamin C --- p.19
Chapter 1.5 --- Ageing --- p.19
Chapter 1.6 --- Antioxidants and CVD --- p.21
Chapter 1.7 --- Traditional Chinese Medicine (TCM) --- p.22
Chapter 1.7.1 --- Danshen --- p.23
Chapter 1.7.2 --- Gegen --- p.25
Chapter 1.7.3 --- Danshen-Gegen Compound Formula (DG) --- p.26
Chapter 1.8 --- Aim of Study --- p.27
Chapter Chapter 2 --- In vitro Foam Cells Formation --- p.29
Chapter 2.1 --- Materials and Methods --- p.29
Chapter 2.1.1 --- Materials --- p.29
Chapter 2.1.2 --- Methods --- p.30
Chapter 2.1.2.1 --- Herbal Preparation by Hot Water Extraction --- p.30
Chapter 2.1.2.2 --- Resident Peritoneal Macrophages Preparation --- p.31
Chapter 2.1.2.3 --- "Colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl Tetrazolium Bromide (MTT) Assay" --- p.31
Chapter 2.1.2.4 --- DG Effect on in vitro Foam Cells Formation --- p.32
Chapter 2.2 --- Results and Discussion --- p.32
Chapter 2.3 --- Summary --- p.39
Chapter Chapter 3 --- In vivo Antioxidant Level --- p.40
Chapter 3.1 --- DG Effect on in vivo Antioxidant Levels on Young-adult Wistar Rats --- p.40
Chapter 3.1.1 --- Materials and Methods --- p.40
Chapter 3.1.1.1 --- Herbal Preparation by Hot Water Extraction --- p.40
Chapter 3.1.1.2 --- Assay Kits --- p.41
Chapter 3.1.1.3 --- Antibodies for Protein Expression Determination in Organs --- p.41
Chapter 3.1.1.4 --- Animals and Experimental Design --- p.41
Chapter 3.1.1.5 --- Plasma Antioxidants --- p.42
Chapter 3.1.1.6 --- Lipid Peroxidation and Protein Expression in Organs --- p.46
Chapter 3.1.1.7 --- Statistics --- p.52
Chapter 3.1.2 --- Results and Discussion --- p.53
Chapter 3.2 --- DG Effect on in vivo Antioxidant Levels on Middle-aged Wistar Rats --- p.74
Chapter 3.2.1 --- Materials and Methods --- p.75
Chapter 3.2.2 --- Results and Discussion --- p.75
Chapter 3.3 --- Summary --- p.87
Chapter Chapter 4 --- Conclusion and Future Work --- p.90
Chapter 4.1 --- Conclusion --- p.90
Chapter 4.2 --- Future work --- p.90
Reference --- p.92
Related Publication --- p.109
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Chen, Yi Dao, and 陳以道. "Development of high-throughput pneumatically-driven perfusion micro 3-dimensional cell culture system and the study of the effect of primary cancer cell culture models on the result of chemosensitivity assays of anti-cancer drugs." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/91807634568958629057.
Full textAbstract:
碩士長庚大學
生化與生醫工程研究所
101
Traditional cell culture devices are widely used in cell culture-based testing (eg: drug testing). However, most of the cell culture tools may not be able to provide a stable, quantitative physiological significance possessed cell culture environment for high-throughput and high accuracy of the drug testing. Therefore, this study aims to develop a miniaturized three-dimensional cell culture perfusion system. The cell culture system main features are: (a) to gas-driven approach to multi-channel transmission medium and (2) the efficient conduct highly accurate small sample (example: three-dimensional cell culture samples) injection. Development section of the device, we polydimethyl siloxane as the material production of the cell culture system, in addition we also evaluated the gas-driven multi-channel medium conveying performance. Finally, we will demonstrate in the original cell culture. On the application in terms of the ultimate vision of this research is the use of cell culture systems developed by anticancer drug sensitivity testing in the hope that the future can provide patients with cancer chemotherapy drug choice of targets. In achieving this goal, some of the cell culture test results for such usage patterns affect basic research will be established. Experimental results show that the Institute is the development of the gas-drive system uses gas operation time and the intervals to control the perfusion flow rate at the action time is greater than one second when the coefficient of variation can reach 2.32% to 1.20% and the culture environment pH reaches stability, and the original cancer cells in different cell culture environment pH value below its physiological performance and growth capabilities were significantly different, so the system in providing stable homogeneous cell culture environment, with good performance. The use of this system for further experimental results also show that the original cancer cells in different cell culture models under its physiological performance and growth are significant differences, while affecting the original cancer cells to anticancer drugs chemical sensitivity, and therefore relevant in vitro experiments, which must be considered and the environment into the cell culture model is selected to obtain a physiological significance of the experimental results.
50
Tsai, Tsung Lin, and 蔡宗霖. "Screening AMP m2163 and m2386 from Lactobacillus casei ATCC 334 or some drugs for studying the antiproliferation against a human colorectal cancer cell and the inhibitory effect on human MIF factor." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/16030813155780757769.
Full textAbstract:
博士國立清華大學
分子醫學研究所
103
In modern society, the occurrence and treatment of cancer disease is still the difficult problem.In order to overcome this difficulty as soon as possible, many newly research and methods are in constant innovation andeach method has its advantages and disadvantages. In our laboratory,we engaged in the study of cancer treatment and hoped able to contribute ondevelop of newly cancer drugs. We focused on the anti-cancer drug development in two relatively new research areas, one of which was the development of protein drugs.We found some antimicrobial peptides fromnatural Lactobacillus and applied on cancer cytotoxicity studies.The result proved the effect on colon cancer cell line growth inhibition and might be able to achieve the prevention and suppression of gastrointestinal related cancers by feedingLactobacilluscarriedthese peptides. The second project was to utilize computer-aided drug design to reduce the seeking time forsearching new anti-cancer drugs.The virtual drug screening focus on an extensive tumor progress related factor MIF. Several new structure compounds were screened and thein vitroexperiments proved their inhibitory effect on MIF protein.This system able to apply on searching new drugs andhelpful ofnew drug design. Therefore, the next section described separately for these two approaching methods, and the following results divided in two chapters for clear described. (1) Since 1945 the finding of antimicrobial activity of antimicrobial peptides (AMPs), a series of studies on the toxicity toward eukaryotic cancer cellhad been conducted. Previously, two novel AMPs named m2163 and m2386 identified from Lactobacillus (L.)caseiATCC 334 had revealed their antimicrobial ability by our laboratory. In this study, we tested the anti-cancer ability of these peptides on human colorectal cancer cell line SW480. The anti-proliferation IC50 defined of both peptides by MTT assay. Cell cycle analysis and AnnexinV/PI double staining showed the cell death subpopulation. Cell death correlated protein regulation analyzed by qPCR and western blot for RNA and protein level respectively. FACS and confocal microscopy revealed the cellular location of peptides at different time point.Both peptides had about 40 μg/ml IC50 for cell growth inhibition. Cell death receptor expression including Fas and TRAILR1 were activated. Furthermore, both peptides increased some of the internal mitochondria and external cytosol apoptosis pathway related proteins such as Smac and caspase 3 expression. The FITC-conjugated peptide location revealed that m2163 and m2386 peptide attached on the cell membrane and could penetrate into the cell cytoplasm at late time. The antimicrobial peptides m2163 and m2386 had the anti-cancer ability on human colorectal cancer cell line SW480 and could cross cell membrane, therefore causing downstream effects including cell death pathway activation. (2) Macrophage migration inhibitory factor (MIF) is an autocrine- and paracrine-acting cytokine that is involved in several inflammatory, autoimmune, infectious, and oncogenic diseases. Clinical data revealed that inhibition of MIF, especially its tautomerase activity, with small compounds being beneficial in some disease models. A virtual screening (VS) experiment is conducted for searching some active compounds from the ZINC database to inhibit the tautomerase activity site of MIF. By using an x-ray–determined MIF structure as template and AutoDock4.2 molecular docking program, we screened out some 17 possible compounds for ranking by docking energy. In vitro experiments for these 17 compoundsinhibition for measuring their inhibitory activity IC50 against the MIF tautomerase. The IC50 measured using both human monocytic THP-1 cell lysate and purified recombinant human MIF protein. We found that the IC50 oftop three searched compounds (namely, ZINC02693801, ZINC00141102, and ZINC12368346) had better inhibitor activity than that determined for ISO-1, a known MIF tautomerase inhibitor and standard used throughout our VS experiment. Moreover, the scaffolds of most of our searched active compounds also quite different from those published drugs previously and showed the potential for further modification and development of new drugs.