Дисертації з теми "NF-kappa B pathway"
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陳俊峯 and Chun-fung Anthony Chan. "Dysregulation of nuclear factor-kappa B (NF-KB) signaling pathway in hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B31227156.
Повний текст джерелаLupica, Joseph A. "Inhibition of the NF-kB signaling pathway and its effects on apoptosis and cancer." Cleveland, Ohio : Cleveland State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=csu1214235115.
Повний текст джерелаAbstract. Title from PDF t.p. (viewed on Oct. 6, 2008). Includes bibliographical references (p. 213-240). Available online via the OhioLINK ETD Center. Also available in print.
Guo, Xiaoxia. "Nuclear Factor Kappa B Pathway and human cancer therapeutics." Thesis, University of Wolverhampton, 2009. http://hdl.handle.net/2436/88553.
Повний текст джерелаSunami, Yoshiaki. "Molecular analysis of the non-canonical NF-kappaB pathway." Université Louis Pasteur (Strasbourg) (1971-2008), 2006. http://www.theses.fr/2006STR13177.
Повний текст джерелаIt is shown here that the canonical/non-canonical NF-B pathways are not independent and a master regulatory role of the canonical pathway is to upregulate activators of the non-canonical pathway. The data further implicate a translation requirement and that LPS stimulation upregulates a potential intermediate in LPS/CD40 signaling which supports activation of the non-canonical pathway. Further, the non-canonical pathway is constitutively activated in HL cells, involving persistent p100 phosphorylation. It was found that transient and constitutive activation of the non-canonical pathway involves incorporation of p100 and p52 into a megadalton complex. TAP was employed to identify novel p100 interacting partners. EDD (an identified molecule) induces processing of p100 upon co-expression. The complex formation of TRAF3 (another p100 interactor) with p100 is mediated by NIK and requires its kinase activity. The expression of NIK promotes recruitment of TRAF3/p100 to the p100 signalosome
Torrie, Lindsay J. "Characterisation of the lipopolysaccharide stimulated NF#kappa#B signal transduction pathway in rat aortic smooth muscle cell." Thesis, University of Strathclyde, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249146.
Повний текст джерелаKonieczkowski, David Joseph. "Systematic approaches to overcoming limitations of MAPK pathway inhibition in melanoma." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11094.
Повний текст джерелаBu, De-xiu. "The nuclear factor k[kappa]B signal transduction pathway : its role in atherogenesis and intimal hyperplasia /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-615-8/.
Повний текст джерелаCai, Chunhui, and 蔡春晖. "TAK1 promotes ovarian cancer aggressiveness through activation of NF-kB pathway." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193410.
Повний текст джерелаpublished_or_final_version
Obstetrics and Gynaecology
Doctoral
Doctor of Philosophy
Shaikh, Raziya Banu. "Light related TNF cytokines and the NF-[kappa]B pathway in development and function of mucosal and NK T cells /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3091315.
Повний текст джерелаCude, Kelly J. "Activation of a novel ERK5-NF-kappaB pathway is required for G2/M progression in the cell cycle /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/5003.
Повний текст джерелаRyan, Sarah-Louise. "Targeting the nuclear factor kappa-light-chain-enhancer of activated b cells (NF-kb) pathway to overcome cisplatin-resistance in non-small cell lung cancer." Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/127346/1/Sarah-Louise_Ryan_Thesis.pdf.
Повний текст джерелаLacey, Derek. "NFκB independent pathway activation of rheumatoid arthritis FLS by macrophage migration inhibitory factor (MIF)". Monash University, Faculty of Medicine, 2003. http://arrow.monash.edu.au/hdl/1959.1/9457.
Повний текст джерелаMazzone, Graciela Lujan. "Role of unconjugated bilirubin in the endothelial dysfunction." Doctoral thesis, Università degli studi di Trieste, 2008. http://hdl.handle.net/10077/2647.
Повний текст джерелаAtherosclerosis, a progressive cardiovascular disease, is characterized by the accumulation of cholesterol in macrophage deposits (foam cells) and the formation of atherosclerotic plaques in the walls large- and medium- sized arteries. The earliest events in the development of atherosclerosis involve progressive modifications in the endothelial micro-environment. This endothelial dysfunction is a complex of multi-step mechanisms, for which reduced NO levels have been reported as a marker, is characterized by increasing expression of adhesion molecules (AMs), which mediate the diapedesis (migration) of inflammatory and immunocompetent cells through the endothelial layer into the arterial wall. NO is synthesized intracellularly by nitric oxide enzymes (eNOS and iNOS) and is regulated by a variety of stimuli. NO acts as an autocrine or paracrine hormone, as well as intracellular messenger, with a critical role in vascular endothelial growth factor-induced angiogenesis and vascular hyperpermeability in vitro. The over-expression of AMs is orchestrated by pro-inflammatory cytokines, particularly TNF-alpha. The two major subsets of AMs participating in these processes are the selectins, in particular E-selectin, and the immunoglobulin gene superfamily, in particular vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Transcriptional regulation of these inflammatory genes requires the participation of several proteins, inducible activators, as: NF-kappa B and (CRE)-binding protein (CREB). The most abundant form of NF-kappa B is an heterodimer of p50 and p65; which is sequestered in the cytoplasm in an inactive form through interaction with the I kappa B inhibitor proteins. Signals that induce NF-kappa B release dimmers to enter to the nucleus and induce gene expression. Pyrridoline dithiocarbamate (PDTC) a metal-chelating compound inhibits NF-kappa B by blocking ubiquitine ligase activity towards phosphorylated I kappa B, in turn downregulating the expression of E-selectin, VCAM-1 and ICAM-1. CREB is a widely expressed DNA-binding protein, downstream target of cAMP, activated by phosphorylation on serine 133. A regulatory site, on the gene promoters of both E-selectin and VCAM-1, binds both NF-kappa B and CREB transcription factors. Unconjugated bilirubin (UCB), long considered to be simply a waste end product of heme metabolism and a marker for hepatobiliary disorders, is now thought to function as an endogenous tissue protector by attenuating free radical-mediated damage to both lipids and proteins. There is increasing epidemiological evidence supporting an inverse association between cardiovascular disease and plasma levels of bilirubin. Recent studies indicated that bilirubin may be protective in the development of atherosclerotic diseases by inhibiting the proliferation of vascular smooth muscle cells by mechanisms yet to be established. It has been proposed that UCB can interfere with the atherosclerotic disease development by inhibiting the trans-endothelial vascular cell adhesion molecule (VCAM-1)-dependent migration of monocytes into the intima. The aim of this study is to investigate the effect of the UCB in the endothelial dysfunction. Specifically UCB effects on NO production, AMs expression and the regulatory transcription factors involve in the inflammatory response. Variable doses of free bilirubin (Bf) (the active form of UCB in plasma), simulating upper normal (15 nM) and modestly elevated levels (30 nM) for plasma, were evaluated in two models of endothelial cells. A) H5V, murine microvascular endothelial cell line, and B) HUVEC (Human Umbilical Vein Endothelial Cells), isolated from the vein of human umbilical cord. TNF-alpha (20 ng/mL) was added in order to reproduce, in vitro, the endothelial dysfunction and describe UCB contribution on its effects. UCB alone reduced the viability in H5V cells by MTT assay in a dose dependent manner after 24 hours while no effect was observed in the LDH released. In the first set of experiments NO production in H5V cells was evaluated, a time-depended increase on NO basal and a dose-dependent decrease on NO concentration after TNF-alpha (20 ng/mL) were observed. NO reduction related TNF-alpha was seen at all times studied. The effect of UCB was studied in co-treatments with TNF-alpha for 24 and 48 hours. UCB (Bf 15 and 30 nM) significantly reversed the reduction of nitrite content induced by TNF-alpha at 48 hours. The gene expression analysis was performed by Real Time PCR technology with specific primers for eNOS, iNOS, E-selectin, VCAM-1 and ICAM-1. In H5V cells, TNF-alpha increased the expression of all the genes studied (except eNOS) at 2, 6 and 24 hours. The co-treatment with UCB, at a Bf that did not themselves affect the expression of the three adhesion molecules, blunts the over-expression of E-selectin, Vcam-1 and iNOS induced by a pro-inflammatory cytokine such as TNF-alpha. The inhibitory effect of UCB was usually modest (20-30%) and detected at 2 and/or 6 hours, but had disappeared 24 hours. Furthermore, a synergistic effect between TNF-alpha and UCB was seen on the expression of iNOS at 24 hours, indicating a biphasic regulation. Moreover, no effects were seen on eNOS. Similar results were observed in the regulation of the gene expression of the AMs and viability in HUVEC cells, indicating the lack of species specific effect. However, no effect of TNF-alpha or UCB was seen in the expression of iNOS, eNOS or NO content. Western blot analysis in H5V cells confirmed that TNF-alpha induced the expression of E-selectin, VCAM-1 and ICAM-1 in a time-dependent manner. This effect was blunted after 24 hours by the presence of UCB (Bf 15 and 30 nM). The contribution of NF-kappa B pathway in UCB effects was investigated by addition of a specific inhibitor, PDTC. The co-treatment with PDTC and UCB for 2 hours produced an additive reduction of TNF-alpha effect on Eselectin, VCAM-1, and iNOS in H5V cells. In addition, UCB prevented the nuclear translocation of NF-kappa B induced by TNF-alpha. Failure of UCB to alter TNF-alpha -induced phosphorylation of CREB (at Ser 133) suggested that the CREB pathway was not involved in the UCB inhibition. The results obtained in the present study shows that unconjugated bilirubin, even at upper-normal physiological (15 nM) and mildly elevated (30 nM) Bf can modulate gene expression and endothelial cell function. Furthermore, UCB may regulate NO levels by a biphasic regulation of iNOS, and in addition influences the expression of the endothelial adhesion molecules. In summary, these data indicates that bilirubin limits the over-expression of the adhesion molecules and regulates the NO metabolism in the pro-inflammatory state induced by the cytokine TNF-alpha. Even though UCB alone does not alter these markers. UCB effects are mediated in part by a modulation of the NF-kappa B transcription factor. These results support the concept that modestly elevated concentrations of bilirubin may help prevent atherosclerotic disease as suggested by epidemiological studies.
La malattia cardiovascolare è la causa di morte e disabilità più importante nel mondo occidentale e tra le malattie cardiovascolari, quella vascolare aterosclerotica rappresenta la percentuale maggiore. Le lesioni aterosclerotiche si creano principalmente nelle arterie di medio e grande calibro con parete muscolare elastica e possono determinare ischemia nei tessuti a valle della lesione stessa. Numerose osservazioni epidemiologiche hanno riscontrato una significativa correlazione inversa tra incidenza di malattia cardiovascolare ischemica e livelli serici di bilirubina. Sono stati pubblicati studi di prevalenza su campioni di popolazione maschile e sulla popolazione generale, studi prospettici su soggetti con iperbilirubinemia non coniugata (Sindrome di Gilbert) o nella popolazione generale. Questi studi hanno confermato l'importanza dei valori di bilirubinemia nella valutazione del rischio d'incidenza di malattia ischemica coronarica. In alcuni casi, il valore di bilirubinemia è addirittura identificabile come fattore di rischio indipendente di malattia. Analoghe osservazioni sono state documentate nella prevalenza della malattia vascolare periferica aterosclerotica. L'endotelio è un tessuto in grado di rispondere ai vari stimoli con la produzione di sostanze vasoattive, tra cui l'ossido nitrico (NO) sintetizato principalmente dagli enzimi ossido nitrico sintetasi (iNOS ed eNOS), e le molecole di adesione (AMs), E-selectina, VCAM-1 e ICAM-1. Il primo evento che si verifica nella insorgenza di una lesione aterosclerotica è la comparsa della disfunzione endoteliale. Per disfunzione endoteliale si intende una successione di condizioni patologiche che coinvolgono l'endotelio vascolare determinate da una ridotta biodisponibilità di NO e un aumento dell'espressione delle molecole di adesione. Questi eventi favorirebbero l'adesione di linfo/monociti e la successiva migrazione nell'intima. Una riduzione di NO e l'incremento dell'espressione dalle AMs nelle cellule endoteliali stesse avviene nel processo infiammatorio attraverso l'induzione di fattori di trascrizioni tra cui NF-kappa B e CREB. Questo progetto di ricerca si pone come obiettivo lo studio degli effetti della bilirubina non coniugata (UCB) a concentrazioni fisiologiche normali o lievemente incrementate sull'insorgenza della disfunzione endoteliale, prima manifestazione della malattia aterosclerotica. Specificamente, studiare l'effetto della UCB libera (Bf), che è la porzione attiva di UCB in plasma non legata all'albumine, nella regolazione della produzione di NO e l'espressione delle AMs. Lo studio è stato condotto utilizzando due modelli in vitro di cellule endoteliali. a) H5V, linea cellulare immortalizzata di topo e b) HUVEC cultura primaria di cellule umane, della vena ombelicale (Human Umbilical Vein Endothelial Cells). La citochina TNF-alpha (20 ng/mL) è stata utilizzata per indurre lo stato di disfunzione endoteliale. Lo studio ha evidenziato che livelli elevati di bilirubina non coniugata libera (Bf 100 nM) riescono a ridurre significativamente la vitalità cellulare valutata attraverso il test MTT senza provocare variazioni nella liberazione di LDH. Inoltre è stato evidenziato un incremento basale del livello extracellulare di NO in maniera tempo dipendente. Il trattamento con TNF-alpha provoca una riduzione dose dipendente del livello extracellulare di NO a tutti i tempi di trattamento. UCB riesce a modulare l'effetto di TNF-alpha dopo 48 ore di cotrattamento. Questo effetto si correla con un incremento nell'espressione genica di iNOS dopo 24 ore. A per tempi brevi di trattamento (2 e 6 ore) UCB riduce l'espressione genica di E-selectina, VCAM-1 in entrambi tipi cellulari, dimostrando l'assenza di un effetto specie-specifico. Inoltre è stata anche osservata, nelle cellule H5V una riduzione dell'espressione di iNOS dopo 2 ore. Alla riduzione dell'espressione genica delle AMs segue la riduzione della espressione proteica dopo 24 ore di trattamento nelle cellule H5V. Un effetto inibitorio additivo all'azione dell'UCB si è ottenuto inibendo in modo specifico il fattore di trascrizione NF-kappa B con PDTC. In seguito a trattamento con UCB si è riscontrata una riduzione della localizzazione di NF-kappa B nel nucleo e nessun effetto sulla fosforilazione del fattore di trascrizione CREB. Questi risultati confermano il coinvolgimento di UCB a concentrazioni fisiologiche normali (Bf 15 nM) o lievemente elevate (Bf 30 nM) nella regolazione dal metabolismo del NO e nella modulazione dell'espressione delle AMs indotte da TNF-alpha, anche se UCB non influisce di per sé su codesti marcatori. Questo lavoro conferma che l'effetto della bilirubina, in moderate concentrazione fisiologiche, è coinvolta nella prevenzione delle malattie aterosclerotiche, secondo quanto suggerito dagli studi epidemiologici.
1977
Lee, Thomas H. "The Role of RIP1 in the TNFR1 Signal Transduction Pathway: a Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/235.
Повний текст джерелаCatley, Matthew Copeland. "The role of NF-kappa B in inflammatory gene expression in pulmonary A549 cells : transduction pathways and mechanisms." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404397.
Повний текст джерелаZhong, Cai-Yun. "Regulation of MAPK/AP-1 and NF-[kappa]B signal pathways in tobacco smoke-induced pulmonary cell proliferation and apoptosis /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2005. http://uclibs.org/PID/11984.
Повний текст джерелаDegree granted in Comparative Pathology. On t.p. "[kappa]" appears as Greek letter. Also available via the World Wide Web. (Restricted to UC campuses)
Astarci, Erhan. "Investigation Of The Inflammatory Pathways In Spontaneously Differentiating Caco-2 Cells." Phd thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613507/index.pdf.
Повний текст джерела) acted downstream of PKC to inactivate Inhibitor of kappa B (IB) and activate NF-&kappa
B in the undifferentiated cells and this axis was inhibited in the differentiated cells. The increase in ICAM1 expression in the differentiated cells was due to a transcriptional upregulation by C/EBP. The protein expressions of both ICAM-1 and VCAM-1, however, were found to decrease in the course of differentiation, with both proteins getting post-translationally degraded in the lysosome. Functionally, a decrease in adhesion to HUVEC cells was observed in the differentiated Caco-2 cells. Thus, the regulation of ICAM-1 and VCAM-1, although both NF-B target genes, appear to be different in the course of epithelial differentiation. microRNAs are known to regulate many cellular pathways. miR-146a, which is known to target NF-&kappa
B, was shown to be highly upregulated in differentiated Caco-2 cells. As a predicted target of miR-146a, mRNA and protein expression of MMP16 was inversely correlated with miR-146a during differentiation of Caco-2 cells. miR-146a could bind to the 3&rsquo
UTR of MMP16 and ectopic expression of miR-146a resulted in a decreased mRNA and protein expression of MMP16 in the undifferentiated Caco-2 and HT-29 cells. Functionally, decreased gelatinase activity determined by gelatin zymography and reduced invasion and migration through Transwells was observed. In the final part of the thesis, the inhibition of NF-&kappa
B via PPAR&gamma
in 15-Lipoxygenase-1 (15LOX1) expressing cells was investigated. The expression of 15LOX1, a member of the inflammatory arachidonate cascade, could lower phosphorylation of I&kappa
B&alpha
and NF-&kappa
B DNA binding activity which was reversed with a 15LOX1 inhibitor. This inhibition was mediated by phospho-PPAR&gamma
, which in turn was phosphorylated by ERK1/2.
Huang, Xuesong. "The study on signal mechanism of protein kinase C zeta-involved NF-kB activation in LPS-stimulated TLR4 signaling pathways." Connect to Online Resource-OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=mco1193663177.
Повний текст джерела"In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences." Title from title page of PDF document. Bibliography: p. 72-96.
Fears, Sharry L. "Effect of Inhibition of S-Nitrosoglutathione Reductase on the NF-κB Pathway". Thesis, 2009. http://hdl.handle.net/1805/1949.
Повний текст джерелаS-nitrosoglutathione reductase (GSNOR) also known as glutathione- dependent formaldehyde dehydrogenase (FDH), is a zinc-dependent dehydrogenase. GSNOR oxidizes long chain alcohols to an aldehyde with the help of a molecule of NAD+. GSNOR was initially identified as FDH because of its role in the formaldehyde detoxification pathway. The only S-nitrosothiol (SNO) substrate recognized by GSNOR is GSNO. A transnitrosation reaction transfers NO from nitrosylated proteins or S-nitrosothiols (RSNO) to glutathione to form S-nitrosoglutathione. This GSNO is finally converted to glutathione disulfide (GSSG) by a two step mechanism. Cellular GSNO is a nitric oxide reservoir that can either transfer to or remove from the proteins a NO group. Reduction of GSNO by GSNOR depletes this reservoir and therefore indirectly regulates protein nitrosylation. GSNOR inhibitors which can increase the basal GSNO levels will be another potential therapy. Several GSNOR inhibitors were identified in our laboratory and the aim of this study was to understand their cellular effects. One of the experiments studied the effect of the compound on protein-SNO. The role of nitric oxide in regulation of NF-κB pathway is reviewed by Bove and van der Vliet. We focused on identification of nitrosylated proteins using protein specific antibodies. We identified nitrosylation of IKKβ. So the question raised was whether nitrosylation of IKKβ affects its activity. IKKβ is responsible for phosphorylation of IκBα and phosphorylation of IκBα results in its degradation and activation of NF-κB pathway. Therefore, we studied the phosphorylation of IκBα in the presence of inhibitor C3. Results showed a dose-dependent decrease of pIκB. So the next question was whether the phosphorylation of IKKβ was affected by nitrosylation. We did not detect any change in pIKKβ with different concentrations of C3. The decreased degradation of IκBα caused by C3 translated into decreased NF-κB activity as seen by a dose-dependent decrease in amounts of ICAM-1 with increasing C3 concentration. This data supports the premise that the activity of transcription factor NF-κB is suppressed by inhibiting GSNOR with compound C3
Moulakakis, Christina [Verfasser]. "Pulmonary surfactant protein A's anti-inflammatory modulation of the IκB-α [I-kappa-B-alpha], NF-κB [NF-kappa-B] signal transduction pathway / vorgelegt von Christina Moulakakis". 2008. http://d-nb.info/990817296/34.
Повний текст джерелаDe, Silva Nilushi. "The alternative NF-kB pathway in mature B cell development." Thesis, 2015. https://doi.org/10.7916/D8125RZK.
Повний текст джерелаYao, Chen [Verfasser]. "Activation of NF-k63B [NF-kappa-B] via the canonical pathway in nephrotoxic serum nephritis in mice : possible therapeutic applications with specific IKKDβ, [IKKD-beta], IKK2 inhibition / vorgelegt von Chen Yao". 2010. http://d-nb.info/1009348531/34.
Повний текст джерелаLucas, Bethany R. "Ectopic expression of TAL-1 increases resistance to TNF[alpha]-induced apoptosis in Jurkat cells via changes in the NF-kB signaling pathway." 2011. http://liblink.bsu.edu/uhtbin/catkey/1642170.
Повний текст джерелаDepartment of Biology
"Deregulated NF-κB signalling pathways in EBV-positive nasopharyngeal carcinoma". 2011. http://library.cuhk.edu.hk/record=b5894717.
Повний текст джерелаThesis (M.D.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (leaves 136-170).
Abstracts in English and Chinese.
Abstract --- p.i
Acknowledgements --- p.v
Table of Contents --- p.vi
List of Figures --- p.x
List of Tables --- p.xiii
List of Publications --- p.xv
Chapter Chapter 1 --- Introduction --- p.1
Chapter 1.1. --- Aims of Study --- p.1
Chapter 1.2. --- Literature Review --- p.2
Chapter 1.2.1. --- Nasopharyngeal Carcinoma --- p.2
Chapter 1.2.1.1. --- Overview --- p.2
Chapter 1.2.1.2. --- Histopathology --- p.2
Chapter 1.2.1.3. --- Epidemiology --- p.3
Chapter 1.2.1.4. --- Etiology --- p.5
Chapter 1.2.1.4.1. --- Epstein-Barr Virus (EBV) Latent Infection --- p.5
Chapter 1.2.1.4.2. --- Environmental Factors --- p.5
Chapter 1.2.1.4.3. --- Genetic Factors --- p.6
Chapter 1.2.1.5. --- Molecular Pathogenesis --- p.7
Chapter 1.2.1.5.1. --- Chromosomal Alterations --- p.7
Chapter 1.2.1.5.2. --- NPC-associated Tumour Suppressor Genes --- p.7
Chapter 1.2.1.5.3. --- NPC-associated Oncogenes --- p.8
Chapter 1.2.2. --- Epstein-Barr Virus --- p.9
Chapter 1.2.2.1. --- Overview --- p.9
Chapter 1.2.2.2. --- Lytic and Latent Infection of EBV --- p.9
Chapter 1.2.2.3. --- EBV Latency Programs and Associated --- p.10
Malignancies --- p.11
Chapter 1.2.2.4. --- The Role of EBV in NPC --- p.12
Chapter 1.2.3. --- NF-kB Signalling Pathways --- p.12
Chapter 1.2.3.1. --- Overview --- p.12
Chapter 1.2.3.2. --- Pathway Components --- p.12
Chapter 1.2.3.2.1. --- NF-kB Subunits --- p.16
Chapter 1.2.3.2.2. --- Inhibitors of kB (IkBs) --- p.16
Chapter 1.2.3.2.3. --- IkB Kinases (IKKs) --- p.17
Chapter 1.2.3.3. --- NF-kB Activation and Signalling --- p.17
Chapter 1.2.3.3.1. --- The Canonical Pathway --- p.18
Chapter 1.2.3.3.2. --- The Non-canonical Pathway --- p.18
Chapter 1.2.3.3.3. --- Physiological Functions of NF-kB --- p.19
Chapter 1.2.3.4. --- NF-kB Signalling and Tumourigenesis --- p.20
Chapter 1.2.3.4.1. --- Oncogenic Activation of NF-kB in Hematological Malignancies --- p.20
Chapter 1.2.3.4.2. --- Oncogenic Activation of NF-kB in Solid and Epithelial Tumours --- p.22
Chapter Chapter 2 --- Material and Methods --- p.22
Chapter 2.1. --- Tumour Specimens --- p.24
Chapter 2.2. --- NPC Tumour Lines and Immortalized NP Cell Lines --- p.24
Chapter 2.2.1. --- Cell Lines --- p.24
Chapter 2.2.2. --- Xenografts --- p.27
Chapter 2.3. --- DNA Sequence Analysis --- p.27
Chapter 2.3.1. --- Genomic DNA Extraction --- p.27
Chapter 2.3.2. --- Polymerase Chain Reaction (PCR) --- p.28
Chapter 2.3.3. --- DNA Sequencing --- p.32
Chapter 2.4. --- RNA Expression Analysis --- p.32
Chapter 2.4.1. --- Total RNA Extraction and Reverse Transcription --- p.33
Chapter 2.4.2. --- Quantitative Real-time Polymerase Chain Reaction (QRT-PCR) --- p.35
Chapter 2.5. --- Protein Expression Analysis --- p.35
Chapter 2.5.1. --- Total Protein Extraction --- p.35
Chapter 2.5.2. --- Nuclear and Cytoplasmic Protein Isolation --- p.36
Chapter 2.5.3. --- Western Blotting --- p.39
Chapter 2.6. --- Immunohistochemical Staining --- p.41
Chapter 2.7. --- Statistical Analysis --- p.41
Chapter 2.8. --- Immunoprecipitation --- p.43
Chapter 2.9. --- Electrophoretic Mobility Shift Assay (EMSA) and Supershift Assay --- p.44
Chapter 2.10. --- Enzyme-Linked Immunosorbent Assay (ELISA) --- p.45
Chapter 2.11. --- Plasmid Preparation --- p.45
Chapter 2.11.1. --- Plasmids --- p.45
Chapter 2.11.2. --- Bacterial Transformation and Plasmid DNA Extraction --- p.46
Chapter 2.12. --- Transfections --- p.46
Chapter 2.12.1. --- Transient Transfection --- p.46
Chapter 2.12.2. --- Stable Transfection --- p.47
Chapter 2.13. --- Immunofluorescence --- p.47
Chapter 2.14. --- Cell Proliferation and Viability Analysis --- p.47
Chapter 2.15. --- Small Interfering RNA (siRNA) Knockdown --- p.49
Chapter 2.16. --- Expression Microarray --- p.49
Chapter 2.16.1. --- Agilent Oligonucleotide Microarray --- p.50
Chapter 2.16.2. --- Data Analysis --- p.51
Chapter Chapter 3 --- Activation of NF-kB Signals in NPC --- p.51
Chapter 3.1. --- Introduction --- p.52
Chapter 3.2. --- Results --- p.52
Chapter 3.2.1. --- Expression Pattern of NF-kB Subunits in NPC Tumour Lines --- p.55
Chapter 3.2.2. --- Distinct NF-kB Complexes in NPC Tumour Lines --- p.60
Chapter 3.2.3. --- Expression of NF-kB Subunits in NPC Primary Tumours --- p.67
Chapter 3.3. --- Discussion
Chapter Chapter 4 --- Alterations of NF-kB Components in NPC --- p.71
Chapter 4.1. --- Introduction --- p.72
Chapter 4.2. --- Results --- p.72
Chapter 4.2.1. --- Homozygous Deletion of IicBa and TRAF3 in NPC Tumour Lines --- p.76
Chapter 4.2.2. --- Mutation of TRAF2 and A20 in NPC Tumour Lines
Chapter 4.2.3. --- Aberrant Expression of Multiple NF-kB Signalling Components in NPC Tumour Lines --- p.80
Chapter 4.2.4. --- Expression of NF-kB Signalling Components in NPC --- p.85
Primary Tumour --- p.92
Chapter 4.3. --- Discussion --- p.99
Chapter Chapter 5 --- Identification of Downstream Targets for NPC-associated NF-kB Signalling --- p.99
Chapter 0.1. --- Introduction --- p.99
Chapter 0.2. --- Results --- p.100
Chapter 0.2.1. --- Target Genes Modulated by p50 --- p.100
Chapter 0.2.2. --- Functional Annotation of p50 Target Genes --- p.105
Chapter 0.2.3. --- Target Genes Modulated by RelB --- p.105
Chapter 0.2.4. --- Functional Annotation of RelB Target Genes --- p.105
Chapter 0.2.5. --- Functional Annotation of Genes Modulated by both p50 and RelB --- p.111
Chapter 0.3. --- Discussion --- p.118
Chapter Chapter 6 --- Functional Role of TRAF3 Inactivation in NPC --- p.118
Chapter 0.1. --- Introduction --- p.118
Chapter 0.2. --- Results --- p.118
Chapter 0.2.1. --- Effect of TRAF3 Restoration on NF-kB Activity --- p.119
Chapter 0.2.2. --- Effect of TRAF3 Expression on Cell Proliferation --- p.123
Chapter 0.2.3. --- TRAF3 Expression Modulates Interferon Transcription in NPC Cells --- p.128
Chapter 0.3. --- Discussion
Chapter Chapter 7 --- General Discussion --- p.132
Chapter Chapter 8 --- Conclusion
Chapter Chapter 9 --- References
Appendix --- p.136
Shakibaei, M., A. Mobasheri, C. Lueders, F. Busch, P. Shayan, and A. Goel. "Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-kappaB and Src protein kinase signaling pathways." 2013. http://hdl.handle.net/10454/6183.
Повний текст джерелаBusch, F., A. Mobasheri, P. Shayan, C. Lueders, R. Stahlmann, and M. Shakibaei. "Resveratrol modulates interleukin-1beta-induced phosphatidylinositol 3-kinase and nuclear factor kappaB signaling pathways in human tenocytes." 2012. http://hdl.handle.net/10454/5903.
Повний текст джерела