Dissertations / Theses on the topic 'Wnt inhibitors'
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Ho, Sze-hang, and 何思恆. "Differential expression of Wnt inhibitors Dickkopf-1 (Dkk-1) and Wnt inhibitory factor-1 (Wif1) in the regulation of urorectal development." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/207999.
Full textpublished_or_final_version
Surgery
Master
Master of Philosophy
Jandu, Arvinder Singh. "Characterization of Novel Canonical WNT Signaling Inhibitors in Prostate and Colorectal Cancers." Thesis, The University of Arizona, 2013. http://hdl.handle.net/10150/297656.
Full textGarcía, Reyes Balbina [Verfasser]. "Validation of new Casein Kinase 1 (CK1) small molecule inhibitor compounds and characterization of Inhibitors of Wnt Production (IWPs) as inhibitors of CK1δ / Balbina García Reyes." Ulm : Universität Ulm, 2018. http://d-nb.info/1151938424/34.
Full textAli, Youmna Tantawy Abdou Ahmed. "Molecular regulation on the activity and expression of human organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs)." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/28906.
Full textQuevedo, Camilo E. "Design and synthesis of Quinazolinone-based libraries for inhibitation of Kinase activity and hit-to-lead optimisation of Wnt pathway inhibitors." Thesis, Institute of Cancer Research (University Of London), 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510367.
Full textKragelund, Dominik [Verfasser]. "Untersuchungen der Serum-Konzentrationen des proinflammatorischen Glykoproteins wnt-5a und seines antiinflammatorischen Inhibitors sFRP-5 bei an Sepsis erkrankten Patienten im Verlauf / Dominik Kragelund." Kiel : Universitätsbibliothek Kiel, 2016. http://d-nb.info/111754060X/34.
Full textPark, Kyoungmin. "The characterization of PEDF's broad activity in the ocular disease." Oklahoma City : [s.n.], 2010.
Find full textNg, Chun-laam, and 吳圳嵐. "Wnt inhibitory factor 1 (Wif-1) coordinates Shh and Wnt signaling activities in urorectal development." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48329629.
Full textpublished_or_final_version
Surgery
Doctoral
Doctor of Philosophy
Sena, Elena. "The Transcription Factor Barhl2 Inhibits Wnt Canonical Signaling during Xenopus Embryogenesis." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS090/document.
Full textEmbryonic development is a highly controlled process where different signaling pathways participate into the elaboration of an organism. One of the main signaling pathways is the Wnt canonical pathway. The long-lasting search to understand Wnt/β-catenin transduction cascade revealed that the net transcriptional read out of Wnt/β-catenin signaling is highly dependent on the cellular context. In X. laevis embryos Wnt/β-catenin signaling is the informative signal for the Spemann Organizer induction. However little is known on what limits Wnt activity in this territory and consequently the size of the Spemann Organizer. The results presented in this manuscript provide evidence that the evolutionarily conserved transcription factor Barhl2 limits the development of the Spemann organizer. In this territory Barhl2 inhibits Wnt activity via its interaction with the co-repressor Groucho and the transcription factor Tcf. It participates to the recruitment of the chromatin remodeling enzyme, Hdac1 that represses the expression of Spemann organizer genes. Using a Xenopus tropicalis Tcf reporter line we demonstrate that Barhl2 inhibitory effect on Groucho-Tcf activities is maintained during embryogenesis and plays a role in the confinement of neural progenitors in the brain. Together, our results provide a new and important mechanism for the control of Wnt transcriptional activity
Alsaedi, Manal. "The role of WNT inhibitory factor I in adipose tissue development." Thesis, Tennessee State University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10158616.
Full textFat tissue is involved in many aspects of biology such as appetite regulation, vascular diseases, diabetes, hypertension, and obesity. It plays an important role in these processes through its endocrine factors and other secretory products. Thus, there is a need to understand better the mechanisms and molecules that control the formation of adipocytes and the expansion of adipose tissue. WNT signaling is one of several important factors that plays a crucial role in development, and may also be important for adipogenesis. The activity of WNT signaling is modulated by a plethora of extracellular modulators that mostly antagonize WNT signaling. The extracellular WNT antagonists consist of four conserved families: Wnt-inhibitory factor 1 (WIF1), secreted frizzled related protein (SFRP), Cerberus, and Dickkopf (Dkk). It has been found that WIF1 is upregulated in abdominal fat tissue in chickens during early development. Thus, we hypothesize that WIF1 plays a role in adipose tissue development by inhibiting WNT signaling, and thereby stimulating adipogenic gene expression. The objective of this research is to examine the in vitro regulation of adipogenesis by WIF1. Mouse WIF1 expression vector (pCMV6-ENTRY-WIF1) was prepared, and used to transfect the mouse pre-adipocyte cell line 3T3-L1.The mRNA levels for WIF1, PPARγ and C/EBPα were then examined with real time RT-qPCR. Results indicate that the transgene was expressed in the transfected cells within 30 hours after transfection, and the mRNA level of WNT target genes and CEBPα were affected. However, the mRNA level of PPARγ was not affected. In conclusion, exogenous WIF1 was expressed in 3T3-L1 cells, at least at the mRNA level. The exogenous WIF1 expression caused an elevation of CEBPα mRNA. Future studies should examine other genes, and more investigation should take place to better understand the mechanisms of adipogenesis.
Watson, A. T. "ARID1a is an inhibitor of Wnt signalling in Xenopus and human." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1468997/.
Full textFlorczak, Kaya. "Wnt/β-Catenin Signalling Inhibits T-Type Calcium Channels in Cardiomyocytes." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/41983.
Full textBarkell, Alice Mary. "Structural and functional characterisation of Dickkopf4 (Dkk4), a key inhibitor of Wnt signalling." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/36938.
Full textCook, David. "Modulation of canonical Wnt signalling in mesenchymal stem cells using a GSK3beta inhibitor." Thesis, University of York, 2013. http://etheses.whiterose.ac.uk/4609/.
Full textAlamri, Mubarak. "Discovery of WNK-SPAK/OSR1 signalling inhibitors as potential therapeutics." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8559/.
Full textBoral, Debasish. "The Role of SOX2 in Colon Cancer Progression." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/dissertations/911.
Full textRudge, Felicity. "Genome-wide cDNA and RNAi screening to identify modulators of responses to a novel Wnt signalling inhibitor." Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/58589/.
Full textBisson, Sarah-Kim, and Sarah-Kim Bisson. "Les inhibiteurs de la voie Wnt dans un modèle animal d'insuffisance rénale chronique avec calcification vasculaire." Master's thesis, Université Laval, 2020. http://hdl.handle.net/20.500.11794/38092.
Full textEn insuffisance rénale chronique (IRC), on observe un déséquilibre minéral qui est associé au développement d’un remodelage osseux anormal et de calcification vasculaire, un processus qui est semblable à la formation osseuse car il implique une trans-différenciation de cellules musculaires lisses vasculaires en cellules ostéoblastiques semblables à celles retrouvées dans l’os. Un lien a été rapporté entre le remodelage osseux ralenti et la calcification vasculaire en IRC mais la cause de ce lien demeure mal comprise. Nous avons étudié l’implication des inhibiteurs de la voie Wnt dans ce lien dans un modèle d’IRC chez le rat avec calcification vasculaire induite par un supplément de calcium, phosphore et vitamine D (Ca/P/vitD). Les animaux IRC+Ca/P/vitD présentaient de la calcification vasculaire, un remodelage osseux ralenti, un défaut de minéralisation et des niveaux sériques et vasculaires d’inhibiteurs de la voie Wnt élevés. La présence dans le vaisseau calcifié d’un inhibiteur de la voie Wnt de source ostéocytaire, la sclérostine, suggère que les cellules ostéoblastiques acquièrent un phénotype ostéocytaire. De plus, les inhibiteurs de la voie Wnt produits par le vaisseau pourraient avoir des conséquences sur l’os, ce qui cadrerait avec la formation ralentie et le défaut de minéralisation observés. Les inhibiteurs de la voie Wnt en circulation pourraient aussi avoir des effets vasculaires puisque les vaisseaux calcifiés présentaient des signes d’inhibition de la voie Wnt/β-caténine, les niveaux d’inhibiteurs de la voie Wnt ne semblant toutefois pas associés à un ralentissement de la calcification. Nos résultats mettent donc en lumière une implication potentielle des inhibiteurs de la voie Wnt dans le lien entre l’os et le vaisseau en IRC.
Chronic kidney disease (CKD) patients suffer from a dysregulation of minerals levels which is associated with abnormal bone remodeling and vascular calcification, a process similar to bone formation in that it implies the trans-differentiation of vascular smooth muscle cells into osteoblast-like cells. A link was reported between decreased bone formation and vascular calcification in CKD, but the cause of this link remains unclear. We have studied the involvement of Wnt pathway inhibitors in this process in a rat model of CKD with vascular calcification induced by a calcium, phosphorus and vitamin D supplement (Ca/P/vitD). CKD+Ca/P/vitD rats presented with vascular calcification, decreased bone turnover, defective mineralization and increased levels of circulating and vascular Wnt inhibitors. The expression by the calcified vessel of sclerostin, a Wnt inhibitor typically produced by osteocytes, suggests that vascular osteoblast-like cells could acquire an osteocytic phenotype as osteoblasts do in bone. Moreover, vascular Wnt inhibitors could have consequences on bone and contribute to the decrease in bone formation and the mineralization defect. The high circulating levels of Wnt inhibitors could also have vascular effects, which is supported by the fact that the Wnt/β-catenin pathway appears to be inhibited in the calcified vessels despite the fact that high levels of Wnt inhibitors were not correlated with a decrease in the severity of vascular calcification. Our results therefore suggest an implication of Wnt pathway inhibitors in the bone-vessels link that is frequently observed in CKD.
Chronic kidney disease (CKD) patients suffer from a dysregulation of minerals levels which is associated with abnormal bone remodeling and vascular calcification, a process similar to bone formation in that it implies the trans-differentiation of vascular smooth muscle cells into osteoblast-like cells. A link was reported between decreased bone formation and vascular calcification in CKD, but the cause of this link remains unclear. We have studied the involvement of Wnt pathway inhibitors in this process in a rat model of CKD with vascular calcification induced by a calcium, phosphorus and vitamin D supplement (Ca/P/vitD). CKD+Ca/P/vitD rats presented with vascular calcification, decreased bone turnover, defective mineralization and increased levels of circulating and vascular Wnt inhibitors. The expression by the calcified vessel of sclerostin, a Wnt inhibitor typically produced by osteocytes, suggests that vascular osteoblast-like cells could acquire an osteocytic phenotype as osteoblasts do in bone. Moreover, vascular Wnt inhibitors could have consequences on bone and contribute to the decrease in bone formation and the mineralization defect. The high circulating levels of Wnt inhibitors could also have vascular effects, which is supported by the fact that the Wnt/β-catenin pathway appears to be inhibited in the calcified vessels despite the fact that high levels of Wnt inhibitors were not correlated with a decrease in the severity of vascular calcification. Our results therefore suggest an implication of Wnt pathway inhibitors in the bone-vessels link that is frequently observed in CKD.
Browne, Andrew. "The effects and regulation of the Wnt inhibitor Dickkopf-1 and the mechanistic target of rapamycin in osteotropic cancers." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-228981.
Full textYao, Hisayuki. "AV-65, a novel Wnt/β-catenin signal inhibitor, successfully suppresses progression of multiple myeloma in a mouse model." Kyoto University, 2012. http://hdl.handle.net/2433/157443.
Full textFunke, Robin [Verfasser], and Jörg [Akademischer Betreuer] Distler. "Epigenetisches Silencing von endogenen Inhibitoren des WNT-Signalweges durch Promoter Methylierung in der Systemischen Sklerose / Robin Funke. Betreuer: Jörg Distler." Erlangen : Universitätsbibliothek der Universität Erlangen-Nürnberg, 2012. http://d-nb.info/1024198901/34.
Full textMatzelle, Melissa M. "Inflammation Inhibits Osteoblast-Mediated Bone Formation in Rheumatoid Arthritis and Regulates the Wnt and BMP Signaling Pathways: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/596.
Full textNagao, Rina. "Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia-adaptation by AV65 - a novel Wnt/β-catenin signaling inhibitor." Kyoto University, 2012. http://hdl.handle.net/2433/157488.
Full textBarat, Samarpita [Verfasser], and Ruben [Akademischer Betreuer] Plentz. "Gamma-secretase inhibitor IX (GSI) impairs concomitant activation of Notch and wnt-beta-catenin pathways in CD44+ gastric cancer / Samarpita Barat ; Betreuer: Ruben Plentz." Tübingen : Universitätsbibliothek Tübingen, 2016. http://d-nb.info/1199615560/34.
Full textEngel, James L. "The Psuedomonas syringae type III effector HopE1 interacts and inhibits an Arabidopsis WNK kinase." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p1459876.
Full textTitle from first page of PDF file (viewed December 18, 2008). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 47-50).
Sack, Ulrike. "New insights into S100A4-induced colon cancer metastasis." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16313.
Full textS100A4 promotes metastasis in colon cancer patients thereby reducing their five-year survival chances to less than 10%. Consequently, inhibition of S100A4 expression is a promising strategy for anti-metastatic treatment of colon cancer patients. The present study characterizes the small molecules niclosamide and calcimycin as transcriptional inhibitors of S100A4 which reduced S100A4 expression concentration- and time-dependently. Niclosamide and calcimycin treatment restricted cell migration, invasion and wound healing capabilities in a S100A4-specific manner, and inhibited cell proliferation and colony formation of colon cancer cells. Both small molecule inhibitors interfere with the constitutively active Wnt pathway. Targeting β-catenin expression by calcimycin or interfering with the β-catenin/TCF transcription activating complex by niclosamide resulted in reduced Wnt target gene transcription, among them S100A4. The study further presents a human colon cancer xenograft mouse model for monitoring S100A4-induced metastasis formation via non-invasive bioluminescence imaging. Treatment of xenograft mice with niclosamide resulted in a significant reduction of the S100A4 mRNA level in the tumor accompanied by inhibition of metastasis formation. Moreover, this study presents evidence that S100A4 is an inhibitor of DKK-1 expression. In colon cancer cells DKK-1 and S100A4 expression was negatively correlated. Ectopic S100A4 overexpression inhibited DKK-1 expression. Targeting S100A4 via shRNA recovered the repressed DKK-1 expression and vice versa. In summary, the study describes a novel positive feedback loop in the Wnt pathway regulation formed by S100A4 repressing its antagonist DKK-1. This novel mechanism further strengthens the need for S100A4 inhibitors such as niclosamide or calcimycin. Consequently, such small molecules provide immense potential for the treatment of colon cancer patients who are at high risk for S100A4-induced colon cancer metastasis.
Salvagnini, Claudio. "Thrombin inhibitors grafting on polyester membranes for the preparation of blood-compatible materials." Université catholique de Louvain, 2005. http://edoc.bib.ucl.ac.be:81/ETD-db/collection/available/BelnUcetd-11232005-103604/.
Full textBenchekroun, Mohamed. "Synthèse multicomposants et évaluation pharmacologique de nouveaux adduits de Ugi et de Passerini pour le traitement de la maladie d'Alzheimer." Thesis, Besançon, 2014. http://www.theses.fr/2014BESA3007/document.
Full textAlzheimer's disease (AD) is thé most common type of dementia affecting elderly people. This neuropathology is characterized by a highiy complex and intricated etiology including cholinergic déficit, amyloid deposits, neurofibrillary tangles and oxidative stress.During this thesis, we sought to apply Ugi and Passerini multicomponent reactions for thé synthesis of new multi-target adducts based on différent antioxidant and anticholinergic scaffolds.Thèse réactions provides access to a broad range of chemical diversity in a one-pot fashion, which makes them suitable for thé expeditious synthesis of molécules having several pharmacophores of interest and hitting différent targets related to thé multifaceted etiology of Alzheimer's disease.A total of 56 final compounds, spread over 5 séries, hâve been synthesized:alpha-acylaminocarboxamides prototypes (A séries)tacrine-ferulic acid hybrids (B séries)tacrine-melatonin-antioxydant acids heterotrimers (C séries)donepezil-ferulic acid hybrids (D séries)Chromone derivatives (E séries)Ail thé séries were tested for their ability to inhibit thé cholinesterases enzymes and for their antioxidant power. Hepatotoxicity of thé B and C séries, bearing a tacrine fragment, was evaluated on HepG2 cells. Moreover, thé study of thé B séries was supplemented by further pharmacological, physicochemical and toxicological tests (NMR conformational study, neuroprotection on SH-SY5Y cells. self-induced Abetai.42 peptide aggregation inhibition, docking ADMET).Such work demonstrated and validated thé use of Ugi and Passerini reactions for thé development of new multi-target directed molécules for thé potential treatment of AD
Morales, Espejo Jesus Hector. "Atmospheric corrosion of quaternary bronzes (Cu-Sn-Zn-Pb): laboratory tests (accelerated ageing in wet & dry conditions)and field studies (the Bottego monument in Parma, Italy)." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amslaurea.unibo.it/2386/.
Full textMelchert, Juliane [Verfasser], Tomas [Akademischer Betreuer] Pieler, and Ernst A. [Akademischer Betreuer] Wimmer. "Expression screen for Wnt signaling-like phenotypes identifies Fam132b as a novel inhibitor of BMP signaling in Xenopus / Juliane Melchert. Gutachter: Tomas Pieler ; Ernst A. Wimmer. Betreuer: Tomas Pieler." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://d-nb.info/1048469948/34.
Full textBrowne, Andrew John [Verfasser], Lorenz [Akademischer Betreuer] [Gutachter] Hofbauer, and Martin [Gutachter] Bornhäuser. "The effects and regulation of the Wnt inhibitor Dickkopf-1 and the mechanistic target of rapamycin in osteotropic cancers / Andrew Browne ; Gutachter: Lorenz Hofbauer, Martin Bornhäuser ; Betreuer: Lorenz Hofbauer." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://d-nb.info/1140735217/34.
Full textBrowne, Andrew [Verfasser], Lorenz [Akademischer Betreuer] [Gutachter] Hofbauer, and Martin [Gutachter] Bornhäuser. "The effects and regulation of the Wnt inhibitor Dickkopf-1 and the mechanistic target of rapamycin in osteotropic cancers / Andrew Browne ; Gutachter: Lorenz Hofbauer, Martin Bornhäuser ; Betreuer: Lorenz Hofbauer." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://d-nb.info/1140735217/34.
Full textLintereur, Phillip. "EFFECTS OF SOURCE WATER BLENDING FOLLOWING TREATMENT WITH SODIUM SILICATE AS A CORROSION INHIBITOR ON METAL RELEASE WITHIN A WAT." Doctoral diss., University of Central Florida, 2008. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/2967.
Full textPh.D.
Department of Civil and Environmental Engineering
Engineering and Computer Science
Electrical Engineering PhD
Martinez, Merizalde Balarezo Nelson, Rivera Mark Monroe, and Romina A. Tejada. "Re: Maud Rijnders, Ronald de Wit, Joost L. Boormans, Martijn P.J. Lolkema, Astrid A.M. van der Veldt. Systematic Review of Immune Checkpoint Inhibition in Urological Cancers. Eur Urol. 2017;72:411–23." Elsevier B.V, 2018. http://hdl.handle.net/10757/624728.
Full textBalke-Want, Hyatt [Verfasser], Roman [Akademischer Betreuer] Thomas, and Alexander [Akademischer Betreuer] Quaas. "Identifizierung genetischer und funktioneller Mechanismen für Sensitivität und Resistenz des Bronchialkarzinoms gegenüber Tyrosinkinase-Inhibitoren / Hyatt Balke-Want ; Akademische Betreuer: Roman Thomas, Alexander Quaas." Köln : Deutsche Zentralbibliothek für Medizin, 2018. http://d-nb.info/117665344X/34.
Full textGanguly, Atish. "Wnt8 Is a Novel Target of the Dorsal/Twist/Snail Network and an Inhibitor of Dorsal in the Gastrulating Drosophila Embryo: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/201.
Full textHumphrey, Peter Saah. "Signal transduction mechanisms for stem cell differentation into cardiomyocytes." Thesis, University of Hertfordshire, 2009. http://hdl.handle.net/2299/3760.
Full textHsioa, Tingfen, and 蕭婷分. "Identification and characterization of potential Wnt signaling inhibitors." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/3d2jkh.
Full text輔仁大學
生命科學系碩士班
100
Hepatocellular carcinoma (HCC) is one of the leading cancers in the world with the mortality of more than half a million deaths per year. Using the platform of Connectivity Map (cmap), which hosts a much greater number of gene expression profiles from culture human cancer cell lines treated with bioactive small molecular, we have identified some drugs may reverse the gene expression signature of HCC and have potentials for treating HCC. Due to the inappropriate activation of Wnt/-catenin signaling pathway in HCC, this thesis prompt to identify the drugs that selected from cmap can also inhibit Wnt/-catenin signaling pathway. Using HCC cells containing β-catenin/Tcf-response reporter, we first screen the drug as potential inhibitor of Wnt/β-catenin pathway. Here, four drugs named 8-azaguanine, thiostrepton, withaferin A and antimycin A have been identified as Wnt/-catenin signaling pathway inhibitors. In addition, dosage-dependent inhibition of Wnt/-catenin signaling pathway can also be demonstrated in two different HCC cells. Moreover, these four drugs show different degree of inhibition on the proliferation of Huh7 and Mahluvu cells. To investigate these drugs mechanistically, we have examine the effects of these potential Wnt/-catenin signaling inhibitors on the expression of -catenin, c-myc and cyclin D1. We find that although 8-azaguanine and thiostrepton can not reduce the protein level of -catenin, they reduce the expression of c-myc and cyclin D1. Since cytosolic -catenin slightly increase, while nucleic -catenin decrease under drug treatment, we conclude that 8-azaguanine and thiostrepton may prohibit the nuclear entry of -catenin, which conduct the inhibition of Wnt/-catenin signaling. Alternatively, withaferin A and antimycin A treatment can decrease the protein level of -catenin, indicating they may promote the degradation of -catenin and abolish following signaling. In addition, withaferin A and antimycin A treatment can increase the protein level of LC3-II, which is a marker of autophagy, and decrease pro-caspase-3. Further studies should be performed to ask whether autophagy play crucial roles in withaferin A and antimycin A conducted cell death. Overall, this thesis has identified four drugs as Wnt/-catenin signaling inhibitors and may serve as potential drugs for treating HCC.
Yang, Chih-Yu, and 楊智宇. "Wnt/β-catenin Signaling Inhibitors in the Pathogenesis of Uremic Ectopic Ossifications." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/6pq969.
Full text國立陽明大學
臨床醫學研究所
103
Background: Uremic patients manifest an accelerated phenotype of soft bone and hard artery. The process of “hard artery”, i.e. vascular calcification, has been associated with the canonical Wnt/β-catenin signaling pathway in cell cultures and animal studies. On the other hand, the uremic “soft bone”, i.e. osteomalacia, has been seen in the alveolar bone, but radiographic evidence has shown that the adjacent pulp chamber is reciprocally obliterated; however, this has not been supported by any pathological evidence. We speculated that Wnt/β-catenin signaling pathway might participate in the pathogenesis of uremic ectopic ossifications of soft tissues including both dental pulp and vasculature. Methods: We used a uremic rat model with secondary hyperparathyroidism induced by 5/6 nephrectomy surgery and high-phosphate diet to examine the dental pulp and adjacent alveolar bone pathology. In addition, we collected pulp tissues for real-time polymerase chain reaction. Meanwhile, because the relationship between Wnt/β-catenin signaling inhibitors and vascular calcification is unknown in uremic patients, we investigated the associations between serum dickkopf-1 (Dkk-1) and sclerostin, two circulating inhibitors of the Wnt/β-catenin signaling pathway, and the severity of aortic calcification (AoC) and cardiovascular outcomes in uremic patients. Results: We found an opposite histopathological presentation of the ossified dental pulp and the osteomalacic adjacent alveolar bone. Furthermore, pulp cells with positive staining for Thy-1, a surrogate stem cell marker, were significantly reduced in the pulp of uremic rats compared to the controls, indicating a paucity of stem cells. This was further evidenced by the reduced pulp expression of dickkopf-1 (Dkk-1), a Wnt/β-catenin signaling inhibitor produced by mesenchymal stem cells. In contrast, expressions of receptor activator of nuclear factor κB ligand (RANKL) and RANK in uremic pulp were up-regulated, probably to counteract the ossifying process of uremic pulp. As for the uremic patients, the circulating sclerostin level was inversely associated with the severity of AoC (p = 0.035) and indicators of the bone turnover rate including serum alkaline phosphatase (ALP) (r = -0.235, p = 0.008) and intact parathyroid hormone (r = -0.523, p < 0.001). Furthermore, Cox regression analysis indicated that the patients with high circulating sclerostin levels were less likely to experience future cardiovascular events [1 pmol/L sclerostin increase, hazard ratio 0.982 (95% CI, 0.967-0.996), p = 0.015] after adjusting for a propensity score. Conclusions: Uremic pulp ossifications were associated with a paucity of stem cells and dysregulated Dkk-1 and RANKL signaling systems, further shifting the imbalance toward osteogenesis. Additionally, in uremic patients, circulating sclerostin is inversely associated with AoCs and future cardiovascular events. Our findings suggest that Wnt/β-catenin signaling inhibitor deficit is associated with both pulp ossification and vascular calcification in uremic subjects. Meanwhile, sclerostin, as a bone-related protein, might act as a communicator between uremic bone and vasculature. Strategies to modulate Wnt/β-catenin signaling inhibitors may offer a therapeutic potential to improve dental and vascular health in uremic patients.
Tschirschmann, Miriam [Verfasser]. "Regulation des WNT-Inhibitors DKK1 im In-vitro-Kondensationsmodell / vorgelegt von Miriam Tschirschmann." 2009. http://d-nb.info/999611216/34.
Full textPerusini, Stephen John. "High-thoughput Screen to Identify Small Molecule Inhibitors of the Canonical Wnt Signaling Pathway." Thesis, 2008. http://hdl.handle.net/1807/17210.
Full textJanečková, Lucie. "Signální dráha Wnt v obnově a tumorigenezi střevního epitelu." Doctoral thesis, 2014. http://www.nusl.cz/ntk/nusl-338480.
Full textFauser, Jane Kathryn. "Medium chain fatty acids and Wnt/β-Catenin inhibitors as adjunctive colorectal cancer chemotherapeutic agents." Thesis, 2013. http://hdl.handle.net/2440/94400.
Full textThesis(Ph.D.)-- University of Adelaide, School of Animal and Veterinary Sciences, 2013
Pospíchalová, Vendula. "Nádorový supresor HIC1- nový inhibitor signalní dráhy Wnt." Master's thesis, 2008. http://www.nusl.cz/ntk/nusl-292043.
Full textCurtis, Courtney Lee. "Wnt signaling in zebrafish fin regeneration : chemical biology using a GSK3β inhibitor." Thesis, 2014. http://hdl.handle.net/1805/4835.
Full textBone growth can be impaired due to disease, such as osteoporosis. Currently, intermittent parathyroid hormone (PTH) treatment is the only approved therapy in the United States for anabolic bone growth in osteoporosis patients. The anabolic effects of PTH treatment are due, at least in part, to modulation of the Wnt/β-catenin pathway. Activation of the Wnt/ β-catenin pathway using a small molecule inhibitor of GSK3β was previously shown to increase markers of bone formation in vitro. Our study utilized a zebrafish model system to study Wnt activated fin regeneration and bone growth. Wnt signaling is the first genetically identified step in fin regeneration, and bony rays are the main structure in zebrafish fins. Thus, zebrafish fin regeneration may be a useful model to study Wnt signaling mediated bone growth. Fin regeneration experiments were conducted using various concentrations of a GSK3β inhibitor compound, LSN 2105786, for different treatment periods and regenerative outgrowth was measured at 4 and 7 days post amputation. Experiments revealed continuous low concentration (4-5 nM) treatment to be most effective at increasing regeneration. Higher concentrations inhibited fin growth, perhaps by excessive stimulation of differentiation programs. In situ hybridization experiments were performed to examine effects of GSK3β inhibitor on Wnt responsive gene expression. Experiments showed temporal and spatial changes on individual gene markers following GSK3β inhibitor treatment. Additionally, confocal microscopy and immunofluorescence labeling data indicated that the Wnt signaling intracellular signal transducer, β-catenin, accumulates throughout GSK3β inhibitor treated tissues. Finally, experiments revealed increased cell proliferation in fin regenerates following LSN 2105786 treatment. Together, these data indicate that bone growth in zebrafish fin regeneration is improved by activating Wnt signaling. Zebrafish Wnt signaling experiments provide a good model to study bone growth and bone repair mechanisms, and may provide an efficient drug discovery platform.
Chen, Yung-Fu, and 陳永富. "Modeling of Kinetics of the Wnt-EGFR Signaling Pathway and Inhibitor Effects on its Kinetic Behaviors." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/91322219733868287084.
Full text國立臺灣師範大學
化學系
100
The Wnt and EGFR signaling pathways are known to relate to cell proliferation, differentiation, and apoptosis. Deregulation of these signaling pathways were found in various kinds of cancers. Toward better understanding of these two pathways, we used computer modeling method to model kinetics of these pathways. Based on currently available models, we expanded the model in order to include more effects in kinetics of these pathways and correlate with available experimental data. First, we added a negative feedback loop on the EGFR pathway which has inhibition effect on Raf-1 by ERKpp. When the K1 value of Raf-1 inhibition reaction was set in the range of 0.01 to 10, the computations gave that addition of this loop results in two different effects in the two models we used. The negative feedback loop has a little effect on ERKpp level in the model which includes Braf. In contrast, the negative feedback loop makes the level of phosphorylated ERK go down in the model without Braf. Second, a crosstalk between EGFR and Wnt pathways was added and kinetic modeling gave that:in the case this is a positive feedback loop, it induces the switch-like behavior of ERKpp expression by varying the concentration of the added factor Y when the β -catenin was not overexpressed. In the case it is a negative feedback loop, due to the stronger v negative feedback effect, that during Wnt signal stimulate the concentration of ERKpp has an oscillation behavior with larger amplitude during the period of Wnt signal stimulation. After that, concentration of ERKpp falls back to low level quickly. In addition, we investigated effect of adding kinase inhibitor(s) on the level of phosphorylated ERK (ERKpp) under the condition of β-catenin overexpression plus undergoing a wnt signal transient stimulation. In the case of adding one kinase inhibitor, the modeling gave that:kinase inhibitor of multiple-targets of the same strength have less inhibitory effect than inhibitor of singlet-target of Raf-1 kinase. Reduction of concentration of ERKpp was as small as to 1/6 fold only compared with the case of singlet-target in the examined model. Furthermore, we investigate effects of multiple-target inhibitors inhibiting Raf-1 and MEK kinases. It was found that in the case the ratio of Raf-1 inhibitor concentration to MEK inhibitor concentration is larger than 1.5, the inhibitor effect is better than one inhibitor of multiple-target with the same inhibition strengths. These results deepen our understanding of these two pathways and should be useful for future multiple-target kinase inhibitor design.
Hsiung, Shih-Chieh, and 熊式潔. "Clozapine Inhibits Colorectal Cancer Cell Growth via Wnt/β-catenin and p21-Dependent Pathways." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/q5p3ra.
Full text國立臺灣海洋大學
生物科技研究所
101
Clinical studies have shown that patients with schizophrenia have a lower cancer incidence than the general population. Several antipsychotics have been demonstrated to confer cytotoxic effects on cancer cells, but the detailed molecular mechanism is unclear. Abnormal activation of the Wnt/β-catenin pathway plays an important role in colorectal cancer. In this study, two human colorectal cancer cell lines, HCT116 and SW480, were used to investigate the effect of clozapine, an antipsychotic widely used to treat patient with refractory schizophrenia, on Wnt/β-catenin pathway. Preliminary data showed that clozapine inhibited proliferation of SW480 and HCT116 cells in time- and dosage-dependent manners. Clozapine suppressed -catenin mRNA and protein levels. Furthermore, clozapine also decreased the expression of β-catenin downstream target gene cyclin D1. These results suggested that clozapine inhibited the growth of colorectal cancer cells through the inhibition of β-catenin transcription. On the other topic, our previous results revealed that clozapine increased p21 protein expression and reactive oxygen species (ROS) in HCT116 cancer cells. Studies have shown that p21 protects cells against oxidative stress. Here, we examined the relationship between clozapine-induced ROS and p21. Clozapine inhibited cell proliferation and colony formation via p53-independent manner and HCT116 p21-/- cells were more sensitive to clozapine. Clozapine increased more ROS and induced apoptosis in HCT116 p21-/- cells compared to HCT116 cells. In HCT116 cells, a ROS scavenger vitamin E (α-Tocopherol) decreased ROS, but also reduced p21 protein expression. The results showed that clozapine-increased ROS caused p21 protein expression. Furthermore, we also demonstrated that p21-mediated ROS is associated with Nrf2, a transcription factor can activate an antioxidant response to decrease ROS. It needs to further verify whether clozapine induces apoptosis via p21 and Nrf2 to control ROS levels.
Miller, Catherine A. "Shifted, the Drosphila homolog of the Wnt inhibitory factor 1, is involved in the Hedgehog signaling pathway." 2004. http://www.library.wisc.edu/databases/connect/dissertations.html.
Full textHUANG, SHIH-YU, and 黃詩于. "Resveratrol Enhance Paclitaxel and Doxorubincin to Inhibits Human Adenocarcinoma (A549) Cell Proliferation through Wnt pathway." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/qwj3es.
Full textBecker, Marco. "Wif1 Inhibits the Growth of Basal Cell Carcinoma." Doctoral thesis, 2015. http://hdl.handle.net/11858/00-1735-0000-0028-867F-F.
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