Dissertations / Theses on the topic 'Sialyltransferases'
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Chiu, Cecilia P. C. "Crystallographic studies of bacterial sialyltransferases." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31274.
Full textMedicine, Faculty of
Biochemistry and Molecular Biology, Department of
Graduate
Sievi, Eeva. "Fate of mammalian golgi sialyltransferases in yeast." Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/eri/biote/vk/sievi/.
Full textToivonen, Suvi. "Acceptor specificity studies of fucosyl- and sialyltransferases." Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/eri/biote/vk/toivonen/.
Full textBurke, Erin E. "Heavy atom and hydrogen kinetic isotope effect studies on recombinant, mammalian sialyltransferases." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0011586.
Full textMALTA, Tiago Barros Santos. "Imunodetecção de sialiltransferase e histoquímica de ácidos siálicos no câncer de mama e sua possível aplicação em diagnóstico, prognóstico e terapia." Universidade Federal de Pernambuco, 2016. https://repositorio.ufpe.br/handle/123456789/18431.
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CAPES, CNPQ, FACEPE
O câncer de mama feminino é o segundo tipo de câncer mais frequente no mundo, com aumento de incidência de 22% a cada ano. Estudos nas últimas décadas revelaram que a transformação maligna está associada a uma variedade de células com padrões de glicosilação alterados, como por exemplo a sialilação. Os ácidos siálicos tem sido relacionados à iniciação e progressão do câncer, tendo assim implicações potenciais na prevenção, diagnóstico e tratamento da doença. Este trabalho avaliou a expressão fenotípica de ST3Gal-I, através da imunohistoquímica, e o perfil de ácido siálico, através da histoquímica com lectinas usando Maackia Amurensis agglutinin II (MAA), em tecidos mamários diagnosticados com fibroadenoma (n=59), carcinoma ductal in situ (CDIS, n=40), carcinoma ductal invasivo (CDI, n=50) e carcinoma lobular (CL, n=42). Todos os tipos de lesões de mama apresentaram alta imunopositividade à ST3Gal-I, sendo observada uma expressão em 93,2% dos casos de Fibroadenoma, 92,5% de CDIS, 96% dos casos CDI e 85,2% de CL. As células apresentaram um padrão de marcação citoplasmático e perinuclear com relação à ST3Gal-I. Diferentes distribuições de resíduos de ácido siálico ⍺2,3-ligados, com um padrão de marcação predominantemente citoplasmático e membranar, foram observados nas lesões de mama estudadas. Os casos de fibroadenoma apresentaram o menor percentual de sialilação entre as lesões analisadas (47,5%), enquanto os de CDI o maior pecentual (98%). Embora este estudo não tenha mostrado diferença significativa na expressão de ST3Gal-I entre as lesões de mama, alterações representativas na presença de ácidos siálicos entre fibroadenoma e lesões malignas (p<0,0001), e também entre CDIS e CDI (p = 0.037) foram notadas. Não foram encontradas correlações significativas entre as expressões de ST3Gal-I e MAA, os marcadores de rotina e as características clinico-histopatológicas dos pacientes. Os resultados indicam uma distribuição particular de ácidos siálicos ⍺2,3-ligados nas células mamárias entre as lesões estudadas sugerindo seu envolvimento na progressão/manutenção do câncer de mama.
The female breast cancer is the second most common type of cancer in the world, with increased incidence of 22% every year. Recent studies in recent decades have revealed that the malignant transformation is associated with a variety of cells with altered glycosylation patterns such as sialylation. Sialic acids have been demonstrated to participate in cancer initiation and progression, thus has potential implications for cancer prevention, diagnosis and treatment. This study evaluated the phenotype expression of ST3Gal-I using immunohistochemistry and the sialic acid residues profile by histochemistry with Maackia amurensis agglutinin II (MAA) in mammary tissues diagnosed as fibroadenoma (n=59), ductal carcinoma in situ (DCIS, n=40), invasive ductal carcinoma (IDC, n=50) and lobular carcinoma (LC, n=42). All types of breast lesions showed high ST3Gal-I immunopositivity, its expression was observed in 93.2% cases of Fibroadenoma, 92.5% of DCIS, 96% of IDC and 85.2% cases of LC. The cells ST3Gal-I staining pattern was mainly cytoplasmatic and perinuclear. The MAA staining in breast lesions showed a diffuse cytoplasmatic and membrane pattern with different distribution of ⍺2,3-linked sialic acids among the lesions studied, fibroadenoma cases showed the lowest percentage among the analyzed lesions (47.5%) while IDC showed the highest (98%). Although this study did not show a significant difference in expression of ST3Gal-I among all lesions, representative alterations in sialic acid content between fibroadenoma and malignant lesions (p<0.0001), and also between CDIS and CDI (p=0.037) were observed. No significant correlations were found between the expressions of ST3Gal-I and MAA, routine markers and clinical-histopathological characteristics of the patients. Results indicate different distribution of ⍺2,3-linked sialic acids on the cells of the studied lesions which seems to be involved in breast cancer progression and/or maintenance.
Pérez, Garay Marta. "Role of alpha 2,3-sialyltransferases ST3Gal III and ST3Gal IV in pancreatic ductal adenocarcinoma." Doctoral thesis, Universitat de Girona, 2011. http://hdl.handle.net/10803/7644.
Full textThis work shows that genes that codifying for the enzymes beta-galactoside alpha-2,3-sialyltransferase 3 (ST3Gal III), and in a lower extent beta-galactoside alpha-2,3-sialyltransferase 4 (ST3Gal IV) , are directly implicated in key steps of tumour progression such as adhesion, migration and metastasis formation in the pancreatic adenocarcinoma cell lines Capan-1 and MDAPanc-28. Moreover, Reactive Oxygen Species (ROS) generated in these cell lines during cell proliferation-differentiation processes or by external oxidant stimuli, play a role in the control of ST3Gal III and SLex levels and in the acquisition of a more aggressive phenotype. And, together with the pro-adhesive role of E-Selectin for circulating cells, this work uncovers sE-Selectin dependent migration and VEGF secretion through a SLex depending mechanism, supporting additional pro-metastatic effects for sE-Selectin-SLex interaction.
Preidl, Johannes Jonas [Verfasser]. "Entwicklung von Fluoreszenzpolarisations-Sonden und affinitätsbasierten Photomarkierern für Sialyltransferasen sowie HT-Screening einer Sialyltransferase / Johannes Preidl." Berlin : Freie Universität Berlin, 2011. http://d-nb.info/1026358213/34.
Full textAbu-Izneid, Tareq, and n/a. "The Synthesis and Evaluation of Functionalised Carbohydrates as Probes of Tumour Metastasis." Griffith University. Institute for Glycomics, 2005. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20061019.111424.
Full textAbu-Izneid, Tareq. "The Synthesis and Evaluation of Functionalised Carbohydrates as Probes of Tumour Metastasis." Thesis, Griffith University, 2005. http://hdl.handle.net/10072/367269.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Institute for Glycomics
Full Text
Eggers, Katinka Caroline [Verfasser]. "Studies on the structural basis of NCAM functions and on the role of (poly)sialyltransferases and their biosynthetic products in onco- and neurodevelopment / Katinka Caroline Eggers." Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover (TIB), 2012. http://d-nb.info/1024938425/34.
Full textWoodard-Grice, Alencia V. "Hyposialylation regulates [alpha]4[beta]1 integrin binding to VCAM-1." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2009r/woodard.pdf.
Full textVergé, Caroline. "Etude de l'implication des acides sialiques dans la régulation de la fusion myoblastique." Thesis, Limoges, 2019. http://www.theses.fr/2019LIMO0054.
Full textMyogenesis is a physiological process which includes the proliferation, the differentiation and the fusion of myoblasts in order to form myotubes and then muscular fibers. These mechanisms are regulated by the MRF (Myogenic Regulatory Factors) and Pax3 and Pax7 proteins which are members of the Pax protein family. The balance between Pax7 and MyoD is the determining factor of the cell fate determination and the entry in differentiation. The myoblasitc fusion requires the presence of glycans on cell surface proteins. We demonstrated that during C2C12 cell differentiation, takes place a decrease of α2,6 sialylation associated with a decrease of gene expression coding for ST6Gal I. We have used the C2C12 myoblastic cell line to analyse the modifications of α2,6 sialylation and its impact on the expression of Pax7 during cell differentiation. For this purpose, we have created C2C12 clones which expressed shRNA against st6gal1. These cells show a slowdown proliferation, a severe decrease of Pax7 expression and an earlier entry in differentiation. The glycanic structures modified during myoblast differentiation were identified by lectinoblotting and mass spectrometry: the sialylated bi-fucosylated N-glycans are the most impacted by the decrease of α2,6 sialylation. The earlier fusion of the clones st6gal1- leads to a decrease of the amount of the reserve cells (Pax7+/MyoD-). The extinction of Pax7 expression during differentiation is due to the decrease of the activation of Notch pathway. The KD of st6gal1 inactivates Smad2/3 pathway associated with the cell proliferation and it activates the Akt pathway which favors the cell fusion. We can conclude that α2,6 sialylation is required for C2C12 proliferation and it contributes to Pax7 activation
Montpetit, Marty L. "Functional Remodeling of the Cardiac Glycome Throughout the Developing Myocardium." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002303.
Full textLelièvre, Mélanie. "Étude de la biosynthèse des motifs di-, oligo- et polysialylés chez les mammifères : identification et caractérisation d'une nouvelle sialyltransférase humaine (hST8Sia VI)responsable de la biosynthèse de motifs diSia sur des O-glycosylprotéines." Lille 1, 2006. http://www.theses.fr/2006LIL10068.
Full textFERREIRA, Steffany de Almeida. "Análise da expressão de glicosiltransferases em tumores cutâneos não melanomas." Universidade Federal de Pernambuco, 2012. https://repositorio.ufpe.br/handle/123456789/12756.
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O câncer de pele ou tumor cutâneo não-melanoma (TCNM), é a neoplasia maligna de maior incidência no Brasil. Os cânceres, em geral, apresentam padrão de glicosilação aberrante na estrutura de oligossacarídeos de superfície celular (fenótipo), determinada pela ação conjunta de glicosiltransferases (genótipo). O presente estudo objetiva avaliar o perfil glicofenotípico de glicoconjugados de superfície celular de TCNM e correlacionar com o padrão de expressão de sialiltransferases. Cortes (4μm) de biópsias de Carcinoma Basocelular (CBC), Carcinoma Espinocelular (CEC), Ceratose Actínica (CA) e Ceratoacantoma (KA) foram ensaiados com as lectinas SNA, Sambucus nigra agglutinin, (específica para ácidos siálicos ligados na posição α-2,6) e MAA, Maakia amurensis agglutinin (específica para ácidos siálicos na posição α-2,3). A inibição da ligação lectina-carboidrato foi realizada com o ácido siálico (300mM). As amostras também foram avaliadas com anticorpos monoclonais anti-ST3Gal I (específico para β-galactosideo α2,3 sialiltransferase) e anti- ST6Gal I (específico para β-galactosideo α2,6 sialiltransferase). Semelhanças no padrão de sialilação entre CEC, CA e KA foram encontradas na histoquímica com lectinas e, principalmente na imunohistoquímica. O CBC não apresentou marcação na maioria dos casos para ambas as técnicas, indicando que este tipo tumoral apresenta um padrão molecular próprio podendo estar associado ao seu comportamento biológico (baixo potencial invasivo e metastático). Os resultados indicam a importância da sialilação no desenvolvimento e manutenção de tumores cutâneos, sendo a histoquímica com lectinas e a imunohistoquímica ferramentas úteis na determinação deste tipo de glicosilação na superfície de células tumorais.
Lee, Hing-leung Eric, and 李慶亮. "Genetic and epigenetic factors controlling the expression of sialyltransferase gene ST6GAL1." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B4150849X.
Full textLee, Hing-leung Eric. "Genetic and epigenetic factors controlling the expression of sialyltransferase gene ST6GAL1." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B4150849X.
Full textReyes, Martinez Juana. "Photobacterium damselae alpha2,6-sialyltransferase and Trypanosoma cruzi trans-sialidase in the synthesis of sialyloligosacharides." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/photobacterium-damselae-alpha26sialyltransferase-andtrypanosoma-cruzi-transsialidase-in-the-synthesis-ofsialyloligosacharides(d61a4152-1819-4264-a49f-2680cc48c52c).html.
Full textCreuzot-Garcher, Catherine. "Expression des gènes et des antigènes des mucines conjonctivales humaines saines et pathologiques." Dijon, 1998. http://www.theses.fr/1998DIJOMU04.
Full textTipton, Jeremiah D. "Mass spectrometry for structural proteomic analysis of recombinant human sialyltransferase and identification of nanoparticle harvested oligonucleotides." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0012681.
Full textBedder, Andrew Edward. "Investigations into the possible role of polysialic acid and sialyltransferase activity in neural plasticity in the domestic chick." Thesis, Open University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368001.
Full textRosenstock, Philip [Verfasser], Iris [Gutachter] Thondorf, Rüdiger [Gutachter] Horstkorte, and Lars-Oliver [Gutachter] Klotz. "Untersuchungen humaner natürlicher Killer-Zellen und ihrer Sialyltransferasen nach Dicarbonyl-Stress / Philip Rosenstock ; Gutachter: Iris Thondorf, Rüdiger Horstkorte, Lars-Oliver Klotz." Halle (Saale) : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2020. http://d-nb.info/1215098855/34.
Full textFerri, Iglesias María José. "Moléculas séricas relacionadas con la fisiopatología del adenocarcinoma pancreático como posibles marcadores tumorales." Doctoral thesis, Universitat de Girona, 2012. http://hdl.handle.net/10803/95812.
Full textEn este trabajo se analizan distintos parámetros séricos relacionados con la fisiopatología del adenocarcinoma pancreático (PDAC), para evaluar su uso como marcadores que permitan distinguir entre pacientes con PDAC y controles sanos (C), otras neoplasias del tracto gastrointestinal (ONEOS) y pancreatitis crónica (PC). La expresión en plasma de sialiltransferasas, ST3Gal III y ST3Gal IV diferencia entre controles y PDAC. Así mismo, los niveles de ST3Gal III permiten diferenciar en PDAC entre estadíos iniciales y metastáticos. El Glasgow Prognostic Score (GPS), medida de la respuesta inflamatoria, diferencia entre todos los grupos del estudio. Los valores de IGF-1 disminuyen en procesos neoplásicos vs C y PC.Se analiza la capacidad diagnóstica de los distintos parámetros individualmente y combinados entre sí respecto al CA19.9. La combinación de CA 19.9, CEA, IGF-1 aumenta la precisión diagnóstica frente al CA19.9 y podría ser útil para distinguir PDAC de PC.
French, Anne Thérèse. "The co-regulation of the mucus associated molecules intelectin, resistin like molecule beta and beta galactoside alpha 2-3 sialyltransferase in a T helper cell type 2 response." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/28071.
Full textDalziel, Martin. "Regulation of peripheral blood B-lymphocytic and serum CMP-NeuSAC : Galβl, 4GlcNAc - #alpha#2,6 sialyltransferase activity in relation to serum polyclonal immunoglobulin G #alpha#2,6 sialylation in rheumatoid arthritis." Thesis, St George's, University of London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252049.
Full textBASSET-CARPENTIER, KARINE. "Synthese chimio-enzymatique d'oligosaccharides. Recherche d'analogues simplifies pour l'etude de la specificite de la gal-beta-(1,3)-galnac-alpha-(2,3)-sialyltransferase de foie de porc, en vue de la preparation du synthon neu5ac-alpha-(2,3)-gal." Paris 7, 1996. http://www.theses.fr/1996PA077168.
Full textLiu, Shan. "NMR active substrates for structure and function studies of sialyltransferases." 2008. http://purl.galileo.usg.edu/uga%5Fetd/liu%5Fshan%5F200812%5Fphd.
Full textWang, Peng-Hui, and 王鵬惠. "Altered expression of sialyltransferases in squamous cell carcinoma of the cervix and their clinical correlation." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/67720684815916190882.
Full text國立陽明大學
臨床醫學研究所
90
Sialic acids including a number of their derivatives are ubiquitous at the terminal positions of oligosaccharides of glycoproteins. Due to their acidic nature, they impart a net negative charge to the cell surface and are important in cell-cell or cell-matrix interaction. The transfer of the sialic acids from cystidine-5-monophospho-N-acetylneuraminic acid (CMP-NeuAc) to the terminal position of carbohydrate group of glycoproteins and glycolipids is catalyzed by a family of sialyltransferases (STs). There is a large body of evidence to suggest that tumor cells have changed surface properties from their normal counterparts, and that these changes are partially due to altered sialo-glycoconjugates expressed on the plasma membrane and that altered sialylation (change in glycoprotein expression), which occurs during certain pathological processes, such as oncogenic transformation, tumor metastases, and invasion, is associated with enhanced ST activity. Increased β1,6-branching, increased Sialyl-Lewis epitopes, increased Sialyl-Tn antigen (Sialyl α GalNAc-O-Ser/Thr), or the general increase in sialylation of cell surface glycoproteins are commonly observed in N-lined and O-lined oligosaccharides of carcinoma cells. Carbohydrate changes occur common in breast cancer, colorectal cancer, lung cancer, hepatic carcinoma, gastric carcinoma, head and neck squamous cell carcinoma, brain tumor, choriocarcinoma, and prostate cancer. More specifically, these changes in glycoprotein expression are reported to play important roles in tumor grade, invasion, metastatic ability, and poor clinical outcome. Some of these studies also evaluated the mRNA expression of STs and found that increased mRNA expression of STs is correlated with poor outcome in breast cancers, and colon carcinoma. There are some studies that only evaluated the relationship between the change of ST mRNA expression and their clinical correlation, including colorectal cancer, and gastric cancer. In Taiwan, carcinoma of the cervix is still the most common female cancer in Taiwan with an incidence rate of 32.1 per 100,000. The prognosis is dependent mostly on many factors; among them, the majority is based on histo-pathological parameters. Many pathological factors including bulky tumor size, poor differentiation, presence of lymph-vascular space involvement, presence of parametrial invasion, and deep stromal invasion are related with lymph node metastases and closely respond to disease-free survival. Besides these conventional pathological parameters for predicting prognosis in an early stage cervical cancer, there are many biological factors (cellular molecules), which show close correlation with aggressive and invasive behaviors in tumors. Among these biological factors, sialic acids are one of the most promising molecules because they involve cell-cell and cell-matrix interactions and cellular recognition. However, so far, altered expression of mRNA of STs in gynecological cancers is still unavailable. In addition, in our laboratory (Department of Biochemistry and Institute of Biochemistry, National Yang-Ming University), Dr. Wu guided by the professor Tsai (the Director in the program of my Ph.D. in Institute of Clinical Medicine, National Yang-Ming University) in his Ph.D. program used the screening strategy to find a very specific ST3Gal I inhibitor- soyasaponin I (Ki = 2.3 μM), which is 20-fold and 25-fold higher affinity to the active site enzyme than nature substrate CMP-Neu5Ac (KM = 46 μM) and product CMP (Ki = 55 μM), respectively. Soyasaponin I contains no significant inhibition activity for other glycosyltransferases and glycosidases, respectively. This unique finding provides a new feasible method to directly elucidate the functional roles of STs by inhibition ST activity under in vivo experiments and highlight the possibility of use the biological inhibitor for cancer prevention and/or treatment. Therefore, I selected this promising topic- altered expression of sialyltransferases in cervix squamous cell carcinoma and their clinical correlation as the study project for my Ph.D. program when I entered the Institute of Clinical Medicine, National Yang-Ming University since 1999, partly because the squamous cell carcinoma of the cervix is still the most common female cancer in Taiwan, partly because the clear-cut and long-term transformation from normal tissues of the cervix, to pre-cancer lesion (cervical intraepithelial neoplasia) and further toward the invasive squamous cell carcinoma of the cervix. Of the most importance, we manage two hundred women with the early-stage squamous cell carcinoma of the cervix (FIGO IB-IIA), which is treated with radical hysterectomy and pelvic lymph node dissection in our department (Department of Obstetrics and Gynecology, National Yang-Ming University based Taipei Veterans General Hospital annually. Based on the basic support from the Institute of Biochemistry (The director; Professor Tsai) and the clinical support from the Department of Obstetrics and Gynecology (The director: Doctor Yuan & The Section Chief: Doctor Chao), I can study the change of different-type sialyltransferases in cervical normal tissues and cervical squamous cell carcinoma first. Then, I can compare the difference between the normal tissues and cancer tissues to search for candidate type of sialyltransferases, and use the same strategy to evaluate the clinical correlation between their changes and the tumor behavior such as deep stromal invasion, lymph-vascular space involvement, parametrial invasion and lymph node metastases in clinical practice. Our goal was to clarify their roles in tumor carcinogenesis of cervical squamous cell carcinoma, and their correlation in clinically poor prognosis. We attempted to use these biochemical parameters combining with histo-pathological parameters to identify the high-risk women with recurrence or therapeutic failure. After confirming their roles in cervical cancer, we can highlight the possible role in cancer prevention and treatment using these specific and selective ST inhibitors in the future. The thesis is divided into four parts: first, to set up the study method including using substrate-enzyme assay for sialyltransferase activity, and letting blotting for measuring amounts of sialic acids on the cell line; second, to use semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) for evaluating the altered mRNA of sialyltransferases in cervical squamous cell carcinoma compared to those in normal cervical tissue; third, to use the above-mentioned methods to evaluate their changes in cervical squamous cell carcinoma to clarify their relationship between conventionally clinico-pathological parameters and expression of sialyltransferases and set up the possible value for clinical practice in the future. In the program part one, we successfully detected the activities of each subtype of sialyltransferases using Galβ1,3GalNAc-acetyl-lactosamine)-Obzl (acceptor for ST3Gal I), Galβ1,3GlcNAcβ1,3Galβ1,4GlcNAc (acceptor for ST3Gal III), Galβ1,4GlcNAc (acceptor for ST3Gal IV), asialo-bovine submaxillary mucin (acceptor for ST6GalNAc I), asialo-fetuin (acceptor for ST6GalNAc II), and fetuin (acceptor for ST6GalNAc III), respectively; we also successfully detected the amounts of sialic acids using fluorescein-conjugated Sambucus nigra agglutinin (SNA) specific for α2,6-sialic acids and fluorescein-conjugated Maackia Amurensis agglutinin (MAA) specific for α2,3-sialic acids. We found that increasing enzyme activity of ST3Gal I and ST6GalNAc II might be important in various kinds of gynecological cancers. More specifically, enhanced activity of sialyltransferases involving α2,6-sialic acid sugar chains might be more important in cancer development. Future studies will investigate whether the enzyme activity of these sialyltransferases can be helpful for clinical practice. Based on these findings, we entered the program part two. We directly switched to study the difference of mRNA expression of 4-type sialyltransferases (ST3Gal I, ST3Gal III, ST3Gal IV and ST6Gal I) between the cervical squamous cell carcinoma and the normal cervical tissue using semiquantitative reverse transcription-polymerase chain reaction method and found that sialyltransferase ST6Gal I expression was enhanced in squamous cell carcinoma of the cervix (p=0.026, Mann-Whitney U test), but mRNA expression from the other three sialyltransferases (ST3Gal I, ST3Gal III, and ST3Gal IV) was significant down-expression in squamous cell carcinoma of the cervix compared to the normal cervix (p=0.003, p<0.001, p=0.001, respectively). High ST6Gal I expression was associated with more invasive property of cervical cancer, such as deep stromal invasion, lymph-vascular space involvement, and poor differentiation (p=0.010, p<0.001, p<0.001, respectively). The conclusion of the study shows that combination of enhanced sialyltransferase ST6Gal I mRNA expression and decreased mRNA expression from ST3Gal I, ST3Gal III, and ST3Gal IV might be important processes in cervical cancer. Therefore, our goal of the next study, the program part three, will investigate whether RT-PCR detection of the expression of these enzymes can be helpful for prognostic purposes. In the program part three, this study further investigates their changes in mRNA expression of the four STs in FIGO stage IB1 squamous cell carcinoma to assess the extent of sialylation associated with lymph node metastases. We evaluated the alterations in ST mRNA expression in FIGO IB1 cervical squamous cell carcinomas using RT-PCR and substrate-enzyme assay methods. We found that both ST6Gal I mRNA and ST3Gal III mRNA expressions were significantly increased in patients with lymph node metastases compared to those without lymph node metastases (p=0.002 and p=0.001, respectively, Mann-Whitney U test). Using receiver operating characteristic (ROC) curves of ST ratio index for accuracy comparison of lymph node metastases, ST3Gal III and ST6Gal I were observed to be fairly interchangeable (area under the curve (AUC) of 3Gal I=0.810; AUC of 6Gal I=0.786, significance of difference between AUC=0.810). High ST6Gal I expression was associated with other invasive properties of cervical cancer, such as deep stromal invasion and presence of lymph-vascular space involvement. ST6Gal I expression seemed to be more enhanced in bigger tumors. Our conclusion suggested that ST3Gal III and ST6Gal I were of importance for the lymph node metastases in FIGO IB1 cervical cancer patients; more specifically, over-expression of ST6Gal I was of crucial relevance for the presence of poor-prognostic factors, such as deep stromal invasion and lymph-vascular space involvement and lymph node metastases. In the program part four, based on the fact that increasing messenger ribonucleic acid (mRNA) expression of ß-galactosideα2,6-sialyltransferase I (ST6Gal I) is important in squamous cell carcinoma (SCC) of the cervix. In many tissues, ST6Gal I is transcriptionally regulated through the use of different promoters that originate in the mRNAs which diverge in the 5’-untranslated regions. In this study, to clarify the roles of ST6Gal I mRNA species in cervical SCC, we investigated their expression including a “constitutive” promoter- placental form (Y + Z form), “hepatic” promoter and a specific lymphoblastic promoter (X form) in normal and SCC tissues of the cervix using real-time quantitative reverse-transcription-polymerase chain reaction (RT-PCR). Expression of the ST6Gal I species was investigated in normal cervices (n = 38) and FIGO IB1 cervical SCC (n = 38) by real-time quantitative RT-PCR, using primers designed for amplification of a portion of the coding region common to all mRNA species, or ones for amplification of the placental transcript (Y + Z form), the hepatic transcript (H form) or lymphoblastic transcript (X form). Our results showed that ST6Gal I mRNA expression was significantly increased in cancerous tissues compared to that in normal tissues (p = 0.004, Mann-Whitney U test). Expressions of the Y+Z form did not appear to be affected by cancer transformation, since it was detected at comparable levels in normal and cancerous tissues (p = 0.13), but the H form expression was significantly enhanced in cancerous tissues compared to that in normal tissues (p < 0.0001). Surprisingly, the X form could be detected in a portion of patients either with or without cancer, but the detection rate was significantly higher in patients with cancers compared to those without cancers (86.8% vs. 52.6%, p= 0.021, Fisher’s exact test), although the X transcript was only detected at a very low level compared to the H and Y + Z transcripts. Therefore, we concluded that an increased levels of hepatic transcripts might be very important in cancer transformation because it contributes to enhanced ST6Gal I expression in cancerous tissues. A high percentage of the X form transcript in cancerous tissues might resulted from lymphocyte infiltration, and may involve a host-tumor interaction, although the clinical evidence for this is not clear yet. According to all findings in this project of Ph.D.- altered expression of sialyltransferases in cervix squamous cell carcinoma and their clinical correlation, we can clearly identify the important and significant role of altered sialyltransferase expression in the cervix squamous cell carcinoma. ST6Gal I overexpression is a very important process during the establishment of cervix SCC. With progressively growth and invasive process, enhanced ST6Gal I expression became more importance. This ST6Gal I overexpression mainly results from the activating 5’ untranslated H form promoter although both Y + Z and H transcripts contribute the total pool of ST6Gal I. When entering the metastatic status, initiated overexpression of ST3Gal III should be occurred, because overexpression of both ST6Gal I and ST3Gal III could predict pelvic lymph node metastases accurately in FIGO IB1 sqamous cell carcinoma of the cervix. We highlight the vision that, with advancing biotechnology, more specific molecules against different kinds of STs might be found in the near future, just like soyasaponin I, which is a potent and specific sialyltransferase inhibitor for ST3Gal I and is first identified in our laboratory. Using this strategy might provide a vision of possibly synergistic therapy in cervical cancer patients or offer an effective tool in cancer prevention, especially for cervix squamous cell carcinoma.
Hsu, Jui-Ching, and 徐瑞靜. "(1)Synthesis of modified lithocholic acids: coumarin, nitro-2,1,3-benzoxadiazole and other functional groups as effective anticancer agents and biological probes.(2)Analogues of Malyngamide 1 and Isomalyngamide A as inhibitors of sialyltransferases: A." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/89679751678651977714.
Full text國立中央大學
化學研究所
96
Part I: Synthesis of modified lithocholic acids: coumarin, nitro-2,1,3-benzoxadiazole and other functional groups as effective anticancer agents and biological probes. Overexpression of sialyltransferase is a vital biological process, which plays a role in various physiological and pathological events, such as cell-cell adhesion, tumor cell metastasis and invasions. To increase the inhibitory potency of sialyltransferase, we prepared the coumarin, NBD (7-nitro-2,1,3-benzoxadiazole) and other functional derivatives of lithocholic acid based on our previous studies. Some of these compounds, 5-25, represent the first examples of nanomolar range sialyltransferase inhibitors with cell permeability which had been demonstrated by the experiment of wound healing and the detection of fluorescence imaging of cells incubated with coumarin or NBD derivative of lithocholic acid. Except the property of antimetastasis in wound healing assay, compounds 5-25 also slightly displayed inhibition of the proliferation of breast cancer cells with the inhibitory percentages ranging from 4~40% under the compound dose at 20 ?M. To investigate the capability of lithocholic acid derivatives attracting the sialyltransferase proteins in vitro and in vivo, nanoparticle-based sialyltransferase inhibitors, 32-36, were prepared to tackle this problem. Part II: Analogues of Malyngamide 1 and Isomalyngamide A as inhibitors of sialyltransferases: A structure activity relationship study of chain-length and functional dependence. Malyngamide 1 and Isomalyngamide A are natural products from Marine and display the significant cytotoxic activity against breast cancer cells at the low micromolar level (IC50 = 12.7 and 2.8 μM). Meanwhile, one of them also inhibited alpha-2,3-sialyltransferase activity at micromolar concentration (IC50 = 66 μM). To find out the pharmacophore, several substructures of malyngamide 1 were synthesized, and their inhibitory properties of sialyltransferase and cytotoxic activities against breast cancer cells were also studied.
Lo, Wei-Lun, and 羅偉倫. "The Screening of sialyltransferase inhibitors and the study of the sialyltransferase activities in the gynecological cancer cell lines." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/01721520317081864512.
Full text國立陽明大學
生物化學研究所
88
ialic acids, a group of characteristic sugar molecules, occur at the terminal positions of the carbohydrate groups of glycoproteins and glycolipids. Some interesting relations between the amounts of sialo-glycoconjugates and embryo developments, cell differentiations, carcinogenesis, or tumor metastasis have been identified. From the viewpoint of glycobiology, cancer is the disease caused by abnormal glycosylation. The patterns of glycosylation are quite different in the transformed cell, either incomplete or over-glycosylated glycoconjugates have been observed. During the process of abnormal glycosylation of the tumor cell, there is an obvious change in the amount of surface sialic acid. In the first section of this study, for the interest of the high specific inhibitor of alpha-2,3 sialyltransferase (ST3Gal I), we developed our STI (sialyltransferase inhibitor) by doing the microorganisms extracts screening. 3,520 microbe samples were tested, we found 17 fungus, 21 bacteria and 24 actinomyces extract exist the ST inhibition activity. Further experiments are underway, including the purification of novel sialyltransferase inhibitors from several microorganisms; carcinogenesis model and tumor metastasis model in mice will be applied for analyzing the in vivo effect of these sialyltransferase inhibitors. The second section, we have focused on the investigation of the sialyltransferase activities in the gynecological cancer cell lines. In this study, the activities of each subtype of sialyltransferase and the amounts of sialic acid of different linkage type were measured in 10 gynecological cancer cell lines. The correlation between the sialyltransferase activities and the cell oncogenesis was there analyzed. Our data showed that the activities of 2 sialyltransferase subtypes, ST3Gal I & ST6GalNAc II, were significantly higher in 10 gynecological cancer cells compared to 2 normal control cells. Further experiments will be required for the understanding the roles of these 2 ST, especially ST6GalNAc II, which they play in the transformation or metastasis processes of gynecological cancers.
Kuo, Yu-Ying, and 郭昱瑩. "α-2,3-Sialyltransferase C-terminal Modification & Immobilization." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/77782999885987373227.
Full textTrębacz, Ewa. "Rola sjalilacji integryny $\alpha5\beta1$ w oddziaływaniach komórek czerniaka z fibronektyną." Praca doktorska, 2011. https://ruj.uj.edu.pl/xmlui/handle/item/276362.
Full textDuring the development of cancer, cells acquire the capacity for migration, adhesion, and forming of new metastasis in distant tissues. Malignant transformation is a complex process, which involves changes in genotype and phenotype of transformed cells. On the surface of tumor cells appears a singular set of adhesion molecules, like integrin $\alpha5\beta1$, responsible for maintaining the consistency of the tissue and proper communication between cancer cells and extracellular matrix. Sialic acids are most commonly added to N-linked glycans in an a2-3, a2-6 or a2-8 linkages and altered profile of cell surface sialylation is a well-accepted hallmark of malignant transformation. The interaction of cells expressing integrin $\alpha5\beta1$ and fibronectin results cancer cell adhesion, migration, and invasion. Presence of sialic acids may modify these interactions. The aim of this study was to determine the impact of sialic acids on interactions between primary WM115 and metastatic WM266-4 melanoma cell lines and fibronectin. The aim of the present study was to analyze gene expression for five sialyltransferases witch added sialic acids to the terminal positions of N-glycans, using RT-PCR method. The results confirmed that expression of sialyltransferase genes are changing during cancer transformation. Upregulation of SIAT1 gene, downregulation of SIAT4c gene in WM266-4 metastatic cell line were observed. In addition lack of transcript for the STX was observed, which may be the determinant of metastatic melanoma cells. Subsequently, the presence of the integrin $\alpha5\beta1$ has been studied using immunodetection. The integrin subunit sialylation was investigated using enzymes digestion as well as lectin precipitation. The results revealed the presence of integrin $\alpha5\beta1$ in cancer cell lysats of both melanoma cell lines. Studies have also shown an increase $\alpha2-6Gal/GalNAc$ sialic acids and decrease of $\alpha2-3Gal$ sialic acids linked to $\alpha5$ integrin subunit. The impact of sialic acid $\alpha2-3Gal$, $\alpha2-6Gal/GalNAc$ and $\alpha2-8Sia$ linked to purified $\alpha5\beta1$ integrin receptor on protein adhesion to fibronectin was investigated using specific sialidases. The results have shown that sialic acid $\alpha2-3Gal$ have decreased integrin adhesion to fibronectin in WM115 cell line. Sialic acids linked to $\alpha5\beta1$ isolated from WM266-4 cell line had no effect on adhesion to fibronectin. Densytometric analysis of gelatin zymography showed increase expression of Pro-MMP-2 and de novo synthesis of MMP-9 by WM266-4 cell line. Expression of Pro-MMP2 and MMP-9 were associated with melanoma progression. Finally the impact of $\alpha5\beta1$ integrin and sialic acids $\alpha2-3Gal$, $\alpha2-6Gal/GalNAc$ and $\alpha2-8Sia$ linked to N-glycans was investigated during (i) wound healing on fibronectin, (ii) adhesion to fibronectin, and (iii) cell invasion by Matrigel in WM115 and WM266-4 cell lines. The results revealed that the presence of $\alpha5\beta1$ integrin increased wound healing of WM115 cell line, but sialic acids linked to N-glycans had similar effect on WM266-4 cell lines. The WM266-4 cells also showed increased adhesion to fibronectin in comparison with primary WM115 cell line. Increased cell adhesion to fibronectin is probably associated with cutaneous melanoma transformation. Integrin $\alpha5\beta1$ was also associated with increased cell adhesion in primary and metastatic cell lines. Sialic acids $\alpha2-3Gal$ and $\alpha2-6Gal/GalNAc$ expression were necessary during WM266-4 adhesion to fibronectin. Study of cell invasion indicated that primary and metastatic WM115 WM266-4 cell lines exhibited similar invasive ability threw Matrigel. Expression of $\alpha5\beta1$ integrin enhanced cell invasion in both tested cell lines. Moreover, presumably there is a change in the function of sialic acids during cell invasion. Sialic acids $\alpha2-3Gal$ promoted cell invasion of primary cell line WM115 but did not affect invasion of the in melanoma cell line WM266-4 through Matrigel. In addition sialic acids $\alpha2-6Gal/GalNAc$ reduced invasion of WM266-4 cells through Matrigel.
柯嘉玲. "α-2,3-Sialyltransferase Functionalized Magnetic Nanoparticle and its Application." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/38130989914311744935.
Full textSzidonya, Erin Marie. "Development of macromolecular acceptors for the sialyltransferase ST6GlcNAcl from bovine glycoproteins." 2002. http://hdl.handle.net/1993/19773.
Full textWu, Chi-Yue, and 吳啟裕. "Discovery of the Potent Sialyltransferase Inhibitors and Their Application in Sialobiology." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/19882997304115360313.
Full text國立陽明大學
生物化學研究所
88
A number of reports illustrated that sialyltransferase is significantly altered during normal development and differentiation, oncogenic transformation, and the metastasis potential. Therefore, it is highly necessary to discover the potent sialyltransferase inhibitors to elucidate the influence of alteration of sialyltransferase expression in the complex biological systems. Up to now, no effective cell membrane-permeable sialyltransferase inhibitor has been developed to use in cell culture system. Therefore, in the thesis, I focus on the discovery of the novel sialyltransferase inhibitors, which can be applied to sialobiology. First, the sialyltransferases were constructed and expressed in mammalian cells. WCY have been discovered to be a novel sialyltransferase inhibitors. It highly specific inhibition for sialyltransferase but not for other glycosyltransferases and glycosidases. For in vivo activity, WCY present the inhibition activity for reducing the expression level of cell surface sialoglycoconjugates. These results indicate that WCY is the first sialyltransferase inhibitor which can be used to inhibit the expression of sialoglycoconjugates in the cell level, and it also provides a new information to design the more potent inhibitor of sialyltransferase to elucidate the functional roles of sialyltransferase and sialoglycoconjugates. 英文摘要 壹、簡介- - - - - - - - - - - - - - - - p.1 貳、實驗材料 - - - - - - - - - - - - - - p.13 參、實驗方法- - - - - - - - - - - - - - p.15 肆、結果- - - - - - - - - - - - - - - - p.30 伍、討論- - - - - - - - - - - - - - - - p.48 陸、總結 - - - - - - - - - - - - - - p.61 柒、參考資料- - - - - - - - - - - - - - p.62 捌、表- - - - - - - - - - - - - - - - p.70 玖、結果圖- - - - - - - - - - - - - - - p.81 拾、論文(1)- - - - - - - - - - - - - - - - p.118 拾壹、論文(2)- - - - - - - - - - - - - - - p.136 拾貳、附圖- - - - - - - - - - - - - - - p.148
Hsu, Chi-Cheng, and 徐啟正. "Screening and Purification of Sialyltransferase Inhibitors and Effects on Tumor Cell." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/01671272758193628047.
Full text國立陽明大學
生化暨分子生物研究所
94
Sialic acids belong to a nine-carbon amino sugar neuraminic acid family, and they are widely distributed in nature as the terminal sugars of oligosaccharide chains of glycoconjugates (glycoproteins and glycolipids). Recently, it has been demonstrated that the sialylation on cell surface is involved in biological and pathological processes, such as differentiation, oncogenic transformation and tumor metastases and invasions. Cell sialylation is dependent on the sialyltransferase which catalyst the transfer of sialic acid from cytidine-5-monophospho-N-acetylneuramic acid (CMP-Neu5Ac) to the terminal position of oligosaccharide chain of glycoconjugate. Therefore, modulation of the sialyltransferase (ST) activity has become an interesting and important subject in the elucidation of the roles played by ST either in normal or pathological processes. In 1980s, although the ST inhibitors based on the analogs of donor substrate were successfully synthesized, these compounds showed no substrate specificity and could not be used in clinical application. Recently, lead compounds based on the transition-state structure of CMP-Neu5Ac have been tested successfully and achieved good inhibition in vitro. However, these transition-state structure-based inhibitors are cell-impermeable and not suitable for in vivo applications. Therefore, in this thesis, we tried to find out new ST inhibitors from natural products and microbial metabolites for potential in vivo application. Sixty-two candidates were screened out from 3520 samples and 9 strains of fungi, 10 strains of bacteria, and 9 strains of actinomyces were obtained. We also tentatively tried to purify the ST inhibitor from the fungus strain 132359 and about 3 g of crude product was successfully obtained from the culture media by using the submerged fermentation method. In 2001, we discovered a new ST inhibitor, soyasaponin I (SsaI), from the soybean extract. In this thesis, the effects of SsaI on the metastatic and invasive behaviors of several cancer cells were also studied. At first, the cytotoxic effect of SsaI on cancer cells were investigated and the results showed that SsaI displayed significant growth inhibition activity only at concentration greater than 100 μM. Then, the ST enzyme activities of various cancer cell lines were measured and it showed that MCF-7 cell has high ST3Gal I enzyme activity; therefore, the MCF-7 cell were chosen for further analysis. The α2,3-ST activity in cellular homogenate prepared from MCF-7 cell could be inhibited by SsaI. When added in culture medium, the SsaI not only reduced the amount of α2,3-sialic acid on MCF-7 cell surface in a dose-dependent manner but also stimulate the adhesion of MCF-7 cell to both type I collagen and the Matrigel-matrix. SsaI also significantly decreased the migration ability of the highly metastastic MDA-MB-231 cell. All together, these studies suggested that SsaI could potentially be used to affect the invasive behavior of tumor cells by modulating the activity of ST. These data suggest that de-regulated α2,3-sialylation could played a crucial role in the invasion and metastases of tumor cells. SsaI is a good candidate for studying the biological roles of ST, and might provide a new preventive strategy in tumor metastasis.
Chiang, Wei-Jen, and 江維恁. "Sialyltransferase Inhibitor-Nanoparticle Conjugates for Diagnosis, Separation, and Enrichment of Functional Proteins." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/62101878992995913512.
Full text國立中央大學
化學研究所
98
Nanoparticles bearing surface-conjugated specific inhibitors are increasingly being utilized for a number of bio-applications including identification, separation and enhancement of desired proteins. These attractive bio-applications involve specific adsorption and recognition; however, these are the major hindrances for nanobiotechnology. To solve this question, we have investigated the effect of nanoparticle surface displaying high affinity molecules, such as sialyltransferase inhibitors. Maintaining a reasonable affinity toward desired protein is generally a prerequisite for proper design of nanoparticle-conjugated specific inhibitors. We prepared sialyltransferase inhibitors, lithocholic acid derivatives with L-Asp or NBD-L-Asp moiety, which have IC50 values at micromolar ranges. Next, magnetic nanoparticle (iron oxide)-conjugated lithocholic acid derivatives, compounds 15~16, were synthesized via click chemistry. Herein, we demonstrated that compounds 15~16 have the ability to identify, separate and enhance binding to the target alpha-2,3(N)-sialyltransferase, a glycol- and membrane-bound protein. The protein band (38 kDa) on SDS-PAGE derived from rat was confirmed by LC MS-MS analysis and proteomics searching. Extending these studies to crude cell lysate in vitro experiment, we found several interesting proteins including talin. Further investigation of talin toward metastasis in cancer is in progress.
Chang, Wei-Wei, and 章微微. "Effects of two sialyltransferase inhibitors,soyasaponin I and rhamnolipids, on cancer cells." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/35737891667023025948.
Full text國立陽明大學
生化暨分子生物研究所
94
The transfer of sialic acids to the non-reducing terminal positions on sugar chains of glycoconjugates is catalyzed by sialyltransferases (STs). These sialylated glycoconjugates not only have a role in providing structural components, but also in mediating cell-cell and cell-microbe interactions. Additionally, increased sialylation is correlated with oncogenic transformation and metastatic potential. Therefore, ST inhibitors may be potentially valuable as anticancer and antimetastatic agents. Previously, our laboratory has found a ST inhibitor, soyasaponin I (Ssa I) from soybean extract. Ssa I can reduce the expression of the alpha2,3-linked sialic acids on B16F10 melanoma cells, and inhibit the migration ability of B16F10 cells. This study demonstrated that Ssa I only specifically inhibited the expression of alpha2,3-linked sialic acids without affecting other glycans on B16F10 cells. Moreover, Ssa I can enhance cell adhesion to extracellular matrix proteins. A pulmonary metastasis assay demonstrated that alteration of glycosylation in this way significantly reduced the ability of tumor cells to distribute to the lungs of mice. Collectively, these findings suggested that alpha2,3-linked sialic acids may play an important role in metastasis potential of B16F10 cells. Additionally, through screening of microbial extracts for ST inhibitors in our laboratory, we found that the extract of fermentation broth from Pseudomonas aeruginosa 5565 had strong inhibitory activity. The active compound was purified and identified as the mixture of two rhamnolipid homologs, 2-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranosyl-beta-hydroxyldecanoyl-beta- hydroxyldodecanoate (RhaRhaC10C12) and 2-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranosyl-beta-hydroxyldodecanoyl-beta-hydroxyldecanoate (RhaRhaC12C10). RhaRha(C10C12) only specifically inhibited ST activity, without affecting fucosyltransferases and galactosyltransferase activity. Kinetic analysis indicated that RhaRha(C10C12) is a competitive inhibitor with respect to the donor CMP-Neu5Ac and a noncompetitive one with respect to the acceptor substrate LacNAc with Ki of 25.7 and 16.3 mM, respectively. The commercial rhamnolipid mixture (JBR599) was used to treat A549 lung cancer cell to determine whether JBR599 altered A549 cell surface glycosylation, the result showed that the expression of the a2,3-linked sialic acids on treated cell surface was reduced significantly. On the contrary, the expression of the asialoGM1 was increased significantly. P. aeruginosa is a major pathogen in lung bacterial colonization. It can adhere to epithelial cells via pili, which recognize a GalNAcbeta1-4Gal disaccharide, exposed in asialylated glycoconjugates such as asialo GM1. Our results also demonstrated that the number of adherent P. aeruginosa on rhamnolipid-treated A549 cells was increased compared with control. It suggests that chronic exposure to rhamnolipids may alter the glycans profile on host cells, and subsequently enhance P. aeruginosa adhesion to host cells and spreading in vivo.
Kuo, Yu-Lun, and 郭于綸. "Partially Fluorinated Lithocholic Acid Analogs as Sialyltransferase Inhibitors: Synthesis and Preliminary Bioactivity Studies." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/75789572131920733797.
Full text國立中正大學
化學暨生物化學研究所
101
According to many reports, abnormal expression of the sialyltransferase has been found to actually connect with many cancers. Therefore,purposes and objectives of this study are making effort to develop effective sialyltransferase inhibitors and regulate the level of sialyltransferase expression. In the thesis, we initially synthesized potential sialyltransferase inhibitors of the fluorine-substituted lithocholic acid derivatives. Then we use lithocholic, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid hyodeoxycholic acid and cholic acid as their parent skeleton, and take a place of a hydrogen atom or hydroxyl groups to single fluorine or two fluorines. Employing the strategy of permutation and combination, twelve fluorine-substituted lithocholic acid derivatives at the C3, C7 and C12 position in the A, B, C ring of the skeleton were synthesized respectively. We next took all the flourine-substituted analogs to do the bioactivity test of wound healing and α2 ,3-sialyltransferase inhibition test. Interestingly, we found that compounds YL-38, YL-44 possess potent anti-metastasis ability and compounds YL-34, YL-72, and YL-80 could be identified as protential α2 ,3-sialyltransferase inhibitors in comparison with the parent compound, lithocholic acid.
Jain, Miten. "Cloning of a sialyltransferase gene to analyze surface sialic acid effects on metastasis." 2008. http://proquest.umi.com/pqdweb?did=1588771241&sid=19&Fmt=2&clientId=39334&RQT=309&VName=PQD.
Full textTitle from PDF title page (viewed on Feb. 11, 2009) Available through UMI ProQuest Digital Dissertations. Thesis adviser: Rittenhouse-Olson, Kate Includes bibliographical references.
Jia-YangChen and 陳家揚. "A novel sialyltransferase inhibitor suppresses FAK/paxillin and angiogenesis signaling and cancer metastasis." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/05299722042690676424.
Full textLIAO, CHIH-CHIN, and 廖芝琹. "Homolithocholic acid: A Unique Template for Human Sialyltransferase Inhibitor, Optimized to Suppress Cancer Metastasis." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/kjqurm.
Full text國立中正大學
化學暨生物化學研究所
107
According to cause of death statistics in ministry of health and welfare, cancer is the most lethal disease. Cancer metastasis is the major cause of death in cancer patients. In previous study, overexpression of sialic acids on the tumor cell surface is a hallmark of cancer, and the upregulation of sialyltransferase activity is associated with cancer metastasis. Sialic acids are monosaccharides, found as terminal unit on the cell surface and should be recognized by siglecs on the immune cells. Sialyltransferases are one of glycosyltransferases, and can transfer sialic acids to glycoproteins or glycolipids. Building on these the results, we want to develop the sialyltransferase inhibitor to retard sialic acid transferring to the cell surface leading to. Reduction of cancer cell growth and suppression of cancer metastasis. Here, we synthesized a new and novel skeleton based on homolithocholic acid, lithocholic acid-analogue, where the structure possessed NBD group and different linkers of N3. The IC50 values of homolithocholic acid analogues are around the range of 6-14 μM against N-glycan ST6GAL1. Furthermore, they did not block the sialylation of O-glycan ST3GAL1, suggesting that this series of sialyltransferase inhibitors demonstrate their specific selectivity toward N-Glycan sialylation versus O-Glycan sialylation. In addition, homolithocholic acid analogues had cytotoxicity, when MTT assays tested under the culture condition without serum. The results of anti-migration effects derived from homolithocholic acid analogues indicated that cytotoxicity is the main reason for the action of mechanism.
Chang, Kai-Hsuan, and 張凱宣. "Design and synthesis of sulfur-Cn-linked analogues of CMP-Neu5Ac as potential sialyltransferase inhibitors." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/20817268958058725242.
Full text國立中央大學
化學研究所
91
Part 1 A new system for hydrogenation of haloalkenes is reported. Cu(II)/Fe(III)-mediated selective hydrogenation of steroidal haloalkenes in the presence of hydrazine proves to be a very efficient method for the synthesis of 17b-halosteroids, potential candidates as antiestrogens or androgen receptor-mediated imaging agents. The reaction stereo- specifically affords b-haloalkanes without any concomitant formation of dehalogenation products. Part 2 A new approach to the synthesis of anomeric sulfur analogues of CMP-Neu5Ac containing alkane or arene linkage is described. The procedure involves the high b-stereoselectivity in sialylation of the peracetylated sialic acid methyl ester with mercaptoalkyl (aryl) trichloroacetate, followed by selective deprotection of the trichloroacetyl group to the corresponding hydroxyalkyl and hydroxyaryl thioglycosides. Subsequent O-phosphitylation, oxidation and deprotection led to the isolation of the target compounds.
HSIAO, HSIANG-YIN, and 蕭翔尹. "Linking Inflammation to Tumor antigens Tn/STn : The Roles of Sialyltransferase,COSMC and T-synthase." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/7u73tz.
Full text國防醫學院
牙醫科學研究所
106
Background: The expression of Tn/STn in inflamed tissue had been discussed before. In our previous experiment, we have found the different expression ratio of Tn/STn in experimental periodontitis rat model. The expression of related transferring enzyme including sialyl-transferase, COSMC and T-synthase are investigated in this study with experimental periodontal rat model also in clinical inflamed human gingiva. Also,the possible signaling pathway is investing through LPS treated HGF(human gingival fibroblast) with inhibitors (NF-kB,ERK,JNK,PI3K,PKC). Method: Experimental periodontitis in rats was induced by either silk-ligature around the molars. The expression of sialyl-transferase, COSMC and T-synthase were examined by immunohistochemistry. In human gingiva fibroblasts (hGFs) induced by Porphyromonas gingivalis lipopolysaccharide (P.g. LPS) was treated with cell signaling inhibitors (NF-kB, ERK, JNK,PI3K,PKC).The in vitro expression of sialyl-transferase, COSMC and T-synthase was observed by real-time PCR. Results: In the ligation-induced periodontits rat model ,the expression of sialyltransferase(ST6GalNAc-1) was gradually enhanced during the period of 6 days. However,the expression of COSMC was gradually reduced through time. And T-synthase(C1GalT1) did not show an obvious correlation with ligation time. A strong positive correlation between the immunoreactivity scores of sialyl-transferase and ligature duration, but a negative correlation in COSMC was observed in the gingiva with ligature. In human gingiva samples, we also performed the IHC stainging.The sample are categorized by the potions of inflammatory cells infiltration, and were graded into 3 degrees.The expression of sialyltransferase was found with higher immunoreactivity score in severe inflamed gingiva tissue.Whereas,COSMC showed an opposite expression pattern,as the inflammatory score gain ,the expression of COSMC decreased.The expression of T-synthase did not show obvious change as the inflammatory score change. In vitro, the expression of sialyltransferase in hGFs was up-regulated after LPS treatment, and showed a highest pick after 7 hours. But the expression of COSMC gene was down-regulated,and had the lowest expression after 3 hours.The expression of T-synthase gene did not show obvious change after LPS treatment. Conclusion: The expression of COSMC decreased as the higher of the inflammatory score, which inhibits the activation of T-Synthase, and block the transformation from Tn to T antigen. Whereas, the expression of sialyltransferase which transfer Tn into STn increased as the higher grading of inflammatory score,and explained the higher expression of STn showed in our previous experiment.
Liu, Ming-Xin, and 劉明鑫. "Synthesis and biology of lithocholic acid C4 fluorine-containing sialyltransferase inhitors and benzoxazinone-related fluorescent probes." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/6ua4tv.
Full text國立中央大學
化學學系
103
PartI. According to many researches, abnormal expression of the sialyltransferase has been found to actually connect with many cancers. Therefore, purposes and objectives of this study are making effort to develop effective sialyltransferase inhibitors and regulate the level of sialyltransferase expression.In the thesis, the main structure of our compounds are lithocholic acid. We used high efficient and selective reagent─Selectfluor to add a fluorine atom at the C4 position as modification, and we synthesized fluorinated compound of Lith-O-Asp-NBD as effective anti-cancer compound further.Through MTT assay and Wound healing assay experiment to discuss fluorinated compound’s influence on biologically activity. Interestingly, We found that compounds JO-5b, JO-13a, JO-13b possess potent anti-metastasis ability. PartII. Fluorescent labeling has the advantage of high sensitivity and good selectivity for the use in a wide range of applications. In recent years, novel molecular imaging agents were developed for the use of clinical translation through early lesion detection, molecular targeted therapy, therapeutic monitoring, and the development of new anti-cancer drugs. This action significantly improves diagnosis and therapy in patients with breast cancer metastasis. In this thesis, the main structure of our compounds is benzoxazinone. We modified its functional group to explore the relationship between structure and fluorescent quantum yield of molecular probes. Through analysis of the optical property, we found that Jo-35 has the highest quantum yield (Φ = 0.39) compared to that of others. Intramolecular hydrogen bond was confirmed in the skeleton between oxygen atom and amino group of the benzene ring. Molecular probes drop the fluorescent property if the intramolecular hydrogen bond is absent due to replacement of the amino group by other atom and/or moiety.
Fast, Darren Glenn. "The role of the carbohydrate chains of Ga1 β1-4 G1cNAc α2-6 sialyltransferase for enzyme activity." 1990. http://hdl.handle.net/1993/17041.
Full text陳曼芸. "A Series of Lithocholic Acid Olefin (C11-C12) Analogs as Sialyltransferase Inhibitors : Synthesis and Preliminary Bioactivity Studies." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/36905303055594242770.
Full text國立臺灣師範大學
化學系
100
Aberrant expressions of sialyltransferases (STs) have been reported to positively correlate with many cancers. Therefore, we interest that the development of sialyltransferase inhibitors to modulate sialyltransferase activity and thus alleviate or inhibit physiological processes (e.g., alteration of sialylation in cell surface and sialylation of glycoproteins/glycolipids) caused by sialyltransferases. In this thesis, we initially designed a potential STs’ inhibitor containing an olefin moiety within C-ring (C-11/C-12) of the lithocholic acid as a parent skeleton (compound EY-22). Synthesis of EY-22 was carried out from deoxycholic acid as the starting material. First, both the carboxylic acid at C-24 and the hydroxyl group at C-3 of deoxycholic acid were selectively protected. The protected deoxycholic acid was esterified to yield the required mesylate ester (mesylation of the hydroxyl group at C-12), which was subsequently converted to the protected lithocholic acid with an olefin at C-11 by the method of demesylation. However, demesylation resulted in a mixture compounds with the presence of desired product and steroidal rearrangement compound in the ratio of 1:1. Efficient formation of demesylation product was obtained from modification of reaction conditions. The final product EY-22 was accomplished after removal of the remaining protecting groups. A series of EY-22 based derivative, EY-36、EY-37、EY-39、EY-43、EY-45 and EY-46 (containing Asp, Glu, NBD and 4-nitrobenzoic acid moieties), were successful prepared according to the procedure described previously. Interestingly, effective disruption of wound closure was observed for cells cultured in the presence of derivatives EY-36、EY-39 and EY-45 compared to deoxycholic acid and DX-5. Assays of sialyltransferase inhibition are underway.
Lu, Po-wei, and 呂柏葦. "A Series of Lithocholic Acid Analogs with Coumarin Moieties as Sialyltransferase Inhibitors: Synthesis and Preliminary Bioactivity Studies." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/62548410018180260067.
Full text國立中央大學
化學學系
101
Recently, aberrant sialylation is found in cancer metastasis frequently. Empolying the strategy of the relationships between structure and activity , we use sialyltrasdferase as the molecular target to develop its inhibitors in order to attenuate cancer metastasis. Preparation of Lith-O-Asp-coumarin derivatives was successfully accomplished through the coupling reaction between Lith-O-Asp and coumarin moieties using DMMTM BF4 (4-(4,6-dimethoxy-(1,3,5)triazin-2-yl)-4-methyl-morpholinium tetrafluoroborate) or SOCl2 as the reagents. Extensive SAR studies were performed using different substituted-coumarin analogs under the wound healing and sialyltransferase inhibitor assays. Among the Lith-O-Asp-coumarin derivatives, the hydroxyl-substituent analogs at C-7 position were observed to have the hightest biological activity. It is also noteworthy that the methyl-substituent analogs at C-8 position also display significantly increased biological activity toward both assays.
Chiang, Chi-hsiang, and 江吉祥. "Inhibition of sialylation of beta1 integrin and CXCR4 by a lithocholic acid-based sialyltransferase inhibitor suppresses cancer metastasis." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/x867qa.
Full text國立中山大學
生物醫學研究所
97
Sialyltransferases (STs), which catalyze the sialylation reaction by adding sialic acids to the terminal positions of oligosaccharide of glycoproteins and glycolipids, are over-expressed in cancer cells and associated with cancer metastasis. Until now, ST inhibitors are not applicable for clinical use because of poor cell permeability, although showing potent effect in vitro. In this study, we synthesize a lithocholic acid-based ST inhibitor AL10 and test its anti-metastatic effect. Overexpression of α-2,3-ST is found in highly metastatic A549 and CL1-5 lung cancer cells. Confocal microscopy demonstrates that AL10 is cell permeable and may attenuate total sialylation on cell surface. AL10 has no cytotoxicity but inhibits adhesion, migration, actin polymerization and invasion of A549 and CL1-5 cells in vitro. Inhibition of adhesion and migration by AL10 is associated with reduced sialylation of beta1 integrin. In addition, activation of the beta1 integrin downstream signaling molecule focal adhesion kinase is also attenuated. More importantly, AL10 suppresses lung metastasis in vivo and this effect may be linked with reduced sialylation of the chemokine receptor CXCR4 which has been found to play a critical role in organ-specific metastasis. Serum biochemical assay indicates that AL10 does not affect liver and kidney functions of experimental animals. Taken together, we conclude that AL10 is an effective sialyltransferase inhibitor and exerts anti-metastatic effect in vivo via suppression of sialylation of beta1 integrin and CXCR4.
Harder, Phyllis Gwen. "The discovery and identification of α1 macroglobulin, as an inhibitor of the acute phase reactant, Galβ1→4GlcNAcα2→6 sialyltransferase." 1996. http://hdl.handle.net/1993/19186.
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