Dissertations / Theses on the topic 'Medical Biochemistry'
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Woodhouse, Jennifer Ann. "Plutonium pharmacokinetics and blood biochemistry." Thesis, University of Central Lancashire, 1997. http://clok.uclan.ac.uk/20148/.
Full textZhong, Sheng-Ping. "Biodegradation of medical polymers." Thesis, University of Liverpool, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333769.
Full textSchrift, Greta Lynn. "Energetic consequences of structural features and dynamics changes upon nucleotide binding to ribonuclease SA molecular basis for nucleotide binding specificity /." Diss., University of Iowa, 2004. http://ir.uiowa.edu/etd/120.
Full textDriver, Cathryn Helena Stanford. "The development of a radiolabelled macromolecule as a therapeutic agent for the treatment of cancer." Doctoral thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/15540.
Full textViljoen, Katie S. "Integrative genomic analyses of bacterially-associated colorectal cancer." Doctoral thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/15761.
Full textEsau, Luke Emmanuel. "Proliferative and survival pathways in oesophageal cancer." Doctoral thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/12279.
Full textIncludes bibliographical references.
Oesophageal squamous cell carcinoma (OSCC) is the 8th most common cancer worldwide with high incidence in areas that include China, Iran and South Africa. The current treatment available for OSCC does not significantly enhance patient survival. A better understanding of proliferative and survival pathways activated in OSCC could allow identification of more specific therapeutic targets, potentially improving management of OSCC. Cell surface receptors are known to play important roles in relaying signals from the extracellular environment...The aim of this study was to determine the role of EGFR, IGF-1R and CXCR2 in proliferation and survival of OSCC cells.
Gordon, Kerry. "Protein-protein interactions of human somatic angiotensin-converting enzyme." Doctoral thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/10535.
Full textMatejcic, Marco. "Identification of genetic polymorphisms associated with oesophageal squamous cell carcinoma risk in South Africa." Doctoral thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/3139.
Full textIncludes bibliographical references.
Oesophageal squamous cell carcinoma (OSCC) is a complex disease, determined by the interaction of genetic factors with environmental risk factors. In South Africa, OSCC is a major malignancy occurring with high incidence in the Black and Mixed Ancestry populations. Previous studies by our research group have reported that genetic polymorphism of xenobiotic metabolizing enzymes influence greatly the detoxification of tobacco-related carcinogens in vivo, and may therefore have an important role in determining susceptibility to oesophageal cancer.
Parker, Ayesha. "The characterisation of the ectodomain shedding of the low density lipoprotein receptor." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3145.
Full textRonacher, Katharina. "Internalisation of the type II gonadotropin-releasing hormone receptor of marmoset monkey." Doctoral thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/8599.
Full textThe mammalian type II GnRH receptor has a C-terminal tail unlike the mammalian type I GnRH receptor, which uniquely lacks the cytoptasmic C- terminal domain. lnternalisation of a mammalian type ll GnRH receptor has never been investigated, therefore this thesis studies the internalisation pathway of the type ll GnRH receptor. As the C-terminal tail mediates rapid internalisation of many G protein-coupled receptors this research investigates the functional role of the C-terminal tail and intracellular loop in receptor internalisation. The internalisation pathway of the type ll GnRH receptor in COS-1 cells was investigated by co expressing dominant negative mutants and wild- type constructs of G protein-coupled receptor kinases (GRKs), dynamin-1 and β-arrestin 1 and 2 with the type II GnRH receptor. The results show that internatisation of the receptor requires GRK 2 and dynamin but does not require β-arrestin 1 and 2. Furthermore, inhibitors to both the caveolae pathway as well as the clathrin coated vesicle endocytosis abolished receptor internalisation indicating that both structures are involved in internalisation of the receptor. Even though in COS-1 cells the type ll GnRH receptor internatises in a β-arrestin independent manner, internalisation of this receptor can be enhanced by over-expression of wild type β-arrestin. This indicates that the type ll GnRH receptor is able to utilise a β-arrestin mediated internaltsation pathway if high levels of β-arrestin are present in the cell. The mammalian type ll GnRH receptor internalises with enhanced rate and extent compared to the tail-less human type I GHRH receptor. The role of the C-terminal tail of the type ll GnRH receptor in internalisation was investigated by measuring internalisation of C-terminally truncated mutants. It was found that the region between Gly 343 and Ser 335 within the C-terminal domain is important for receptor internalisation. Substitution of putative phosphorylation sites within this region revealed that Ser 338 and Ser 339 are critical for rapid receptor internalisation. Furthermore a serine residue in intracellular loop three (Ser 251) was shown to play a role in signalling as well as in internalisation. Since dominant negative GRK 2 could not inhibit internalisation of a mutant lacking all three serine residues, but could reduce internalisation of the wild-type receptor, we suggest that Ser 251, 338 and 339 are target of phosphorylation by GRK. However these phosphorylation sites as well as the C-terminal tail are not necessary for β-arrestin dependent internalisation. Taken together this thesis elucidates the internalisation pathway of a mammalian type lI GnRH receptor and identified residues within the C-terminal tail and intracellular loop three that are critical for rapid internalisation.
Sutherland, Jason Robert. "The role of seminal plasma in cervical carcinoma." Doctoral thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/10617.
Full textCervical cancer is a worldwide public health problem with in excess of 370,000 cases being reported each year. It is the leading cause of death from cancer among women in the developing world where 80% of cases occur. Human papilloma virus (HPV) has been identified as the main causative factor linked with the development and progression of cancer of the cervix, although other factors are known to exist and include genital warts, consenting to sex at an early age, smoking, long term use of contraceptive pills and multiple sexual partners.
Coetsee, Marla Catherine. "Ligand-induced selective signalling at the gonadotrophin releasing hormone receptor." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3123.
Full textIncludes bibliographical references (p. 179-202).
The pituitary gonadotrophin releasing hormone (GnRH) receptor regulates reproduction by activation of Gq/11 proteins. In contrast, GnRH receptors at extrapituitary sites induce anti-proliferative effects that do not correlate with Gq/11 activation. We propose that the two endogenous ligands, GnRH I and GnRH II, and certain antagonists selectively activate distinct signalling pathways by stabilisation of distinct active conformations of the GnRH receptor, a concept termed ligand-induced selective signalling (LiSS). This dissertation has investigated LiSS at the GnRH receptor using several approaches. The sequences of GnRH I and II differ in positions 5, 7 and 8. I investigated the interaction of position 5 of GnRH I and GnRH II with Tyr6.58 of the receptor. Compared with the Leu and Ala mutants, the Tyr6.58Phe mutant had higher affinity for native GnRHs, but not Ala5-substituted GnRHs, suggesting that Tyr5 of GnRH I and His5 of GnRH II interact with Tyr6.58 by aromatic interactions. Our molecular models show that GnRHs interact with distinct rotamer conformations of Tyr6.58. This is supported by the Tyr6.58Leu receptor, which makes compensatory interactions that improve binding affinity and receptor activation for GnRH II, but not GnRH I, compared with the Tyr6.58Ala receptor. Together these results suggest that GnRHs stabilise distinct receptor active conformations. To identify the most proximal signalling proteins that mediate GnRH receptordependent anti-proliferative effects, I established a range of [35S]GTPS binding assays. I confirmed that the GnRH receptor activates Gq/11, but in contrast to previous proposals, my results show that the GnRH receptor cannot directly activate Gi. I subsequently identified a novel GnRH receptor signalling partner, the SH2 domaincontaining phosphatase 2 (SHP-2). I propose that SHP-2 mediates the antiproliferative effects of the receptor. I show that the SHP-2 pathway is activated independently of Gq/11 and suggest that signalling occurs by a direct interaction of SHP-2 and src with the GnRH receptor. Furthermore, this pathway is activated by a classical Gq/11 antagonist or by Gq/11-uncoupled GnRH receptor mutants. My results provide convincing evidence supporting LiSS at the GnRH receptor and may facilitate development of therapeutics with increased signalling specificity at this receptor.
Abera, Aron Berhanie. "Characterization of signalling cross-talk between the EP2 and FP receptors in endometrial epithelial cells." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3159.
Full textMaranyane, Hapiloe 'Mabaruti. "Phosphoglucomutase 1 (PGM1) expression and regulation in cancer cells." Doctoral thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/16694.
Full textCancer cells undergo metabolism that is significantly different to normal cells, with an increased dependence on glucose metabolism as a hallmark of most cancers. Changes in global gene expression patterns are the major driving forces behind cancer progression. These changes trigger events that result in the dysregulation of key enzymes associated with metabolic processes. Gene expression profiling studies done previously in our laboratory identified a group of genes involved in glucose metabolism to be differentially expressed in cervical cancer patient material. Of these, Phosphoglucomutase 1 (PGM1) was identified to have elevated expression in the cancer group. PGM1 is a phosphotransferase that catalyses the reversible conversion of the glycogen breakdown product, glucose-1-phosphate into glucose-6-phosphate, a substrate for glycolysis and the pentose phosphate pathway. This places PGM1 at a critical traffic point of glucose metabolism. In this study we investigated the expression, regulation and biological significance of PGM1 in cancer cells. Our results showed that PGM1 expression was elevated in cervical cancer tissue compared to normal. Its expression was also high in cervical, oesophageal and breast cancer cell lines. Elevated PGM1 expression associated with high promoter activity as well as with E2F and HIF1α activities in cancer cells. PGM1 expression at the level of mRNA, protein and promoter activation was significantly stimulated in hypoxia mimicking conditions. Our data showed that PGM1 expression in cancer cells was required mainly for glycogen accumulation with marginal changes on glycolysis and the pentose phosphate pathway. While PGM1 expression did not appear necessary for cancer cell proliferation in normoxia and nutrient sufficiency, our data shows that it is required for proliferation under conditions of glucose deprivation combined with hypoxia. Together these findings suggest that PGM1 expression is altered in cancer cells, that it is required for aberrant glycogen expression in cancer cells and that it has a role in cancer biology during severe stress conditions.
Teng, Huajian. "Identification of signalling pathways regulating TBX2 gene expression and its target genes." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3151.
Full textIncludes bibliographical references (leaves 83-97).
Members of the T-box family of transcription factors provide an important link between development and cancer. T-box factors play critical roles in embryonic development and results from recent studies suggest that they function in controlling cell cycle progression and also in the genesis of cancer. Importantly, the T-box factors Tbx2 and Tbx3 are overexpressed in several cancers including melanoma, small cell lung carcinoma, breast, pancreatic, liver and bladder cancers and can suppress senescence, a cellular process which serves as a barrier to cancer development. However, the precise role of most T-box factors is poorly defined, in part, because their target genes are still poorly characterised and very little is known of the signalling pathways that regulate their expression and activity. The broad aim of this study was therefore to contribute towards the identification of Tbx2 target genes as well as to identify signalling pathways that regulate TBX2 expression. The specific aims were thus to (1) investigate the regulation of type1 collagen gene expression by Tbx2; (2) clone the human TBX2 regulatory region and to identify cis-acting elements involved in the basal transcription of the TBX2 gene and (3) investigate the regulation of TBX2 gene expression by signalling pathways.
Peters, Julian S. "Comprehensive proteomic profiling of clinically relevant strains of Mycobacterium tuberculosis." Doctoral thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/12959.
Full textTuberculosis is an airborne infectious disease caused by the bacillus known as Mycobacterium tuberculosis. Despite limited genetic variability, Mycobacterium tuberculosis strains exhibit vast discrepancies in phenotypic presentation in terms of virulence, elicited immune response and transmissibility. This study aims to use Mass Spectrometry (MS) tools to quantitatively and qualitatively investigate the total proteome expressed by various epidemiologically significant strains within the Mycobacterium tuberculosis complex (MTBC) as well as a clinically relevant non-tuberculous Mycobacteria (NTM) strain when cultured in vitro. We aim to use the experimental data obtained using discovery mass spectrometry to identify candidate proteins to use in the design of multiple reaction monitoring (MRM) MS experiments for targeted biomarker validation in patient derived biological samples such as sputum. Liquid chromatography mass spectrometry (LC MS/MS) and data capture were carried out using the LTQ Orbitrap Velos. 1D LC was carried out on gel fractionated samples to increase proteome coverage. This allowed a significant increase in the number of protein identifications of up to 80% proteome coverage per strain. Comparative analysis of the datasets was carried out to identify and define the core-proteome expressed across all strains as well as to identify differentially expressed proteins amongst the strains.
Chang, Cheng-Fu. "Structure-function and regulation studies of angiotensin-converting enzyme 2." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3122.
Full textDzobo, Kevin. "Matrix-mediated regulation of type 1 collagen synthesis and degradation in cultured fibroblasts." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3125.
Full textIncludes bibliographical references (leaves 122-157).
Stromal cells and the extracellular matrix (ECM) components provide the microenvironment that is pivotal for cell growth, motility, attachment and differentiation. Fibroblasts are some of the cells responsible for the synthesis of most of the extracellular matrix proteins. Type I collagen is the most abundant extracellular matrix protein in the human body and is found in tissues requiring high tensile strength. In this study we investigated the effect of a pre-formed fibroblast-derived extracellular matrix on the expression of type I collagen and associated matrix metalloproteinases in fibroblasts.
Kröger, Wendy Lee. "A molecular basis for the C-domain selectivity of angiotensin-converting enzyme." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3134.
Full textMwapagha, Lamech Malagho. "The role of viral sequences in genetic aberrations and malignant transformation." Doctoral thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/12870.
Full textCancer is a leading cause of death worldwide and viral infections such as HBV/HCV and HPV have been known to be responsible for up to 20% of cancers in low- and middle-income countries. Approximately 500,000 of these deaths are due to oesophageal squamous cell carcinoma (OSSC) alone, one of the major cancers in Eastern and Southern Africa, Latin America and Asia. Previous studies have shown HPV DNA to be integrated in nearly 40% of oesophageal tumours whereas it was present in only 3% of normal healthy asymptomatic individuals, implicating it as a possible risk factor. The aim of this study was to compare the roles and effects of the E6 gene from the low risk HPV11 and high risk HPV18 on the cellular gene expression profile in order to identify genes required for the initiation of cellular transformation and also to identify genomic alterations associated with oesophageal squamous cell carcinoma. Cancer is a leading cause of death worldwide and viral infections such as HBV/HCV and HPV have been known to be responsible for up to 20% of cancers in low- and middle-income countries. Approximately 500,000 of these deaths are due to oesophageal squamous cell carcinoma (OSSC) alone, one of the major cancers in Eastern and Southern Africa, Latin America and Asia. Previous studies have shown HPV DNA to be integrated in nearly 40% of oesophageal tumours whereas it was present in only 3% of normal healthy asymptomatic individuals, implicating it as a possible risk factor. The aim of this study was to compare the roles and effects of the E6 gene from the low risk HPV11 and high risk HPV18 on the cellular gene expression profile in order to identify genes required for the initiation of cellular transformation and also to identify genomic alterations associated with oesophageal squamous cell carcinoma.
Larmuth, Kate Morgan. "Angiotensin-converting enzyme cleavage of the Alzheimer's beta-amyloid peptide." Doctoral thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/16561.
Full textAngiotensin-1 converting enzyme (ACE) is a zinc metallopeptidase that consists of two homologous catalytic domains (N and C) with different substrate specificities. ACE is a central component of the intrinsic brain renin angiotensin-aldosterone system (BRAAS), well renowned as the regulator of blood pressure. The BRAAS has alternate functions that extend beyond fluid and blood pressure homeostasis into areas such as neurological function. As a result, it is implicated in many neurodegenerative diseases including Alzheimer's disease (AD). ACE's specific mechanistic role in AD is not entirely clear and is somewhat controversial. However, it has been shown that ACE hydrolyses the amyloid beta (Aβ) peptide, the putative causative agent of AD. This study aimed to investigate the molecular basis of ACE hydrolysis of Aβ by determining : 1) the kinetic parameters of five different forms of human ACE with various N-terminal amyloid beta (Aβ) substrates; 2) the specific active site determinants of Aβ-domain selectivity; and 3) the high-resolution crystal structures of the N-domain of ACE in complex with Aβ(1-16), Aβ(10-16), Aβ(4-10), the FRET Aβ(4-10)Y and Aβ(35-42) peptides. For the physiological Aβ(1-16) peptide, a novel ACE cleavage site was found at His14/Gln15. Furthermore, Aβ(1-16 ) was preferentially cleaved by the truncated N-domain; however, the presence of an inactive C-domain in full-length ACE greatly reduced enzyme activity and affected domain-selectivity. Two fluorogenic substrates, designed specifically to assess ACE's mechanism of Aβ hydrolysis Aβ(4-10)Q and Aβ(4-10)Y, underwent endoproteolytic cleavage at the Asp7/Ser8 bond. The Aβ(4-10)Q peptide was a poor substrate of ACE but was N-selective, with a selectivity driven largely by interactions with the domain-specific residues of the S2 and S2' pockets. The selectivity of the S2' residues were confirmed with a similar, more physiological, fluorogenic Aβ(4-10)Y peptide. This work provides further understanding towards the substrate determinants of N-selectivity, highlighting the importance of the S2' Ser357. ACE C-domain hydrolysed Aβ(4-10)Y with modest efficiency compared to the other substrates, where hydrolysis under the same conditions did not occur. Moreover, Aβ(4-10)Y also displayed N-domain selectivity. In contrast to Aβ(1-16) and Aβ(410)Q, both sACE and the double C-domain (CC-sACE) construct showed positive domain cooperativity towards Aβ(4-10)Y. The high-resolution crystal structures of the N-domain in complex with five Aβ peptide fragments provided an overlapping, conserved, molecular mechanism of peptide binding and evidence of the enzyme's broad exoprotease activity. In addition to the kinetic and structural studies, ACE's signalling response to the N-selective Aβ(1-16) and Aβ(1-42) was investigated using immunodetection and mass spectrometry. Similar to the ACE inhibitor lisinopril, the Aβ peptides elicited ACE signalling by phosphorylation of the cytoplasmic Ser1270 residue and JNK activation. The signalling response of ACE was coupled to increased ACE activity an d expression on treatment with Aβ(1-42). These studies allowed us to rationalise the increased ACE activity and expression found in AD, may arise through direct interactions with Aβ. This work provides a kinetic, structural and mechanistic understanding of the selective cleavage of Aβ by the N and C catalytic sites of ACE. Due to the broad substrate specificity of the two domains of ACE, and the overarching N- selectivity of Aβ hydrolysis, these findings provide rationale for further in vivo pharmacological studies on the mechanism of action C- domain-selective inhibitors, in the context of AD.
Chi, Ru-pin Alicia. "Investigating a novel small molecule inhibitor of nuclear import as an anti-cancer approach." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/22896.
Full textWoodman, Zenda. "Characterisation of the ectodomain shedding of angiotensin-converting enzyme." Doctoral thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/3156.
Full textZemanay, Widaad. "Altered protein expression patterns in oesophageal cancer." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3157.
Full textIncludes bibliographical references (leaves 125-143).
Oesophageal squamous cell carcinoma presents a significant health burden in South Africa. It is one of the most common causes of cancer-related mortality of South African black males, as a result of its asymptomatic progression leading to late diagnosis and poor prognosis. The aim of this study was to identify membrane or membrane-associated proteins that are expressed at different levels in oesophageal tumour tissue when compared to normal tissue. The identification of such proteins would be an important step towards the development of better diagnostic and therapeutic strategies for this disease. Two proteomic approaches, were employed to identify differentially expressed proteins.
Douglas, Ross Gavin. "Significance of active site residues in the n-domain selectivity of angiotensin-converting enzyme." Doctoral thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/11786.
Full textDuarte, Jessica Da Gama. "Proteomic studies on patient responses to chemotherapy, radiotherapy and immunotherapy in cancers." Doctoral thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/20261.
Full textEbrahim, Roshan. "Biogenesis of lysosomes in macrophages : intracellular pathway of lysosomal membrane protein to lysosomes." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3126.
Full textVan, der Watt Pauline Janet. "Expression and regulation of the nuclear transport proteins, Crm1 and Kpnß1, in cervical cancer and transformed cells." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3152.
Full textFaurholm, Bjarne. "Gene structure, transcripts and transcriptional regulation of primate type II gonadotropin-releasing hormone receptors." Doctoral thesis, University of Cape Town, 2004. http://hdl.handle.net/11427/3127.
Full textRose, Beverley Ann. "The regulation of type I collagen gene expression in stromal fibroblast by breast tumour cells." Doctoral thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/10861.
Full textIncludes bibliographical references (leaves 110-135).
Recent studies have revealed that interactions between tumour cells and the surrounding stroma play an important role in facilitating tumour growth and invasion. Stromal fibroblasts produce most of the extracellular matrix (ECM) components found in the stroma, including type I collagen. Previous in vivo studies in our laboratory have shown that type I collagen mRNA levels are decreased in stage II and III breast tumour tissue compared to adjacent normal tissue.
Anthony, Colin Scott. "The importance of N-linked glycosylation on the N-domain of angiotensin-I converting enzyme." Doctoral thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/10051.
Full textLokanga, Rachel Adihe. "Somatic expansion of premutation alleles and the role of the mismatch repair and base excision repair proteins on repeat expansion in a mouse model of the fragile X-related disorders." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/20853.
Full textWatermeyer, Jean Margaret. "Structural determinants of the domain-selectivity of novel inhibitors of human testis angiotensin-converting enzyme." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3154.
Full textSales, Kurt Jason. "Expression and functional role of cyclooxygenase enzymes in cervical carcinoma." Doctoral thesis, University of Cape Town, 2001. http://hdl.handle.net/11427/3149.
Full textCervical cancer is considered an important clinical problem in sub-Saharan Africa. Recent studies have suggested that epithelial tumors may be regulated by cyclooxygenase enzyme products. The purpose of this thesis was to determine the expression, localisation and possible functional role of cyclooxygenase enzymes in cervical carcinomas. The initial aim of the study was to determine whether cyclooxygenase-1 and cyclooxygenase-2 expession and prostglandin E₂ synthesis are up-regulated in cervical cancers. Real-time quantitative reverse-transcriptase polymerase chain reaction and Western blot analysis confirmed cyclooxygenase-1 and cyclooxygenase-2 ribonucleic acid and protein expression in all cases of squamous cell carcinoma and adenocarcinoma investigated. In contrast, minimal expression of cyclooxygenase-1 or cyclooxygenase-2 was detected in histologically normal cervix. Immunohistochemical analyses localised the site of cyclooxygenase-1 and cyclooxygenase-2 expression and prostaglandin E₂ synthesis to neoplastic epithelial cells of all squamous cell carcinomas and adenocarcinomas studied.
Siyo, Vuyolwethu Penelope. "Molecular mechanisms involved in the anticancer activity of BISPMB in oesophageal cancer cells." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/20422.
Full textLi, Dong-Ping. "Genetic polymorphisms in the drug metabolizing genes and their roles in the development of oesophageal cancer." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3137.
Full textAlthough the incidence and mortality due to the oesophageal squamous cell carcinoma (OSCC) in Black South Africans is extremely high, very little is known about the aetiology and molecular biology of the disease. In order to make a contribution to the understanding to the causes of this disease we investigated the role of the polymorphisms in the genes coding for the cytochrome P450 (CYP1A1, CYP1A2, CYP1B1, CYP2E1), sulphotransferase 1A1 (SULT1A1), glutathione S-transferases (GSTT1. GSTM1 and GSTP1) alcohol dehydrogenase (ADH2 and ADH3) and aldehyde dehydrogenase (ALDH2) because the products of these genes are involved in the metabolism or biotransformation of harmful compounds.
Shunmoogam-Gounden, Nelusha. "An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer." Doctoral thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/13237.
Full textCurrent chemotherapies for oesophageal cancer display poor efficacy and tolerability, highlighting an unmet need for novel chemotherapeutic agents. Artemisinin derivatives, currently used to treat malaria, were recently shown to possess potent anticancer activity. This study investigated the potential of two first generation artemisinin derivatives (artesunate and dihydroartemisinin), together with novel artemisinin hybrid compounds, as cancer chemotherapeutic agents and explored the mechanism of action in oesophageal cancer. Artesunate and dihydroartemisinin including seventeen other artemisinin derivatives were screened against oesophageal cancer cells using the 3 - [4,5-dimethylthiazol-2 -yl]-2,5 - diphenyltetrazolium bromide (MTT) assay and GraphPad Prism Software to calculate IC 50 (50% inhibitory concentration) values. Novel halogenated artemisinin - isatin hybrid compounds displayed the best activity against oesophageal cancer cells, and were more potent than artesunate and dihydroartemisinin in a small panel of oesophageal, breast and cervical cancer cell lines tested. The novel derivatives induced a G0/ G1 cell cycle arrest whilst the parental compounds induced a G2/ M block of the cell cycle, using flow cytometry. This suggested a different mechanism of action for the novel compounds. Dihydroartemisinin and the most active novel hybrid, EXP57EA, were investigated to understand their molecular mechanisms of action in oesophageal cancer.
Moorad, Razia. "Computer-aided drug design and the biological evaluation of anti-cancer drugs." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/20715.
Full textStrydom, Erin. "Investigating Karyopherin B1: small molecule interactions for cancer therapy." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/22897.
Full textFromme, Bernhard Johannes. "The role of extracellular loop three of the human gonadotropin releasing hormone receptor in ligand selectivity." Doctoral thesis, University of Cape Town, 2001. http://hdl.handle.net/11427/3129.
Full textThe hypothalamic neuropeptide, gonadotropin releasing hormone (GnRH) perferentially inteacts with GnRH type I receptors on the gonadotropes in the anterior pituitary. Activation of the GnRH receptor is required for the biosynthesis and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which regulate reproductive function. Multiple forms of GnRH are present in most vertebrate species and are thought to have physiological functions in addition to regulating pituitary hormone release. The mammalian type I GnRH receptor is proposed to discriminate between endogenous forms of GnRH (King and Millar, 1995). In this thesis the mechanism of the GnRH selectivity by a mammalian type I GnRH receptor is examined at molecular level and previous hypotheses are re-evaluated.
Folefoc, Asongna Theresia Forkem. "Functional consequences of South African mutations of the HIV-1 co-receptor, CCR5." Doctoral thesis, University of Cape Town, 2007. http://hdl.handle.net/11427/3128.
Full textFour mutations of the CCR5 receptor have been identified in the South African population, but the effects of these mutations on CCR5 function and HIV infection are unknown. We have used in vitro methods to assess the ffect of the mutations, Asp2Val, Leu107Phe, Arg225Gln and Arg225stop, on CCR5 interactions with chemokine ligands and HIV.
Matsha, Tandi Edith. "Human Papillomaviruses in oesophageal cancer." Doctoral thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/3140.
Full textBracher, Jacqueline Claire. "Expression and regulation of N-Myc Downstream- Regulated gene 1 in squamous cell carcinoma of the oesphagus." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3120.
Full textWei, Wei. "Functional analysis of N-MYC downstream regulated gene 1 (NDRG1) in Oesophageal squamous cell carcinoma." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3155.
Full textWhibley, Catherine Evelyn. "South African marine compounds as anticancer agents." Doctoral thesis, University of Cape Town, 2006. http://hdl.handle.net/11427/8393.
Full textOesophageal cancer is the most common cause of cancer related deaths among black males in South Africa. Currently there are very limited treatment options, and patients have a very poor prognosis, due in part to the late stage at which this cancer is usually detected. In this thesis we describe the establishment of a screening assay using an oesophageal cancer cell line as a model. It was our hope that this screen would allow us to identify compounds which have activity against oesophageal cancer, that could be used as lead agents for further development of chemotherapeutic agents. Once our screen was established, we tested a wide range of extracts from southern African marine organisms, supplied by our collaborators from Rhodes University, South Africa. The marine environment represents a rich, untapped repository of novel and interesting compounds, and through our collaboration we had access to a wide range of marine-derived extracts and compounds. During the course of this project we provided screening data to assist in activity-directed fractionation from five active marine extracts, giving rise to 15 compounds of varying activity. These included several groups of novel active compounds such as the makaluvic acids from the sponge Strongylodesma aliwaliensis and the malonganenones from the octocoral Leptogorgia gi/christii. The identification of a number of novel, active compounds through our screening program highlights the potential of marine organisms from the southern African coast as a source of novel drug leads.
Phillips, Pumza Samantha. "The role of Gai in the Gonadotropin-releasing hormone (GnRH) receptor inhibition of cell proliferation." Master's thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/11787.
Full textIncludes bibliographical references (leaves 72-78).
The activation of Gonadotropin-releasing hormone receptor (GnRHR) by the GnRH ligand has been shown to mediate antiproliferative effects in extra-pituitary cells and in reproductive cancer cell lines. The GnRHR couples to Gαq in pituitary gonadotropes. However, the GnRHR expressed in reproductive cancer cell lines is thought to couple to Gαi. Recent evidence also suggests that the antiproliferative effects may be mediated via Gαq in these cells. Therefore our study involved determining the role of Gαi in the antiproliferative effects mediated by the GnRHR. The results suggest that the Gαi pathway could play a role in mediating the antiproliferative effects of GnRH.
Nair, Omesan. "Functional effects of cytochrome P450 variants on drug metabolism and adverse drug reactions: developing and extending high throughput P450 protein technology platforms." Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/13238.
Full textCytochrome P450 (CYPs) are a superfamily of heme containing enzymes that catalyse a diverse range of biological reactions. They are responsible for over 80% of primary metabolism of currently available drugs and are therefore central to its medical importance. Investigating the effects of these enzymes on drugs by metabolite detection and kinetic studies is a step forward to the vision of personalised medicine. The enzyme family is known to be associated with the development of adverse drug reactions which are usually only discovered in late stages of drug development, therefore screening for potential adverse drug reactions earlier on would aid minimising such adverse events occurring. There is therefore a need to analyse the interaction profile of new drugs with CYPs in a cost effective and high throughput manner for early stage screening, since drug discovery efforts tend to utilise large compound libraries. Recently, a novel functional CYP microarray has been developed in the Blackburn laboratory at UCT to enable label-dependent analysis of metabolism of substrates by the major CYP3A4 isoform in a high throughput manner. This thesis describes efforts involved in expanding the functional CYP microarray format to the other major CYP isoforms namely, CYP2C9 and CYP2D6 and developing a new immobilisation-free technology with label-free mass spectrometric identification and quantitation of metabolites formed. The goals of expansion of functional CYP microarrays were achieved by using microarray or confocal fluorescence scanning in conjunction with atomic force microscopy to more accurately quantitate active CYP3A4, CYP2C9 and CYP2D6 protein levels for catalytic substrate-dependent turnover rates. Finally the label- and immobilisation-free CYP technology was evaluated using probe substrates and a complex drug, rifampicin. These two platforms are primed to be a useful tool in pre-clinical drug screening for use in the drug discovery field by the academic, pharmaceutical and biotechnology industries.
Ujma, Sylvia. "The role of surfaceant protein A in immunity to HPV16 pseudovirus infection." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29526.
Full textMayevu, Ntateko Merriam Immogen. "The contribution of His7.36(305) of the GnRH receptor to ligand binding and receptor activation." Master's thesis, University of Cape Town, 2004. http://hdl.handle.net/11427/3141.
Full textThe current study was perfonned to give insights into the role of individual amino acid residues of both the GnRH receptor and the GnRH ligand in receptor function. A His7.36(3o5) residue on transmembrane helix seven of the GnRH receptor was investigated for its contribution to the overall function of the receptor.
Wagiet, Mateen. "Modulating ADAM-10 activity and expression in cervical and oesophageal cancer cells." Master's thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/22732.
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