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DC Field | Value | Language |
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dc.date.accessioned | 2020-01-08T11:19:36Z | - |
dc.date.available | 2020-01-08T11:19:36Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Refalo M. (2017). Endometrial cancer and its response to treatment and the quality of life after treatment (Master's dissertation). | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/50206 | - |
dc.description | M.SC.REPRODUCTIVE HEALTH | en_GB |
dc.description.abstract | The pituitary gland is integral in hormone secretion and regulation. Pituitary adenomas (PA) are the most frequent pituitary neoplasms, however molecular pathogenesis is largely unknown. The AHR is a ligand-activated transcription factor that regulates expression of various genes that mediate cellular response against xenobiotics, and is also involved in other physiological and pathological processes. Several AHR variants, particularly the Arg554Lys (rs2066853) and Val570Ile (rs4986826) have raised interest due to their location in ex on 10 of the AHR gene, which codes for the transactivation domain (TAD). The TAD domain plays a critical role in mediating transactivation activity of dioxin-responsive genes via recruitment of co-activators, hence suggesting that SNPs occurring within this region should interfere with AHR target gene expression. However, their exact functional role has not been established yet due to inconsistent results from different studies. Studies suggest that these mutations increase risk of developing P A, however functional analysis of these SNPs in a pituitary setting has never been carried out. In this research study, the two AHR variants were introduced in the wildtype AHR expression plasmid by site-directed mutagenesis (SDM). The wildtype and mutants AHR were introduced in GH3 cells by magnetofaction and were treated with 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Functional analysis of transfected GH3 cells treated with TCDD was carried out using luciferase assays and real-time PCR to detect and quantify AHR-transcriptional activity. Cell proliferation of transfected and TCDD treated GH3 cells was measured using the MTT assay. In the absence and presence of low TCDD concentration, over-expression of AHR and AHR mutants did not affect the proliferative capacity of GH3 cells. Gene expression analysis and quantification analysis of AHR-target genes suggested that these AHR mutants might interfere with AHR target gene expression. However further studies are required to elucidate the precise mechanisms. Genotyping of the Arg554Lys in patients with PA gave a MAF of 3% vs 0% in neonatal controls using allele specific PCR. | en_GB |
dc.language.iso | en | en_GB |
dc.rights | info:eu-repo/semantics/restrictedAccess | en_GB |
dc.subject | Therapeutics | en_GB |
dc.subject | Endometrium -- Cancer -- Treatment | en_GB |
dc.subject | Cancer -- Patients -- Malta | en_GB |
dc.subject | Quality of Life | en_GB |
dc.title | Endometrial cancer and its response to treatment and the quality of life after treatment. | en_GB |
dc.type | masterThesis | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder | en_GB |
dc.publisher.institution | University of Malta | en_GB |
dc.publisher.department | Faculty of Medicine and Surgery. | en_GB |
dc.contributor.supervisor | Vella, Alberto | - |
dc.description.reviewed | N/A | en_GB |
dc.contributor.creator | Refalo, Mario | - |
Appears in Collections: | Dissertations - FacHSc - 2017 Dissertations - FacM&S - 2017 |
Files in This Item:
File | Description | Size | Format | |
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Refalo_Mario_Endometrial Cancer and its response to treatment and quality of life after treatment.pdf Restricted Access | 15.7 MB | Adobe PDF | View/Open Request a copy |
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