Glioma genetic profiling: The role of DNA repair and telomerase
type: CreativeWork
description: Brain cancers inflict a disproportional burden of mortality upon sufferers. Due to the difficulties of diagnosis and treatment, survival is low with most patients succumbing to the disease within a year of diagnosis. This has been the imperative factor to underpin some of the molecular mechanisms regulating gliomas and to aid with the development of novel disease biomarkers specifically targeting immortalisation (telomerase). 1[mmortalisation not only requires telomerase but also an imbalance/inactivation of DNA repair functions such as 06 methylguanine-DNAmethyltransferase (MGMI) which is a major obstacle with regards to glioma chemotherapy. The primary focus of this study was to evaluate whether there was an association betweenh TERT and its many subunits: TEPI (human telomerase-associated protein 1), TNKS ( tankyrase), DCKI (dyskerin) and PARPI (poly (ADP-ribose) polymerase1 ) in human glioma compared to normal brain tissues and cell lines. Evidence suggests that hTERT was the only gene that was transcribed in all the glioma cell lines and tissues, while absent in the normal. Thus hTERT may represent a simple but reliable biological marker for distinguishing glioma tissues from normal. The hTERT gene is subjected to its own highly coordinated regulation in normal and cancer cells however, whether hTERT is regulated via methylation/demethylation in glioma is unknown. 5azadC treatment reduced hTERT expression, which resulted in the downregulation of telomerase protein and its activity. However, an inverse correlation between hTERT and MGMT expression was observed after treatment. Evidence shows that hTERT inactivation enhances sensitivity towards some chemotherapeutic agents, thus a combination of 5azadC with various chemotherapeutic agents proved to be more effective than chemotherapy administered on its own. Although 5azadC treatment activates MGMT and subsequently hyposensitises glioma cells toward alkylating agents, specifically TMZ (temozolomide), it may compe…
abstract: Brain cancers inflict a disproportional burden of mortality upon sufferers. Due to the difficulties of diagnosis and treatment, survival is low with most patients succumbing to the disease within a year of diagnosis. This has been the imperative factor to underpin some of the molecular mechanisms regulating gliomas and to aid with the development of novel disease biomarkers specifically targeting immortalisation (telomerase). 1[mmortalisation not only requires telomerase but also an imbalance/inactivation of DNA repair functions such as 06 methylguanine-DNAmethyltransferase (MGMI) which is a major obstacle with regards to glioma chemotherapy. The primary focus of this study was to evaluate whether there was an association betweenh TERT and its many subunits: TEPI (human telomerase-associated protein 1), TNKS ( tankyrase), DCKI (dyskerin) and PARPI (poly (ADP-ribose) polymerase1 ) in human glioma compared to normal brain tissues and cell lines. Evidence suggests that hTERT was the only gene that was transcribed in all the glioma cell lines and tissues, while absent in the normal. Thus hTERT may represent a simple but reliable biological marker for distinguishing glioma tissues from normal. The hTERT gene is subjected to its own highly coordinated regulation in normal and cancer cells however, whether hTERT is regulated via methylation/demethylation in glioma is unknown. 5azadC treatment reduced hTERT expression, which resulted in the downregulation of telomerase protein and its activity. However, an inverse correlation between hTERT and MGMT expression was observed after treatment. Evidence shows that hTERT inactivation enhances sensitivity towards some chemotherapeutic agents, thus a combination of 5azadC with various chemotherapeutic agents proved to be more effective than chemotherapy administered on its own. Although 5azadC treatment activates MGMT and subsequently hyposensitises glioma cells toward alkylating agents, specifically TMZ (temozolomide), it may compe…
author: Patel, Rahima
language: en
keywords: F410 - Forensic science
date published: 2008-04
date modified: 2026-07-24T01:36:23Z
provider: University of Central Lancashire
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Central Lancashire