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Title: Telomerase : a tumor marker in the peripheral blood of colorectal cancer patients
Author: Khair, Ghaith
ISNI:       0000 0004 2705 8296
Awarding Body: University of Hull
Current Institution: University of Hull
Date of Award: 2008
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Colorectal cancer (CRC) recurrence after curable resection is still high. This fact strongly suggests that the dissemination of circulating tumour cells (CTC) occurs early in the disease process. The first clinical results obtained suggest that CTC detection and enumeration can be used to estimate prognosis and may serve as an early marker to assess anti-tumour activity of a treatment. Telomerase is an RNA-dependant DNA polymerase that synthesises telomeric DNA sequences on the tip of chromosomes and is widely considered to be one of the most abundant and common tumour markers. Telomerase consists of two components; one is the functional RNA (hTR), which acts as a template for telomeric DNA synthesis. The second component is human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, which is concomitantly associated with telomerase activation during carcinogenesis. Its expression in tumours has been very commonly described using reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore hTERT peptides were found to be immunogenic both in vitro and in vivo and hence may be a suitable target for novel cancer immunotherapy. The aim of this study was to detect circulating tumour cells (CTC) in the peripheral blood of CRC patients using telomerase as a tumour marker. Telomerase presence and activity were measured using a combination of approaches including; ELISPOT assay to detect viable CTL that can recognise hTERT peptides in 30 patients with CRC. The results showed that 71% of pre-operative samples and 54% post-operative samples had CTL reaction towards hTERT peptides. The second approach was to study the enzyme activity using TeloTAGGG Telomerase TRAP assay. In this study 97 patients were recruited, and telomerase activity was positive in 11% of patients. Finally the RT-PCR approach used in this thesis failed to detect hTERT mRNA in serum samples as a result of long duration of samples storage. In conclusion: CTC detection in the peripheral blood is a rare event especially in none metastatic disease, There is an urgent need for standardised isolation and analysis techniques to be adopted thus allowing large-scale, appropriately controlled, multicenter trials to be undertaken on the most promising candidate marker.
Supervisor: Not available Sponsor: Not available
Qualification Name: Not available Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine