Cranfield University at Silsoe (1975-2008)

Permanent URI for this community

https://dspace.lib.cranfield.ac.uk/handle/1826/6

Browse

Browsing Cranfield University at Silsoe (1975-2008) by Supervisor "Bailey, Tracey A."

Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    An investigation into minichromosomal maintenance proteins (MCMs) for the diagnosis of prostate cancer, as a possible alternative to prostate specific antigen (PSA)
    (Cranfield University, 2005-02) Watkins, Jane Louise; Bailey, Tracey A.; O'Donnell, J. O.; Woodman, Anthony C.
    The current strategy for the diagnosis of prostate cancer includes serum prostate specific antigen (PSA) measurement. There is however debate into its specificity and sensitivity, so new diagnostic markers are under investigation. Minichromosomal maintenance proteins (MCMs) are potential markers for the diagnosis of neoplasia, as they are involved in cellular replication. The aim of this study is to assess MCM2, 5 and 7 as new diagnostic markers for prostate cancer, to compare the clinical usefulness of PSA and to develop a less invasive technique for diagnosis. PSA specificity was investigated in several human cellular lines, and a clinical study was performed to assess expression in prostatic tissue and blood serum. MCM2, 5 and 7 was investigated by translational and transcriptional means in two prostate cell lines PNT1A and PC-3. In addition, a clinical study was performed to assess the expression of MCM2, 5 and 7 in prostate tissue, urine and blood The results suggest that PSA is not prostate specific, as it is synthesised and secreted by several non-prostatic cell lines. In addition PSA testing does not conclusively indicate neoplastic tissue and serum testing only has 63% sensitivity and 60% specificity in accurately identifying prostate cancer. The in vitro results suggest that the PC-3 cells express less MCM2, 5 and 7 on both the protein and mRNA level compared to the PNT1A cells, suggesting that MCM2, 5 and 7 maybe performing a bigger role than just replication of DNA. The tissue results indicate that there is an increase in MCM2, 5 and 7 epithelial nuclei staining for neoplastic condition compared to BPH. While the clinical study on urine sediment indicates increased MCM2, 5 and 7 staining in prostatic neoplasia compared to BPH and the transcriptional study on MCM5 can identify neoplastic tissue from BPH as 11/12 cancerous patients expressed MCM5 compared to only 3/23 BPH patients. Finally the transcriptional study on the blood samples is inconclusive and need to be repeated These results suggest that serum PSA testing is not ideal for the diagnosis of prostate cancer, that MCM2, 5 and 7 appear to have potential as new diagnostic markers and may aid the histopathologist to allocate Gleason score. Also the MCMs may have potential in the development of a less invasive technique through the use of urine sediment.
  • Thumbnail Image
    ItemOpen Access
    Investigations of a possible link between age-related macular degeneration and atherosclerosis
    (Cranfield University, 2005-08) Sivaprasad, Sobha; Bailey, Tracey A.; Chong, Victor N. H.; Woodman, Anthony C.
    Increasing epidemiological evidence suggests a link between atherosclerosis and age-related macular degeneration (AMD). There are two main hypotheses that explain the link. One hypothesis is that AMD and atherosclerosis are tissue responses to injury. The ‘Response to Injury’ hypothesis defined as ‘abnormal reparative response to chronic, recurrent injurious stimuli’ speculates that AMD and atherosclerosis may be cellular effects of chronic or repetitive risk factors. The second hypothesis suggests that AMD is secondary to vascular insufficiency caused by atherosclerosis. The research in this thesis is an attempt to test these hypotheses to better understand the correlation of AMD and atherosclerosis. Both basic and clinical science approaches are employed. Part one focuses on the role of extracellular matrix (ECM) proteins in the pathogenesis of AMD. Both serum elastin derived peptides (S-EDP) and matrix metalloproteinases (MMP-2 and MMP-9) are raised in subjects with atherosclerosis. The circulating levels of these matrix components were tested in patients with varying degree of severity of AMD and compared to age-matched controls. Both S-EDP and MMP-9 were found to be significantly raised in patients with AMD, while MMP-2 did not correlate with it. S-EDP is elevated in abdominal aortic aneurysm (AAA), a manifestation of atherosclerosis. Since S-EDP correlates with size of both AAA and severity of AMD, this research looked at a possible association between the two diseases but found no significant correlation. The second part of this thesis investigates whether chronic inflammation may explain the co-existence of the two diseases. With the recent finding that Complement Factor H (CFH) is related to AMD, this study focused on the role of complement activation in AMD, speculating that the final common pathway of both diseases may be chronic inflammation. Increased systemic complement activation was found in neovascular AMD, as assessed by the measurement of C3a des Arg. Part three of this thesis tested the second hypothesis that AMD is secondary to the vascular insufficiency caused by atherosclerosis. Both the choroidal blood flow and retinal vessel calibre in patients with asymmetric AMD were studied and no significant changes in ocular haemodynamics were noted. In conclusion, this research favours the concept that atherosclerosis and AMD are parallel responses to chronic, recurrent injurious stimuli, with extracellular matrix remodelling and probably inflammatory response being the common cellular responses. This research did not find any significant ocular haemodynamic changes in subjects with asymmetric AMD.