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Fluorescence in situ hybridisation (FISH) analysis of chromosomal aberrations in gastric tissue: The involvement of "Helicobacter pylori". / Lisa Williams

Swansea University Author: Lisa Williams

Abstract

Gastric cancer is a common cause of cancer death in the UK. It most often presents in patients when the disease is advanced, and hence treatment options are limited. As such, studies on the pre-malignant stages of gastric cancer, and interest in the mechanisms of the carcinogenic process (reactive o...

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Published: 2004
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa43067
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last_indexed 2019-10-21T16:48:58Z
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spelling 2018-09-03T10:21:24.7365640 v2 43067 2018-08-02 Fluorescence in situ hybridisation (FISH) analysis of chromosomal aberrations in gastric tissue: The involvement of "Helicobacter pylori". ab7a848b573e9a5350aa6ab991494a61 NULL Lisa Williams Lisa Williams true true 2018-08-02 Gastric cancer is a common cause of cancer death in the UK. It most often presents in patients when the disease is advanced, and hence treatment options are limited. As such, studies on the pre-malignant stages of gastric cancer, and interest in the mechanisms of the carcinogenic process (reactive oxygen species, ROS) and the agents that may drive the carcinogenic pathway {Helicobacter pylori infection), are important, with a view to improving disease outcome. This series of experiments has firstly shown, using CBMN assay +/- kinetochore staining and interphase FISH, that ROS causes aneuploidy of chromosomes 4, 8, 20 and 17(p53) in a human cell line. Secondly, gastric cells have been collected using endoscopic cytology brush techniques, and prepared, such that interphase FISH could be performed. Again, aneuploidy of chromosomes 4, 8, 20 and 17(p53) were detected in normal gastric mucosa, gastritis and intestinal metaplasia. The level of aneuploidy detected increased as disease severity increased. Amplification of chromosome 4, amplification of chromosome 20 and deletion of chromosome 17(p53) were the more significant findings. The degree of chromosomal abnormalities detected increased further, in a stepwise manner, when gastric dysplasia and gastric adenocarinoma cells were studied. Hence, a role for these abnormalities may exist in the initiation of, and the progression to, gastric cancer. The presence of H. pylori was also determined in the gastric tissue studied using histological analysis and PCR technology. Detection rates were comparable. The more virulent strain of H. pylori, Cag A, was found to be associated with increased disease pathology and chromosomal abnormalities, yet numbers were small. The amplification of chromosome 4 in gastric tissue was again highlighted in association with H pylori infection, hence it may reflect a role for chromosome 4 in the initiation of gastric cancer. E-Thesis Gastric cancer, helicobacter pylori 31 12 2004 2004-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-09-03T10:21:24.7365640 2018-08-02T16:24:31.2098145 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Lisa Williams NULL 1 0043067-02082018162544.pdf 10821459.pdf 2018-08-02T16:25:44.0630000 Output 14623833 application/pdf E-Thesis true 2018-08-02T16:25:44.0630000 false
title Fluorescence in situ hybridisation (FISH) analysis of chromosomal aberrations in gastric tissue: The involvement of "Helicobacter pylori".
spellingShingle Fluorescence in situ hybridisation (FISH) analysis of chromosomal aberrations in gastric tissue: The involvement of "Helicobacter pylori".
Lisa Williams
title_short Fluorescence in situ hybridisation (FISH) analysis of chromosomal aberrations in gastric tissue: The involvement of "Helicobacter pylori".
title_full Fluorescence in situ hybridisation (FISH) analysis of chromosomal aberrations in gastric tissue: The involvement of "Helicobacter pylori".
title_fullStr Fluorescence in situ hybridisation (FISH) analysis of chromosomal aberrations in gastric tissue: The involvement of "Helicobacter pylori".
title_full_unstemmed Fluorescence in situ hybridisation (FISH) analysis of chromosomal aberrations in gastric tissue: The involvement of "Helicobacter pylori".
title_sort Fluorescence in situ hybridisation (FISH) analysis of chromosomal aberrations in gastric tissue: The involvement of "Helicobacter pylori".
author_id_str_mv ab7a848b573e9a5350aa6ab991494a61
author_id_fullname_str_mv ab7a848b573e9a5350aa6ab991494a61_***_Lisa Williams
author Lisa Williams
author2 Lisa Williams
format E-Thesis
publishDate 2004
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Gastric cancer is a common cause of cancer death in the UK. It most often presents in patients when the disease is advanced, and hence treatment options are limited. As such, studies on the pre-malignant stages of gastric cancer, and interest in the mechanisms of the carcinogenic process (reactive oxygen species, ROS) and the agents that may drive the carcinogenic pathway {Helicobacter pylori infection), are important, with a view to improving disease outcome. This series of experiments has firstly shown, using CBMN assay +/- kinetochore staining and interphase FISH, that ROS causes aneuploidy of chromosomes 4, 8, 20 and 17(p53) in a human cell line. Secondly, gastric cells have been collected using endoscopic cytology brush techniques, and prepared, such that interphase FISH could be performed. Again, aneuploidy of chromosomes 4, 8, 20 and 17(p53) were detected in normal gastric mucosa, gastritis and intestinal metaplasia. The level of aneuploidy detected increased as disease severity increased. Amplification of chromosome 4, amplification of chromosome 20 and deletion of chromosome 17(p53) were the more significant findings. The degree of chromosomal abnormalities detected increased further, in a stepwise manner, when gastric dysplasia and gastric adenocarinoma cells were studied. Hence, a role for these abnormalities may exist in the initiation of, and the progression to, gastric cancer. The presence of H. pylori was also determined in the gastric tissue studied using histological analysis and PCR technology. Detection rates were comparable. The more virulent strain of H. pylori, Cag A, was found to be associated with increased disease pathology and chromosomal abnormalities, yet numbers were small. The amplification of chromosome 4 in gastric tissue was again highlighted in association with H pylori infection, hence it may reflect a role for chromosome 4 in the initiation of gastric cancer.
published_date 2004-12-31T03:54:11Z
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score 11.013148