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Fluorescence in situ hybridisation (FISH) analysis of Chromosome 1 and gene expression levels of MAD2 and BUB1 levels in premalignant stages of gastric tissue. / Amudha Somasekar

Swansea University Author: Amudha Somasekar

Abstract

Gastric cancer is a common cause of cancer death in the world. The mortality rate from gastric cancer is high in UK as it often presents late, often with local or distant metastasis. This makes the treatment options limited. The pathogenesis of gastric cancer occurs in a multi step pathway with pre...

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Published: 2011
Institution: Swansea University
Degree level: Doctoral
Degree name: M.D
URI: https://cronfa.swan.ac.uk/Record/cronfa43141
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spelling 2018-08-29T15:17:19.9903559 v2 43141 2018-08-02 Fluorescence in situ hybridisation (FISH) analysis of Chromosome 1 and gene expression levels of MAD2 and BUB1 levels in premalignant stages of gastric tissue. a1aceeef9c530e4e0f9f62f6f0372769 NULL Amudha Somasekar Amudha Somasekar true true 2018-08-02 Gastric cancer is a common cause of cancer death in the world. The mortality rate from gastric cancer is high in UK as it often presents late, often with local or distant metastasis. This makes the treatment options limited. The pathogenesis of gastric cancer occurs in a multi step pathway with pre cancerous conditions leading to cancer eventually. It is important to understand this carcinogenic process (aneuploidy and abnormal gene expression levels) and the driving forces (eg. Helicobacter Pylori infection) which will enable us to alter the disease outcome.This series of experiment included cytogenetic investigation which involved obtaining gastric cells using brush cytology and using Fluorescent insitu hybridisation technique to look for aneuploidy levels of chromosome 1 and 4. These two chromosomes were chosen as chromosome 1 has been recently shown to be abnormal in early in premalignant stages of gastric cancer. Chromosome 4 was chosen as hyperploidy of chromosome 4 was the predominant chromosomal aberration in Barrett’s oesophagus. This study has shown that the aneuploidy level of chromosome 1 progressively increased with the progression of the histological stages according to the Correa’s premalignant gastric cancer pathway. Significant increase in aneuploidy levels of chromosome 1 was seen in H. Pylori associated gastritis, implying that H. Pylori play a very important role in the progression of the disease.Aneuploidy can occur due to various genetic defects that may potentially occur during mitosis. Spindle cell check points play a vital role in preventing the cells from proceeding to the anaphase stage if there is any defect in the kinetochore attachment. Certain genes like MAD2 and BUB1 are thought to be instrumental in controlling the spindle cell check points and it is believed a steady state of genes like MAD2 and BUB1 are required for this. In the second part of this study, the MAD2 and BUB1 expression levels were measured and correlated to the aneuploidy stages. There was no significant difference in their expression levels in patients with significant aneuploidy level. MAD2 levels were increased in H.Pyloriassociated gastritis, which implies that H. Pylori plays an important role in the pathogenesis of gastric cancer. E-Thesis Gastric cancer 31 12 2011 2011-12-31 COLLEGE NANME College COLLEGE CODE Swansea University Doctoral M.D 2018-08-29T15:17:19.9903559 2018-08-02T16:24:31.3970206 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Amudha Somasekar NULL 1 0043141-02082018162549.pdf 10821533.pdf 2018-08-02T16:25:49.7730000 Output 10001445 application/pdf E-Thesis true 2018-08-02T16:25:49.7730000 false
title Fluorescence in situ hybridisation (FISH) analysis of Chromosome 1 and gene expression levels of MAD2 and BUB1 levels in premalignant stages of gastric tissue.
spellingShingle Fluorescence in situ hybridisation (FISH) analysis of Chromosome 1 and gene expression levels of MAD2 and BUB1 levels in premalignant stages of gastric tissue.
Amudha Somasekar
title_short Fluorescence in situ hybridisation (FISH) analysis of Chromosome 1 and gene expression levels of MAD2 and BUB1 levels in premalignant stages of gastric tissue.
title_full Fluorescence in situ hybridisation (FISH) analysis of Chromosome 1 and gene expression levels of MAD2 and BUB1 levels in premalignant stages of gastric tissue.
title_fullStr Fluorescence in situ hybridisation (FISH) analysis of Chromosome 1 and gene expression levels of MAD2 and BUB1 levels in premalignant stages of gastric tissue.
title_full_unstemmed Fluorescence in situ hybridisation (FISH) analysis of Chromosome 1 and gene expression levels of MAD2 and BUB1 levels in premalignant stages of gastric tissue.
title_sort Fluorescence in situ hybridisation (FISH) analysis of Chromosome 1 and gene expression levels of MAD2 and BUB1 levels in premalignant stages of gastric tissue.
author_id_str_mv a1aceeef9c530e4e0f9f62f6f0372769
author_id_fullname_str_mv a1aceeef9c530e4e0f9f62f6f0372769_***_Amudha Somasekar
author Amudha Somasekar
author2 Amudha Somasekar
format E-Thesis
publishDate 2011
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
document_store_str 1
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description Gastric cancer is a common cause of cancer death in the world. The mortality rate from gastric cancer is high in UK as it often presents late, often with local or distant metastasis. This makes the treatment options limited. The pathogenesis of gastric cancer occurs in a multi step pathway with pre cancerous conditions leading to cancer eventually. It is important to understand this carcinogenic process (aneuploidy and abnormal gene expression levels) and the driving forces (eg. Helicobacter Pylori infection) which will enable us to alter the disease outcome.This series of experiment included cytogenetic investigation which involved obtaining gastric cells using brush cytology and using Fluorescent insitu hybridisation technique to look for aneuploidy levels of chromosome 1 and 4. These two chromosomes were chosen as chromosome 1 has been recently shown to be abnormal in early in premalignant stages of gastric cancer. Chromosome 4 was chosen as hyperploidy of chromosome 4 was the predominant chromosomal aberration in Barrett’s oesophagus. This study has shown that the aneuploidy level of chromosome 1 progressively increased with the progression of the histological stages according to the Correa’s premalignant gastric cancer pathway. Significant increase in aneuploidy levels of chromosome 1 was seen in H. Pylori associated gastritis, implying that H. Pylori play a very important role in the progression of the disease.Aneuploidy can occur due to various genetic defects that may potentially occur during mitosis. Spindle cell check points play a vital role in preventing the cells from proceeding to the anaphase stage if there is any defect in the kinetochore attachment. Certain genes like MAD2 and BUB1 are thought to be instrumental in controlling the spindle cell check points and it is believed a steady state of genes like MAD2 and BUB1 are required for this. In the second part of this study, the MAD2 and BUB1 expression levels were measured and correlated to the aneuploidy stages. There was no significant difference in their expression levels in patients with significant aneuploidy level. MAD2 levels were increased in H.Pyloriassociated gastritis, which implies that H. Pylori plays an important role in the pathogenesis of gastric cancer.
published_date 2011-12-31T03:54:20Z
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