Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma

Osteosarcoma is the most common primary malignancy of bone with worldwide incidence of 2 to 4 million/year. This tumor usually developed at distal part of fast growing bone and associated with instability of chromosome 6. Despite that, the preceding molecular mechanism leading to the instability is...

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Main Author: Ramli, Mohd Rozi
Format: Thesis
Language:English
Published: 2019
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Online Access:http://ir.unimas.my/id/eprint/25380/1/Mohd%20Rozi%20Ramli%20ft.pdf
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spelling my-unimas-ir.253802023-06-27T09:14:02Z Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma 2019-06-24 Ramli, Mohd Rozi RB Pathology Osteosarcoma is the most common primary malignancy of bone with worldwide incidence of 2 to 4 million/year. This tumor usually developed at distal part of fast growing bone and associated with instability of chromosome 6. Despite that, the preceding molecular mechanism leading to the instability is not fully known. Following the local ethical committee review, a total of 31 cases within 12 years were collected to investigate the copy number of gene encoding Vascular Endothelial Growth Factor (VEGF) located at chromosome 6p21 using Fluorescence in situ Hybridization (FISH) and the general chromosomal instability as indicated by micronuclei formation. In addition to VEGF, Hypoxia inducible factor 1α (HIF-1α) and p53 diagnostic immunohistochemistry (IHC) staining were performed as to investigate relationship of hypoxic stress and tumor growth suppress. Furthermore, the Mitogen Activated Protein Kinase (MAPK) cellular proliferation pathway molecules; ERK, p38 and JNK IHC were also examined. Findings showed VEGF expression at both protein and gene level (6p21). On top of that, expressed ERK, p38 but not JNK; and expressed HIF & p53 in those cases suggest tumor cell survival by evading the natural cell death program, apoptosis. In conclusion, this study presented a possible molecular mechanism underlying chromosomal instability in human osteosarcoma. Universiti Malaysia Sarawak (UNIMAS) 2019-06 Thesis http://ir.unimas.my/id/eprint/25380/ http://ir.unimas.my/id/eprint/25380/1/Mohd%20Rozi%20Ramli%20ft.pdf text en validuser masters Universiti Malaysia Sarawak Faculty of medicine and health sciences
institution Universiti Malaysia Sarawak
collection UNIMAS Institutional Repository
language English
topic RB Pathology
spellingShingle RB Pathology
Ramli, Mohd Rozi
Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma
description Osteosarcoma is the most common primary malignancy of bone with worldwide incidence of 2 to 4 million/year. This tumor usually developed at distal part of fast growing bone and associated with instability of chromosome 6. Despite that, the preceding molecular mechanism leading to the instability is not fully known. Following the local ethical committee review, a total of 31 cases within 12 years were collected to investigate the copy number of gene encoding Vascular Endothelial Growth Factor (VEGF) located at chromosome 6p21 using Fluorescence in situ Hybridization (FISH) and the general chromosomal instability as indicated by micronuclei formation. In addition to VEGF, Hypoxia inducible factor 1α (HIF-1α) and p53 diagnostic immunohistochemistry (IHC) staining were performed as to investigate relationship of hypoxic stress and tumor growth suppress. Furthermore, the Mitogen Activated Protein Kinase (MAPK) cellular proliferation pathway molecules; ERK, p38 and JNK IHC were also examined. Findings showed VEGF expression at both protein and gene level (6p21). On top of that, expressed ERK, p38 but not JNK; and expressed HIF & p53 in those cases suggest tumor cell survival by evading the natural cell death program, apoptosis. In conclusion, this study presented a possible molecular mechanism underlying chromosomal instability in human osteosarcoma.
format Thesis
qualification_level Master's degree
author Ramli, Mohd Rozi
author_facet Ramli, Mohd Rozi
author_sort Ramli, Mohd Rozi
title Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma
title_short Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma
title_full Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma
title_fullStr Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma
title_full_unstemmed Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma
title_sort elucidating the underlying molecular pathways mediating chromosomal instability in human osteosarcoma
granting_institution Universiti Malaysia Sarawak
granting_department Faculty of medicine and health sciences
publishDate 2019
url http://ir.unimas.my/id/eprint/25380/1/Mohd%20Rozi%20Ramli%20ft.pdf
_version_ 1783728296897282048