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Evaluating The Utility Of Protein Biomarker, S100a7, And Diagnostic Test, Straticyte, In Predicting The Progression Of Oral Dysplasia, Lachlan Mclean

Electronic Thesis and Dissertation Repository

Five-year survival of oral cancer has remained relatively unchanged despite advancements in treatment, mostly because diagnosis is often made at an advanced stage of disease. The progression of dysplasia to oral cancer often follows a stepwise progression. Histopathology is considered the ‘gold standard’ for diagnosing dysplasia and lesions at a high risk of progression to oral cancer, but lends itself to subjectivity. The protein biomarker, S100A7, in oral dysplasia and squamous cell carcinoma has shown some predictive value for the transformation of dysplasia to cancer. Straticyte, a diagnostic test utilizing S100A7 to predict the probability of progression of oral dysplasia …

The Role Of Kidney Injury Molecule-1 In The Metastasis Of Renal Cell Carcinoma, Jasper Lee

Electronic Thesis and Dissertation Repository

Over 30% of patients with renal cell carcinoma (RCC) present with metastases, with median survival of 2 years. Kidney injury molecule 1 (KIM-1) is a cell-surface glycoprotein expressed by >90% of RCC tumours. Preliminary data mined from The Cancer Genome Atlas RNA-sequencing database indicates that KIM-1 overexpression predicts overall survival in patients. Here we sought to determine if tumour KIM-1 plays a role in RCC cell extravasation and metastasis to the lungs. In vitro invasion and in vivo metastasis assays were performed to investigate the metastatic potential of KIM-1-expressing cells, and RNA-seq was conducted to identify differentially expressed genes between …

Functional Investigation Of The Role Of The Retinoblastoma Protein In Genome Stability, Aren E. Marshall

Electronic Thesis and Dissertation Repository

Genome instability is an enabling characteristic of cancerous cells. It has recently been discovered that the retinoblastoma protein (pRB), typically known for its role in cell cycle regulation, also aids in the maintenance of genome stability. Intriguingly, mutations to the pRB gene, RB1, can arise late in tumorigenesis in cancer cells whose cell cycle regulation is already compromised by another mutation. This suggests that pRB’s functions in genome stability could underlie cancer relevant characteristics that are independent of its ability to negatively regulate proliferation. The overall aim of this thesis is to characterize the different means through which pRB …

Applications Of Phosphotyrosine Superbinding Sh2 Domain Variants, Xuguang Liu

Electronic Thesis and Dissertation Repository

Protein tyrosine kinases (PTKs, or TKs) have emerged as one of the most intensively pursued targets in the development of anti-cancer therapeutics, due to their critical roles in the phosphotyrosine (pTyr)-mediated signaling network that regulates many cancer-related cellular activities. The TKs, tyrosine phosphorylation phosphatases (PTPs) and pTyr recognition SH2 proteins are intensively tyrosine phosphorylated, which play a pivotal role in determining the signaling outcome of this network. More than 50% of all human proteins are tyrosine phosphorylated and many of these TK substrates have been proven functional in TK regulated cellular activities. Therefore, proteomics studies of tyrosine phosphorylation are of …

Characterization Of Genomic Copy Number Variation In Mus Musculus Associated With The Germline Of Inbred And Wild Mouse Populations, Normal Development, And Cancer, Maja Milojevic

Electronic Thesis and Dissertation Repository

Mus musculus is a human commensal species and an important model of human development and disease with a need for approaches to determine the contribution of copy number variants (CNVs) to genetic variation in laboratory and wild mice, and arising with normal mouse development and disease. Here, the Mouse Diversity Genotyping array (MDGA)-approach to CNV detection is developed to characterize CNV differences between laboratory and wild mice, between multiple normal tissues of the same mouse, and between primary mammary gland tumours and metastatic lung tissue.

A CNV detection pipeline was used in conjunction with evaluated probe sets, targeting 925,378 loci …