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Full-Text Articles in Medicine and Health Sciences

Pathway‐Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Bagchee‐Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan Dec 2020

Pathway‐Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Bagchee‐Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan

Biochemistry Publications

Cancer chemotherapy responses have been related to multiple pharmacogenetic biomarkers, often for the same drug. This study utilizes machine learning to derive multi‐gene expression signatures that predict individual patient responses to specific tyrosine kinase inhibitors, including erlotinib, gefitinib, sorafenib, sunitinib, lapatinib and imatinib. Support vector machine (SVM) learning was used to train mathematical models that distinguished sensitivity from resistance to these drugs using a novel systems biology‐based approach. This began with expression of genes previously implicated in specific drug responses, then expanded to evaluate genes whose products were related through biochemical pathways and interactions. Optimal pathway‐extended SVMs predicted responses in …


An Exploration Of Facial Skin Scarring, Its Impact And Contemporary Evaluation, Michael G. Brandt Nov 2020

An Exploration Of Facial Skin Scarring, Its Impact And Contemporary Evaluation, Michael G. Brandt

Electronic Thesis and Dissertation Repository

Facial skin cancer secondary to surgical treatment may be distressing due to the malignancy itself and from the consequences of its treatment. A visible postsurgical scar is an obvious reminder of the condition. This investigation sought to broaden our understanding of facial scarring and develop a novel tool for its objective evaluation. To this end, skin cancer as the most common etiology of facial scarring was reviewed. The scar scale literature was evaluated in the context of assessing scars through a biopsychosocial lens. Finally, the development of a novel scar scale was presented. Thirty-four individuals completed 13,056 ratings using a …


Pan-Cancer Analysis Of Telomerase Reverse Transcriptase (Tert) Isoforms, Mathushan Subasri Oct 2020

Pan-Cancer Analysis Of Telomerase Reverse Transcriptase (Tert) Isoforms, Mathushan Subasri

Electronic Thesis and Dissertation Repository

Reactivation of the multi-subunit ribonucleoprotein telomerase is the primary telomere maintenance mechanism in cancer, but it is rate-limited by the enzymatic component, telomerase reverse transcriptase (TERT). While regulatory in nature, TERT alternative splice variant/isoform regulation and functions are not fully elucidated and are further complicated by their highly diverse expression. In this thesis, I characterized TERT expression across normal and neoplastic tissues using TCGA and GTEx RNA-sequencing data. In doing so, I demonstrated the global overexpression and splicing shift towards full-length TERT in neoplastic tissue. Furthermore, my studies identified tumour subtype expression differences possibly regulated by subtype-specific characteristics, detailed heterogeneity …