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Full-Text Articles in Medicine and Health Sciences

Concomitant Targeting Of The Mtor/Mapk Pathways: Novel Therapeutic Strategy In Subsets Of Non-Small Cell Lung Cancer, Dennis Ruder Dec 2016

Concomitant Targeting Of The Mtor/Mapk Pathways: Novel Therapeutic Strategy In Subsets Of Non-Small Cell Lung Cancer, Dennis Ruder

Dissertations & Theses (Open Access)

Over the last decade, a paradigm-shift in lung cancer therapy has evolved into targeted-driven medicinal approaches. However, patients frequently relapse and develop resistance to available therapies. Herein, we utilized genomic mutation data from advanced chemorefractory non-small cell lung cancer (NSCLC) patients enrolled in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-2) clinical trial to characterize novel actionable genomic alterations potentially of clinical relevance. We identified RICTOR alterations (mutations, amplifications) in 17% of lung adenocarcinomas and found RICTOR expression correlates to worse overall survival. There was enrichment of MAPK pathway genetic aberrations in key oncogenes (e.g. KRAS, BRAF, …


Development Of An In Silico Kir Genotyping Algorithm And Its Application To Population And Cancer Immunogenetic Analyses, Howard Rosoff Aug 2016

Development Of An In Silico Kir Genotyping Algorithm And Its Application To Population And Cancer Immunogenetic Analyses, Howard Rosoff

Dissertations & Theses (Open Access)

Gene content determination and variant calling in the complex KIR genomic region are useful for immune system function analysis, pathogenesis and disease risk factor elucidation, immunotherapy development, evolutionary investigations, and human migration modeling. Sequence-specific oligonucleotide and sequence-specific primer PCR methods are the de facto standards for KIR presence/absence identification, but the current platforms are unsuitable for SNP calling, impractical for KIR typing large cohorts of DNA samples, and inapplicable for typing repositories in which sequence data, but not cells or cell analytes, are available. Alternative typing methods, such as in silico sequence-based typing, can address the problems associated with amplicon-based …


Genomic Drivers Of Cutaneous Squamous Cell Carcinoma Development, Vida Chitsazzadeh May 2016

Genomic Drivers Of Cutaneous Squamous Cell Carcinoma Development, Vida Chitsazzadeh

Dissertations & Theses (Open Access)

Skin cancer is the most common malignancy in humans. Annually, in U.S. there are over 3 million cases with an estimated overall economic impact of $2 billion. Cutaneous Squamous Cell Carcinoma (cuSCC) comprises 15-20% of all skin cancers. cuSCC has the best-defined progression from a distinct precancerous lesion, the Actinic Keratosis (AK), to invasive cuSCC. Destructive therapies for AK treatment must be used repetitively, causing significant morbidity. There is a tremendous need for targeted diagnostics and therapy for AKs, representing an important opportunity for secondary skin cancer prevention. Our knowledge of the molecular and cellular events that lead to the …


Accurate Mutation Annotation And Functional Prediction Enhance The Applicability Of -Omics Data In Precision Medicine, Tenghui Chen May 2016

Accurate Mutation Annotation And Functional Prediction Enhance The Applicability Of -Omics Data In Precision Medicine, Tenghui Chen

Dissertations & Theses (Open Access)

Clinical sequencing has been recognized as an effective approach for enhancing the accuracy and efficiency of cancer patient management and therefore achieve the goals of personalized therapy. However, the accuracy of large scale sequencing data in clinics has been constrained by many different aspects, such as clinical detection, annotation and interpretation of the variants that are observed in clinical sequencing data. In my Ph.D thesis work, I mainly investigated how to comprehensively and efficiently apply high dimensional -omics data to enhance the capability of precision cancer medicine. Following this motivation, my dissertation has been focused on two important topics in …