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Full-Text Articles in Life Sciences
The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le
The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le
Dissertations & Theses (Open Access)
Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …
Involvement Of Jak/Stat Signaling And A Basement Membrane-Associated Protein During Air Sac Primordium Development In Drosophila Melanogaster, Nathan Anthony Powers
Involvement Of Jak/Stat Signaling And A Basement Membrane-Associated Protein During Air Sac Primordium Development In Drosophila Melanogaster, Nathan Anthony Powers
Masters Theses & Specialist Projects
Tumor metastasis currently presents the greatest obstacle for effective cancer remediation. Metastatic growth necessitates both degradation of a specialized form of extracellular matrix (ECM) known as the basement membrane (BM) and the invasion of surrounding tissues thereafter. The thoracic air sacs of fruit flies (Drosophila melanogaster), which develop and operate in a fashion comparable to the human lung, provide a unique model for identifying and characterizing factors that contribute to its own development as well as tumoral invasion. We investigated the involvement of both Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signaling and a BMassociated protein during the …
Integrated Regulation Of Class Ii Human Endogenous Retroviruses In A Breast Cancer Cell Line, Yingguang Liu, Tam D. Nguyen
Integrated Regulation Of Class Ii Human Endogenous Retroviruses In A Breast Cancer Cell Line, Yingguang Liu, Tam D. Nguyen
Proceedings of the International Conference on Creationism
Endogenous retroviruses (ERVs) are still regarded as foreign invaders by most biologists. Because of structural and positional homology of ERVs in human and ape genomes, they have been considered molecular evidences of common ancestry. Using a breast cancer cell line, we analyzed the regulatory features of a group of human endogenous retroviruses (HERV-K), and found that they contain multiple sequence motifs subjecting them to regulation by sex hormones, a stem cell-specific transcription factor (OCT4), and DNA methylation. Mutation of the OCT4 motif abrogates their response to sex hormones, while methylation of a progesterone-response element enhances receptor-binding. We also found that …
Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin
Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin
University Scholar Projects
Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates used …
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
Dissertations & Theses (Open Access)
DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is …
Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro
Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro
Senior Honors Projects
In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other …
Computational Insights Into The Generation Of Chromosomal Copy Number Changes, Yihua Liu
Computational Insights Into The Generation Of Chromosomal Copy Number Changes, Yihua Liu
Dissertations & Theses (Open Access)
Deviations from a diploid configuration of the human genome, spanning single genes or entire chromosomes, can have wide-ranging impacts on the variation of human phenotypes, including Mendelian and complex forms of diseases. These chromosomal alterations — such as duplications, deletions or copy-neutral loss-of-heterozygosity — are thus important forms of genetic variation for phenotyping populations of individuals as well as populations of cells. Indeed, copy number variants (CNVs) serve as hallmarks of critical changes in the development of particular diseases such as cancer and thus may be used as biomarkers. These CNVs may be either inherited (transmitted by germ cells, originating …
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal
Dissertations & Theses (Open Access)
Altered DICER1 protein levels are associated with developmental disorders, infertility, macular degenerative blindness, aging, and cancer in humans. Recently, post-translational regulation of Dicer1 via phosphorylation has been described in C. elegans. Oscillation of Dicer1 phosphorylation to regulate its activity is essential for germ cell development and embryogenesis in worms. These observations led us to posit that Dicer1 protein levels and activity are under tight regulation for normal mammalian homeostasis. To test whether phosphorylation of Dicer1 regulates its activity in mammals, I generated phospho-mimetic knock-in mouse models by replacing Serines 1712 and 1836 with Aspartic acids individually or together (dual …
Genotype-Specific Insertion Of Cytotoxic Genetic Elements Into Cancer Cells, Ryan Englander
Genotype-Specific Insertion Of Cytotoxic Genetic Elements Into Cancer Cells, Ryan Englander
University Scholar Projects
The new gene editing system CRISPR/Cas9, composed of a complex composed of a guide RNA and the Cas9 endonuclease, promises to revolutionize biological research and potentially allow clinicians to directly modify patient DNA in vivo. While its applications in the treatment of genetic diseases and in modifying immune cells for immunotherapy are currently being explored, CRISPR/Cas9’s potential utility as a modular system for targeting tumor-specific mutated sequences has not as of yet been explored. While CRISPR/Cas9 is specific enough to target small insertions and deletions or gross chromosomal rearrangements, it is not specific enough to reliably restrict editing to …
The Role Of Thymine-Dna Glycosylase In Transcriptional Regulation, Bart Kolendowski
The Role Of Thymine-Dna Glycosylase In Transcriptional Regulation, Bart Kolendowski
Electronic Thesis and Dissertation Repository
Precise control over transcriptional regulation is required for normal cell function. Errors in transcriptional regulation underpin many diseases including cancer. Thymine DNA Glycosylase (TDG) is a base excision repair protein and a coregulator that has been implicated in a diverse set of fundamental biological processes including embryonic development, nuclear receptor signaling and Wnt signaling. Importantly, TDG has been shown to play an important role in transcriptional regulation in a wide variety of systems. Details surrounding the mechanism through which TDG acts remain unclear. In this thesis we explore the role of TDG in Estrogen Receptor (ER)-dependent signaling and in cellular …
Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach
Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach
Honors Undergraduate Theses
Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding the …
Missing Heritability And Novel Germline Risk Loci In Hereditary Ovarian Cancer: Insights From Whole Exome Sequencing And Functional Analyses, Jaime Lyn Stafford
Missing Heritability And Novel Germline Risk Loci In Hereditary Ovarian Cancer: Insights From Whole Exome Sequencing And Functional Analyses, Jaime Lyn Stafford
Wayne State University Dissertations
While 25% of ovarian cancer (OVCA) cases are due to inherited factors, most of the genetic risk remains unexplained. This study addressed this gap by identifying previously undescribed OVCA risk loci through the whole exome sequencing (WES) of 48 BRCA1/BRCA2 wild type women diagnosed with OVCA, selected for high risk of genetic inheritance. Five clearly pathogenic variants were identified in this sample, four of which are in two genes featured on current multi-gene panels; (RAD51D, ATM). In addition, a high impact variant in FANCM (R1931*) was identified. FANCM has been recently implicated in familial breast cancer risk but is not …