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Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad Feb 2024

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …

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Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner Feb 2024

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

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Early Stage Or Curable Cancer Diagnoses In Minorities: A Journey Of Survivors, Lora Asberry Jul 2023

Early Stage Or Curable Cancer Diagnoses In Minorities: A Journey Of Survivors, Lora Asberry

Master of Science in Integrative Biology Theses

Patients diagnosed with early-staged or curable forms of cancer experience physical, as well as, mental challenges associated with disease progression and treatment. Previous studies have demonstrated that minorities and underrepresented communities did not receive the same level of care in comparison to their non-minority counterparts. Previous studies have also demonstrated that health disparities among minorities affected their cancer journey. This study addressed: how medical disparities varied between minorities and non-minorities, the overall effects of the cancer diagnoses in minorities compared to non-minorities, whether these perspectives differed in male vs. female participants, and whether there were any possible communication barriers between …

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Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono May 2023

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

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Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha May 2023

Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha

Dissertations & Theses (Open Access)

Human papillomavirus (HPV) is the causative agent of cervical cancer and some cancers of the penis, vulva, vagina, anus, and oropharynx. Current therapies for these cancers include a combination of surgery, radiotherapy, and chemotherapy that often results in permanent, life altering adverse effects. Immunotherapy is partially effective, but with significant recurrence and lower long-term survival. Importantly, there are no few biomarker-selective targeted therapies for these cancers. To address this unmet need, our collaborators conducted a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human …

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Computational Modeling Of The Fanconi Anemia Gene Network And Its Connection To Cancer, Alyssa Warren-Belford May 2023

Computational Modeling Of The Fanconi Anemia Gene Network And Its Connection To Cancer, Alyssa Warren-Belford

Biological Sciences Undergraduate Honors Theses

Fanconi anemia (FA) is a rare genetic condition in which the cell’s DNA repair machinery is dysregulated, significantly increasing the chances of tumorigenesis. Further research is being done in order to improve patient outcomes and incidences of cancer. Our group created a computational model of the FA DNA repair gene network, which removes interstrand crosslinks found in damaged DNA and repairs it so DNA synthesis can continue. Computer simulations show the number of DNA damage indicators decreased as the pathway continued. This was expected as the FA pathway repairs DNA damage. The goal of this project was to provide further …

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Transcriptional Silencing Of Cdk18 And Its Role In Lung Carcinogenesis Of Brg1-Mutant Lung Cancers, Loryn M. Phillips Apr 2023

Transcriptional Silencing Of Cdk18 And Its Role In Lung Carcinogenesis Of Brg1-Mutant Lung Cancers, Loryn M. Phillips

Biology ETDs

BRG1 is mutated in 10% of lung cancers, making this mutation clinically relevant. The downstream effects of BRG1 included significantly affecting the cell cycle control and chromosomal replication pathway. CDK18, a cyclin-dependent kinase, was determined to be the gene with significantly decreased expression (p

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Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi Jan 2023

Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi

CMC Senior Theses

Chimeric Antigen Receptor T (CAR-T) cells have demonstrated anti-tumor activity against aggressive and invasive cancers such as glioblastoma (GBM); however, clinical response rates remain low in clinical trial studies. Tumor heterogeneity and tumor microenvironment conditions pose significant challenges for treatment of GBM, thus continuous optimization of CAR-T cell therapies and identification of novel, widely expressed, and highly specific GBM antigens are vital to better patient outcomes. A newly developed CAR-T cell construct incorporating chlorotoxin (CLTX) as the targeting domain exhibited broad GBM-targeting capabilities and elicited potent cytotoxic effects during preclinical studies and is currently being tested in a phase I …

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Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty Jan 2023

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

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Modeling Vascular Diffusion Of Oxygen In Breast Cancer, Tina Giorgadze Jan 2023

Modeling Vascular Diffusion Of Oxygen In Breast Cancer, Tina Giorgadze

Senior Projects Spring 2023

Oxygen is a vital nutrient necessary for tumor cells to survive and proliferate. Oxygen is diffused from our blood vessels into the tissue, where it is consumed by our cells. This process can be modeled by partial differential equations with sinks and sources. This project focuses on adding an oxygen diffusion module to an existing 3D agent-based model of breast cancer developed in Dr. Norton’s lab. The mathematical diffusion module added to an existing agent-based model (ABM) includes deriving the 1-dimensional and multi-dimensional diffusion equations, implementing 2D and 3D oxygen diffusion models into the ABM, and numerically evaluating those equations …

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Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey Jan 2023

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

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The Effects Of Cucurbitacin B And Silmitasertib On Metastasis And Itga6 Using The Zebrafish Tumor-Xenograft, Alexandra Griffis Jan 2023

The Effects Of Cucurbitacin B And Silmitasertib On Metastasis And Itga6 Using The Zebrafish Tumor-Xenograft, Alexandra Griffis

Electronic Theses and Dissertations

Ninety percent of cancer deaths are resultant from the metastasis of cancer cells. When cancer cells translocate through blood vessels or the lymphatic system, they may form tumors outside of their primary site. The processes of metastasis can begin quickly; after onset, metastasis is unforgiving, as it does not participate with the body’s physiological systems in an orderly way. In the past, our lab produced results indicating that a cell adhesion molecule, Integrin Alpha-6, may contribute to cancer cells' ability to metastasize. Integrins mediate interactions between the cell and the Extracellular Matrix (ECM), regulating cell attachment and cell migration. With …

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Protacs – A Novel And Rapidly Developing Field Of Targeted Protein Degradation, Hannah R. Gatley Jan 2023

Protacs – A Novel And Rapidly Developing Field Of Targeted Protein Degradation, Hannah R. Gatley

Theses and Dissertations

There is a continued need for new technology and strategies for tackling cancer and other diseases, and within the current century a novel therapeutic strategy has emerged in the realm of targeted protein degradation called Proteolysis-Targeting Chimeras (PROTACs). This technology specifically targets and degrades disease-causing proteins via the ubiquitin-proteasome system, and has seen an explosion of research and intrigue in both academia and industry over the past two decades. The diversity of PROTAC classes based on the E3 ligase recruiting ligand and the target protein allows for a universal molecular structure that can be customized for a specific target and …

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Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess Dec 2022

Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess

Open Access Theses & Dissertations

Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …

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Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario Oct 2022

Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario

Doctoral Dissertations

Macrophages are white blood cells of the innate immune system that have the ability to change phenotypically depending on the stimuli present in their surroundings through a process commonly referred to as polarization. Macrophage phenotypes broadly range from pro-inflammatory, anti-tumor (M1) to immune-suppressing (M2). Of particular interest to this work, breast cancer progression and metastasis rely on the presence of M2-like tumor-associated macrophages (TAMs). While many studies have shown the involvement of macrophages in tumor progression and metastasis, there remains a need to further explore these interactions and the polarization process, including tracking of macrophage subtypes. Toward this end, I …

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Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham Aug 2022

Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham

Legacy Theses & Dissertations (2009 - 2024)

The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …

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The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown Jul 2022

The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown

Dartmouth College Ph.D Dissertations

The Epithelial-to-Mesenchymal transition, a critical cellular process in development, is frequently co-opted by solid tumors to promote invasion and metastasis. In particular, the hybrid or intermediate EMT state, possessing both epithelial and mesenchymal characteristics, is associated with increased cancer stemness and plasticity. Similarly, intra-tumoral heterogeneity in solid tumors, in particular breast cancer, is associated with poor prognosis, tumor growth, proliferation, drug resistance, and metastasis. We sought to understand the link between the generation of intra-tumoral heterogeneity and the intermediate EMT state and their impact on tumor progression and patient prognosis. As part of my thesis work, I developed a model …

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The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams Jun 2022

The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams

Electronic Thesis and Dissertation Repository

B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with recurrent mutations and high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine was tested for its ability to prolong lifespan of a mouse model of B-ALL and reduce frequency of mutations. Mice treated with 1g/L of N-acetylcysteine in drinking water were found to have delayed onset of B-ALL at 11 weeks of age and changes in gene expression relating to B cell development, calcium-apoptosis signaling, and pathways in cancer, although no differences in lifespan were observed. Tumours from treated …

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Characterization Of The Influence Of A Small Molecule Inhibitor On Ras-Related Proteins Interactions, Emilio Duverna May 2022

Characterization Of The Influence Of A Small Molecule Inhibitor On Ras-Related Proteins Interactions, Emilio Duverna

Graduate Theses and Dissertations

The Ras superfamily of small G proteins are involved in cell-signaling processes that, if not regulated, may lead to cell multiplication, apoptosis inhibition, and tumorigenesis. They function as molecular switches, which through GTP/GDP exchange cycle, switch on or off cellular activities. Overexpression and/or hyperactivity of these proteins have been linked to many diseases including various cancers. CDC42, a member of the Rho subfamily of the Ras superfamily of small G proteins, participates in the regulation of many cellular processes including cell adhesion, mitosis, and cytoskeletal rearrangements. CDC42 binds to and activates many effector proteins including CDC42-activated kinase (ACK). Abnormal activities …

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Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier May 2022

Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier

Biomedical Engineering Undergraduate Honors Theses

Knowledge of colorectal cancer biology is improving how we approach cancer treatment. Specifically, the tumor microenvironment and abnormal angiogenesis are of particular interest. Optical methods are a prime candidate for research of the tumor microenvironment due to their ability to quantitively assess tissue structure and perfusion in real time. Particularly, the “transport scattering regime” has been identified as a method of obtaining high-resolution images and reflectance spectroscopy data; this light scattering regime has been demonstrated compatible with endoscopic imaging systems. In this study, a proof-of-concept optical imaging system is presented, capable of resolving absorbers within scattering turbid media using a …

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Developing Novel Water-Soluble Porphyrins For Potential Use As Photosensitizers In Photodynamic Therapy, Kayla R. Whittington Apr 2022

Developing Novel Water-Soluble Porphyrins For Potential Use As Photosensitizers In Photodynamic Therapy, Kayla R. Whittington

Honors Theses

Photodynamic therapy (PDT) is a treatment modality for various illnesses, including some types of cancer. Lung cancer is the leading cause of cancer death in the United States. The prevalence of lung cancer in certain gender, racial, ethnic, and socioeconomic groups add to existing health disparities in the United States. For this reason, it is necessary to address the social determinants underlying lung cancer disparities, as well as improve treatment options. These treatment options should be cost effective, convenient, and increase survival rates. This research focused on synthesizing novel water-soluble porphyrin compounds for use as photosensitive agents in PDT for …

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Analysis Of Invasion Proteins Mmp2, Mmp9, Adam12, And Adam17 In Glioblastoma U87mg Cells Treated With Anti-Cancer Compound 3,4-Dimethoxybenzaldehyde, Andras Muranyi Apr 2022

Analysis Of Invasion Proteins Mmp2, Mmp9, Adam12, And Adam17 In Glioblastoma U87mg Cells Treated With Anti-Cancer Compound 3,4-Dimethoxybenzaldehyde, Andras Muranyi

Honors Theses

This research tested the effectiveness of novel compound 3,4-dimethoxybenzaldehyde, demonstrated to have anti-cancer properties. U87MG Glioblastoma cells were exposed to the compound at its LC50 concentration, then processed to collect proteins from the cells. Proteins were analyzed via Western blotting for specific protein levels of matrix metalloproteinase 2 and 9 (MMP) and disintegrin and metalloprotease 12 and 17 (ADAM). Previous research indicates these proteins are involved in the invasive properties of glioblastoma cells. Westerns were quantified with ImageJ and compared using a one-way ANOVA. Results indicate the compound has minimal effect upon the expression of MMP2, MMP9, ADAM12, ADAM17 proteins.

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Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph Jan 2022

Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph

Electronic Theses and Dissertations

The aberrant fibrous, extracellular, and intracellular proteinaceous deposits in cells, organs and tissues are referred to as amyloids. These deposits are dominated by β-sheet structures that have been implicated in several neurodegenerative diseases and cancer. In this work, the types of amyloidosis studied include Parkinson’s disease (PD) using UA196 and NL5901 strains of Caenorhabditis elegans (C. elegans), Alzheimer’s disease (AD) using GMC101 strain of C. elegans, and cancer-associated mutant p53 aggregation in MIA PaCa-2 mutant cells. Several molecules including SK-129, NS132, NS163, bexarotene, a polyphenol (-)-epi-gallocatechine gallate (EGCG), ADH40, RD148, and RD242 were screened in vitro and in …

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The Relationship Between Inflammatory Diet Score And Cancer Outcomes: Systematic Review And Meta-Analysis, Eric Han Jan 2022

The Relationship Between Inflammatory Diet Score And Cancer Outcomes: Systematic Review And Meta-Analysis, Eric Han

Honors Undergraduate Theses

Cancer remains one of the most prevalent diseases in the United States and a leading cause of death. Large prospective studies have found significant correlations between dietary intake and cancer. Chronic inflammation promotes pro-cancer inflammatory environments promoting the formation and growth of tumors while preventing effective anti-tumor responses. Nutrition can impact inflammation, with the intake of certain food items increasing biomarkers for systemic inflammation thus, the objective of this research was to explore the relationship between inflammatory diet score measured by the Dietary Inflammatory index and all-cause mortality, cancer-specific mortality, and cancer recurrence among cancer survivors. Web of Science, Medline, …

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Intracellular Trafficking And Distribution Of Cd And Inp Quantum Dots In Hela And Ml-1 Thyroid Cancer Cells, Min Zhang Jan 2022

Intracellular Trafficking And Distribution Of Cd And Inp Quantum Dots In Hela And Ml-1 Thyroid Cancer Cells, Min Zhang

MSU Graduate Theses

The study of the interaction of engineered nanoparticles, including quantum dots (QDs), with cellular constituents and the kinetics of their localization and transport, has provided new insights into their biological consequences in cancers and for the development of effective cancer therapies. The present study aims to elucidate the toxicity and intracellular transport kinetics of CdSe/ZnS and InP/ZnS QDs in late-stage ML-1 thyroid cancer using well-tested HeLa cells as a control. The XTT viability assay showed that ML-1 cells, and non-cancerous mouse fibroblast cells, exhibit no viability defect in response to these QDs, whereas HeLa cell viability decreases. These results suggest …

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Functional Characterization Of Cancer-Associated Dna Polymerase Ε Variants, Stephanie R. Barbari Dec 2021

Functional Characterization Of Cancer-Associated Dna Polymerase Ε Variants, Stephanie R. Barbari

Theses & Dissertations

Replicative DNA polymerases ε (Polε) and δ (Polδ) achieve high fidelity DNA synthesis through a precise balance of polymerization and exonucleolytic proofreading. Errors that escape proofreading are corrected by DNA mismatch repair (MMR). Ultramutated human cancers with proficient MMR carry alterations in the exonuclease domain of Polε, which were initially predicted to abolish proofreading. However, functional studies in yeast of the most recurrent Polε-P286R variant suggested defects beyond a loss of exonuclease activity. Indeed, biochemical analysis of the yeast Polε-P286R analog revealed increased polymerization capacity in addition to decreased proofreading, which enables efficient mismatch extension and bypass of replication-blocking non-B …

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Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach Dec 2021

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

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Role Of Sex Differences On Cancer Cachexia Progression And Fibrosis During Cancer Cachexia Development, Wesley Haynie Dec 2021

Role Of Sex Differences On Cancer Cachexia Progression And Fibrosis During Cancer Cachexia Development, Wesley Haynie

Graduate Theses and Dissertations

Cancer cachexia is a multifactorial wasting syndrome characterized by losses in bodymass >5% and occurs in approximately 80% of all cancer patients. Chronic inflammation and fibrosis play roles in cancer cachexia and a greater understanding of these contributing pathways to this pathology will pave the way for potential therapeutic avenues. While inflammation and fibrosis have been researched in various models of cancer cachexia, little to no studies have been performed in both sexes as most previous studies focus on males. PURPOSE The purpose of these studies is to investigate the role of fibrosis on cancer cachexia development as well as …

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Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc Aug 2021

Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc

Arts & Sciences Electronic Theses and Dissertations

Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …

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Understanding The Pathogenesis Of Renal Medullary Carcinoma, Melinda Soeung Aug 2021

Understanding The Pathogenesis Of Renal Medullary Carcinoma, Melinda Soeung

Dissertations & Theses (Open Access)

Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the …

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