Cancer Biology Commons^™

The Role Of Myocardin In The Progression Of Non-Small Cell Lung Cancer, Soromidayo Akinsiku

Biotechnology Theses

Lung cancer is the leading cause of cancer-related mortality in the world and NSCLC accounts for 85% of all lung cancer cases. The mainstay of treatment for patients with stage I, II and IIIA NSCLC is surgery, followed by post-operative cisplatin-based chemotherapy. Additional adjuvant therapy involving targeted tyrosine kinase inhibitors has been in use, however even for the targeted therapy, resistance eventually develops. Therefore, there is a need for identifying novel targets for this life-threatening disease. Given that preliminary studies in Ikebe lab revealed that myocardin knockdown significantly promoted caspase-3 degradation, in this study, using myocardin siRNA, we investigated the …

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 …

Revolutionary Advances In The Treatment Of Genetic Disease, Emma Kaitlyn Carrigan

Honors Theses and Capstones

No abstract provided.

Targeting Stat3 In Triple Negative Breast Cancer Using Gsk3Ꞵ And Integrin Inhibitors, Emily A. Pratt

Honors Theses and Capstones

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and is known for its chemoresistance and high rate of recurrence. TNBC lacks the hormone receptors that are found in other types of breast cancer, and therefore cannot be treated with hormonal therapies. Although the initial response to chemotherapy is favorable, many TNBC patients experience a recurrence of this cancer at a secondary location and this recurrence is often more lethal than the original tumor. The Signal Transducer and Activator of Transcription (STAT) pathway is a major contributor to cancer growth and metastasis, and STAT3 is constitutively …

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 …

Understanding The Role Of Peroxiredoxin Iv In Colorectal Cancer Development, Pratik Thapa

Theses and Dissertations--Toxicology and Cancer Biology

Reactive oxygen species (ROS) are oxygen-containing free radicals and/or molecules that are more reactive than O₂. ROS such as hydroxyl radical (•OH) and hydrogen peroxide (H₂O₂) are produced naturally in the body as a result of reactions such as aerobic respiration and oxidative protein folding. ROS undergo reduction-oxidation (redox) reactions and mediate cell signaling. Accumulation of excessive ROS can damage DNA, RNA, protein and lipids. Antioxidants are enzymes and small molecules that react with ROS to modulate redox signaling and to prevent and repair oxidative damage. Examples of antioxidants include glutathione, thioredoxin, superoxide dismutase, …

Targeting Ezh2 To Improve Outcomes Of Lung Squamous Cell Carcinoma, Tanner Ducote

Theses and Dissertations--Toxicology and Cancer Biology

Only 20% of patients diagnosed with lung squamous cell carcinoma (LSCC) respond to immunotherapy. Anti-PD1 immunotherapy is most commonly prescribed to these patients; however, most will become refractory. It is important to understand the mechanisms underlying this problem to increase durability and survival. Building upon the work of other groups, our lab has demonstrated that the inhibition of the histone methyltransferase, EZH2, is crucial to maintaining an immunologically responsive microenvironment. Based on our data, we hypothesize that combining EZH2 inhibitors with anti-PD1 therapy will increase response and durability. To study non-small cell lung cancers (NSLC) our lab uses a variety …

Characterization Of Cell Type-Specific Molecular Heterogeneity In Cancer Using Multi-Omic Approaches, Min Kyung Lee

Dartmouth College Ph.D Dissertations

Tumors are composed of heterogeneous cell types each with its own unique molecular profiles. Recent advances in single cell genomics technologies have begun to increase our understanding of the molecular heterogeneity that exists in tumors with particular focus on gene expression and chromatin accessibility profiles. However, due to limitations in methods for certain sample types and high cost for single cell genomics, bulk tumor molecular profiling has been and remains widely used. In addition, other facets of single cell epigenomic profiling, particularly methylation and hydroxymethylation, remains underexplored. Thus, investigations to understand the cell type specific epigenetic heterogeneity and the cooperation …

Bioinformatic Analysis Of Proteomic And Genomic Data From Nsclc Tumors On Prognostic And Predictive Factors Of Immunotherapy Treatment, Mark Wuenschel

Theses and Dissertations--Pharmacy

Recent lung cancer research has led to advancements in molecular immunology, resulting in development of small molecule inhibitors, or immune checkpoint inhibitors, that propagate an anti-tumor T cell response. Despite increased overall and progression-free survival with reduced adverse effects compared to traditional chemotherapy, treating advanced stage lung adenocarcinoma patients remains non-curative, and evidence of non-responders or tumor recurrence to immune checkpoint inhibitor therapy is growing. Also, compared to traditional chemotherapy, there is a lower percentage of patients who respond to small molecule inhibitors. In this analysis of proteomic and genomic data from The Cancer Proteome Atlas and Global Data Commons …

Investigation Of Inflammation And Apoptosis Mediated Toxicity In Response To Metal Oxide Nanoparticles In Ml-1 And Ca77 Cancer Cell Lines, Alyse N. Peters

Graduate Theses/Dissertations

Metal oxide nanoparticles (MONPs) are becoming more popular in today’s environment. They contribute significantly to the technologies in agriculture and food development but there is little understanding to how MONPs, including ZnO, CuO, TiO2, and SnO2, impact human health and the environment. Our growth assay revealed that none of these negatively affects viability in the budding yeast, Saccharomyces cerevisiae. In contrast, both human thyroid cancer cells (ML-1) and rat medullary thyroid cancer cells (CA77) displayed a significant reduction in viability with the treatment of CuO and ZnO. The production of ROS in these cell lines when treated with CuO and …

The Links To Cancer: How Golf Became Dangerous And What We Can Do To Save The Game, Meredith Boos

Undergraduate Theses, Professional Papers, and Capstone Artifacts

This study is a comprehensive meta-analysis on health claims linked to exposure to golf courses, more specifically the chemicals used to maintain their appearance. It provides a brief history of the golf industry and how its growth exacerbated the environmental impact as well as an explanation of the legal landscape that will affect golf course management. Golf courses can disrupt local ecologies, contaminate ground water, rivers, lakes and streams with run-off, and be responsible for the bioaccumulation of chemicals which remain dangerous for decades. Despite the adverse effects of golf courses on the environment, there remains an opportunity to transform …

Cellular Glycosphingolipid Imbalance Modulates Emt In Cancer Cells, Laura E. Clark, Amanda Dickinson, Santiago Lima

Undergraduate Research Posters

Sphingolipids are key components of the plasma membrane and are regulators of complex biological processes often altered in cancer cells. In human tumors, genes of key enzymes that regulate levels of glucosylceramide and lactosylceramide are often amplified. However, it is unknown why these traits are positively selected in transformed cells. In this work, we used CRISPR-Cas9 to knockout two key enzymes amplified in tumors in HeLa and H1703 tumor-derived cell-lines. As expected, the knockout lines had dramatic accumulation of GlcCer and LacCer. However, unexpectedly, they showed significantly decreased in-vitro wound-healing capacity and an almost complete loss of in-vitro extra-cellular matrix …

Dissecting The Role Of Selenoprotein P And Thioredoxin Reductase In Pancreatic Cancer Metabolism, Alyssa A. Abbas

Dissertations, Master's Theses and Master's Reports

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of US cancer-related deaths, has a stark 5-year survival rate of 9%, emphasizing an urgent need for effective therapies. A well-established characteristic of cancer, metabolic dysregulation, presents an opportunity for developing therapies that target specific metabolic susceptibilities inherent in cancer cells. Our recent studies have discovered a susceptibility in PDAC; deprivation of cystine or blocking its uptake by erastin (a cystine transport inhibitor) triggers significant lipid peroxidation, thereby inducing ferroptosis specifically in the mesenchymal subtype of PDAC, but not in the epithelial subtype. This study aims to elucidate the roles of Selenoprotein …

Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy, Isaac Tuffour

Electronic Theses and Dissertations

Multidrug resistance (MDR) remains a major challenge in cancer treatment, accounting for over 90% of chemotherapeutic failures. Cancers utilize sugar residues to engage in multidrug resistance. The underlying mechanism of action involving glycans, specifically the glycan sialic acid (Sia) and its various functional group alterations, has not been explored. ATP-binding cassette (ABC) transporter proteins, key proteins utilized by cancers to engage in MDR pathways, contain Sias in their extracellular domains. Modulating the expression of acetylated-Sias on Breast Cancer Resistance Protein (BCRP), a significant ABC transporter implicated in MDR, in lung and colon cancer cells directly impacted the ability of cancer …

Deep Learning-Based Technique For The Perception Of The Cervical Cancer, Aya Haraz, Hossam El-Din Moustafa, Abeer Twakol Khaleel, Ahmed H. Eltanboly

Mansoura Engineering Journal

In third-world countries, cervical cancer is the most prevalent and leading cause of death. It is affected by a variety of factors, including smoking, poor nutritional status, immunological inadequacy, and prolonged use of contraception. The Pap smear test, which is intended to prevent cervical cancer, finds preneoplastic changes in cervical epithelial cells. This study framework classified cervical cancer cells from Pap smears into five specified cell types using machine learning-based classification algorithms. The SIPaKMeD database is used in this investigation. This public dataset, which was manually cropped from 966 cluster cell images taken from Pap smear slides, has 4045 isolated …

Cell Signaling And Stress Response In The Yeast Saccharomyces Cerevisiae: A Study Of Snf1, Scott E. Arbet Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Saccharomyces cerevisiae are yeast that are unicellular eukaryotic organisms that are well studied as a model organism for understanding fundamental cellular processes. The ability of yeast to sense nutrient availability is crucial for their survival, growth, and reproduction. Yeast cells use various mechanisms to sense and respond to nutrient availability, including transporter-mediated uptake, receptor-mediated signaling, and sensing of metabolites. The subcellular localization of nutrient-sensing components is crucial for yeast function in nutrient sensing and signaling. Protein complexes, such as the AMP-activated protein kinase (AMPK) pathway, in nutrient sensing and response, as well as the downstream effects of these pathways …

Enhancing The Conformational Stability Of The Cl-Par-4 Tumor Suppressor Via Site-Directed Mutagenesis, Samjhana Pandey, Krishna K. Raut, Antoine Baudin, Lamya Djemri, David S. Libich, Komala Ponniah, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Intrinsically disordered proteins play important roles in cell signaling, and dysregulation of these proteins is associated with several diseases. Prostate apoptosis response-4 (Par-4), an approximately 40 kilodalton proapoptotic tumor suppressor, is a predominantly intrinsically disordered protein whose downregulation has been observed in various cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) is active and plays a role in tumor suppression by inhibiting cell survival pathways. Here, we employed site-directed mutagenesis to create a cl-Par-4 point mutant (D313K). The expressed and purified D313K protein was characterized using biophysical techniques, and the results were compared to that of the wild-type (WT). We have …

Advancements In Glycogen Detection And Spatial Profiling Reveals A New Therapeutic Path For Ewing Sarcoma: A Non-Traditional Glycogen Storage Disease, Lyndsay E. A. Young

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the primary glucose storage carbohydrate in mammals, and it is synthesized in most tissues. As glycogen architecture modulates its role in metabolism, it is essential to accurately evaluate and quantify glycogen, glycogen phosphate, and chain length of glucose monomers. Simultaneous quantitation of glycogen architecture is challenging. This work describes a highly-sensitive method for the detection of both glycogen-derived glucose and glucose-phosphate esters utilizing gas-chromatography coupled mass spectrometry (GCMS). We then integrated this glycogen quantitation workflow into a routinely utilized metabolomics-based assay. The work presented describes a workflow for the normalization of polar metabolites utilizing amino acids derived from …

The Role Of Dynamin Related Protein 1-Mediated Mitochondrial Dynamics In Colorectal Cancer, Sumati Raj Hasani

Theses and Dissertations--Molecular and Cellular Biochemistry

Cancer cells are known for their ability to adapt variable metabolic programs depending on the availability of specific nutrients. Consequently, metabolic reprogramming has been increasingly recognized as a major mechanism that fuels tumorigenesis and disease progression. Here, we have investigated the role of a pro-fission factor, Dynamin-Related Protein 1 (Drp1), in promoting metabolic adaptation in colon cancer.

Our studies have shown that fatty acid (FAs) uptake alters cellular metabolic pathways in colon cancer cells to favor fatty acid oxidation through the activation of Drp1. Uptake of FAs induces mitochondrial fragmentation by promoting ERK-dependent phosphorylation of Drp1 at the S616 site, …

Exploring The Relationship Between The Epigenome And Metabolism In Mycn-Amplified Neuroblastoma, Krista M. Dalton

Theses and Dissertations

High risk neuroblastoma (NB) is responsible for nearly 15% of all cancer related deaths in the pediatric population. The transcription factor MYCN is the most studied oncogene in NB, automatically conferring high-risk and has been found to be difficult to target. One way that MYCN amplification in NB functions to support tumorigenicity is through altered metabolism, satisfying the demand for rapid proliferation by increasing the nutrient flux through biosynthetic pathways. We performed an unbiased screen on select metabolic targeted therapy combinations and correlated sensitivity with over 20 subsets of cancer. We found that MYCN-amplified NB is hypersensitive to the …