Medicine and Health Sciences Commons^™

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …

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 …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …

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 …

Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett

Biological Sciences Undergraduate Honors Theses

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized …

Sit Less, Move More: A National Study Of Physical-Activity Behavior And Cancer, Stella O. Nwogugu

Dissertations, Theses, and Capstone Projects

Background: Physical activity is associated with lower risks of cancer, the second leading cause of death among Americans. Yet, sedentary behavior is the prevailing lifestyle for about 80% of American adults. Additionally, cancer survivors remain significantly inactive, even though physical activity has been shown to decrease risk of cancer and cancer recurrence, improve tolerance of cancer therapy, and reduce mortality. This research explores the relative impact of personal agency, social support, and key demographic variables on physical-activity behavior for a national sample of adults as well as how these relationships differ for cancer survivors and their counterparts.

Methods: Using the …

Promoting Healthier Treatment Outcomes In Obese Cancer Patients Taking High Dose Methotrexate, Carly Dell'ova

Walden Dissertations and Doctoral Studies

Cancer and obesity rates continue to rise, creating enormous public heath burdens to the individual and at the national and global levels, reducing quality of life, and increasing spending. Moreover, the relationships between cancer and obesity are not well understood. A commonly used chemotherapy for several types of cancer is high dose methotrexate (HDMTX). Along with chemotherapy, especially at high doses, comes toxicity to specific organs and the entire body. However, limited research has been conducted on obese cancer patients as they are often excluded from clinical studies. Practitioners need to better understand how to dose these patients to provide …

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 …

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 …

Genetic And Pharmacogenetics Associations Of Cancer Disparities In Appalachia, Nan Lin

Theses and Dissertations--Pharmacy

Individuals residing in Appalachian regions have significant health disparities, including higher cancer incidence and mortality rates. Previous studies have addressed the impact of socioeconomic status and environmental risk factors on Appalachia cancer disparities, while few studies have evaluated genetic risk factors.

Germline whole exome sequencing samples from 7,078 individuals with cancer (759 Appalachians) were evaluated. Demographics and relatedness were assessed using KING. Ethnicity was verified by principal component analysis using TRACE, which included 6,034 individuals (85%) of European genetic ancestry. After QC filtering, 5,980 individuals were analyzed. To assess the overall predisposition of hereditary disease, gene level frequency of likely …

Movement As Medicine: Dance/Movement Therapy For Individuals With Autism, Parkinson’S Disease, And Cancer, Alessia Zanobini

CMC Senior Theses

Dance/movement therapy (D/MT) is the psychotherapeutic use of expressive, creative movement to support holistic well-being. D/MT views the human being as a single body-mind unit and movement as a manifestation of life experiences. While typically practiced as a mental health intervention, D/MT can be adapted for a variety of populations. This thesis evaluates scientific data for the non-traditional use of D/MT for three conditions: autism, Parkinson’s disease, and cancer. For individuals on the autism spectrum, D/MT can strengthen attunement skills, provide creative communication outlets, and relieve harmful physical manifestations of autism. For individuals with Parkinson’s disease, D/MT can simultaneously ease …

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 …