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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 …

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 …

Construction And Performance Optimization Of Bioconjugated Nanosensors For Early Detection Of Breast Cancer And Pro-Inflammatory Diseases, Pooja Gaikwad

Dissertations, Theses, and Capstone Projects

In recent years, nanosensors have emerged as a tool with strong potential in medical diagnostics. Single-walled carbon nanotube (SWCNT) based optical nanosensors have notably garnered interest due to the unique characteristics of their near-infrared fluorescence emission, including tissue transparency, photostability, and various chiralities with discrete absorption and fluorescence emission bands. Additionally, the optoelectronic properties of SWCNT are sensitive to the surrounding environment, which makes them suitable for in vitro and in vivo biosensing. Single-stranded (ss) DNA-wrapped SWCNTs have been reported as optical nanosensors for cancers and metabolic diseases. Breast cancer and cardiovascular diseases are the most common causes of death …

Examining Factors Related To Tobacco Treatment Engagement Among Tobacco Dependent Black/African American; Hispanic/Latino Cancer Patients: An Analysis Of Memorial Sloan Kettering Cancer Center’S Tobacco Treatment Program, Gleneara E. Bates-Pappas

Dissertations, Theses, and Capstone Projects

Among patients diagnosed with cancer, persistent tobacco use is associated with adverse clinical outcomes such as worse treatment side effects, decreased effectiveness of cancer treatment (chemotherapy, radiotherapy, and surgery), all increasing risk of recurrence, second primary cancers, and poor survival. Despite the clinical importance of tobacco cessation in the context of high quality cancer care, engaging Black/African American and Hispanic/Latino cancer patients in tobacco treatment programs can be challenging. Prior studies with the general adult population demonstrate that Black/African American and Hispanic/Latino smokers are referred to and accept tobacco cessation treatment at lower rates compared to non-Hispanic White smokers. This …

Optimized Peptide Nanomaterials As Delivery Vehicles For Hydrophobic Metal-Based Anticancer Agents, Yaron Marciano

Dissertations, Theses, and Capstone Projects

Enzyme-responsive materials have been well explored, particularly as therapeutic and diagnostic agents. In this thesis we demonstrate that anionic self-assembling peptides can be utilized as delivery vehicles for metal-based hydrophobic payloads. The tunability of the system is highlighted as well as the increase in cytotoxicity and selectivity in vitro. The rapid degradation of peptides in cell media may lead to the formation of new peptide-drug bioconjugates with increased activity and selectivity. The physiological stability of these peptide delivery vehicles has been optimized by capping the N-terminus with an acetyl group. This simple backbone modification was shown to not prevent self-assembly, …

Race, Gender, Physical Activity, And Cancer: A Quantitative Investigation, Shawna A. Townsend

Dissertations, Theses, and Capstone Projects

Black women are more likely to die from cancer than any other population in the United States. Physical activity is known to be associated with preventing and reducing cancer burden. However, Black women are less physically active than their White counterparts and have a higher prevalence of diseases related to lack of physical activity than any other female group. To better understand these issues, this study employed the self-and-family management framework and intersectionality as theoretical frameworks through a secondary analysis of the Health Information National Trends Survey (HINTS) dataset and hierarchical regression modeling to examine the relative impact of (a.) …

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 …

"It Was Handed To Them": The Origins Of Targeted Delivery And The Spirit Of Nanomedicine, Marzena Woinska

Dissertations, Theses, and Capstone Projects

Nanotechnology is widely recognized as an important field. Since the 2000s, nano-based targeting has been a cutting-edge approach in cancer research. To specify what nanomedicine means and describe its significance at the cultural level, this study harnesses data from peer-reviewed articles published in leading scientific journals.

Balancing precariously between sociological theory and science and technology studies, this project turns to nanomedicine’s origins to address broader questions regarding the relationship between science and society and the causes of scientific discovery and technological innovation. It tells the story of nanotechnology's discursive formations taking on a life of their own and congealing into …

Anti-Cancer Effects By Interleukin 24, Xuelin Zhong

Dissertations, Theses, and Capstone Projects

Cancers develop as some cells acquire the ability, either by exogenous stimulation or by spontaneous mutation, to keep growing despite normal restraints. Up-regulating translation of oncogenes involved in cell proliferation and tumor development and down-regulating translation of tumor-suppressors that normally suppress tumor development are two most common mechanisms by which cancers develop. Therefore, it is crucial to study how these proteins get either up-regulated or down-regulated at translational level.

The eukaryotic translation initiation factor, which is composed of subunits such as eIF4A, eIF4G and eIF4E, is one of the key factors that contribute to efficient translation initiation. Interleukin 24 (IL-24), …

Leveraging Antibodies For Positron Emission Tomography And Near-Infrared Fluorescence Imaging Of Cancer, Kimberly C. Fung

Dissertations, Theses, and Capstone Projects

The high specificity and affinity of antibodies make them attractive for developing drugs to diagnose and treat cancer. The overarching goal of this work is to explore the synthesis and use of antibody-based imaging agents in preclinical models of cancer. This work can be described as two-fold. In the first part, we investigated how the use of a glycans-specific bioconjugation strategy affects Fc gamma RI binding and why it results in improved in vivo performance of immunoconjugates. To do so, we used the clinically relevant positron emission tomography (PET) imaging agent, ⁸⁹Zr-DFO-pertuzumab, in mouse models of human breast cancer. …

Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren

Dissertations, Theses, and Capstone Projects

Oleocanthal is a phenolic compound found in varying concentrations in extra virgin olive oil. Oleocanthal has been shown to be active physiologically, benefiting several diseased states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal induced damage to cancer cells’ lysosomes leading to cellular toxicity in vitro. Non-cancer cells were significantly less affected. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, …

Examining Financial Stress And Coping Among U.S. Cancer Patients And Survivors: Quantitative Analyses Of Survey Data., Meredith J. Doherty

Dissertations, Theses, and Capstone Projects

Financial hardship, a growing problem for cancer patients and survivors, is associated with increased pain and symptom burden, reduced quality of life and psychological wellbeing, poor treatment adherence, and early mortality. Nearly one in three cancer patients reports that cancer caused some financial stress or strain. Emerging research has begun to explore the coping strategies used by cancer-affected individuals to manage the direct and indirect costs associated with cancer and its treatment. This dissertation seeks to answer three research questions: (1) what are the measurable characteristics of different cost-coping strategies? (2) what behavioral, institutional, and social factors are associated with …

Relational Processes In Support-Related Communication Among Young Adults With Cancer, Kathleen Darabos

Dissertations, Theses, and Capstone Projects

Despite decades of studies reporting positive associations of social support with cancer-related quality of life, little attention has been paid to understanding how relational qualities (e.g., self-disclosure, perceived support member disclosure, perceived support member responsiveness) of cancer-related support exchanges might influence psychological adjustment and intimacy among young adults with cancer. Further, little attention has been paid to understanding how young adults with cancer communicate with their social support networks among different modes of communication [(face-to-face vs. technology-related (e.g., text message, social media)] remains poorly understood. Questionnaire data from 45 young adults with cancer combines these two separate but related literatures …

The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud

Dissertations, Theses, and Capstone Projects

Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death are …

The Role Of Oxidative Stress And Signal Transduction In Chemotherapy-Mediated Cognitive Impairment In The Menopause Rat Model, Ciara Bagnall

Dissertations, Theses, and Capstone Projects

Systemic chemotherapy treatment is associated with long-term cognitive impairment in breast cancer survivors. While many studies have established the forms of cognition and corresponding regions in the brain most affected, very little is revealed about the potential molecular mechanisms that mediate these changes. The effects of systemic treatment on the brain is likely attributed to many different mechanisms including oxidative stress and immune dysregulation. Earlier studies from our lab have investigated the effects of the chemotherapy cocktail doxorubicin and cyclophosphamide (AC Chemotherapy) in an ovariectomized menopause animal model of ‘chemo brain’ (Salas-Ramirez et al., 2015). We observed that animals injected …

Parp Pet Imaging Agents, Brandon Carney

Dissertations, Theses, and Capstone Projects

The poly (adenosine-diphosphate (ADP) ribose) polymerase (PARP) family of enzymes has been of interest to researchers and clinicians for over fifty years, especially the first member of the family, PARP1. This enzyme has become a target for cancer therapeutics due the reliance of highly proliferating cells on PARP1 for genomic maintenance. In the coming age of individualized medicine, however, highly specific therapeutic agents like PARP inhibitors are in need of similarly highly specific companion diagnostic agents. These kind of agents have been made possible with the quickly progressing field of molecular imaging. Specifically, positron emission tomography (PET) has enabled the …

New Dyes For Cancer Theranostics, Waqar Rizvi

Dissertations, Theses, and Capstone Projects

Porphyrinoids are robust heterocyclic dyes studied extensively for applications in medicine and as photonic materials because of their tunable photophysical properties, diverse means of modifying the periphery, and the ability to chelate most transition metals. Commercial applications include phthalocyanine dyes in optical discs, porphyrins in photodynamic therapy, and as oxygen sensors. Most applications of these dyes require exocyclic moieties to improve solubility, target disease, modulate photophysical properties, or direct self-organization into architectures with desired photonic properties. The synthesis of the porphyrinoid depends on the desired application, but the de novo synthesis often involves several steps, is time consuming, and results …

Lim Protein Ajuba Directly Interacts With Replication Protein A To Prevent Atr Dna Damage Response, Sandy Wan Shan Fowler

Dissertations, Theses, and Capstone Projects

Integrity of the human genome is essential for viability and proliferation of human cells. Intrinsic (endogenous replication stress) or extrinsic (UV, chemotherapy drugs) agents threaten the stability of the genome by generation of single stranded (ss) DNA or double stranded (ds) DNA breaks. The DNA damage response (DDR) pathways are conserved in evolution and constitute systems that perform the surveillance, signaling, and repair of the damage in the nucleus. Unchecked and accumulation of DNA damage can lead to deleterious effects such as replication fork collapse, chromosome fusion and breakage. The dysregulations of DNA damage response pathways are hallmarks of tumorigenesis. …

The Role Of T-Box Proteins In Vertebrate Germ Layer Formation And Patterning, Sushma Teegala

Dissertations, Theses, and Capstone Projects

All of the tissues in triploblastic organisms, with the exception of the germ cells, arise from the three germ layers, ectoderm, mesoderm and the endoderm. The identification of the genes that underlie the differentiation of these layers is crucial to our understanding of development. T-box family proteins are DNA-binding transcriptional regulators that play important roles during germ layer formation in the early vertebrate embryo. Well-characterized members of this family, including the transcriptional activators Brachyury and VegT, are essential for the proper formation of mesoderm and endoderm, respectively. To date, T-box proteins have not been shown to play a role in …

Latino/A Adolescents And Young Adults Coping With Parental Cancer Within A Cultural Context, Amanda Mia Marin-Chollom

Dissertations, Theses, and Capstone Projects

Parental cancer has a strong influence on the psychological well-being of children at all ages. Children and adolescents whose parents have more distress and advanced disease tend to have lower rates of healthy psychological adjustment. Children from the U.S. Latino/a population may face additional challenges, such as racism and acculturative stress that compound the stress of having a parent with cancer. At the same time, facets of the Latino/a culture may play a crucial role in how Latino/a adolescents adapt to parental cancer, specifically the Latino/a cultural values of familismo (familism), espíritu (spirit), and respeto (respect).

This cross-sectional study examined …

The Lived Experience Of Fathers With Advanced Cancer, Maria Mowassee

Dissertations, Theses, and Capstone Projects

Historically, fathers have been neglected as a research population in the nursing and oncology literature. This was in relation to their role being viewed as a disciplinarian and breadwinner instead of a nurturer. Fast-forward to modern day society, their role has evolved into a more involved parent that is necessary for their child’s development and well-being. The literature has also evolved and in recent years, this population has been gaining recognition and it is of great importance to understand their role, perception, and concerns as it pertains to being involved fathers. Therefore, when considering fathers with advanced cancer when death …

Lipid Dependence In Ras-Driven Tumors, Darin Salloum

Dissertations, Theses, and Capstone Projects

Over past decade, metabolic alterations in cancer cells have received a substantial amount of interest. It had been established that cancer cells undergo a significant amount of metabolic alterations, and some of these alterations are similar to those in normal highly proliferative cells. However, it is becoming more apparent that many of the metabolic alterations are specific to particular oncogenic signaling pathways. Although altered metabolic machinery makes cancer cells more efficient at promoting growth when nutrients are supplied at the sufficient amounts, the dependency of cancer cells on particular metabolic reprogramming deems cancer cells susceptible to disruptions within metabolic network. …

Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena

Dissertations, Theses, and Capstone Projects

Growth factors (GFs) as well as nutrient sufficiency regulate cell division in metazoans. The vast majority of mutations that contribute to cancer are in genes that regulate progression through the G1 phase of the cell cycle. A key regulatory site in G1 is the growth factor-dependent Restriction Point (R), where cells get permissive signals to divide. In the absence of GF instructions, cells enter the quiescent G0 state. Despite fundamental differences between GF signaling and nutrient sensing, they both have been confusingly referred to as R and therefore by definition considered to be a singular event in G1. Autonomy from …