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The Association Between Uncertainty, Reproductive Distress, And Avoidance In Assigned Female At Birth Adolescent And Young Adult (Aya-F) Cancer Survivors, Devon Ann Pons

Doctoral Dissertations

Family building and fertility is a complex component of survivorship for assigned female at birth Adolescent and Young Adult’s (AYA-F’s), often accompanied by a mix of cognitive uncertainty, emotional uncertainty, reproductive distress, and avoidance. These psychological components present in survivorship for AYA-F’s can impact coping, identity development, and individualized care plans throughout survivorship. This novel examination of data from a cross sectional study shed light on the associations between reproductive distress, uncertainty, and avoidance and how they are experienced differently by various subgroups within the sample.

Results demonstrate that reproductive distress fully mediated the association between emotional uncertainty and avoidance, …

Reprogramming And Imaging Of Tumor Associated Macrophages Using Spuramolecular Nanoparticles, Anujan Ramesh

Doctoral Dissertations

Macrophages are highly plastic cells that are a part of the mononuclear phagocytic system and play a crucial role in both the innate and the adaptive immune systems. Although they have functionally diverse roles involved in physiological and pathological processes, they primarily act as phagocytes that aid in clearing infections. During these instances of tissue injury or infections, circulating monocytes are recruited to the site of the injury, where they differentiate to give rise to macrophages that have a pro-inflammatory function. These monocytes derived macrophages, however, exist across a spectrum of phenotypes based on the local tissue environment. The two …

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 …

The Experiences And Needs Of Individuals With A Variant Of Uncertain Significance (Vus) On Genetic Tests For Hereditary Cancer Syndromes: A Grounded Theory Study, Danielle Gould

Doctoral Dissertations

Background: The use of multigene panel testing for identifying individuals with hereditary cancer susceptibility has expanded in recent years. The number of individuals who have a variant of unknown significance (VUS) result is increasing. However, little is known about the experiences and needs of this group. This study’s purpose was to describe the experiences and needs of individuals with a VUS result by focusing on their experiences in communicating with healthcare providers and family members. Methods: A constructivist grounded theory approach was used. Recruitment took place from January–July 2021 through social media: the Prospective Registry of Multiplex Testing (PROMPT), and …

Nonparametric Bayesian Deep Learning For Scientific Data Analysis, Devanshu Agrawal

Doctoral Dissertations

Deep learning (DL) has emerged as the leading paradigm for predictive modeling in a variety of domains, especially those involving large volumes of high-dimensional spatio-temporal data such as images and text. With the rise of big data in scientific and engineering problems, there is now considerable interest in the research and development of DL for scientific applications. The scientific domain, however, poses unique challenges for DL, including special emphasis on interpretability and robustness. In particular, a priority of the Department of Energy (DOE) is the research and development of probabilistic ML methods that are robust to overfitting and offer reliable …

Formulation And Evaluation Of Gemcitabine Plus Romidepsin + Cisplatin Combination For Controlling Tumors, Pawat Pattarawat

Doctoral Dissertations

Cancer is a deadly malignant disease that is costly to treat and still impossible to cure. Cancer treatments often come with side effects that impact the overall health of patients. Breast cancer is the most common type of cancer in the United State and bladder cancer mortality and recurrence rates are still high among cancer patients. Thus, safe and effective regimens are needed to combat these diseases.

In this study, the safe and efficacious combination of gemcitabine, cisplatin, and romidepsin (Gem plus Rom+Cis) to treat two types of cancer: bladder and breast cancer, was formulated. In vitro data from this …

Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter

Doctoral Dissertations

Metastasis is the leading cause of cancer related deaths, yet it remains the most poorly understood aspect of tumor biology. This can be attributed to the lack of relevant experimental models that can recapitulate the complex and lengthy progression of metastatic relapse observed in patients. Mouse models have been widely used to study cancer, however they are critically limited to study metastasis. Most models generate aggressive metastases in the lung without the use of unique cell lines or specialized injection techniques. This limits the ability to study disseminated tumor cells (DTCs) in other relevant metastasis prone tissues. Prolonged observation of …

Defining The Let-7 Microrna-Mediated Molecular Mechanisms Regulating T Cell Differentiation, Constance C. Angelou

Doctoral Dissertations

CD4⁺ and CD8⁺ T cells are lymphocytes of the adaptive immune system that play essential roles in immunity. Both T cell subsets recognize their cognate antigen through the T cell receptor (TCR), which induces the proliferation and differentiation of these antigen-specific cells into effector T cells. CD4⁺ T cells have the potential to differentiate into one of multiple lineages of helper T (Th) cells and participate indirectly in antigen clearance by orchestrating the function of other cells. CD8⁺ T cells differentiate into cytotoxic T lymphocytes (CTL), which directly contributes to the resolution of an infection by …

Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das

Doctoral Dissertations

Bioorthogonal catalysis offers a strategy for chemical transformations complementary to bioprocesses and has proven to be a powerful tool in biochemistry and medical sciences. Transition metal catalysts (TMCs) have emerged as a powerful tool to execute selective chemical transformations, however, lack of biocompatibility and stability limits their use in biological applications. Incorporation of TMCs into nanoparticle monolayers provides a versatile strategy for the generation of bioorthogonal nanocatalysts known as “nanozymes”. We have fabricated a family of nanozymes using gold nanoparticles (AuNPs) as scaffolds featuring diverse chemical functional groups for controlled localization of nanozymes in biological environments, providing unique strategies for …

Chemical Biology Of 6-Nitrochrysene Induced Deoxyadenosine Dna Adduct And Formamidopyrimidine Dna Lesion: Mutagenesis And Genotoxicity In E. Coli And Human Cells, Brent V. Powell

Doctoral Dissertations

The environmental pollutant, 6-nitrochrysene (6-NC) is the most potent carcinogen evaluated by the newborn mouse assay. The genotoxicity of 6-NC is derived from its ability to form electrophilic species in cells which can react with nucleophilic sites of 2'-deoxyguanosine (dG) and 2’-deoxyadenosine (dA) in DNA to generate DNA-carcinogen adducts. DNA lesions derived from 6-NC can play important roles in the development of human cancer by inducing mutations in crucial genes resulting in the disruption of gene expression. Mutations in an oncogene, a tumor-suppressor gene such as p53, or a gene that controls the cell cycle can lead to uncontrolled …

Investigation On Nanoparticle Based Combination Therapy For Targeted Cancer Treatment, Muhammad Raisul Abedin

Doctoral Dissertations

“The current treatment methods in cancer are associated with toxicity in healthy tissues, partial therapeutic response, drug resistance and finally recurrence of the disease. The cancer drugs are challenged by non-specific binding, undesired toxicity in healthy cells, low therapeutic index and finally poor therapeutic outcome. In this work, a targeted nanoscale therapeutic system Antibody Drug Nanoparticle (ADN) was engineered to selectively inhibit the breast cancer cell growth with reduced toxicity in healthy cells. The ADNs were designed by synthesizing rod shaped anoparticles using pure chemotherapeutic drug and covalently conjugating a therapeutic monoclonal antibody (mAb) on the surface of the drug …

An Integrative Healthcare Program For Cancer Patients: Longitudinal Effects On Emotional Health And Immune Function, Rebecca Shorter

Doctoral Dissertations

Evidence supports potential short-term benefits of integrative healthcare (IH) for cancer patients, which combines conventional Western medicine with adjunctive, complementary treatments; however, the long-term efficacy of IH has not been systematically studied. The current study examined the short- and long-term effectiveness of IH for cancer patients, relative to treatment as usual (TAU), in improving emotional and immune health. Also examined were systematic differences at baseline (i.e., emotional distress, sociodemographic and cancer variables) associated with IH usage. Patients were recruited from a University Medical Center (n = 178) and were eligible to participate irrespective of cancer diagnosis and stage. Patients opted …

Cholesterol-Based Polymeric Nanoparticles For Improved Chemotherapy, Laura Gonzalez

Doctoral Dissertations

Polymeric nanoparticles from amphiphilic copolymers are deemed as flexible platforms for effective delivery of chemotherapeutic drugs to tumor tissues. The use of cholesterol as the hydrophilic segment can confer stability upon dilution and high drug loading capacity to these type of nanoparticles due to the tendency of cholesteryl groups to aggregate and form liquid crystal phases. On the other hand, the incorporation of polyethylene glycol as the hydrophilic block provides colloidal stability and reduced opsonization. Building on previous research in the laboratory, the overall goal of the present dissertation was to further advance the development and understanding of novel and …

Design, Synthesis, Characterization And Anti-Cancer Effects Evaluation Of Interchain Cysteine Linked Antibody Drug Conjugates, Ke Li

Doctoral Dissertations

"Antibody drug conjugates (ADCs) are emerging therapeutic products specially designed for the treatment of cancers. Potent cytotoxic agents are linked to antibodies via linkers. Antibody drug conjugates, which take advantage of both antibodies and cytotoxic agents, showed high selectivity towards cancer cells. Cytotoxic agents are delivered to the cancer cells selectively and kill them from inside while leaving low or non-toxicity towards normal cells. Antibody drug conjugates are actually heterogeneous mixtures. The major heterogeneities mainly lie in the drug to antibody ratio (DAR) and drug linking positions, both of which potentially affect the therapeutic index of ADCs. In this research, …

Elucidating The Mechanisms Of Apoptosis Induced By A Novel Geranylgeranyl Diphosphate Synthase Inhibitor In T-Cell Acute Lymphoblastic Leukemia, Sherry Agabiti

Doctoral Dissertations

Archival abstract submitted

Distress During Cancer Treatment And Its Relation To Posttraumatic Stress Symptoms, Matthew Robert Moore

Doctoral Dissertations

This dissertation focuses on the psychological response to stress in cancer patients. Specifically, it examines the factors which increase the likelihood of experiencing distress and posttraumatic stress (PTSS), as well as the relationship between distress and PTSS. The dissertation is composed of three manuscripts, the first of which presents a review of the current literature on distress and PTSS in adult cancer patient populations. It indicates that distress is prevalent in cancer patient populations, and that increased levels of distress may be related to PTSS. Furthermore, risk and protective factors are identified, including older age and social support, which may …

Lung And Colon Cancer Chemoprevention By Polymethoxyflavones, Mingyue Song

Doctoral Dissertations

Cancer has been a leading cause of morbidity and mortality worldwide and characterized by the uncontrolled cell proliferation and an absence of cell death. Polymethoxyflavones (PMFs) is a unique class of flavonoids that almost exclusively found in the peel of citrus fruit. Studies have shown that PMFs exhibited numerous health promoting effects, including anti-carcinogenic and anti-inflammatory ones. Nobiletin (5,6,7,8,3’,4’-hexamethyoxflavone, NBT) is a major citrus flavonoid and has been the most studied PMFs for its potential health benefits. 5-Demethylnobiletin (5-hydroxy-6,7,8,3’,4’-pentamethoxyflavone, 5DN) is a unique flavonoid found in citrus fruits with potential chemopreventive effects against human cancers. In this dissertation, we first …

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …

Characterizing Colorectal Cancer Cells And Their Interactions With Polymethoxyflavones By Raman Microscopy, Hua Zhang

Doctoral Dissertations

Polymethoxyflavones (PMFs), especially Nobiletin (NBT) and 5-demethylnobiletin (5DN), have been widely studied and proved to have anti-cancer effects. However, their exact modes of action against cancer cells are not fully understood. Raman spectroscopy is a molecular vibrational spectroscopy can be used to measure overall biochemical function of single cells noninvasively and without adding any chemical labels. Herein, we characterized the cellular responses of human colorectal cancer HT29 and HCT116 cells, that grow on the gold coated slides, to the treatments of NBT and 5DN using Raman microscopy. Raman microscopic images obtained indicated the different modes of action of these two …

Psychometric Properties Of Three Common Depression Measures In Breast Cancer Patients With Major Depressive Disorder, Audrey Ashton File

Doctoral Dissertations

Breast cancer is the most frequently diagnosed cancer among women in the United States and MDD is the most common mental health problem in women with breast cancer. There is lack of research on measures of depression in this population. This study examined the psychometric properties of three commonly used depression measures, the BDI-II, CES-D, and HRSD, with clinically depressed breast cancer patients (n = 127). Findings revealed the measures displayed good distributional characteristics, internal consistency, and convergent validity. Discriminative validity with the BAI was not demonstrated, however, and confirmatory factor analyses indicated that the existing models of these …

Alternative Methods For The Treatment Of Chemo-Resistant Cancers, Kaitlyn Wong

Doctoral Dissertations

Great strides have been made in cancer therapy in the past century, yet it remains one of the leading causes of death in the United States today. This work aimed to shed light on novel methods to treat a variety of aggressive and often chemo-resistant cancers both in vitro and in vivo. The first aim of this work was to evaluate the therapeutic efficacy of poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) prodrugs compared to standard chemotherapeutic agents. Conjugation of polyMPC to drugs such as doxorubicin (Dox) can result in its improved solubility, prolonged half-life and therapeutic efficacy. PolyMPC and polyMPC-Dox (at a …

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …

Engineering Novel Detection And Treatment Strategies For Bacterial Therapy Of Cancer, Jan T. Panteli

Doctoral Dissertations

Finding and treating cancer is difficult due to limited sensitivity and specificity of current detection and treatment strategies. Many chemotherapeutic drugs are small molecules that are limited by diffusion, making it difficult to reach cancer sites requiring high doses that lead to systemic toxicity and off-target effects. Tomographic detection techniques, like PET, MRI and CT, are good at identifying macroscopic lesions in the body but are limited in their ability to detect microscopic lesions. Biomarker detection strategies are extremely sensitive and able to identify ng/ml concentrations of protein, but are poor at discriminating between healthy and disease state levels due …

Electrochemical Based Detection Of Cancer Biomarker Proteins Using Multi-Labeled Magnetic Particles In Microfluidic Systems, Colleen Ellen Krause

Doctoral Dissertations

Time is measured as a moment, hour, day or year as indicated by a clock or calendar. To someone facing cancer it seems to count backwards from a date determined by an incurable disease. Even with the advances in research and technology cancer is still a leading cause of death in the United States as no cure exists. Biomedical research is constantly struggling with cancer detection, diagnosis, treatment, and prevention. Currently, cancer detection is expensive, diagnoses are sometimes erroneous, treatment is invasive, and prevention is a challenge.

The primary goal of the cancer detection is to develop simple non-invasive tests …

Design Of A Targeted Bacterial Drug Delivery Vector For The Treatment Of Cancer And Metastases, Charles Alexander Swofford

Doctoral Dissertations

Engineered Salmonella possess unique capabilities that make them ideal drug delivery vectors for tumors. Targeted bacterial delivery of anticancer proteins has the ability to overcome therapeutic resistance in tumors that limits the efficacy of chemotherapeutics. In my doctoral research, I identified a protein-drug that can be expressed by bacteria and rapidly kills cancer cells. I also created a density dependent switch that initiates gene expression in tumors and prevents expression in healthy tissue. Combining these two systems has created a potent anti-cancer system that targets tumors with minimal toxicity. I cloned genes for five potential anti-cancer proteins into Salmonella. …

Selection Of A Nanoparticle Stabilizer For A Calcium Phosphate Drug Delivery System, Jessica L. Woodman

Doctoral Dissertations

Overall cancer survival rates steadily decline each year following diagnosis and side effects of chemotherapy restrict its use. The chemotherapeutic cis-diamminedichloro-platinum (cisplatin, CDDP) is poorly soluble and has dose limiting side effects. Nanoparticle delivery systems can deliver a higher dose of drug directly to the tumor by both active and passive targeting, holding promise of fewer side effects and greater anti-tumor efficacy. To date, few nanoparticle systems have been FDA approved for the treatment of cancer due to complicated physicochemical characterization, drug inactivation by the delivery system, scale-up challenges, and lack of demonstrated in vivo safety and efficacy. Further research …

Towards The Development Of Tropolone Natural Product Derivatives As Novel, Potent Anticancer Therapeutics That Selectively Target Histone Deacetylase (Hdac) Enzymes, Sophia Nnenna Ononye

Doctoral Dissertations

Cancer is the second leading cause of death in the United States. Inhibitors that target key enzymes involved in epigenetic alterations, particularly histone deacetylases (HDACs), are garnering interest in cancer research because of their unique ability to reversibly induce terminal differentiation of transformed cells by influencing chromatin structure. Through an in-house collaborative effort, derivatives of hinokitiol, a troplone-related non-benzenoid aromatic compound, are being synthesized and characterized by the Wright and Anderson laboratories as HDAC inhibitors (HDACi). Given the novelty of these tropolones as antineoplastic agents, a number of biochemical and functional studies were conducted in order to develop tropolones as …

Identification Of Novel Molecular Targets Of Resveratrol In Colorectal Carcinogenesis, Nichelle Chantil Whitlock

Doctoral Dissertations

Current research suggests resveratrol, a phytoalexin found predominately in grapes, may function as a chemopreventive and/or chemotherapeutic agent for various cancers, including colorectal cancer. However, the underlying mechanism(s) involved in these activities remain elusive. Thus, the objective of the studies discussed here sought to investigate the effect of resveratrol treatment on gene modulation in human colorectal cancer cells in order to identify and characterize novel molecular targets that contribute to the observed anticancer activities of resveratrol. Here, we identify activating transcription factor 3 (ATF3) and early growth response-1 (Egr-1) as novel targets of resveratrol and provide data to elucidate the …

Characterizing The Role Of Dna Repair Proteins In Telomere Length Regulation And Maintenance: Fanconi Anemia Complementation Group C Protein And 8-Oxoguanine Dna Glycosylase, David Beomjin Rhee

Doctoral Dissertations

Telomeres are the chromosome end structures consisting of telomere-associated proteins and short tandem repeat sequences, TTAGGG, in humans and mice. Telomeres prevent chromosome termini from being recognized as broken DNA ends. The structural integrity of DNA including telomeres is constantly threatened by a variety of DNA damaging agents on a daily basis. To counteract the constant threats from DNA damage, organisms have developed a number of DNA repair pathways to ensure that the integrity of genome remains intact. A number of DNA repair proteins localize to telomeres and contribute to telomere maintenance; however, it is still unclear as to what …

Functional Analysis Of Chromodomain Helicase Dna Binding Protein 2(Chd2) Mediated Genomic Stability, Sangeetha Rajagopalan

Doctoral Dissertations

Histone modifying enzymes and chromatin remodeling complexes play an important regulatory role in chromatin dynamics that dictate the interaction of regulatory factors involved in processes such as DNA replication, recombination, repair and transcription, with DNA template. The CHD (Chromodomain Helicase DNA Binding Protein) family of proteins is known to be involved in the regulation of gene expression, recombination and chromatin remodeling via their chromatin specific interactions and activities. Phenotypic analysis of the Chd2 mutant mouse model developed by our laboratory indicates that the Chd2 protein plays a critical role in tumor suppression as the heterozygous mutant mice develop spontaneous lymphomas. …