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Diet By Genomic Interactions In Determining Metabolic Traits And Profiles On Glucose Metabolism Among Mexican Americans In Starr County, Texas, Shinhye Chung Aug 2023

Diet By Genomic Interactions In Determining Metabolic Traits And Profiles On Glucose Metabolism Among Mexican Americans In Starr County, Texas, Shinhye Chung

Dissertations and Theses (Open Access)

Worsening glycemia, prediabetes and diabetes, is one of the essential diseases in public health, considering their high prevalence, the enormous impact on multiple organs, and the economic burden on the community. Various factors can affect the pathogenesis of worsening glycemia, and this study focused on macronutrient intake, genes, and their interactions with metabolome data. 616 self-reported Mexican American participants in Starr County were recruited with informed consent. 308 identified and 2,471 unidentified metabolites were used for the analysis, and all the metabolites were inverse normalized with less than half of the missing rate. Each of the five glycemic and lipid …


Economic And Policy Determinants Of National Abortion Rates: A Cross-National Study, Olufunke Akiyode Aug 2023

Economic And Policy Determinants Of National Abortion Rates: A Cross-National Study, Olufunke Akiyode

Dissertations and Theses (Open Access)

Abortion is as old as humanity and exists in all cultures. The number and rate of abortions differ among countries and regions of the world. Some determinants of abortion may include economic indicators and policy restrictiveness. This study analyzes the economic and policy determinants of abortion by evaluating the association of income and policy on abortion rates. It uses a panel data regression to examine the association between income, Gini Coefficient and abortion rates. Gini Coefficient measures income inequality, and GNI represents a country’s income. Publicly available longitudinal data obtained from the World Bank, United Nations, United Nations Population Development …


Baby Boomer Gay Men’S Lived Experiences With Primary Healthcare: A Qualitative Study, Aaron J. Loeb Aug 2023

Baby Boomer Gay Men’S Lived Experiences With Primary Healthcare: A Qualitative Study, Aaron J. Loeb

Dissertations and Theses (Open Access)

Background: Baby boomer gay men have experiences discrimination in healthcare settings. Members of the LGBTQIA+ population are often studied as a single entity, which fails to account for the distinct cultural and social generational differences within this population that may affect their experiences of health care. A paucity of research is available on baby boomer gay men’s perspectives about primary healthcare experiences. Such knowledge is necessary to improve inclusiveness in healthcare settings and health outcomes.

Purpose: The purpose of this study was to describe baby boomer gay men’s lived experiences with primary healthcare. The specific aims are to describe: (1) …


Toward Nonparametric Propensity Score Estimation With Guaranteed Covariate Balance, Yan Li Aug 2023

Toward Nonparametric Propensity Score Estimation With Guaranteed Covariate Balance, Yan Li

Dissertations and Theses (Open Access)

Establishing clear causality between exposures and outcomes is often complicated by confounders in observational studies, which leads to imbalance in covariate distributions between treatments and biased treatment effect inference. The propensity score (PS) has been widely used to adjust this covariate imbalance in observational data. However, the propensity score analysis methods rely on a correctly specified parametric PS model. When the model is misspecified, the covariate imbalance may occur, which leads to biased estimation of the treatment effect. Therefore, it is necessary to study how to improve the model misspecification in propensity score analysis.

My Ph.D. dissertation consists of three …


The Development Of Artificial Intelligence-Based To Ols For Expert Peer Review Of Radiotherapy Treatment Plans, Mary Gronberg Aug 2023

The Development Of Artificial Intelligence-Based To Ols For Expert Peer Review Of Radiotherapy Treatment Plans, Mary Gronberg

Dissertations and Theses (Open Access)

Creating a patient-specific radiation treatment plan is a time-consuming and operator-dependent manual process. The treatment planner adjusts the planning parameters in a trial-and-error fashion in an effort to balance the competing clinical objectives of tumor coverage and normal tissue sparing. Often, a plan is selected because it meets basic organ at risk dose thresholds for severe toxicity; however, it is evident that a plan with a decreased risk of normal tissue complication probability could be achieved. This discrepancy between “acceptable” and “best possible” plan is magnified if either the physician or treatment planner lacks focal expertise in the disease site. …


Interrogations Of The Tumor Microenvironment Using Magnetic Resonance Imaging, Tianzhe Li Aug 2023

Interrogations Of The Tumor Microenvironment Using Magnetic Resonance Imaging, Tianzhe Li

Dissertations and Theses (Open Access)

Both tumor acidosis and tumor hypoxia are characteristics commonly found in the microenvironment of solid malignant tumors. Accurate characterization of the two phenomena could provide important information to clinicians for devising suitable treatment plans. Tumor acidosis and hypoxia are closely linked to each other. Tumor acidosis is caused by the inclination of cancer cells towards anaerobic respiration, and one of the main contributing factors for the avoidance of aerobic respiration is tumor hypoxia. Both phenomena can indicate the high metastatic potential of cancers and can also cause resistance of the cancer systems against anti-cancer therapies. Therefore, developing novel molecular imaging …


Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro Aug 2023

Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro

Dissertations and Theses (Open Access)

DICER1 is a multidomain enzyme discovered and widely recognized for its function in small non-coding microRNA (miRNA) synthesis. In cancer development, DICER1 functions as a haploinsufficient tumor suppressor which regulates miRNAs and Epithelial-to-Mesenchymal Transition (EMT). The Arur laboratory discovered that DICER1 is phosphorylated by active ERK and that ERK-mediated phosphorylation triggers DICER1 to translocate from the cytoplasm to the nucleus of cells in worms, mice and humans. Further, a heterozygous allele of a genetically engineered mouse model of phosphomimetic Dicer1 when combined with heterozygous Kras oncogenic background contributes to lung tumor progression in vivo. Mechanisms through which phosphomimetic Dicer1 …


Auto-Segmentation In Pancreatic And Liver Radiation Therapy, Cenji Yu Aug 2023

Auto-Segmentation In Pancreatic And Liver Radiation Therapy, Cenji Yu

Dissertations and Theses (Open Access)

Background

Gastrointestinal cancers exhibit a high mortality rate compared to other cancer types. Among these, pancreatic cancer ranks as the fourth leading cause of cancer-related deaths worldwide. The five-year survival rate remains alarmingly low at a mere 9%. Hepatocellular carcinoma (HCC), another aggressive form of cancer, is rapidly becoming the primary cause of cancer-related deaths in the United States. The treatment of both liver cancer and pancreatic cancer heavily relies on a multidisciplinary approach. Innovative treatment strategies involving dose-escalated regimens, such as stereotactic body radiation therapy (SBRT), are emerging as an important pillar of the management of liver and pancreatic …


Isolation Of Therapeutic Antibodies Against Microseminoprotien To Potentially Overcome Resistance To Anti-Angiogenic Therapy, Mason Ruiz Aug 2023

Isolation Of Therapeutic Antibodies Against Microseminoprotien To Potentially Overcome Resistance To Anti-Angiogenic Therapy, Mason Ruiz

Dissertations and Theses (Open Access)

High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. Angiogenesis is a vital function for both wound healing and oxygen homeostasis and is one of the hallmarks of cancer in solid tumors. To combat the formation of tumors, an anti-VEGF drug, bevacizumab, is used to starve tumors of blood that provide essential nutrients. While platinum-taxane doublet therapy in addition to cytoreductive surgery has been the gold standard treatment for patients with ovarian cancer, greater than 70% of patients will develop relapsed disease and be burdened with a terminal …


Spanish-Speaking Limited English-Proficient Patient Satisfaction And Comfort When Comparing Spanish-Speaking Provider To An Interpreter, Cindy Hernandez Aug 2023

Spanish-Speaking Limited English-Proficient Patient Satisfaction And Comfort When Comparing Spanish-Speaking Provider To An Interpreter, Cindy Hernandez

Dissertations and Theses (Open Access)

A large population of Americans have limited or no English proficiency (LEP) with about 64% of those being Spanish-speaking. This creates challenges in navigating the American healthcare system, where the majority of providers are solely English-speaking. Studies have demonstrated that when patients have language discordant appointments without interpreters, they are more likely to feel less understood, have questions and comments ignored, and are less likely to receive patient-centered care in communication. It is expected that interpreters improve access to healthcare, especially for Spanish-speaking patients. However, the patient comfort and satisfaction in language discordant genetic counseling appointments has not yet been …


A Larval Zebrafish (Danio Rerio) Model Of Adherent-Invasive Escherichia Coli Infections, Erika Flores, Erika Flores Aug 2023

A Larval Zebrafish (Danio Rerio) Model Of Adherent-Invasive Escherichia Coli Infections, Erika Flores, Erika Flores

Dissertations and Theses (Open Access)

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a broad term for chronic intestinal disorders that severely impact patient morbidity and quality of life. The global prevalence of IBD is rising, with over one million patients affected in the US alone. Adherent-invasive E. coli (AIEC) is a pathobiont frequently found in IBD biopsies. AIEC adhere to and invade epithelial cells, and can survive inside macrophages in vitro. However, how AIEC contributes to IBD in vivo remains unclear. Here a larval zebrafish (Danio rerio) model of AIEC was established, which facilitates the study of the …


Protein L Functionalized Microparticles For Early Detection Of Surface Markers In Heterogeneous Colorectal Lesions, Saleh Ramezani Aug 2023

Protein L Functionalized Microparticles For Early Detection Of Surface Markers In Heterogeneous Colorectal Lesions, Saleh Ramezani

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths among both men and women worldwide, a statistic that can be improved with early detection. Increased understanding of the tumor landscape has identified surface antigens that can be utilized to distinguish normal and cancerous tissue lining the colonic lumen. Use of antibodies conjugated to nano/micromaterials offers a means to detect these antigens, however, the heterogeneous nature of tumors makes it unlikely that antibodies against a single antigen will have sufficient sensitivity and specificity to detect all tumors. A versatile micromaterial able to be functionalized with more than one targeting …


Uncertainty In The Physical Basis Of Estimates Of Relative Biological Effectiveness In Carbon Radiotherapy, Shannon Hartzell, Shannon Hartzell Ph.D. Aug 2023

Uncertainty In The Physical Basis Of Estimates Of Relative Biological Effectiveness In Carbon Radiotherapy, Shannon Hartzell, Shannon Hartzell Ph.D.

Dissertations and Theses (Open Access)

Carbon ion radiotherapy is a novel modality used for the treatment of tumors that are unresectable, close to critical structures, or resistant to standard radiotherapy. A unique benefit of this therapy is the relative biological effectiveness (RBE) of the beam (i.e., how biologically potent carbon ions are as compared to x-rays), which is significantly elevated. This RBE also varies as a function of many parameters, and there are currently several models implemented in clinical and research-based treatment planning systems with which to predict RBE. These algorithms are computationally expensive and there are currently no means of validating their implementation within …


Risk And Risk Factors For Colorectal Subsequent Malignancies In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Constance A. Owens Aug 2023

Risk And Risk Factors For Colorectal Subsequent Malignancies In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Constance A. Owens

Dissertations and Theses (Open Access)

Survivors of childhood cancer are at risk for colorectal subsequent malignant neoplasms (SMNs); notably, these cancers are amenable to screening. To identify at-risk survivors that may benefit from early screening, descriptive and risk factor analyses were performed to ascertain risk factors for colorectal SMN in childhood cancer survivors. In particular, we explored detailed radiation therapy (RT) data – colorectal and substructure dose-volume metrics – as risk factors for colorectal SMN risk; metrics that have yet to be thoroughly investigated. We developed a novel population-based anatomical colorectal model with substructures for RT dosimetry in late effects studies of childhood cancer survivors; …


Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni Aug 2023

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations and Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …


Symptom Experience Of Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy, Natalie Jackson-Carroll Aug 2023

Symptom Experience Of Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy, Natalie Jackson-Carroll

Dissertations and Theses (Open Access)

Background: Immune checkpoint inhibitors (ICIs) are novel therapeutic agents utilized in the management of advanced melanoma. Though generally well-tolerated, patients receiving ICIs experience treatment-related toxicities at varying onset and intensity. Assessment and evaluation of these toxicities and their impact on a quality of life is essential to comprehensive cancer care. Patient-reported outcomes (PRO) contribute vital data to a clinical assessment, supporting clinicians in their ability to improve outcomes. To date, there is no melanoma-specific or ICI-specific PRO measure of symptom burden available.

Purpose: The purpose of this study was to describe the symptom experience from the patient's perspective and how …


Ai-Enabled Online Plan Adaptation For Mr-Guided Stereotactic Ablative Radiotherapy (Sabr) Of Head And Neck Cancer, Yao Zhao Jun 2023

Ai-Enabled Online Plan Adaptation For Mr-Guided Stereotactic Ablative Radiotherapy (Sabr) Of Head And Neck Cancer, Yao Zhao

Dissertations and Theses (Open Access)

Head and neck cancer (HNC) is a prevalent cancer type worldwide. Stereotactic ablative radiotherapy (SABR) has emerged as an effective treatment for HNC, delivering highly conformal doses to the tumor target while sparing surrounding normal tissues with a sharp dose gradient. However, the accuracy of the treatment delivery is limited by setup errors, anatomical changes, and intra-/inter-fraction organ motion. The emergence of MR-guided adaptive radiotherapy (ART) has the potential to further improve the SABR of HNC, by providing superior visualization of soft tissue and enabling real-time plan adaptation based on the daily anatomical changes of patients. This novel technology has …


Shared Decision Making In Self-Care Management And Health Outcomes Of Adolescents And Young Adults With Sickle Cell Disease, Judith M. Odityo May 2023

Shared Decision Making In Self-Care Management And Health Outcomes Of Adolescents And Young Adults With Sickle Cell Disease, Judith M. Odityo

Dissertations and Theses (Open Access)

Background: Shared decision making (SDM) is a model of care with a potential to guide disease self-care management and promote optimal health outcomes in adolescents and young adults (AYA) with sickle cell disease (SCD).

Aims: To identify the perceived involvement of AYA with SCD in the SDM process and examine its association with self-care management and health outcomes.

Methods: Data were collected from a major sickle cell center. Using a cross-sectional design, participants completed surveys and data were analyzed with descriptive statistics, analysis of variance, multiple linear regression, and correlational statistics.

Results: Participants (N=25) were on average age 22.72 (SD …


Endothelial To Mesenchymal Transition In Human And Murine Congenital Diaphragmatic Hernia Pulmonary Hypertension, Jamie L. Gilley May 2023

Endothelial To Mesenchymal Transition In Human And Murine Congenital Diaphragmatic Hernia Pulmonary Hypertension, Jamie L. Gilley

Dissertations and Theses (Open Access)

Background: Congenital diaphragmatic hernia (CDH) is one of the most complex congenital disorders, characterized by pulmonary hypertension and hypoplasia. CDH-associated pulmonary hypertension (CDH-PH) features devastating morbidity and mortality (25-30%) among neonates. An unmet need is determining the mechanisms triggering CDH-PH to save infants and improve their quality of life. Prior data suggest abnormal remodeling of the pulmonary vascular extracellular matrix, presumed to be driven by endothelial-to-mesenchymal transition (EndoMT), hinders postnatal vasodilation and limits efficacy of anti-PH therapy in CDH. Although abnormal vascular development and remodeling are known CDH traits, there is limited data on the role of EndoMT in CDH-PH. …


Noninvasive Screening Of Nonalcoholic Fatty Liver Disease Among People Living With Hiv, Essi M. Havor May 2023

Noninvasive Screening Of Nonalcoholic Fatty Liver Disease Among People Living With Hiv, Essi M. Havor

Dissertations and Theses (Open Access)

Background: Nonalcoholic fatty liver disease (NAFLD) disproportionately affects up to 75% of people living with HIV (PLWH). Given the high HIV prevalence in Houston and Harris County, knowledge of the prevalence of NAFLD in PLWH is needed to inform prevention efforts. In addition, such knowledge is required to raise awareness among at-risk individuals and healthcare professionals.

Specific Aims: This cross-sectional study aimed (1) to examine the demographic, behavioral, clinical, and psychosocial characteristics of PLWH in Houston/Harris County, Texas, and to estimate the prevalence of NAFLD, (2) to determine factors associated with the severity of NAFLD, and (3) to identify specific …


Difference In Smoking Patterns And Quitting Status Between Premium And Non-Premium Cigar Users After Two Years Of Follow Up In Us Adults: Findings From The Population Assessment Of Tobacco And Health (Path) Study, 2016-2019, Sarah Valencia May 2023

Difference In Smoking Patterns And Quitting Status Between Premium And Non-Premium Cigar Users After Two Years Of Follow Up In Us Adults: Findings From The Population Assessment Of Tobacco And Health (Path) Study, 2016-2019, Sarah Valencia

Dissertations and Theses (Open Access)

Previous studies have described the demographics, purchasing behaviors, trends in frequencies of cigar use, and quitting status among cigar poly users, however, there has not been a study that evaluates differences in demographic characteristics and quitting status for premium and non-premium U.S. adult cigar users. This study used secondary data analyses of the Population Assessment of Tobacco and Health (PATH) Study public-use files dataset for adult traditional cigar users in wave 4 (2016-2018) and wave 5 (2018-2019). Traditional cigars were classified as premium or non-premium at wave 4 (2016-2018) using the brand and price per stick of cigar that was …


Viral Particle Detection In Wastewater, Katelyn Clark May 2023

Viral Particle Detection In Wastewater, Katelyn Clark

Dissertations and Theses (Open Access)

Wastewater is an underutilized resource for recognizing the epidemiology of pathogen transmission and infections within a community that has the potential to mitigate disease outbreaks. Pathogens of public health concern, such as adenovirus, norovirus, and SARS-CoV-2, occur in wastewater from excretion of infected individuals. Despite the potential for wastewater pathogen data to predict future outbreaks, the relationship between viral shedding patterns in wastewater and case counts of infectious disease remains unclear. An evaluation of the peer-reviewed literature was conducted to compile characteristics of adenovirus, norovirus, and SARS-CoV-2 in the wastewater environment. These characteristics were considered in prioritizing the key pathogens …


Prevalence Of Sars-Cov-2 Antibodies By Rural-Urban Residential Status In Texas, Breanna Bailey Ellis May 2023

Prevalence Of Sars-Cov-2 Antibodies By Rural-Urban Residential Status In Texas, Breanna Bailey Ellis

Dissertations and Theses (Open Access)

Understanding the health disparities associated with SARS-CoV-2 antibody status across Texas is essential. These differences can guide healthcare professionals and local public health officials to identify vulnerable populations needing COVID-19 prevention and treatment resources. This study aims to contribute to the literature by determining if rural and urban geographical locations are disproportionately impacted by SARS-CoV-2 infection and vaccination in the state of Texas. I utilized the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a large ongoing prospective population-based survey among 5–90-year-olds from the Texas general population that began collecting seroprevalence data in October 2020 (1). Participants in the survey are …


The Substance Use Disorder Peer Workforce In Texas And The United States: Assessing And Addressing The Workforce Development And Economic Evaluation Gaps, Sierra Castedo De Martell May 2023

The Substance Use Disorder Peer Workforce In Texas And The United States: Assessing And Addressing The Workforce Development And Economic Evaluation Gaps, Sierra Castedo De Martell

Dissertations and Theses (Open Access)

The infrastructure for addressing problematic substance use and substance use disorder (SUD) across the US has shortages in many areas, and suffered additional challenges during the COVID-19 pandemic. One method to address shortages in SUD care infrastructure relatively quickly is to expand the peer workforce delivering peer recovery support services (PRSS). This workforce has expanded to cover most US states over the past two decades, but gaps in the evidence base for peer workforce development and economic evaluations of PRSS have persisted. To address these gaps, three studies were undertaken with the following aims: (1) Conducted a systematic review of …


Lymphatic Dysfunction And Associated Systemic Inflammation In Lymphedema, Assessed By Nirf-Li Imaging And Plasma Cytokine/Chemokine Analysis, Anna Vang May 2023

Lymphatic Dysfunction And Associated Systemic Inflammation In Lymphedema, Assessed By Nirf-Li Imaging And Plasma Cytokine/Chemokine Analysis, Anna Vang

Dissertations and Theses (Open Access)

Breast cancer-related lymphedema (BCRL) manifests as swelling of the upper extremities and trunk as a result of lymphatic fluid buildup due to radiation therapy (RT), surgical lymph node removal, or chemotherapy. As there is currently no cure, BCRL treatment aims to improve quality of life (QOL). First-line treatment involves specialized massage therapy and the use of compression garments. Second-line treatments include reparative lymphatic microsurgeries such as lymphovenous bypass (LVB) and/or vascularized lymph node transplant (VLNT). There is a need for better understanding of the etiology of BCRL and lymphatic microsurgery outcomes. Blood specimens and near-infrared fluorescent lymphatic imaging (NIRF- LI)data …


The Safe And Effective Clinical Deployment Of Artificial Intelligence To Ols, Kelly Nealon May 2023

The Safe And Effective Clinical Deployment Of Artificial Intelligence To Ols, Kelly Nealon

Dissertations and Theses (Open Access)

18 million new cancer cases are diagnosed each year. Roughly half of these patients will be treated with radiation therapy, a complex technique that requires an interdisciplinary team of clinical staff and expensive equipment to be delivered safely. Cancer centers in Low- and Middle-Income Countries (LMIC) have an especially difficult time meeting the demands of radiation therapy as the complexity of treatment techniques increase, with only 37% of patients in these regions having access to the care they need. Artificial Intelligence (AI) based tools are being developed to simplify the treatment planning and quality assurance processes to increase the number …


Gene Expression–Based Algorithms For The Identification Of Drug Combinations In Personalized Medicine, Lon Fong May 2023

Gene Expression–Based Algorithms For The Identification Of Drug Combinations In Personalized Medicine, Lon Fong

Dissertations and Theses (Open Access)

Three of the major problems facing cancer therapeutics are 1) drug resistance, the intrinsic or acquired ability of cancer cells to evade the effect of the therapies used to treat them; 2) heterogeneity among individual patients’ disease at the molecular level and the resulting variability in therapeutic response; and 3) the limitations of genomics biomarkers in matching patients to the most effective therapy. One possible solution to drug resistance is the use of combination therapies rather than monotherapies. Use of multiple drugs, each with a different mechanism of action, lowers the chances that the cancer cells will develop or have …


The Cx3cl1-Cx3cr1 Chemokine Axis Contributes To Tumor Immune Evasion And Its Blockade Enhances Responses To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri May 2023

The Cx3cl1-Cx3cr1 Chemokine Axis Contributes To Tumor Immune Evasion And Its Blockade Enhances Responses To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri

Dissertations and Theses (Open Access)

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. While CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration, the mechanisms employed by this axis on these cells to mediate immune suppression remain poorly understood. Here, we explore the immune evasion strategies implemented by this axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of mediators to attract …


Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel May 2023

Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …


Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li May 2023

Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li

Dissertations and Theses (Open Access)

Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted the transfer of the CAR-cognate-antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their targets, (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen expressing NK cells (NKTROG+) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both …