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- Blood-brain barrier (2)
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Articles 1 - 22 of 22
Full-Text Articles in Medicine and Health Sciences
Intervention To Reduce Tobacco Use Among Prostate Cancer Patient And Informal Caregiver Dyads, Trupti Dhumal
Intervention To Reduce Tobacco Use Among Prostate Cancer Patient And Informal Caregiver Dyads, Trupti Dhumal
Graduate Theses, Dissertations, and Problem Reports
Prostate cancer is the leading cancer in men. Continued tobacco use after prostate cancer diagnosis may affect a patient’s treatment outcomes, quality of life, and mortality. Despite the potential negative outcomes, 10-20% of prostate cancer patients continue to use tobacco after their cancer diagnosis. Considering risks associated with continued tobacco use, there is a lack of evidence-based tobacco cessation strategies to address tobacco cessation specifically in prostate cancer. Given the increasing prevalence of prostate cancer, the ongoing difficulty in tobacco cessation, and the limited evidence-based tobacco cessation interventions in the literature, it is important to prioritize reducing tobacco use in …
Right Treatment Wrong Time: Immunotherapy Administration Post-Radiotherapy Decreases Tumor Burden In A Preclinical Model Of Brain Metastasis, Kathryn Elizabeth Blethen
Right Treatment Wrong Time: Immunotherapy Administration Post-Radiotherapy Decreases Tumor Burden In A Preclinical Model Of Brain Metastasis, Kathryn Elizabeth Blethen
Graduate Theses, Dissertations, and Problem Reports
This dissertation (a) provided an in-depth literature review of methods to modulate the blood-brain and blood-tumor barriers to increase drug delivery and efficacy in brain metastases, (b) evaluated the effects of whole-brain radiation therapy on the blood-brain barrier in immunocompetent and immunocompromised mouse models and proposed a mechanism by which the immune response to radiation disrupts the blood-brain barrier, and (c) developed a syngeneic lung cancer brain metastasis model to determine the impact of coordinated immunotherapy administration with radiotherapy. The blood-brain barrier is an impediment to drug delivery to the brain. The inherent leakiness of the blood-tumor barrier does not …
Long-Term Prescription Opioid Use, Cancer Stage, And Economic Burden Among Older Cancer Survivors With Non-Cancer Chronic Pain Conditions, Rudi Safarudin
Long-Term Prescription Opioid Use, Cancer Stage, And Economic Burden Among Older Cancer Survivors With Non-Cancer Chronic Pain Conditions, Rudi Safarudin
Graduate Theses, Dissertations, and Problem Reports
Opioids are commonly prescribed to treat pain conditions, which are highly prevalent among older adults (≥65 years). Recent evidence shows that opioids may have carcinogenic effects through immunosuppression and free-radical pathways, which could promote cancer growth. Two population-based studies have reported an association of opioid use with incident cancer. Many individuals with non-cancer chronic pain conditions (NCPCs) may use opioids for a long term. However, the association of long-term prescription opioid (LPO) use with cancer stage at diagnosis is still unknown. Furthermore, evidence suggests that individuals with cancer and pre-existing NCPCs may persistently use opioids, even in the absence of …
Clinical And Economic Burden Of Inflammatory Chronic Conditions Among Adults In The United States: Evidence From Three Nationally Representative Surveys, Mohammad Ikram
Graduate Theses, Dissertations, and Problem Reports
A significant proportion of adults in the United States (US) suffer from various inflammatory chronic conditions (ICCs). They include a wide range of diseases such as diabetes, rheumatoid arthritis, asthma, and chronic obstructive pulmonary diseases. ICCs are not curable, and their management typically involves medications such as NSAIDs and corticosteroids. Recently, a whole health approach that places patients’ well-being at the center is increasingly being used for better management of ICCs. The whole health approach uses an integrated approach that includes multimodal management with complementary and alternative medicines (CAM) and prescription drugs. However, the use of CAM and prescription drugs …
Chemotherapy-Induced Pdl-1 Expression In Cancer-Associated Fibroblasts Promotes Chemoresistance In Nsclc, Gayathri Heenatigala Palliyage
Chemotherapy-Induced Pdl-1 Expression In Cancer-Associated Fibroblasts Promotes Chemoresistance In Nsclc, Gayathri Heenatigala Palliyage
Graduate Theses, Dissertations, and Problem Reports
A cure for cancer is out of reach for most patients due to chemoresistance. Cancer-associated fibroblasts (CAFs), one of the most abundant types of stromal cells in the tumor microenvironment, are known to provide functional and structural support for tumor progression. These cells also play a role in cancer chemoresistance, but a detailed understanding of the process, particularly in chemoresistant lung cancer, is lacking. In this study, we investigated programmed death-ligand 1 (PDL-1) as a potential biomarker for CAF-induced chemoresistance and evaluated its role and underlying mechanisms of chemoresistance in non-small cell lung cancer (NSCLC). We demonstrated that chemotherapy-stimulated CAFs …
Targeting Vulnerabilities In Cell State And Calcium Signaling For The Treatment Of Lung Cancer, Clark Jones
Targeting Vulnerabilities In Cell State And Calcium Signaling For The Treatment Of Lung Cancer, Clark Jones
Graduate Theses, Dissertations, and Problem Reports
Lung cancer remains the deadliest of all cancers due to the high mutational burden associated with the disease. Combating mutational drivers and drug resistance proves to be essential in the development of novel therapies to improve patient outcomes. A first-in-class cyclic peptide known as MTI-101 has been shown to induce necrotic cell death in a caspase independent manner. MTI-101 was derived from the linear peptide known as HYD1 that was found in a high throughput screen to block cell adhesion with the extracellular matrix. The compound was further optimized and cyclized to the currently used MTI-101 that was found to …
Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala
Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala
Graduate Theses, Dissertations, and Problem Reports
Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …
Investigating The Mitochondrial Protein Mitoneet In C. Elegans Models Of Aging And Alzheimer's Disease, Jacob Ryan Boos
Investigating The Mitochondrial Protein Mitoneet In C. Elegans Models Of Aging And Alzheimer's Disease, Jacob Ryan Boos
Graduate Theses, Dissertations, and Problem Reports
Oxidative stress is an imbalance between reactive oxygen species production and elimination, favoring the former. Reactive oxygen species serve as important signaling molecules for physiological homeostasis. However, when produced in excess, these once important signaling molecules become detrimental, disrupting cellular functions, and ultimately leading to cell death. In aging, reactive oxygen species production is increased, accompanied with reductions in oxidative stress resistance, increasing the risk for developing age-related diseases including cardiovascular disease, cancer, stroke, and neurodegenerative diseases. The outer mitochondrial membrane iron-sulfur cluster containing protein mitoNEET (CISD1; gene CISD1) has shown to be a mediator of mitochondrial function and …
Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson
Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson
Graduate Theses, Dissertations, and Problem Reports
Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …
Understanding The Variable Drivers Of Toxicity For The Broad Class Of Carbon Nanotubes And Nanofibers From U.S. Facilities, Kelly E. Fraser
Understanding The Variable Drivers Of Toxicity For The Broad Class Of Carbon Nanotubes And Nanofibers From U.S. Facilities, Kelly E. Fraser
Graduate Theses, Dissertations, and Problem Reports
Pulmonary exposure to carbon nanotubes or nanofibers (CNT/F) is known to induce inflammation, toxicity, or tumorigenesis, and is a concern in the occupational setting. U. S. facility employees are at risk of inhalation exposure of multi-walled carbon nanotubes and carbon nanofibers during primary and secondary manufacturing. To date, only one MWCNT, Mitsui-7 has been classified as possibly carcinogenic to humans (Group 2B), while all other materials were subsequently categorized as unclassifiable (Group 3). This class of material has recently been listed as a high priority to the International Agency for Research on Cancer due to this significant knowledge gap. Furthermore, …
From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest
From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest
Graduate Theses, Dissertations, and Problem Reports
Photoreceptors are specialized neuroepithelial cells which are optimized for efficient capture of light and initiation of visual transduction. These cells have several compartments which are very important for proper visual function and segregation of cellular processes, including the outer segment (OS), inner segment (IS), nucleus, and synapse. The IS houses all of the cellular organelles and biosynthetic molecular machinery the cell requires and is the site of protein synthesis. The light-sensing OS is a highly modified, primary cilium, which contains many stacks of double membranous discs which house proteins required for formation and maintenance of OS structure, as well as …
Association Of Incident Cancer To Low-Value Care And Healthcare Cost Burden Among Elderly Medicare Beneficiaries, Chibuzo Iloabuchi
Association Of Incident Cancer To Low-Value Care And Healthcare Cost Burden Among Elderly Medicare Beneficiaries, Chibuzo Iloabuchi
Graduate Theses, Dissertations, and Problem Reports
In the United States (US), 25% of healthcare spending is considered wasteful because it is spent reimbursing low-value care. Low-value care is the utilization of healthcare services, medical tests, and procedures that have unclear or no clinical benefit to patients but still exposes them to risk. World-wide, low-value care imposes a significant economic burden on patients, payers, governments, and society. Cancer care among older adults > 65 years is one of the biggest drivers of healthcare expenditure in the US and accounts for nearly 40% of all spending, and low-value care among cancer patients is prevalent and contributes to the financial …
Investigation Of Novel Mitoneet Ligand Nl-1 As A Therapeutic For Cerebral Ischemia And Reperfusion Injury, Pushkar Saralkar
Investigation Of Novel Mitoneet Ligand Nl-1 As A Therapeutic For Cerebral Ischemia And Reperfusion Injury, Pushkar Saralkar
Graduate Theses, Dissertations, and Problem Reports
Cerebral ischemia reperfusion injury, a common type of stroke, is a neurodegenerative disorder which is the leading cause of permanent disability in the United States. The underlying pathophysiology of ischemic stroke involves an occlusion in the vasculature supplying oxygen and glucose to the brain tissue, leading to infarction and eventual necrosis in the brain. MitoNEET is an outer mitochondrial protein that plays a role in the cellular bioenergetics and its redox physiology. Although its endogenous ligands are under investigation, mitoNEET binds molecules with a thiazolidinedione moiety, such as NL-1. This dissertation investigates NL-1 as a potential cytoprotective agent, and its …
Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls
Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls
Graduate Theses, Dissertations, and Problem Reports
This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …
Targeting Calcium Homeostasis For The Treatment Of Multiple Myeloma, Osama M. Elzamzamy
Targeting Calcium Homeostasis For The Treatment Of Multiple Myeloma, Osama M. Elzamzamy
Graduate Theses, Dissertations, and Problem Reports
Multiple myeloma (MM) is a hematological malignancy characterized by the neoplastic proliferation of the plasma cells. MM is a relatively rare cancer that accounts for about 1.8% of all cancers and is the second most common hematologic malignancies, and despite the advancement from untreatable to treatable malignancy, it is yet incurable. Calcium ions (Ca2+) play an important role as second messengers in regulating a plethora of physiological and pathological processes, hence cytoplasmic Ca2+ is tightly regulated with strict spatial and temporal control to initiate, maintain, and terminate appropriate signaling pathways and phenotypes including cellular proliferation, cell cycle …
Predictors Of Cardiovascular And Gastrointestinal Disorders, Inappropriate Nonsteroidal Anti-Inflammatory Drug Use, And Alzheimer’S Disease And Related Dementia In Older Adults With Osteoarthritis, Jayeshkumar Patel
Graduate Theses, Dissertations, and Problem Reports
Osteoarthritis (OA) is a degenerative arthritis affecting over 30 million Americans most of whom are over 65 years or older. Its clinical management is complicated by several disease- and treatment-specific factors. These include the co-occurrence of cardiovascular and gastrointestinal disorders (CV-GID), the inappropriate use of non-steroidal anti-inflammatory drugs (NSAID) to manage pain, and the risk of certain age-related chronic conditions like Alzheimer’s disease and related dementia (ADRD). Moreover, older adults with OA are at a higher risk of CV-GID, inappropriate NSAID use, and ADRD. Additionally, these factors can also affect one another in both a positive and a negative way. …
Asthma-Copd Overlap: Economic Burden And Medication Adherence, Mona Nili
Asthma-Copd Overlap: Economic Burden And Medication Adherence, Mona Nili
Graduate Theses, Dissertations, and Problem Reports
In many older adults, asthma and chronic obstructive pulmonary disease (COPD) coexist as “Asthma-COPD overlap” (ACO). This dissertation pursued three Aims: 1) estimate the economic burden of ACO and its contributory factors; 2) evaluate the association of ACO to “cost-related medication nonadherence” (CRN); and 3) identify adherence trajectory patterns and examine the impact of initial maintenance therapies (IMT) type (inhaled corticosteroids monotherapy (ICS) vs. fixed-dose combination of ICS and long-acting beta agonist (ICS/LABA)) on adherence trajectory patterns among older adults Medicare Beneficiaries. The first and second Aims were cross-sectional studies by using Medicare Current Beneficiary Survey data. For the third …
Multimorbidity, Immune Checkpoint Inhibitor Use, And Healthcare Expenditures Among Older Patients With Late-Stage Melanoma, Pragya Rai
Graduate Theses, Dissertations, and Problem Reports
With decades of unchanged cancer care with no added survival benefit, immune checkpoint inhibitors (ICI) changed the treatment landscape of late-stage melanoma in 2011. A key factor in determining the use of ICIs is the presence of pre-existing chronic conditions, which can influence the outcome. However, the prevalence of multimorbidity (defined as presence of two or more chronic conditions) among older patients with late-stage melanoma remains unknown. It also remains unknown if the presence of multimorbidity factors into the use of ICIs. Hospital-related factors associated with ICI use have been studied. Yet, patient-level factors, such as age, sex, marital status, …
Applications Of Machine Learning Methods In Health Outcomes Research: Heart Failure In Women, Khalid Abdullah Alhussain
Applications Of Machine Learning Methods In Health Outcomes Research: Heart Failure In Women, Khalid Abdullah Alhussain
Graduate Theses, Dissertations, and Problem Reports
There is robust evidence that heart failure (HF) is associated with substantial mortality, morbidity, poor health-related quality of life, healthcare utilization, and economic burden. Previous research has revealed that there are sex differences in the epidemiology, etiology, and disease burden of HF. However, research on HF among women, especially postmenopausal women, is limited. To fill the knowledge gap, the three related aims of this dissertation were to: (1) identify knowledge gaps in HF research among women, especially postmenopausal women, using unsupervised machine learning methods and big data (i.e., articles published in PubMed); (2) identify emerging predictors (i.e., polypharmacy and some …
The Interplay Of Progestins, Matrix Metalloproteinases, And The Aging Brain, Keyana Nicole Porter
The Interplay Of Progestins, Matrix Metalloproteinases, And The Aging Brain, Keyana Nicole Porter
Graduate Theses, Dissertations, and Problem Reports
Progestins are synthetic hormones that are designed to mimic the biological actions of progesterone. They, however, possess other pharmacological actions and properties, in addition to their progestational activities. Medroxyprogesterone Acetate (MPA) is a progestin used globally in the hormonal contraceptive, Depo Provera®, by women in their reproductive prime and is a major compound found in hormone therapy (HT) formulations used by menopausal women. MPA is used by approximately 1 in 5 adolescents and adult women in the United States who are sexually active. Globally, nearly 48 million women utilize injectable contraceptives to prevent pregnancy, with most users utilizing MPA as …
Predictors And Health Outcomes Of Treatment-Resistant Depression Among Adults With Chronic Non-Cancer Pain Conditions And Major Depressive Disorder, Drishti Shah
Graduate Theses, Dissertations, and Problem Reports
Understanding major depressive disorder (MDD) as a comorbidity in patients with chronic non-cancer pain conditions (CNPC) is of importance because of the high prevalence and well documented bi-directional relationship between MDD and pain. Furthermore, presence of CNPC among adults with MDD often reduces benefits of antidepressant therapy, thereby increasing the possibility of treatment resistance. Treatment-resistant depression (TRD) commonly defined as insufficient response to multiple antidepressant trials, often worsens depression and pain symptoms and can amplify the clinical and economic burden among adults with CNPC and MDD. Additionally, long-term opioid therapy (LTOT) may be prescribed at a higher rate to adults …
Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg
Graduate Theses, Dissertations, and Problem Reports
Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …