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Articles 1 - 9 of 9
Full-Text Articles in Medicine and Health Sciences
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 …
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 …
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 …
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, …
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 …
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 …
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 …
Exposure To Mild Blast Forces Induces Neuropathological Effects, Neurophysiological Deficits And Biochemical Changes, Adan Hernandez, Chunfeng Tan, Florian Plattner, Aric F. Logsdon, Karine Pozo, Mohammad A. Yousuf, Tanvir Singh, Ryan C. Turner, Brandon P. Luke-Wold, Jason D. Huber, Charles L. Rosen, James A. Bibb
Exposure To Mild Blast Forces Induces Neuropathological Effects, Neurophysiological Deficits And Biochemical Changes, Adan Hernandez, Chunfeng Tan, Florian Plattner, Aric F. Logsdon, Karine Pozo, Mohammad A. Yousuf, Tanvir Singh, Ryan C. Turner, Brandon P. Luke-Wold, Jason D. Huber, Charles L. Rosen, James A. Bibb
Faculty & Staff Scholarship
Direct or indirect exposure to an explosion can induce traumatic brain injury (TBI) of various severity levels. Primary TBI from blast exposure is commonly characterized by internal injuries, such as vascular damage, neuronal injury, and contusion, without external injuries. Current animal models of blast-induced TBI (bTBI) have helped to understand the deleterious effects of moderate to severe blast forces. However, the neurological effects of mild blast forces remain poorly characterized. Here, we investigated the effects caused by mild blast forces combining neuropathological, histological, biochemical and neurophysiological analysis. For this purpose, we employed a rodent blast TBI model with blast forces …