Immunotherapy Commons^™

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

A Novel Immunostimulatory Platform For Amplifying The Abscopal Response Rates Of Radiation Therapy, Patrick A. Paez

Theses and Dissertations

Radiation therapy (RT) is one of the primary treatment modalities for head and neck squamous cell carcinoma (HNSCC). At the time of diagnosis two-thirds of HNSCC patients have local-advanced disease and 50-60% of these patients will experience a local-regional or metastatic relapse within three years. Improving the immunogenic response of RT may help address this clinical problem. However, current RT regimens have failed to reliably generate robust antitumor immunity as evidenced by the rarity of clinical abscopal responses. Recently we engineered a chimeric fusion molecule called Flagrp170, a novel immunostimulatory agent highly capable of promoting antigen presentation and T-cell activation. …

Anti-Tumor Functions Of Sphingosine Kinase 1 And Sphingosine Kinase 2 In Breast Cancer Development, Melissa A. Maczis

Theses and Dissertations

Bioactive sphingolipid metabolite sphingosine-1‐phosphate (S1P) circulating levels have been implicated in breast cancer (BC) progression. BCs usually respond to 17β-Estradiol (E2) through canonical receptor ERα66 for genomic effects, however, E2 also triggers rapid, non-genomic responses. E2 has been shown to activate sphingosine kinase 1 (SphK1), increasing S1P for S1P receptors signaling important for BC. The E2 receptor activating SphK1 has not been identified. We demonstrate triple negative BC cells, expressing only novel ERα splice variant ERα36, E2-induced SphK1 activation for S1P secretion. Tamoxifen, first-line BC endocrine therapy, an ERα66 antagonist but ERα36 agonist, activates SphK1 and increases S1P secretion in …

Augmenting Guadecitabine To Promote Anticancer Immunity In Murine Breast Cancer, Timothy M. Smith Jr.

Theses and Dissertations

In immune-competent individuals, tumor growth occurs due to a failure of the immune system to recognize and destroy malignant cells. Immune surveillance can be curtailed by the presence of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs) which both serve to dampen antitumor immunity. These studies utilize a metronomic low-dose therapeutic approach to examine the effects of anticancer drugs against murine breast cancer and the effects on the immune cell compartments. The focus of these studies revolve around the drug guadecitabine (guad), a second-generation DNA methyl-transferase inhibitor (DNMTi). DNMTi’s have been shown to dysregulate the methylation …

Enhancing Chemosensitivity Of Lung Cancers By Manipulating The Tumor Microenvironment: Local Lung Delivery And Nanocarrier-Based Therapies, Hanming Zhang

Theses and Dissertations

Cancer is the second leading cause of death in United States causing an estimated six hundred thousand death in 2019. Among different types of cancer, lung cancer is the leading cause of cancer related death in both male and female. While targeted therapy and immunotherapy have shown promising clinical outcomes, currently there remain a significant proportion of patients who do not benefit from these strategies or who cannot tolerate them, making Pt based doublet chemotherapy still an indispensable component in almost all stages of treatment. However, partially due to the poor tumor distribution of small molecule drug, the development of …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Gliotoxin Production In Aspergillus Fumigatus, Susan Musyimi

Theses and Dissertations

Aspergillus fumigalus is a ubiquitous fungus that causes an infection called aspergillosis in immune-compromised surgery patients (Latge, 2001, 384; Bok et al. 2006). Aspergillosis cases have increased in the past decade due to the increasing number of patients undergoing immunosuppressive therapy and receiving organ transplants (Bok et al. 2006). Although there is still disagreement as to the causative agent of the symptoms accompanying aspergillosis, many scientists suspect that the compound, gliotoxin, plays a major role, hi this study, we compared the amounts of gliotoxin produced from clinical and environmental isolates of A. fumigatus. We hypothesized that the amount of gliotoxin …