Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 15 of 15
Full-Text Articles in Medicine and Health Sciences
Challenges And Opportunities In Glioblastoma And Immunovirotherapy With Oncolytic Herpes Simplex Virus Type 1, Dagoberto Estevez-Ordonez
Challenges And Opportunities In Glioblastoma And Immunovirotherapy With Oncolytic Herpes Simplex Virus Type 1, Dagoberto Estevez-Ordonez
All ETDs from UAB
This dissertation covers data from published and pre-published studies exploring challenges and opportunities in the treatment of malignant glioma with emphasis in glioblastoma and oncolytic immunovirotherapy with an oncolytic herpes simplex virus type 1 (HSV-1) designed to induce expression of IL-12, M002 (murine IL-12) and M032 (human IL-12).It starts with the report of a study that uncovered important racial and socioeconomic disparities experienced by patients with glioblastoma treated in Alabama. Notable results also include the unexpected finding of increased survival in African American patients with glioblastoma even after controlling for factors associated with survival and socioeconomic disparities. The implications of …
Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones
Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones
All ETDs from UAB
Treatment options for the universally lethal brain tumor, glioblastoma (GBM), are severely limited and often unsuccessful in fully eradicating the disease. Extremely aggressive in nature, GBM cells often implore suppressive mechanisms to evade therapeutic detection which aids in the dismal 15-month median survival rate. Facilitating disease severity and more importantly, disease recurrence, are the immunosuppressive and chemoresistant phenotypes of GBM cells. Specifically, the DNA alkylating agent, temozolomide (TMZ) possesses lymphodepleting properties shunting robust immune cell infiltration into an immunologically cold tumor microenvironment. Additionally, through inherent or acquired mechanisms, GBM tumors commonly become resistant to the DNA damaging effects of TMZ …
Understanding The Protumorigenic Functions Of St6gal1 In Glioblastoma Stemness And Metabolism, Sajina Gc
Understanding The Protumorigenic Functions Of St6gal1 In Glioblastoma Stemness And Metabolism, Sajina Gc
All ETDs from UAB
Glioblastoma (GBM) is a rare but deadly cancer with median survival of just 15 months despite of aggressive treatment. Advancement in novel treatment modalities is hindered by its heterogeneous nature, which includes subsets of neural stem cell-like brain tumor initiating cells (BTICs) that are highly tumorigenic and therapy-resistant. bgalactoside a-2,6-sialyltransferase 1 (ST6Gal1) is elevated in most tumors including in normal and neoplastic stem cells. ST6Gal1 imparts oncogenic phenotypes such as invasion, apoptosis evasion, therapy resistance, TIC maintenance among others via sialylation of critical receptors like, Fas, TNFR1, EGFR and more. Yet ST6Gal1 led regulation of BTIC specific cell surface proteins …
Restoring The Sphingolipid Balance In Glioblastoma, Cyntanna C. Hawkins
Restoring The Sphingolipid Balance In Glioblastoma, Cyntanna C. Hawkins
All ETDs from UAB
Glioblastoma (GBM) is a highly aggressive brain tumor with a median survival of 15 months even with standard of care—surgical resection, radiotherapy, and chemotherapy. Two of the key characteristics contributing to this malignancy are its highly invasive phenotype and resistance to the chemotherapy, temozolomide (TMZ). We, and others, have identified the sphingolipid balance as a driver of these phenotypes with dysregulated sphingolipid metabolism seen in GBM patient samples. The ceramidases, specifically acid ceramidase (ASAH1), mediate the balance between ceramides and sphingosine-1-phosphate (S1P). ASAH1 breaks down ceramides ultimately forming S1P. While ceramides induce cell death, S1P promotes migration and cell survival. …
A Novel In Vitro Model To Study Immune Interactions In Glioblastoma, Hasan Alrefai
A Novel In Vitro Model To Study Immune Interactions In Glioblastoma, Hasan Alrefai
All ETDs from UAB
Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults. Despite decades of research, GBM has a median survival of approximately 14 months, necessitating the development of novel GBM therapeutics. The drug-development process has been hindered due to the lack of high-fidelity pre-clinical models. While in-vitro models of patient-derived xenografts (PDX) present an interesting approach to modeling GBM, they typically fail to incorporate the non-cancerous cells that support tumor growth and progression. Others have attempted to address this problem by using techniques such as 3D bioprinting to incorporate astrocytes and macrophages in an extracellular matrix; however, they …
Alternative Splicing Of Anxa7 Dictates Receptor Tyrosine Kinase Fates In Glioblastoma, Sindhu Nair
Alternative Splicing Of Anxa7 Dictates Receptor Tyrosine Kinase Fates In Glioblastoma, Sindhu Nair
All ETDs from UAB
Alternative splicing (AS) is a tightly regulated process essential for lineage specification in complex tissues like the brain. Dysregulated splicing in glioblastoma (GBM) is a mechanism exploited by tumor cells to retain or splice out exons consequently rewiring isoform-specific protein interactions to sustain tumor phenotypes. Receptor tyrosine kinases (RTK) amplifications are frequent events in GBM driving tumor growth and progression and are key targets for chemotherapy. However, RTK targeting in GBM has achieved limited success predominantly due to adaptive mechanisms of resistance in a constantly evolving tumor microenvironment. Clonal populations and crosstalk between RTKs sustain heterogeneity within a tumor leading …
Molecular Regulation Of Glioblastoma Spatial Heterogeneity And Therapeutic Resistance, Soniya Bastola
Molecular Regulation Of Glioblastoma Spatial Heterogeneity And Therapeutic Resistance, Soniya Bastola
All ETDs from UAB
Glioblastoma multiforme (GBM) is a highly invasive, highly vascularized, and heterogeneous malignant tumor of the brain. Due to the highly infiltrative phenotype of GBM, surgery often leaves behind residual tumor cells. In many cases, recurrence occurs close to the surgical margin suggesting the role of these remaining cells in promoting tumor aggressiveness. Rapidly growing tumor creates subsequent hypoxic, and hypovascular core due to limited nutrients, whereas tumor cells in the leading edge have access to nutrients from vasculature enriched microenvironment. Studies have identified the cellular and molecular heterogeneity between the tumors in core and edge. Still, their mechanisms of intercellular …
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
All ETDs from UAB
Glioblastoma (GBM) is the most common adult primary malignant brain tumor with a median survival of about 15 months, even after aggressive treatment. Treatment of GBM is difficult for multiple reasons including the location of the tumor, tumor invasiveness, and the high degree of both inter-and intra-tumoral heterogeneity. Contributing to intratumoral heterogeneity are highly tumorigenic, stem-like tumor cells, with the capacity to self-renew and propagate the tumor, termed brain tumor initiating cells (BTICs). BTICs are also commonly therapy resistant, highly invasive, and metabolically plastic with elevated expression of glucose transporter 3 (GLUT3) allowing them to preferentially survive in low nutrient …
Exploring The Roles Of Long Non-Coding Rnas In Glioblastoma Tumor Recurrence And Therapy Resistance, Christian Tyler Stackhouse
Exploring The Roles Of Long Non-Coding Rnas In Glioblastoma Tumor Recurrence And Therapy Resistance, Christian Tyler Stackhouse
All ETDs from UAB
ABSTRACT Glioblastoma (GBM) is the most common and devastating primary CNS brain tumor with a median survival time of around 14 months. Most patients succumb to re-current disease which is often more malignant than the primary tumor and is frequently therapy resistant. There have not been significant advances in the treatment of GBM despite decades of research. This is partly due to the lack of accurate preclinical models and of the focus on primary rather than recurrent tumors. We created a 350 gene custom GBM-specific panel which contains 16 molecular signatures including molecular sub-typing signatures. We have demonstrated concordance of …
Acetylcholine Signaling In Glioblastoma Invasion And Peritumoral Hyperexcitability, Emily Grace Thompson
Acetylcholine Signaling In Glioblastoma Invasion And Peritumoral Hyperexcitability, Emily Grace Thompson
All ETDs from UAB
Glioblastomas are the most common and deadly form of primary brain cancer in adults. Current treatment strategies are aggressive, including a combination of surgical resection, radiotherapy, and chemotherapy. However, median patient survival has remained stagnant at 12 to 15 months for the last several decades. This dismal patient outcome has prompted efforts to understand the unique characteristics of these tumors, since traditional therapeutics have not been efficacious. Extensive invasion is a salient feature of glioblastomas that significantly diminishes the effectiveness of current treatment strategies and is ultimately the cause of tumor recurrence within 2 years in approximately 80% of patients. …
Marcks Effector Domain: Functions In Glioblastoma Progression And Novel Cytolytic Therapy, Nicholas James Eustace
Marcks Effector Domain: Functions In Glioblastoma Progression And Novel Cytolytic Therapy, Nicholas James Eustace
All ETDs from UAB
Glioblastoma (GBM; grade IV astrocytoma) is the most common primary adult brain malignancy and remains incurable despite tremendous advances in our understanding of this heterogeneous disease. In this dissertation, we explore the challenges encountered in the treatment of GBM and discuss a promising new therapeutic approach gleaned from studies of the phospholipid binding “effector” domain (ED) of the protein Myristoylated alanine-rich protein C kinase substrate (MARCKS). Following an introduction to central nervous system (CNS) tumors and the grading of diffuse gliomas, we explain how recent advancements to our understanding of the cellular and molecular composition of CNS tu-mors, and the …
The Anti-Tumor Effects Of Hur Inhibition In Glioblastoma, Jiping Wang
The Anti-Tumor Effects Of Hur Inhibition In Glioblastoma, Jiping Wang
All ETDs from UAB
Glioblastomas (GBMs) are the most malignant primary brain tumor. GBMs represent 14.7% of total primary CNS tumors and 47.7% of malignant CNS tumors. The median survival of GBM is 18-20 months, while five-year survival rate is only 5.6%. GBMs are maintained by glioma stem cells (GSCs), and poor treatment outcomes are linked to the high resistance of GSCs to radiation and chemotherapy, and the immunosuppressive tumor microenvironment. The mRNA binding protein HuR is a key regulator of tumor growth and development based upon the fact that HuR targets mRNAs that are broadly involved in tumorigenesis. We have previously shown that …
Analysis Of The Gtp Cyclohydrolase I/Tetrahydrobiopterin Pathway In Glioblastoma Biology, Anh Tran
Analysis Of The Gtp Cyclohydrolase I/Tetrahydrobiopterin Pathway In Glioblastoma Biology, Anh Tran
All ETDs from UAB
Glioblastomas (GBMs) are the most common primary malignant brain tumors in adults and one of the most aggressive cancers with high rates of recurrence and therapeutic resistance. In GBMs, subpopulations of highly tumorigenic cells called brain tumor initiating cells (BTICs) have the unique capacity to promote tumor maintenance, therapeutic resistance, and angiogenesis. Depending on the level, differentiation state, and tumor stage, reactive nitrogen and oxygen species inhibit or increase cancer growth and BTIC maintenance. GTP cyclohydrolase 1 (GCH1) is the rate limiting enzyme in a pathway that can regulate reactive species production but has not been thoroughly investigated in GBM. …
Microenvironmental Regulation And Epigenetic Control Of Glioma Pathogenesis, Nathaniel H. Boyd
Microenvironmental Regulation And Epigenetic Control Of Glioma Pathogenesis, Nathaniel H. Boyd
All ETDs from UAB
Tumor microenvironments can promote stem cell maintenance, tumor growth, and therapeutic resistance, findings linked by the tumor initiating cell hypothesis. The ischemic microenvironment characterized by low oxygen and glucose, and acidic stress occurs in both solid tumors and non-neoplastic tissue injury. Standard of care for glioblastoma (GBM) includes the chemotherapy temozolomide, which is not curative due, in part, to residual therapy-resistant brain tumor initiating cells (BTICs). Temozolomide efficacy may be increased by targeting carbonic anhydrase 9 (CAIX), a hypoxia and acidic stress responsive gene important for maintaining the altered pH gradient of tumor cells. Using patient-derived GBM xenograft cells, we …
Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe
Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe
All ETDs from UAB
Glioblastoma multiforme (GBM) is the most common and deadly primary brain malignancy necessitating improved understanding of GBM biology. In this study, we explore the role of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS) in the context of GBM. We have discovered that the MARCKS protein regulates GBM growth as well as response to radiation therapy through its effects on proliferation, senescence, and DNA repair based on our studies in cell culture and in patient-derived xenograft tumors implanted in mice. Importantly, our analysis of clinical patient data demonstrates that MARCKS is an independent predictor for outcome in GBM patients. Indeed, high MARCKS …