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Full-Text Articles in Medicine and Health Sciences
Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde
Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde
All ETDs from UAB
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal malignancies with a five-year survival of ~10%. Recent studies in the US population suggest PDAC as the fourth leading cause of cancer-related deaths in 2022. ST6 β-galactoside α2,6-sialyltransferase (ST6GAL1) is a glycosyltransferase which is known to be upregulated in cancer. It acts as a master regulator of a cell by being the predominant sialyltransferase catalyzing the addition of a bulky negatively charged sialic acid to the galactose sugar in an α2,6-linkage. Due to this, the sialic acid changes the structure and function of cell surface receptor proteins and regulates signal …
Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang
All ETDs from UAB
Tumor suppressor gene TP53 is the most frequently mutated gene across human cancers (~50%). Patients with Li-Fraumeni syndrome (LFS) who carry germline p53 mutations exhibit a diverse spectrum of childhood- and adult-onset malignancies. Despite over 40 years of dedicated studies to understand the role of p53 in tumor prevention, there are still many unanswered questions regarding the underlying mechanisms of p53. Previous studies have supported the notion that p53 exerts its tumor-suppressive function through its transcriptional activities. Therefore, strategies to enhance p53’s functions in tumor suppression via manipulating of downstream target gene activities in cancers show promising. To better investigate …
Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden
Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden
All ETDs from UAB
The determination of cell fate is a dynamic process regulated by hundreds of proteins that converge into complex cell signaling pathways. Upon irreparable intracellular stress, a cell undergoes programmed cell death, a process known as intrinsic apoptosis. Apoptosis is regulated by the Bcl-2 family, a class of proteins that act either as pro-survival or pro-death signaling molecules. Due to the oncogenic upregulation of pro- survival Bcl-2 family proteins across human cancer cell types, a novel class of small molecule inhibitors called ‘BH3-mimetics’ have emerged as promising anti-cancer therapeutics currently under clinical investigation. Here, we highlight the crosstalk between anti-apoptotic Bcl-2 …
Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker
Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker
All ETDs from UAB
Protein-protein interactions are critical for cell life. One aspect of cellular regulation where such protein-protein interactions occur is in the highly regulated process of programmed cell death (or apoptosis). Apoptosis is critical for normal tissue homeostasis, differentiation, and if dysregulated is a driver of disease including cancers. At the center of apoptotic regulation is the BCL2 protein family whose intra-familial protein-protein interactions balance cell stress signaling either allowing the cell to survive or inducing mitochondrial cell death. These BCL2 protein interactions are accomplished through the BH3 motif. While unique to the BCL2 family, a similar motif, the reverse BH3, has …
Post-Transcriptional Regulation Of Myeloid Cell Leukemia 1 In Cancers, Jia Cui
Post-Transcriptional Regulation Of Myeloid Cell Leukemia 1 In Cancers, Jia Cui
All ETDs from UAB
Apoptosis, a highly regulated process of programmed cell death, is essential for maintaining normal tissue homeostasis. Myeloid cell leukemia 1 (MCL1), an anti-apoptotic BCL-2 family protein, lies at the center of apoptosis regulation. Overexpression of MCL1 has been identified as a key contributor to tumorigenesis and further enables resistance to anti-cancer chemotherapies and radiation. Due to the critical roles of MCL1 in cancer, it is essential to understand the regulatory mechanisms of MCL1 expression in cells. Previous studies have detailed how MCL1 expression is controlled by multiple mechanisms. However, characterization of the post-transcriptional regulation of MCL1 mRNA has been poorly …
Examining The Role Of G Protein-Coupled Estrogen Receptor 1 (Gper) Activation In 17beta-Estradiol-Mediated Protection In Traumatic Brain Injury, Nicole Day
All ETDs from UAB
Traumatic brain injury (TBI) affects millions of persons per year, potentially leading to permanent disability or death, and exacts a staggering financial toll. Despite the severity of this public health problem, there are no clinically proven pharmacotherapeutics available that effectively attenuate the secondary neurochemically-mediated damage that follows the initial biomechanical insult. In addition, the heterogeneous nature of TBI and complexity of secondary injury cascades suggest that a polytherapeutic approach could be a powerful strategy with which to simultaneously target more than one deleterious pathway. Recently, sex steroid hormones have sparked interest as possible neuroprotective agents after traumatic injury. One of …
Regulation Of Cell Death By Autophagy In Glial Neoplasms, Latika R. Kohli
Regulation Of Cell Death By Autophagy In Glial Neoplasms, Latika R. Kohli
All ETDs from UAB
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive malignancies of the peripheral nervous system. The majority of MPNSTs arise in patients of the autosomal dominant genetic disorder neurofibromatosis type I (NF1) although they also arise sporadically. In the absence of any effective chemotherapeutic options and with surgery constituting the mainstay of treatment, MPNST patients face an extremely poor prognosis. This underscores the need to develop novel therapeutic strategies against this tumor type. It is well accepted that the crosstalk between autophagy and apoptosis can be exploited to derive maximal therapeutic benefit, especially through combinatorial therapies. However, this interaction is extremely …
Regulation Of Neuronal Cell Death By Bh3-Only Proteins, Arindam P. Ghosh
Regulation Of Neuronal Cell Death By Bh3-Only Proteins, Arindam P. Ghosh
All ETDs from UAB
Apoptosis in metazoan organisms plays critical roles in normal development, tissue homeostasis and immunity, and its disturbed regulation leads to many pathological states, including cancer, autoimmunity, infection and degenerative disorders. Apoptosis can be triggered by the engagement of `death receptors' of the tumor necrosis factor receptor family on the cell surface or by diverse intracellular signals that act upon the BCL2 (B-cell CLL/lymphoma 2) protein family, which controls the integrity of the mitochondrial outer membrane through the complex interactions of family members. Both the pathways lead to cellular demolition by dedicated proteases termed caspases. Different BH3-only proteins (or combinations of …
The Role Of St6gal-I Sialylation In Fas (Cd95) Death Receptor Function And Tumorigenesis, Amanda F. Swindall
The Role Of St6gal-I Sialylation In Fas (Cd95) Death Receptor Function And Tumorigenesis, Amanda F. Swindall
All ETDs from UAB
The golgi glycosyltransferase, ST6Gal-I, adds a negatively-charged sialic acid in an alpha-2-6 linkage to N-linked glycans. ST6Gal-I is upregulated in many cancers, and is associated with increased metastasis and poor patient prognosis. ST6Gal-I expression has been shown to be driven by oncogenic-ras signaling. However, mechanistic details of the role ST6Gal-I plays in tumor initiation and progression are not well defined. Historically, studies have focused on contributions of ST6Gal-I to the malignant cell phenotypes of migration and invasion. Emerging evidence including studies contained in this dissertation have begun to elucidate a role for ST6Gal-I as a regulator of apoptotic signaling by …
Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin
Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin
All ETDs from UAB
The most common and most malignant gliomas are the Grade IV Glioblastoma Multiforme (GBM), characterized by a highly proliferative tumor mass and extremely invasive phenotype that allows for profuse dispersal of tumor cells throughout the brain. GBM cells must specifically regulate their cell volume to thrive within the edematous tumor mass and infiltrate throughout the tortuous extracellular spaces of the brain. These rapid and directed volume changes are governed by the controlled flux of potassium and chloride ions across the cell membrane, which move osmotically obliged water. The goal of this dissertation was to investigate the role of calcium-activated potassium …
Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm
Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm
All ETDs from UAB
Breast cancer is the second leading cause of cancer-related death in American women and metastatic breast cancer has a 5-year survival rate of only 26%. Current targeted treatments for this disease include anti-estrogen strategies for estrogen receptor positive tumors (~60%) and anti-Her2/Neu strategies for tumors overexpressing this receptor (20-25%). A percentage of breast cancer patients, however, are resistant to these therapies and are left without any effective treatment options. One of the agents currently being investigated to improve breast cancer survival is TRA-8, an agonistic monoclonal antibody to death receptor 5 (DR5), which induces apoptosis in various types of cancer …
A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik
A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik
All ETDs from UAB
The E2F family of transcription factors are important regulators of cell proliferation, and are often dysregulated in cancers. One member of the E2F family, E2F1, also has the ability to induce apoptosis; therefore, uncovering how E2F1-induced apoptosis is controlled is of interest in understanding tumorigenesis. To this end, we identified RRP1B as a novel target specifically induced by E2F1. RRP1B expression is specifically upregulated by E2F1 overexpression, but not other E2F family members. RRP1B expression is correlated with E2F1 expression during the cell cycle, and is significantly induced after DNA damage. The minimal RRP1B promoter region responsive to E2F1 was …
Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke
Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke
All ETDs from UAB
Apoptosis, or programmed cell death, is essential for the development and maintenance of mammalian tissues. Activation of cysteinyl aspartate specific proteases, called caspases, is crucial to the implementation apoptosis. During apoptosis, the second mito-chondrial derived activator of caspase (Smac), augments caspase activity by antagonizing the inhibitor of apoptosis proteins (IAPs) down-regulation of caspase function. Smac protein synthesis occurs in the cytosol from a nuclear gene. Mitochondrial import of Smac leads to proteolytic removal of the first 55 amino acids, exposing a novel amino-terminus composed Ala56-Val-Pro-Ile59, which is an inhibitor of apoptosis binding motif (IBM). The IBM facilitates the interactions with …
Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros
Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros
All ETDs from UAB
Old World and New World hantaviruses, family Bunyaviridae, mature intracellularly within cellular compartments. Although it is generally accepted they assemble and bud in the Golgi apparatus the site remains controversial for New World hantaviruses, because some studies have raised the possibility of their maturation at the plasma membrane. Furthermore, the site of assembly hantaviruses still remains undetermined. The nucleocapsid (N) protein has been proposed to play a key role in facilitating assembly. To gain insight into the assembly pathways of Old World hantaviruses, we examine the intracellular trafficking of the Hantaan (HTN) virus N protein. We show progressive redistribution of …