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Full-Text Articles in Medicine and Health Sciences
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
All ETDs from UAB
Cerebral blood flow is regulated by vasoactive molecules released by astroglial cell processes that ensheath the entire cerebrovasculature. This regulation of blood flow in response to neuronal activity is a process known as functional hyperemia. Astrocytes, along with their associated neurons and microvessels, are organized into a functional system called the gliovascular unit (GVU). The astroglial component of the GVU is integral in both regulation of blood flow and maintenance of the blood-brain barrier (BBB). In disease, this system can be disrupted. We found that glioma cells displace astrocytic processes, called endfeet, and prevent their communication with associated vessels, leading …
Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert
Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert
All ETDs from UAB
Malignant gliomas are the most prevalent primary brain tumor. They are highly aggressive and lack effective treatment options. Standard therapy includes a combination of radiation, chemotherapy, and tumor resection; however, even with aggressive treatment, median patient survival remains a dismal 12 – 14 months after diagnosis. Research has focused on understanding the unique biological mechanisms involved in glioma growth and survival in an effort to design novel therapies to treat this devastating disease. In the unique environment of the brain, gliomas have developed the ability to grow and survive at the cost of the normal surrounding brain tissue. Glutamate, the …
Effect Of Protons On The Biology Of Human Gliomas, Avinash Vinayak Honasoge
Effect Of Protons On The Biology Of Human Gliomas, Avinash Vinayak Honasoge
All ETDs from UAB
Gliomas are the most common and most deadly primary brain cancer. Patient outcome for the most malignant variety, the World Health Organization (WHO) Type IV glioblastoma multiforme (GBM), has stagnated over the last several decades - the best combination treatment of surgical resection, radiation, and chemotherapy results in median survival of just over a year. To escape treatment, GBM must multiply and migrate in a confined brain environment. Both of these aspects of tumor cell invasion rely on the cell's ability to volume regulate; cell division involves a stage called "pre-mitotic condensation" in which the cells shrink immediately prior to …
Regulation Of Glioma Cell Migration And Proliferation By A Non-Selective Cation Channel., Arun Kumar Rooj
Regulation Of Glioma Cell Migration And Proliferation By A Non-Selective Cation Channel., Arun Kumar Rooj
All ETDs from UAB
Two of the most striking features of brain tumors are their unusual ability to robustly proliferate and migrate in the brain. Previous results from our laboratory suggest that glioma cells express a non-selective cation channel that is composed of Epithelial Sodium Channel (ENaC) and Acid Sensing Ion Channel (ASIC) subunits. We hypothesize that this glioma specific current regulates glioma cell migration and proliferation by modulating an intracellular signaling pathway. To test our hypothesis, we have attenuated this cationic conductance by either pharmacological blockers (psalmotoxin-1 and benzamil), or by knocking down expression of a particular subunit of this cross-clade ion channel …
Glioma-Vasculature Interactions, Stacey Watkins
Glioma-Vasculature Interactions, Stacey Watkins
All ETDs from UAB
Malignant gliomas are highly invasive brain tumors, which lack effective treatment options. To date, the standard therapy includes surgical debulking followed by chemotherapy and radiation. Despite efforts to eradicate the disease, the median patient survival time is only 14 months. In an attempt to discover novel therapies, research has focused on understanding the heterogeneous biological mechanisms employed by these cells. Uniquely, they do not metastasize through the vasculature or lymphatics like other solid cancers but alternatively, glioma cells utilize the abluminal surface of the vasculature to guide invasion and migration throughout the brain. The intimate association between glioma cells and …
Regulation Of P27kip1 By Trip6 And Its Implications In Cancer Progression, Victor T G Lin
Regulation Of P27kip1 By Trip6 And Its Implications In Cancer Progression, Victor T G Lin
All ETDs from UAB
TRIP6 is a focal adhesion molecule that functions as an adaptor protein to mediate diverse cellular functions, including motility and antiapoptotic signaling, through a wide variety of protein-protein interactions. We were able to characterize a novel interaction between TRIP6 and p27KIP1, a CDK inhibitor which can both suppress and promote tumorigenesis, depending on its regulation. TRIP6 expression specifically promotes the AKT-mediated phosphorylation of p27KIP1 at T157, which leads to its cytosolic retention, and accelerates the protein turnover rate of p27KIP1. We also found that phosphorylation of T157 by itself promotes cell motility and can be linked to the formation of …
Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu
Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu
All ETDs from UAB
Changes in the glioma microenvironment including oxygen (O2) levels, supply of amino acid such as L-glutamate and L-cystine and glutathione (GSH) concentrations play a critical role in glioma biology. Previous data from our laboratory and others have implicated the L-cystine/L-glutamate exchanger, system xc- in the invasion and proliferation of cancers including glioma. The central aim of this dissertation was to characterize the contribution of L-cystine uptake, GSH synthesis and L-glutamate release to migration and proliferation of glioma cells. In my first study, I examined the role of system xc- mediated L-glutamate release on glioma migration. I show that activation of …
The Sodium-Potassium-Chloride Cotransporter In Glioma Biology, Brian R. Haas
The Sodium-Potassium-Chloride Cotransporter In Glioma Biology, Brian R. Haas
All ETDs from UAB
The most common malignant primary brain tumor, gliomas usually derive from glial cells including oligodendrocytes and astrocytes. These tumors are characterized by high rates of proliferation and aberrant migration which make them notoriously difficult to treat using standard treatment paradigms such as chemotherapy and radiation. In order for glioma cells to migrate into the surrounding brain tissue, they must undergo rapid and dynamic volume changes. Previous work published by the Sontheimer laboratory and others indicates glioma utilize the flux of ions across the cell membrane to aid in volume changes associate with cell migration. In this dissertation, I show the …
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 …
Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben
Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben
All ETDs from UAB
ROLE OF TRANSIENT RECEPTOR POTENTIAL CANONICAL CHANNELS IN GLIOMA CELL BIOLOGY VALERIE C. BOMBEN DEPARTMENT OF NEUROBIOLOGY ABSTRACT Gliomas, primary brain tumors derived from glial cells, constitute the majority of malignant tumors within the central nervous system. The most malignant of these tumors, grade IV Glioblastoma multiforme, are characterized by extensive proliferation, cellular and nuclear atypia, angiogenesis, areas of necrosis, and widespread invasion into the brain parenchyma. Data from our lab and others have implicated ion channels in the invasion and proliferation of glioma cells. Moreover, calcium signaling in gliomas and other cells has been implicated in both migration and …