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You searched for subject:(Glioma physiopathology 60). Showing records 1 – 2 of 2 total matches.

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1. Ernest, Nola Jean Sieber. The role of chloride in the volume regulation of human glioma cells.

Degree: PhD, 2007, University of Alabama – Birmingham

According to the Central Brain Tumor Registry of the United States, the most common primary brain tumors are gliomas, tumors composed of cells of glial origin, most commonly astrocytes and oligodendrocytes. The most aggressive of these tumors are characterized by hyperproliferation, marked cellular and nuclear atypia, extensive infiltration into surrounding normal brain tissue, and large areas of cell and tissue death. Previous data published by our lab and others suggest that these biological processes may involve regulated cell volume changes. Using cell volume regulation in the presence of an anisosmotic challenge as a model for cell swelling and shrinkage, cell volume changes have been shown to involve the movement of molecules, or osmolytes, across the plasma membrane through channels and transporters. Water is osmotically obliged to follow the net movement of molecules, resulting in a net flux of water across the plasma membrane and an overall change in cell volume. As the most abundant anion in biological systems, chloride has been shown to be involved in the volume regulation of several cell types. However, chloride-mediated volume changes in human glioma cells have not been extensively studied. It is the primary goal of this dissertation to examine the mechanisms employed by human glioma cells to dynamically regulate their cell volume at rest, in the presence of anisosmotic conditions, and importantly during the biological processes of apoptosis and migration. We confirm the expression of the voltage gated chloride channels ClC-2, 3, and 5 in human glioma cell lines and patient biopsies. In addition, we demonstrate the expression of the cation chloride cotransporters, KCC1, KCC3, and NKCC1. Using a variety of techniques, including electrophysiology, Coulter Counter, and chloride-sensitive fluorescent dyes, we establish that the resting intracellular chloride concentration and cell volume are maintained by the basal activity of chloride cotransporters. While pharmacological inhibition of these cotransporters suggests that they are also involved in cell volume regulation during an aniosomotic challenge, chloride efflux through channels plays a more significant role in post-hyposmotic volume decrease. Similarly, inhibition of chloride channels, but not chloride cation cotransporters, inhibits the cell condensation that occurs in the presence of apoptotic stimuli. Cells treated with chloride channel inhibitors also demonstrated limited caspase 3 activity and DNA fragmentation, suggesting that the volume decrease is necessary for apoptosis. Finally, transwell migration of human glioma cells was blocked in the presence of chloride channel and transport inhibitors, suggesting that the mechanisms involved in cell shrinkage are necessary in glioma cell migration.

xi, 176 p. : ill., digital, PDF file

Neurobiology

Joint Health Sciences

glioma astrocytoma chloride channels migration apoptosis volume regulation

UNRESTRICTED

Advisors/Committee Members: Sontheimer, Harald, Benos, Dale <br>, Brenner, Michael <br>, Guay-Woodford, Lisa <br>, Hablitz, John.

Subjects/Keywords: Brain Neoplasms  – physiopathology <; br>; Cell Size <; br>; Chloride Channels  – physiology <; br>; Glioma  – physiopathology <; br>

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Ernest, N. J. S. (2007). The role of chloride in the volume regulation of human glioma cells. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,86

Chicago Manual of Style (16th Edition):

Ernest, Nola Jean Sieber. “The role of chloride in the volume regulation of human glioma cells.” 2007. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 08, 2021. http://contentdm.mhsl.uab.edu/u?/etd,86.

MLA Handbook (7th Edition):

Ernest, Nola Jean Sieber. “The role of chloride in the volume regulation of human glioma cells.” 2007. Web. 08 Mar 2021.

Vancouver:

Ernest NJS. The role of chloride in the volume regulation of human glioma cells. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2007. [cited 2021 Mar 08]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,86.

Council of Science Editors:

Ernest NJS. The role of chloride in the volume regulation of human glioma cells. [Doctoral Dissertation]. University of Alabama – Birmingham; 2007. Available from: http://contentdm.mhsl.uab.edu/u?/etd,86

2. Habela, Christa Whelan. Progression through the cell cycle is regulated by dynamic chloride dependent changes in cell volumes.

Degree: PhD, 2008, University of Alabama – Birmingham

The hypothesis that cell volume and the progression of the cell cycle are interdependent has surfaced off and on in the cell cycle literature for the past 30 years. However, a conclusion as to how cell volume is mechanistically involved in cell division has not been reached in mammalian cells. The aim of this dissertation was to establish how volume changes modulate cell cycle progression. Most of the studies addressing this question have examined mass content yet, more recently, focus has been placed on intracellular water, which is determined by the balance between mechanical and osmotic forces. As a result, ion channels and transporters which regulate intracellular osmotic content are integral to the maintenance of cell volume. In this dissertation, I show that a large, rapid and regulated volume decrease occurs as glioma cells progress through mitosis. I refer to this process as pre-mitotic condensation (PMC). This process is functionally linked to DNA condensation prior to cell division as the two events occur simultaneously, and inhibition of PMC results in a prolongation of DNA condensation. Further, my data demonstrates that glioma cells actively accumulate chloride, which acts as the primary energetic driving for cell volume changes in these cells. During the process of PMC, this gradient drives the efflux of chloride through ClC3 channels, which mediates water loss and the volume decrease. Interestingly, chloride accumulation to similar levels can be observed in immature astrocytes and neurons, suggesting that glioma cells recapitulate the biology of immature proliferating cells in the brain. This also suggests that my findings may have broader applicability to cell division in both neural cells and cancer.

xii, 132 p. : ill., digital, PDF file.

Neurobiology

Joint Health Sciences

Voltage Gated Chloride Channels Pre-miotic Condensation DND Condensation C1C3 Mitosis Volume Regulation

UNRESTRICTED

Advisors/Committee Members: Sontheimer, Harald, Bevensee, Mark<br>Engler, Jeffrey<br>Pozzo-Miller, Lucas<br>Theibert, Anne.

Subjects/Keywords: Cell Cycle  – physiology<; br>; Cell Movement  – physiology<; br>; Cell Proliferation<; br>; Cell Size<; br>; Chloride Channels  – physiology<; br>; Chlorides  – metabolism<; br>; Cytokinesis  – physiology<; br>; Glioma  – physiopathology<; br>; Mitosis  – physiology<; br>; Neuroglia  – physiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Habela, C. W. (2008). Progression through the cell cycle is regulated by dynamic chloride dependent changes in cell volumes. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,444

Chicago Manual of Style (16th Edition):

Habela, Christa Whelan. “Progression through the cell cycle is regulated by dynamic chloride dependent changes in cell volumes.” 2008. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 08, 2021. http://contentdm.mhsl.uab.edu/u?/etd,444.

MLA Handbook (7th Edition):

Habela, Christa Whelan. “Progression through the cell cycle is regulated by dynamic chloride dependent changes in cell volumes.” 2008. Web. 08 Mar 2021.

Vancouver:

Habela CW. Progression through the cell cycle is regulated by dynamic chloride dependent changes in cell volumes. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2008. [cited 2021 Mar 08]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,444.

Council of Science Editors:

Habela CW. Progression through the cell cycle is regulated by dynamic chloride dependent changes in cell volumes. [Doctoral Dissertation]. University of Alabama – Birmingham; 2008. Available from: http://contentdm.mhsl.uab.edu/u?/etd,444

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