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Glioma

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Articles 1 - 21 of 21

Full-Text Articles in Cancer Biology

The Effect Of The Loss Of Lgl1 In Murine Neural Progenitor Cells On Mapk Signaling And Proliferation, Monique R. Lacourse Jan 2018

The Effect Of The Loss Of Lgl1 In Murine Neural Progenitor Cells On Mapk Signaling And Proliferation, Monique R. Lacourse

Theses and projects

Glioblastoma is an incurable, aggressive, and highly invasive type of brain tumor that harbors tumor initiating cells characterized by disrupted polarized cell divisions. A cell polarity gene lethal (2) giant larvae 1 (Lgl1) has been implicated in gliomas and is a tumor suppressor initially identified in Drosophila with roles in proliferation. The loss of Lgl1 in Drosophila activates the MAPK protein kinase JNK and the Ras pathway and therefore its downstream kinase ERK, a transcription factor modulator. Furthermore, when Lgl1 is knocked out in mice, a phenotype similar to glioma is seen. Loss of the human form of Lgl1, Hugl1 ...


The Overexpression Of Basigin-3 In Glioblastoma, Samantha M. Wightman Aug 2016

The Overexpression Of Basigin-3 In Glioblastoma, Samantha M. Wightman

All NMU Master's Theses

Glioblastoma (GBM) is one of the most aggressive forms of brain tumor. With the current standard of care, survival prognosis for GBM patients is 15 months with a five-year survival rate of less than 3%. An increased understanding of the molecular mechanisms leading to cell growth and survival of GBMs may result in novel treatments to target and eradicate the disease. The protein Basigin-2 (aka EMMPRIN) induces the expression of matrix metalloproteinase (MMP) enzymes, and its expression level is positively correlated with GBM tumor grade. In 2011, Liao et al. reported that a splice variant of the basigin gene, called ...


Igfbp2 Potentiates Egfr-Stat3 Signaling In Glioma, Yingxuan Chua May 2015

Igfbp2 Potentiates Egfr-Stat3 Signaling In Glioma, Yingxuan Chua

UT GSBS Dissertations and Theses (Open Access)

Gliomas are clinically challenging brain tumors with dismal survival rates due to its infiltrative nature and ineffective standard therapy. Insulin-like growth factor binding protein 2 (IGFBP2) is a pleiotropic oncogenic protein that has both extracellular and intracellular functions. Despite a clear causal role in cancer development, the contributions of intracellular IGFBP2 to tumor development and progression are poorly understood. Here we present evidence that both exogenous IGFBP2 treatment and cellular IGFBP2 overexpression lead to aberrant activation of EGFR, which subsequently activates STAT3 signaling. Furthermore, we demonstrate that IGFBP2 augments the nuclear accumulation of EGFR to potentiate STAT3 transactivation activities, via ...


Atrx Loss-Of-Function In Mouse Neuroprogenitor Cells As A Model Of Early Events In Gliomagenesis, Hannah E. Goldberg Feb 2015

Atrx Loss-Of-Function In Mouse Neuroprogenitor Cells As A Model Of Early Events In Gliomagenesis, Hannah E. Goldberg

Electronic Thesis and Dissertation Repository

ATRX is a chromatin remodeling protein important for neural development, and ATRX inactivation leads to genomic instability, mitotic defects and TP53-mediated apoptosis. In the last few years, ATRX mutations were identified in a large proportion of paediatric and adult gliomas that often coincide with mutations in the tumor suppressor TP53. The present work shows that combinatorial loss of ATRX and TP53 function in vitro causes genomic instability while improving cell viability, identifying potential early events in gliomagenesis. Furthermore, several gene transcripts associated with glioma development and known oncogenic pathways were significantly upregulated in the Atrx-null neonatal mouse forebrain. Finally ...


Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart Jan 2015

Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart

Theses and Dissertations--Clinical and Translational Science

Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin ...


Car-Modified T Cells Capable Of Distinguishing Normal Cells From Malignant Cells, Hillary G. Caruso May 2014

Car-Modified T Cells Capable Of Distinguishing Normal Cells From Malignant Cells, Hillary G. Caruso

UT GSBS Dissertations and Theses (Open Access)

T cells can be redirected to target tumor-associated antigen (TAA) by genetic modification to express a chimeric antigen receptor (CAR), which fuses the specificity derived from an antibody to T-cell activation domains to result in lysis of TAA-expressing cells. Due to the potential for on-target, off-tissue toxicity, CAR+ T-cell therapy is currently limited to unique or lineage-restricted TAAs. Glioblastoma, a grade IV brain malignancy, overexpresses epidermal growth factor receptor (EGFR) in 40-50% of patients. EGFR also has widespread normal tissue expression. To target EGFR on glioblastoma while reducing the potential for normal tissue toxicity, EGFR-specific CAR generated from cetuximab, Cetux-CAR ...


Quantification Of Protoporphyrin Ix Accumulation In Glioblastoma Cells – A New Technique, Johnathan Lawrence, Ashish Patel, Richard Rovin, Robert Belton, Catherine Bammert, Robert Winn Dec 2013

Quantification Of Protoporphyrin Ix Accumulation In Glioblastoma Cells – A New Technique, Johnathan Lawrence, Ashish Patel, Richard Rovin, Robert Belton, Catherine Bammert, Robert Winn

Johnathan Lawrence

Introduction. 5-Aminolevulinic Acid (5-ALA) is a precursor of heme synthesis. A metabolite, protoporphyrin IX (PpIX), selectively accumulates in neoplastic tissue including glioblastoma. Presurgical administration of 5-ALA forms the basis of fluorescence-guided resection (FGR) of glioblastoma (GBM) tumors. However, not all gliomas accumulate sufficient quantities of PpIX to fluoresce, thus limiting the utility of FGR. We therefore developed an assay to determine cellular and pharmacological factors that impact PpIX fluorescence in GBM. This assay takes advantage of a GBM cell line engineered to express yellow fluorescent protein. Methods. The human GBM cell line U87MG was transfected with a YFP expression vector ...


Astrocyte Elevated Gene-1, A Novel Modulator Of Astrocyte Function: Implications For Neuroaids, Aging And Glioblastoma, Neha Vartak Dec 2013

Astrocyte Elevated Gene-1, A Novel Modulator Of Astrocyte Function: Implications For Neuroaids, Aging And Glioblastoma, Neha Vartak

Theses and Dissertations

Vartak-Sharma, Neha N., Astrocyte elevated gene-1, a novel modulator of astrocyte function: Implications for NeuroAIDS, aging and glioblastoma. Doctor of Philosophy (Biomedical Sciences), Nov, 2013, 180 pp., 1 table, 40 illustrations, 336 bibliographies. Recent attempts to analyze human immunodeficiency virus (HIV)-1-induced gene expression changes in astrocyte identified a multifunctional oncogene, astrocyte elevated gene-1 (AEG-1), as an HIV-1 and tumor necrosis factor-inducible transcript. Subsequently, due to its homology to mouse breast cancer metastasis protein, metadherin, AEG-1 was largely implicated in carcinogenesis of diverse cancer types. However, the role of AEG-1 in astrocytes, the original cell type in which AEG-1 ...


Involvement Of Estrogen Receptor Beta 5 In The Progression Of Glioma, Wenjun Li May 2013

Involvement Of Estrogen Receptor Beta 5 In The Progression Of Glioma, Wenjun Li

Theses and Dissertations

Emerging evidence suggests a decline of ERβ expression in various peripheral cancers and ERβ has been proposed as a cancer brake that inhibits tumor cell growth and proliferation. In the current study, we have identified ERβ5 as the predominant isoform of ERβ in human glioma and its expression was significantly increased in human glioma as compared with non-neoplastic brain tissue. Hypoxia and activation of hypoxia inducible factor (HIF) increased ERβ transcription in U87 cells, suggesting elevated ERβ expression in glioma might be induced by the hypoxic stress in the tumor. Overexpression of either ERβ1 or ERβ5 increased PTEN expression and ...


Phenytoin Reduces 5-Ala Mediated Fluorescence In Glioblastoma Cells, Christopher Steele, Johnathan E. Lawrence, Richard A. Rovin, Robert J. Winn Dec 2012

Phenytoin Reduces 5-Ala Mediated Fluorescence In Glioblastoma Cells, Christopher Steele, Johnathan E. Lawrence, Richard A. Rovin, Robert J. Winn

Johnathan Lawrence

Glioblastoma multiforme (GBM) is a devastating form of cancer, and essentially all GBM tumors recur causing fatality. A new surgical technique, fluorescence-guided resection of GBM using 5-aminolevulinic acid (5-ala), improves the extent of resection and positively impacts the length and quality of patient survival. The fluorescence achieved in neoplastic tissue depends directly on the accumulation of porphyrins derived from the metabolism of the 5-ala prodrug within the cancer cell. However, 5-ala induced fluorescence has been reported to be inconsistent. In an effort to determine the cause of the inconsistent fluorescence, the authors investigated the effect of medications commonly prescribed to ...


Glioblastoma Derived Exosomes Induce Apoptosis In Cytotoxic T Cells Through A Fas Ligand Mediated Mechanism, Keith Sabin, Richard Rovin, Johnathan Lawrence, Robert Belton, Robert Winn Dec 2011

Glioblastoma Derived Exosomes Induce Apoptosis In Cytotoxic T Cells Through A Fas Ligand Mediated Mechanism, Keith Sabin, Richard Rovin, Johnathan Lawrence, Robert Belton, Robert Winn

Johnathan Lawrence

INTRODUCTION: Glioblastoma multiforme deploy s a number of weapons to thwart the immune system. Within the tumor microenvironment, cytotoxic T cells fall victim to Fas ligand (FasL) induced apoptosis. In prostate and colorectal cancer, exosomes can mediate this FasL induced T cell apoptosis. Exosomes are tiny, membrane bound vesicles that are released from a cell. They contain functional mRNA and protein and have cell surface molecules representative of their parent cell. It is not known if GBM derived exosomes can also mediate FasL triggered apoptosis. In this study, the role of tumor derived exosomes as the delivery vehicle for FasL ...


Leptin Promotes Glioblastoma, Johnathan Lawrence, Nicholas Cook, Richard Rovin, Robert Winn Dec 2011

Leptin Promotes Glioblastoma, Johnathan Lawrence, Nicholas Cook, Richard Rovin, Robert Winn

Johnathan Lawrence

The hormone leptin has a variety of functions. Originally known for its role in satiety and weight loss, leptin more recently has been shown to augment tumor growth in a variety of cancers. Within gliomas, there is a correlation between tumor grade and tumor expression of leptin and its receptor. This suggests that autocrine signaling within the tumor microenvironment may promote the growth of high-grade gliomas. Leptin does this through stimulation of cellular pathways that are also advantageous for tumor growth and recurrence: antiapoptosis, proliferation, angiogenesis, and migration. Conversely, a loss of leptin expression attenuates tumor growth. In animal models ...


Effects Of ß3-Adrenergic Receptor Agonist On Gene Expression Of Leptin In Glioblastoma, Johnathan E. Lawrence, Nicholas J. Cook, Richard A. Rovin, Robert J. Belton, Robert J. Winn Dec 2011

Effects Of ß3-Adrenergic Receptor Agonist On Gene Expression Of Leptin In Glioblastoma, Johnathan E. Lawrence, Nicholas J. Cook, Richard A. Rovin, Robert J. Belton, Robert J. Winn

Johnathan Lawrence

In the 25 years since temozolomide entered phase I clinical trials, few new primary or adjuvant therapies have been developed for the treatment of glioblastoma multiforme (GBM) tumors. Our laboratory has been exploring novel methods for the treatment of GBMs. Recent studies indicate that the expression of the hormone leptin and its receptor (OBR) increases in gliomas and positively correlates with the malignancy of the tumor. Interestingly, ß3-adrenergic receptor agonists are known to decrease leptin expression in adipocytes but have not been examined in GBM cells. We hypothesized that b3-adrenergic agonists downregulate the expression of leptin and its receptor. In ...


Mechanisms Of Adenovirus-Mediated Autophagy, Erin White Aug 2011

Mechanisms Of Adenovirus-Mediated Autophagy, Erin White

UT GSBS Dissertations and Theses (Open Access)

A patient diagnosed with a glioma, generally, has an average of 14 months year to live after implementation of conventional therapies such as surgery, chemotherapy, and radiation. Glioblastomas are highly lethal because of their aggressive nature and resistance to conventional therapies and apoptosis. Thus other avenues of cell death urgently need to be explored. Autophagy, which is also known as programmed cell death type II, has recently been identified as an alternative mechanism to kill apoptosis- resistant cancer cells. Traditionally, researchers have studied how cells undergo autophagy during viral infection as an immune response mechanism, but recently researchers have discovered ...


Blocking The Notch Pathway With Gamma-Secretase Inhibitors Enhances Temozolomide Treatment Of Gliomas Through Therapy-Induced Senescence: A Dissertation, Candace A. Gilbert May 2011

Blocking The Notch Pathway With Gamma-Secretase Inhibitors Enhances Temozolomide Treatment Of Gliomas Through Therapy-Induced Senescence: A Dissertation, Candace A. Gilbert

GSBS Dissertations and Theses

Glioma therapy relies on induction of cytotoxicity; however, the current combination of surgery, irradiation (IR) and temozolomide (TMZ) treatment does not result in a long-term cure. Our lab previously demonstrated that a small population of glioma cells enters a transient cell cycle arrest in response to chemotherapy. Treatment with TMZ significantly decreases initial neurosphere formation; however, after a short recovery period, a small number of cells resume neurosphere formation and repopulate the culture. This recovery of neurosphere growth recapitulates the inevitable glioma recurrence in the clinic. The focus of our laboratory is to study direct-target therapies that can be combined ...


Β3-Adrenergic Agonists Mimic Eustress Response And Reduce Leptin-Mediated Proliferation In A Gbm Cell Line, Johnathan E. Lawrence, Nicholas J. Cook, Richard A. Rovin, Robert J. Winn Dec 2010

Β3-Adrenergic Agonists Mimic Eustress Response And Reduce Leptin-Mediated Proliferation In A Gbm Cell Line, Johnathan E. Lawrence, Nicholas J. Cook, Richard A. Rovin, Robert J. Winn

Johnathan Lawrence

A great deal of mental stress, depression, and anxiety often overwhelm cancer patients; those diagnosed with glioblastoma multiforme (GBM) are no exception. Different types of stress invariably impact what has been termed “the brain-adipocyte BDNF/leptin axis” (Dr. Cao and colleagues of the Comprehensive Cancer Center at The Ohio State University). For example, eustress (good stress) and distress (bad stress) both lead to increased sympathetic activity and adrenal gland stimulation, yet eustress reduces leptin levels and attenuates tumor growth while distress increases leptin levels and augments tumor growth. Complicating matters in GBM is that leptin and its receptor are expressed ...


Glioblastoma Derived Exosomes Contribute To Tumor Immune Evasion, Keith Z. Sabin, Danny Lebert, Vanessa Thibado, Richard A. Rovin, Johnathan E. Lawrence, Robert J. Winn Dec 2010

Glioblastoma Derived Exosomes Contribute To Tumor Immune Evasion, Keith Z. Sabin, Danny Lebert, Vanessa Thibado, Richard A. Rovin, Johnathan E. Lawrence, Robert J. Winn

Johnathan Lawrence

Glioblastoma multiforme (GBM) is the most frequent and lethal primary brain tumor in adults. Despite intense biomedical research, the median survival after diagnosis is 15 months. One factor contributing to this poor prognosis is the immune protection afforded by the tumor microenvironment. Tumors have a diverse repertoire of immune-evasive techniques. One method of evasion not well explored is the release of tumor-derived exosomes. Exosomes are tiny membrane-bound vesicles of endocytic origin that contain viable mRNA and functional proteins that can affect the physiology of recipient cells. Exosome release has been reported for numerous cancer types, including GBM. Exosomes from colon ...


Survival Prediction For Brain Tumor Patients Using Gene Expression Data, Vinicius Bonato May 2010

Survival Prediction For Brain Tumor Patients Using Gene Expression Data, Vinicius Bonato

UT GSBS Dissertations and Theses (Open Access)

Brain tumor is one of the most aggressive types of cancer in humans, with an estimated median survival time of 12 months and only 4% of the patients surviving more than 5 years after disease diagnosis. Until recently, brain tumor prognosis has been based only on clinical information such as tumor grade and patient age, but there are reports indicating that molecular profiling of gliomas can reveal subgroups of patients with distinct survival rates. We hypothesize that coupling molecular profiling of brain tumors with clinical information might improve predictions of patient survival time and, consequently, better guide future treatment decisions ...


Expression Of Hcmv Ie1 In The U87mg Cell Line Augments Resistance To Temozolomide, Richard Rovin, Johnathan Lawrence, Justin Segula, Robert Winn Dec 2009

Expression Of Hcmv Ie1 In The U87mg Cell Line Augments Resistance To Temozolomide, Richard Rovin, Johnathan Lawrence, Justin Segula, Robert Winn

Johnathan Lawrence

INTRODUCTION: Human cytomegalovirus (HCMV) DNA and protein are found in gliomas but not in normal brain or other primary brain tumors. The role of HCMV infection in glioma biology is unclear. While it is unlikely that HCMV infection causes glioma, viral proteins might impart a proliferative and antiapoptotic phenotype that confers a survival advantage. Does this oncomodulation translate into a clinically relevant effect in glioma cells? To answer this question, we compared the response of the U87IE1 and U87MG malignant glioma cell lines to temozolomide. U87IE1 cells are U87MG cells that have been genetically engineered to produce HCMV IE1 protein ...


Combining Cytotoxic And Immune-Mediated Gene Therapy To Treat Brain Tumors, James Curtin, Gwendalyn King, Marianela Candolfi, Remy Greeno, Kurt Kroeger, Pedro Lowenstein, Maria Castro Jan 2005

Combining Cytotoxic And Immune-Mediated Gene Therapy To Treat Brain Tumors, James Curtin, Gwendalyn King, Marianela Candolfi, Remy Greeno, Kurt Kroeger, Pedro Lowenstein, Maria Castro

Articles

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will ...


Gene Therapy And Targeted Toxins For Glioma, James Curtin, Gwendalyn King, Marianela Candolfi, Kurt Kroeger, Pedro Lowenstein, Maria Castro Jan 2005

Gene Therapy And Targeted Toxins For Glioma, James Curtin, Gwendalyn King, Marianela Candolfi, Kurt Kroeger, Pedro Lowenstein, Maria Castro

Articles

The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic ...