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Biomedical subjects

G N Fuller

Publications and source records attributed to G N Fuller.

At least 19 recordsLinked to original sources
PubMed2006

Tumor suppressor in lung cancer-1 (TSLC1) functions as a glioma tumor suppressor.

Tumor suppressor in lung cancer-1 (TSLC1) loss is common in many human cancers, including meningioma. In this study, we demonstrate that TSLC1 protein and RNA expression is lost in 60% to 65% of high-grade gliomas, and that TSLC1 reintroduction into glioma cells results in growth suppression. Moreover, Tslc1 loss in mice results in increased astrocyte proliferation in vivo and in vitro. These data indicate that TSLC1 functions as a glioma tumor suppressor.

Animals↗
PubMed2002

Cerebellar degeneration and autoimmunity to zinc-finger proteins of the cerebellum.

The serum of a patient with subacute cerebellar dysfunction was used to probe a cDNA expression library and isolate two genes: Zic1 (zinc-finger of the cerebellum) and Zic4. The patient had intrathecal synthesis of Zic antibodies, suggesting that the Zic proteins were autoantigens of the neurologic disorder. The Zic proteins are involved in cerebellar development and are reported as being preferentially expressed by medulloblastomas. It was found that the expression of Zic proteins is enriched in, but not limited to, medulloblastomas and primitive neuroectodermal tumors.

Aged↗
PubMed2001

PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo.

We present evidence that some low-grade oligodendrogliomas may be comprised of proliferating glial progenitor cells that are blocked in their ability to differentiate, whereas malignant gliomas have additionally acquired other mutations such as disruption of cell cycle arrest pathways by loss of Ink4a-Arf. We have modeled these effects in cell culture and in mice by generating autocrine stimulation of glia through the platelet-derived growth factor receptor (PDGFR). In cell culture, PDGF signaling induces proliferation of glial precursors and blocks their differentiation into oligodendrocytes and astrocytes. In addition, coexpression of PDGF and PDGF receptors has been demonstrated in human gliomas, implying that autocrine stimulation may be involved in glioma formation. In this study, using somatic cell type-specific gene transfer we investigated the functions of PDGF autocrine signaling in gliomagenesis by transferring the overexpression of PDGF-B into either nestin-expressing neural progenitors or glial fibrillary acidic protein (GFAP)-expressing astrocytes both in cell culture and in vivo. In cultured astrocytes, overexpression of PDGF-B caused significant increase in proliferation rate of both astrocytes and neural progenitors. Furthermore, PDGF gene transfer converted cultured astrocytes into cells with morphologic and gene expression characteristics of glial precursors. In vivo, gene transfer of PDGF to neural progenitors induced the formation of oligodendrogliomas in about 60% of mice by 12 wk of age; PDGF transfer to astrocytes induced the formation of either oligodendrogliomas or mixed oligoastrocytomas in about 40% of mice in the same time period. Loss of Ink4a-Arf, a mutation frequently found in high-grade human gliomas, resulted in shortened latency and enhanced malignancy of gliomas. The highest percentage of PDGF-induced malignant gliomas arose from of Ink4a-Arf null progenitor cells. These data suggest that chronic autocrine PDGF signaling can promote a proliferating population of glial precursors and is potentially sufficient to induce gliomagenesis. Loss of Ink4a-Arf is not required for PDGF-induced glioma formation but promotes tumor progression toward a more malignant phenotype.

Animals↗
PubMed2001

Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells.

Increases in abundance of cathepsin B transcript and protein correlate with increases in tumor grade and alterations in subcellular localization and activity of cathepsin B. The enzyme is able to degrade the components of the extracellular matrix (ECM) and activate other proteases capable of degrading ECM. To investigate the role played by this protease in the invasion of brain tumor cells, we transfected SNB19 human glioblastoma cells with a plasmid containing cathepsin B cDNA in antisense orientation. Control cells were transfected with vector alone. Clones expressing antisense cathepsin B cDNA exhibited significant reductions in cathepsin B mRNA, enzyme activity and protein compared to controls. Matrigel Invasion assay showed that the antisense-transfected cells had a markedly diminished invasiveness compared with controls. When tumor spheroids containing antisense transfected SNB19 cells expressing reduced cathepsin B were co-cultured with fetal rat brain aggregates, invasion of fetal rat brain aggregates was significantly reduced. Green Fluorescent Protein (GFP) expressing parental cells and antisense transfectants were generated for detection in mouse brain tissue without any post-chemical treatment. Intracerebral injection of SNB19 stable antisense transfectants resulted in reduced tumor formation in nude mice. These results strongly support a role for cathepsin B in the invasiveness of human glioblastoma cells and suggest cathepsin B antisense may prove useful in cancer therapy.

Animals↗
PubMed2001

Choroid plexus cyst and chordoid glioma. Report of two cases.

Several types of mass lesions may occur in the third and lateral ventricles. Typically they arise from the lining of the ventricular cavity or from contiguous structures, by extension into the ventricle. The authors describe two patients, each of whom presented with a different rare lesion of the ventricular system. The first was a 53-year-old woman with a history of hypertension who sustained a blunt traumatic injury to the occipital region and subsequently developed a progressively worsening right-sided headache. Radiological examinations over the next 2 years revealed an enlarged right lateral ventricle and, ultimately, a choroid plexus cyst in its anterior and middle third, near the foramen of Monro, which is a rare location for these lesions. The cyst was removed en bloc, and follow-up examinations showed a significant improvement in her headache and a minimal differences in size between right and left ventricles. The authors also describe a 57-year-old man with hypertension, diabetes mellitus, and an old mycardial infarct, who presented to an outside institution with a progressively worsening headache, generalized malaise, and loss of olfactory sensation. Diagnostic imaging revealed a 1.5-cm oval lesion centered in the lamina terminalis region, an open craniotomy was performed, and evaluation of a biopsy sample demonstrated the mass to be a chordoid glioma of the third ventricle, a recently described glioma subtype. Two days after surgery, he suffered a left parietal stroke and an anterior mycardial infarction. After convalescing, he presented to The University of Texas M. D. Anderson Cancer Center for radiotherapy and follow up; 7 months later he was readmitted complaining of headache, short-term memory loss, and worsening confusion and disorientation. Neuroimaging revealed progression of the tumor (now 2 cm in diameter), which was removed by gross-total resection. His headache resolved immediately, and 2 months later his only complaint was of episodes of confusion. Three weeks later he died of a massive myocardial infarction. These two patients represent the sixth case of an adult with a choroid plexus cyst in the anterior lateral ventricle and the 19th case of an adult with a chordoid glioma of the third ventricle, respectively.

Brain Diseases↗
PubMed2001

Limitations of stereotactic biopsy in the initial management of gliomas.

Stereotactic biopsy is often performed for diagnostic purposes before treating patients whose imaging studies highly suggest glioma. Indications cited for biopsy include diagnosis and/or the "inoperability" of the tumor. This study questions the routine use of stereotactic biopsy in the initial management of gliomas. At The University of Texas M. D. Anderson Cancer Center, we retrospectively reviewed a consecutive series of 81 patients whose imaging studies suggested glioma and who underwent stereotactic biopsy followed by craniotomy/resection (within 60 days) between 1993 and 1998. All relevant clinical and imaging information was reviewed, including computerized volumetric analysis of the tumors based on pre- and postoperative MRI. Stereotactic biopsy was performed at institutions other than M. D. Anderson in 78 (96%) of 81 patients. The majority of tumors were located either in eloquent brain (36 of 81 = 44%) or near-eloquent brain (41 of 81 = 51%), and this frequently was the rationale cited for performing stereotactic biopsy. Gross total resection (>95%) was achieved in 46 (57%) of 81 patients, with a median extent of resection of 96% for this series. Diagnoses based on biopsy or resection in the same patient differed in 40 (49%) of 82 cases. This discrepancy was reduced to 30 (38%) of 80 cases when the biopsy slides were reviewed preoperatively by each of three neuropathologists at M. D. Anderson. Major neurologic complications occurred in 10 (12.3%) of 81 surgical patients and 3 (3.7%) of 81 patients undergoing biopsy. Surgical morbidity was probably higher in our series than it would be for glioma patients in general because our patients represent a highly selected subset of glioma patients whose tumors present a technical challenge to remove. Stereotactic biopsy is frequently inaccurate in providing a correct diagnosis and is associated with additional risk and cost. If stereotactic biopsy is performed, expert neuropathology consultation should be sought.

Adolescent↗
PubMed2001

Non-Hodgkin's lymphoma involving the gynecologic tract: a review of 88 cases.

Non-Hodgkin's lymphoma (NHL) involving the gynecologic tract is unusual and may cause confusion for the pathologist not familiar with its clinical and histologic features. The literature regarding this topic is also confusing, as modern NHL classification systems were not used or patients were not staged according to the Ann Arbor system in many prior reports. In addition, immunophenotypic data is not available for many cases, particularly in older studies. In the past year, there has been an interest in NHL involving the gynecologic tract and 88 cases have been collected. These cases were reviewed in the Pathology Department of M.D. Anderson Cancer Center during the past two decades, and many of these patients were treated at this hospital. In this review, these cases are reported using updated terminology and almost all cases were immunophenotyped using immunohistochemical methods or flow cytometric methods in a small subset of cases. These cases have also been segregated into two groups: 1) localized NHL, that presumably initially arose in the gynecologic tract and therefore are primary; and 2) NHL that involved the gynecologic tract as a part of systemic disease, and therefore most likely represent secondary involvement of the gynecologic tract. The differential diagnosis of NHL involving gynecologic organs is discussed.

Biopsy↗
PubMed2001

Statistical pattern analysis of gene expression profiles for glioblastoma tissues and cell lines.

The recent development and refinement of cDNA array and genechip techniques allows for large-scale parallel screening of gene expression and thereby provides a global assessment of molecular events transpiring in cell populations. We hypothesized that such an approach might help illuminate current issues in glioma research. To what degree are glioblastoma multiforme (GBM) cell lines representative of primary GBM tumors? We carried out a gene expression profiling study using cDNA array technology on 10 GBM primary tissues and 3 GBM cell lines. The gene expression levels were quantified, and the within-subject ranks of the gene expression levels were subsequently evaluated by hierarchical clustering analysis, multidimensional scaling analysis, and principal component analysis. Hierarchical cluster analysis shows that the 3 cell lines form one main cluster and the 10 tissue samples form a separate cluster. Multidimensional scaling and principal components analysis provided further graphical demonstration that the cell lines are clearly different from the tissue samples and that the cell lines are more different between themselves than are the tissues.

Central Nervous System Neoplasms↗
PubMed2001

Expression of tissue factor pathway inhibitor 2 inversely correlates during the progression of human gliomas.

Protease inhibitors regulate a variety of physiological and pathological processes including angiogenesis, embryo implantation, intravascular fibrinolysis, wound healing, and tumor invasion. Tissue factor pathway inhibitor (TFPI) 2 is a Mr 32,000 Kunitz-type serine protease inhibitor that inhibits plasmin, trypsin, chymotrypsin, cathepsin G, and plasma kallikrein but not urokinase-type plasminogen activator, tissue plasminogen activator, or thrombin. In this study, we determined the relative amounts of TFPI-2 in low-, intermediate-, and high-grade human glioma cell lines and tumor tissue samples. TFPI-2 protein and mRNA levels (measured by Western and Northern blotting) were highest in low-grade glioma cells (Hs683), lower in anaplastic astrocytoma cells (SW1088 and SW1783), and undetectable in high-grade glioma cells (SNB19). Analysis of TFPI-2 protein in human normal brain and in glioma tumor tissues for TFPI-2 revealed the highest levels in normal brain, lesser amounts in low-grade gliomas and anaplastic astrocytomas, and undetectable amounts in glioblastomas. In situ hybridization of TFPI-2 mRNA with normal brain tissues revealed the greatest positivity in neurons, with moderate positivity in both glial and endothelial cells and moderate, little, or no TFPI-2 mRNA in low-grade glioma, anaplastic astrocytoma, and glioblastoma tumor tissue samples, respectively. We also found that recombinant TFPI-2 inhibited the invasiveness of SNB19 glioblastoma cells in a Matrigel assay in a dose-dependent manner. Collectively, these results suggest that TFPI-2 has a regulatory role in the invasiveness of gliomas in vitro and in vivo.

Astrocytoma↗