Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Southern blot analyses of the 9p-localized type I interferon (IFN) genes in DNAs obtained from malignant glioma cell lines and glial tumor tissue have indicated that homozygous deletions of the IFN-alpha and IFN-beta genes often occur during the development of the highly malignant central nervous system neoplasm, glioblastoma. We have applied a set of markers that span the IFN region on 9p to the analysis of DNAs from 30 human glioma cell lines in order to define the region of homozygous deletion associated with this cancer more precisely. Fourteen of the cell lines revealed either complete (12 cases) or partial (2 cases) homozygous deletions of the IFN-alpha gene cluster; no instances of homozygous deletions were observed that did not involve the IFN-alpha region. Genomic DNA identified by the markers nearest to and flanking the IFN-alpha genes were retained in 5 of the cases with homozygous deletions. Consequently, these results limit the extent of homozygous deletions in glioma cell lines to a small region of 9p21-p22 that includes most of the type I IFN locus.
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PMID:Localization of chromosome 9p homozygous deletions in glioma cell lines with markers constituting a continuous linkage group. 833 74

We studied the expression of ten genes (encoding the receptors for glucocorticoid, mineralocorticoid, progesterone, androgen, estrogen, thyroid, retinoid acid, vitamin D) belonging to the steroid-thyroid hormone receptor superfamily (STRS) in 12 neuroepithelial tumors, 12 meningiomas and 2 human glioblastoma cell lines. Our method, based on the polymerase chain reaction, allowed the simultaneous amplification of cDNAs of the STRS genes. On average, 7 STRS genes were simultaneously expressed in each sample. Our study indicates that many STRS gene are commonly co-expressed in human CNS tumors. The importance of our results for the ongoing and proposed hormonal treatment trials is discussed.
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PMID:The expression of genes of the steroid-thyroid hormone receptor superfamily in central nervous system tumors. 835 54

Glioblastoma multiforme is the most common primary central nervous system neoplasm. Its dismal prognosis has led to investigation of new treatment strategies such as immunogene therapy. We transduced the human glioblastoma cell line D54MG in vitro with genes encoding the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), the T cell co-stimulatory molecule B7-2, or both (in a bicistronic vector) via retroviral vectors. Therapeutic gene expression by D54MG was high after transduction and selection (30 ng/10(6) cells/day for GM-CSF and > 2 orders of magnitude fluorescence shift on flow cytometry for B7-2). The effect of GM-CSF and/or B7-2 transduction on D54MG tumor growth in vivo was monitored in a novel allogeneic human peripheral blood lymphocyte-severe combined immunodeficiency mouse (Hu-PBL-SCID) model. GM-CSF- or B7-2-transduced tumors showed growth suppression in hu-PBL-reconstituted mice compared to untransduced and/or unreconstituted controls. Growth suppression was greatest for B7-2. Furthermore, vaccination with irradiated GM-CSF/B7-2-transduced tumor cells markedly inhibited growth of wild-type tumors at distant sites. Thus, this study illustrates a potential gene therapy strategy for glioblastoma multiforme patients using GM-CSF and/or B7-2 transduced tumor vaccines. Although extension of these allogeneic studies to an autologous system is critical, this is the first demonstration of in vivo efficacy of combination GM-CSF and B7-2 immunogene therapy for human glioblastoma multiforme.
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PMID:Granulocyte-macrophage colony-stimulating factor and B7-2 combination immunogene therapy in an allogeneic Hu-PBL-SCID/beige mouse-human glioblastoma multiforme model. 918 65

In order to study the clinicopathological features, histogenesis and prognosis, 12 cases of gliosarcoma were reported representing 0.4% of a series of 2743 patients undergoing biopsy for CNS tumors. All the tumors originated from the cerebral hemispheres with a predilection for the temporal lobes. Half of the cases show more firm consistency and are rather well demarcated from brain tissue. Clinically, they are sometimes mistaken for meningiomas. Of the 10 patients with follow-up, 9 have died. The mean survival period after operation was 8 months, 1 cases is still alive and well for 3.2 years. There were some cases in which the origin of spindle cell populations could not be determined by H & E staining. Glioblastoma and malignant fibrous histiocytoma (MFH) element of the tumor was confirmed by electron microscopical examination and immunohistochemical stains for GFAP, Mac 387, VIM, FV III RA, etc. Osteosarcoma component in the tumor was detected in one case. It was accepted that MFH arose from the primitive uncommited mesenchyme.
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PMID:[A clinical and pathological study of gliosarcoma]. 927 62

The clotting factor XIIIa (FXIIIa) has been shown to be present both in tumor cells and in tumor-associated macrophages of different neoplasms such as Hodgkin's disease, giant cell tumor of bone, malignant fibrous histiocytoma, meningeal tumors, and hemangiopericytoma. The biological significance of these findings, however, are still unclear. This study investigates the immunohistochemical distribution of FXIIIa in 186 tumors of the central nervous system (CNS) in order to evaluate its possible diagnostic or prognostic significance in neuro-oncology. High-grade gliomas such as glioblastoma, gliosarcoma, astrocytoma (grade III WHO), and ependymoma (III) as well as meningiomas and meningeal hemangiopericytomas consistently contained factor XIIIa-positive cells, whereas low-grade glial tumors did not do so. One desmoplastic medulloblastoma and one anaplastic schwannoma also showed FXIIIa-positive cells. With the exception of hemangiopericytomas, however, the major source of FXIIIa expression in all these tumors consisted of a subpopulation of tumor-associated macrophages, the exact role of which still remains unclear. Because of its non-discriminatory staining in a wide variety of CNS tumors, the differential diagnostic contribution of FXIIIa in neuro-oncology seems to be limited.
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PMID:Factor XIIIa-immunoreactivity in tumors of the central nervous system. 956 29

Germline p53 mutations carry an increased risk of development of breast cancer, soft tissue and osteosarcomas, brain tumors, leukemia and adrenocortical carcinomas. Cerebral neoplasms are usually of astrocytic lineage and occur in 40% of affected families. This report presents clinical, neuropathological and molecular genetic data from 2 families in France with an identical p53 germline mutation in codon 248 (CGG->TGG; Arg->Trp) and a clustering of CNS tumors. The youngest patient in each family developed a malignant choroid plexus tumor while several young adults of both kindred succumbed to low-grade astrocytoma, anaplastic astrocytoma or glioblastoma. The only non-neural neoplasm was an adrenocortical carcinoma in a boy aged 4 years who developed an anaplastic choroid plexus papilloma 2 years later. Of 2 previously reported inherited choroid plexus tumors, 1 occurred in a family which also carried a germline mutation in codon 248. It remains to be shown whether this unusual pattern of CNS tumors is due to an organ-specific effect of this particular p53 mutation or whether it reflects the genetic background of the affected families.
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PMID:Astrocytomas and choroid plexus tumors in two families with identical p53 germline mutations. 982 43

DaunoXome is a liposome formulation containing daunorubicin (DM). Encapsulation of the drug in liposomes presents the advantage of low-level systemic exposure and better drug penetration into the tumor. We studied the distribution of DM and its 13-dihydro metabolite, daunorubicinol (DMol), in surgical biopsies from different parts of glioblastomas. The study was performed in eight patients with recurrent glioblastoma, all of whom had previously undergone surgery and been treated with radiotherapy and chemotherapy, who received 50 mg of DaunoXome as a 1-h infusion. Surgery was performed at 24 and 48 h after the infusion in seven cases and one case, respectively. Biopsies were divided into three parts: the central area of the tumor, peripheral tumor tissue, and brain-adjacent tumor (BAT) tissue. A complete plasma pharmacokinetics study was conducted in seven cases, with samples being taken for up to 48 h after the end of the infusion. DM and DMol were determined in plasma and tissue by high-performance liquid chromatography with fluorescence detection after solvent extraction. At 24 h, concentrations of DM and DMol in the central part of the tumor ranged between < 0.005 and 0.80 microg/g and between 0.005 and 1.58 microg/g, respectively. Concentrations were similar in the peripheral tumor and in BAT tissue. From the data obtained on the patient who underwent surgery at 48 h it appears that DM and DMol remain in tumor tissue for a long time, the concentrations being 0.4 and 2.8 microg/g, respectively. DaunoXome was rapidly cleared from the body, with the plasma levels of DM and DMol determined at 48 h lying in the range of < 5-50 and < 5-20 ng/ml, respectively. The mean (+/-SD) half-life and plasmatic clearance of DM were 4.8+/-1.0 h and 0.2+/-0.06 l h(-1) m(-2). In conclusion, DaunoXome achieved and maintained potentially cytotoxic levels of both DM and DMol in glioblastoma for a long time in association with low-level systemic exposure. Further studies are therefore warranted. Although only preliminary and obtained in previously treated patients, these data suggest that DaunoXome merits investigation in CNS tumors.
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PMID:Distribution of daunorubicin and daunorubicinol in human glioma tumors after administration of liposomal daunorubicin. 1041 54

Brain tumors based on their histogenesis, consist of all tumors, derive from the entirely tissue in the intracranial space, both from the neuro-ectodermal/neuro-epithelial tissue and the mesenchymal tissue. By their location they can be divided into infratentorial or supratentorial, and further into deep vs. superficial. The interesting and unique, there are age distribution or location-sex specificity of some brain tumors (BT). WHO Histopathological Typing of Tumors by the CNS, also showing progress on both of their members and new special types of some BT, especially for the meningiomas and neuro-epithelial/neuroglial type. Periodic investigations by the Department of Anatomic Pathology, the Faculty of Medicine, University of Indonesia did not show major changes in their BT types, but there was on their tumors ranging. Astrocytoma (including glioblastoma multiforma) for a while was replaced by meningioma as the most common CNS/Intracranial tumor. There are some techniques for the handling of CNS specimens depending on further purposes through on biomolecular activities or defects. The routine technique using light microscope examination was the most useful one for daily diagnosis for many years. Some immunohistochemistry techniques are needed for difficult cases, e.g., GFAP, NE 14, NSE, S100, and MBP. Diagnostic problems could be caused by tissue- or cell-sampling errors, which are influenced by the tumor location itself. Thus, neurosurgeons encounter problems to pick biopsy intraoperative, or by mishandling by the laboratory of anatomic pathology. Formerly, as final diagnosis, grading of CNS tumors must be put according to the Clinical interest for further management of the patient. CNS grading ranges from grade I (benign looking) to IV (malignant). Morphological grading is based on Kernohan and Adson (1949), or Kernohan and Sayre (1952).
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PMID:Pathological aspects of brain tumors. 1089 65

Tumors of the central nervous system (CNS) can be devastating because they often affect children, are difficult to treat, and frequently cause mental impairment or death. New insights into the causes and potential treatment of CNS tumors have come from discovering connections with genes that control cell growth, differentiation, and death during normal development. Links between tumorigenesis and normal development are illustrated by three common CNS tumors: retinoblastoma, glioblastoma, and medulloblastoma. For example, the retinoblastoma (Rb) tumor suppressor protein is crucial for control of normal neuronal differentiation and apoptosis. Excessive activity of the epidermal growth factor receptor and loss of the phosphatase PTEN are associated with glioblastoma, and both genes are required for normal growth and development. The membrane protein Patched1 (Ptc1), which controls cell fate in many tissues, regulates cell growth in the cerebellum, and reduced Ptc1 function contributes to medulloblastoma. Just as elucidating the mechanisms that control normal development can lead to the identification of new cancer-related genes and signaling pathways, studies of tumor biology can increase our understanding of normal development. Learning that Ptc1 is a medulloblastoma tumor suppressor led directly to the identification of the Ptc1 ligand, Sonic hedgehog, as a powerful mitogen for cerebellar granule cell precursors. Much remains to be learned about the genetic events that lead to brain tumors and how each event regulates cell cycle progression, apoptosis, and differentiation. The prospects for beneficial work at the boundary between oncology and developmental biology are great.
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PMID:The developmental biology of brain tumors. 1128 16

Tumor cells arising from a particular tissue may exhibit the same gene expression patterns as their precursor cells. To test this proposition, we have analyzed the expression of a neural RNA-binding protein, Musashi1, in primary human central nervous system (CNS) tumors. In rodents, Musashi1 is expressed predominantly in proliferating multipotent neural precursor cells, but not in newly generated postmitotic neurons. The expression of Musashi1 is downregulated with the successive progression of neurogenesis. In normal adult human tissues, we detected low levels of Musashi1 expression in brain and testis by RT-PCR analysis. In an RNA panel of 32 cancer tissues and cell lines, elevated expression of Musashi1 was seen in all five malignant gliomas studied, in contrast to the slight expression seen in other tumor cells, including those in several melanomas and a prostate cancer. Western blot analysis showed strong Musashi1 expression in malignant gliomas compared with nonneoplastic brain tissue. Glioblastomas, the most malignant form of glioma, showed higher Musashi1 expression than less malignant gliomas by immunohistochemical analysis. Tumors with strong Musashi1 expression tended to have high proliferative activity. Thus, the expression of Musashi1 correlated with the grade of the malignancy and proliferative activity in gliomas. These results suggest that primary CNS tumors may share gene expression patterns with primitive, undifferentiated CNS cells and that Musashi1 may be a useful marker for the diagnosis of CNS tumors.
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PMID:Expression of the neural RNA-binding protein Musashi1 in human gliomas. 1128 14


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