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)

Tumor cells of a particular tissue may show a pattern of gene expression characteristic of the precursor cells of this tissue. To test this proposition for tumors of the central nervous system (CNS) we have used immunohistochemistry to analyze the expression of nestin in primary human CNS tumors and corresponding nonneoplastic brain tissue. Nestin defines a recently discovered sixth class of intermediate filament proteins and in the rat is expressed predominantly in CNS stem cells. In the adult nonneoplastic human brain we have detected only nestin expression in occasional endothelial cells. In contrast, a variety of primary CNS tumors contained substantially elevated nestin levels. The nestin-positive cells in the tumor tissue were tumor cells and/or endothelial cells. Glioblastomas expressed higher nestin levels than less malignant gliomas. This may indicate a correlation between nestin expression and malignancy within the glioma tumor group. In the primitive neuroectodermal class of tumors we observed both nestin-expressing and nonexpressing tumors, suggesting that nestin expression could be used to further characterize this complex and heterogeneous tumor group. Nine metastatic carcinomas were studied, and none showed nestin immunoreactivity in tumor cells. In conclusion, our data support the notion that primary CNS tumors share gene expression patterns with primitive, undifferentiated CNS cells and that nestin, like other intermediate filaments, may be useful in tumor diagnosis.
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PMID:Expression of the class VI intermediate filament nestin in human central nervous system tumors. 138 41

Glutathione (GSH) and Glutathione S-transferase (GST) plays an important role in the protection of cells against damage from free radicals and also influences cytotoxicity to some kinds of chemotherapeutic agents. GST comprises a group of abundant and widely distributed catalytic and binding proteins that facilitate the conjugation of GSH with the electrophilic center of a large spectrum of hydrophilic molecules. Multiple GST isozymes in mammalian tissues arise from dimeric combination of a number of distinct subunits grouped into three major classes: alpha (alpha), mu (mu), and pi (p). We report the total GST, GST-p activity and GSH content of human brain tumors, C6 rat glioma cells and drug resistant C6 cells. The values of total GST activity in 42 normal brain and brain tumors were quantitatively analyzed. Total GST activity was 92.6 +/- 25.1 units (mean +/- standard deviation) in 8 samples of normal brain tissues, 126 +/- 58.8 units in five grade II or III astrocytomas (154 +/- 63.3 units in grade II astrocytomas, 84.4 +/- 2.7 units in 2 grade III astrocytoma), 66.2 +/- 29.3 in 5 glioblastoma cases, 94.7 +/- 47.7 units in 3 metastatic tumors, 302 +/- 114 unit in 8 meningiomas and 213 +/- 90.4 units in 3 neurinomas. Differences of GST activity between glioblastomas and meningiomas, grade II or III astrocytomas and meningioma, in normal brain tissues and meningioma were statistically significant (p < 0.01). The difference between normal brain tissues and benign tumors (meningiomas and neurinomas), gliomas and benign tumors were also statistically significant (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Quantitative analysis of glutathione and glutathione S-transferase in human brain tumors, C6 rat glioma cells and drug resistant C6 cells]. 140 41

CD44 is an integral membrane glycoprotein of approximately 90 kDa which has been implicated in the binding of hyaluronate to the cell surface. The expression of CD44 in astrocytes was investigated by means of indirect immunofluorescence on cultured cells. The vast majority of these cells were found to express CD44. Western blot analysis of these cells revealed a highly polydisperse species having an M(r) corresponding to 74-86 kDa. In order to visualize hyaluronate-binding cells, living cultures were probed with fluorescein-conjugated hyaluronate (FI-HA). Some astrocytes were able to bind FI-HA, provided that they were first treated with hyaluronidase. Streptomyces hyaluronidase, which is hyaluronate-specific, was effective in exposing the hyaluronate-binding capacity of these cells. This leads one to conclude that hyaluronate is bound to the surface of these cells and that it masks their capacity to bind hyaluronate. Provided that they were first treated with hyaluronidase, the U-87 MG (glioblastoma-astrocytoma), U-373 MG (glioblastoma), and Hs 683 (glioma) cell lines were also able to bind FI-HA. The U-138 MG (glioblastoma) cell line was unable to bind FI-HA, with or without prior hyaluronidase treatment. A quantitative assay was developed with the use of [3H]hyaluronate ([3H]HA). This revealed the binding to be highly specific, inasmuch as the addition of unlabeled hyaluronate, but not other glycosaminoglycans, was effective in inhibiting the binding of the [3H]HA. An anti-CD44 monoclonal antibody, 50B4, was able to inhibit the binding of the [3H]HA to the U-373 MG cell line. In this cell line, then, CD44 functions as a hyaluronate receptor and one may infer that this is also the case in some astrocytes.
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PMID:Hyaluronate binding and CD44 expression in human glioblastoma cells and astrocytes. 142 53

Biological effects of human natural tumor necrosis factor-alpha (TNF) on glioblastoma cells in vitro and on glioma patients were investigated. TNF treatment on glioblastoma cells, even at a high dose (256 U/ml), exhibited no remarkable cytocidal activity in MTT assay, but at lower doses significantly inhibited colony forming and DNA synthesis. TNF at a low dose (10 U/ml) stimulated production of prostaglandin E2, Mn-superoxide dismutase, interleukin (IL)-6 and IL-8 by glioblastoma cells. These results indicated that the direct effect of TNF on human glioblastoma cells is rather antiproliferative than cytotoxic and is to modulate their metabolic pathways. In an early Phase I clinical trial, TNF was administered intracranially to six patients bearing glioblastoma. In this trial, the author studied in vivo immunological responses in the cerebrospinal fluid and regional fluid after the regional TNF injections. TNF in these body fluids were detected with a half life of several hours. There occurred a substantial number of leukocyte migration after the TNF administration. Neutrophils appeared first peaking at 8 to 12 hours, and then CD4+CD8-T cells and CD11b+CD13+CD14+ monocytes followed. IL-8 activity in the cerebrospinal fluid simultaneously corresponded to peak of the neutrophil migration. Increases in IL-6, IL-1 beta and prostaglandin E2 levels in the cerebrospinal fluid, regional fluid or both occurred peaking at 8 to 12 hours after TNA infection. Neither IL-2 nor interferons was detected. In conclusion, TNF may act as an antineoplastic agent by its direct cytostatic effects and indirectly through immune modulatory effects.
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PMID:[In vitro and in vivo immunobiological responses of glioblastoma to human natural tumor necrosis factor-alpha]. 142 94

A total of 307 adult patients with glioma were treated with high-activity removable iodine-125 interstitial brain implants at the University of California at San Francisco from December 1979 to June 1990. Recurrent gliomas underwent brain implant alone whereas previously untreated (primary) tumors underwent brain implant boost after external beam radiotherapy. Of these patients, 106 had primary glioblastoma multiforme, 68 had primary non-glioblastoma glioma, 66 had recurrent glioblastoma multiforme and 67 had recurrent nonglioblastoma glioma. Median follow-up for living patients was 143 weeks. Median survival from diagnosis for primary glioblastoma multiforme and high and low grade nonglioblastoma glioma was 88 weeks, 142 weeks, and 226 weeks, respectively. Median survival measured from the date of implant for recurrent glioblastoma multiforme and high and low grade nonglioblastoma glioma was 49 weeks, 52 weeks, and 81 weeks, respectively. Ninety-two percent of patients had no toxicity or transient acute side effects. Severe acute toxicity was seen in 6% of patients, life threatening acute toxicity in 1% of patients, and fatal toxicity in less than 1% of patients. Forty percent of patients with malignant glioma underwent reoperation at a median of 33 weeks after brain implant, with tumor found in 95% of specimens at reoperation. This large experience demonstrates that interstitial implant is well-tolerated and prolongs survival in patients with primary and recurrent glioblastoma multiforme, as evidenced by the 3-year survival rates of 22% and 15%, respectively.
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PMID:High activity iodine-125 interstitial implant for gliomas. 142 79

Here I discuss quantitative and qualitative activation of several receptor-type molecules in tumor cells. Recently we have shown that EGF-R gene is frequently mutated in human glioblastoma. Mutant EGF-R had a 801-bp deletion within the ligand binding domain, and showed a ligand-independent, constitutive elevation of tyrosine kinase activity. This EGF-R mutation is detected only in glioma and associated with gene amplification, suggesting a relationship in the molecular mechanism between deletion mutation and initiation of gene amplification in these cases. Secondly I have shown an activation of mouse CD43 gene by amplification and rearrangement in erythroleukemia cell lines. Intracellular domain of CD43 has no kinase domain but a highly conserved structure among mammals, probably interacting with intracellular signal transducers. Recently CD43 has been demonstrated to be specifically associated with a cell-adhesion molecule ICAM-1. Thus, CD43-ICAM-1 system might be a new type of cytokine system which regulate cell-proliferation through cell-cell interaction. In addition, activation of EpoR and v-mpl is also discussed.
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PMID:[Membrane receptors and cell transformation]. 143 60

This paper reports clinicopathological findings concerning an enlarged bulky cyst and the tumor cavity following local administration of an anticancer agent combined with radiotherapy in two patients suffering from malignant glioma. Case 1: This 69 year-old man who had been diagnosed as having glioblastoma in the right parietal lobe had received local chemotherapy after the first operation. Simultaneously radiotherapy of 69 Gy in total dose was performed. At the second operation for the tumor, cyst formation was clinically confirmed and necrotomy as well as evacuation of the large cyst was performed after adjuvant therapy. The patient died at a time ten months after the first surgical operation. Case 2: This is the case of a 48 year-old man who was diagnosed as having gemistocytic astrocytoma in the left frontal lobe. The first surgical operation was performed and was followed by local chemotherapy as well as radiotherapy (total dose of 90 Gy in two sessions). The second surgical operation of the recurrent tumor, with necrotomy and evacuation of the large cyst were performed after adjuvant therapy. The patient expired at a time sixty-five months after the first surgical operation. Relevant to the chemotherapy, adriamycin (ADM) (0.5mg) and methotrexate (MTX) (1mg) were administered through the Ommaya's reservoir into the tumor bed at craniotomy. The usual doses of ADM and MTX amounted to 5.0mg respectively. Through conventional CT and MRI, formation of a cyst including abundant membranous debris or septi was identified in both cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cyst formation following local chemotherapy of malignant brain tumor: a clinicopathological study of two cases]. 144 92

Beginning in 1986, using software to optimize radiation dosimetry, we have stereotactically placed removable catheters containing high activity I-125 sources into malignant gliomas in 56 patients. There were 32 men and 24 women, age 7 to 73. Forty-four had glioblastoma multiforme, and 12 anaplastic astrocytoma. Mean Karnofsky performance score was 75, range 50-100. Twenty patients (all with glioblastoma) were implanted after resection before further therapy, and 36 were implanted at recurrence following resection, external irradiation and chemotherapy. Six thousand cGy was delivered to the enhancing tumor contour on CT scan. Mean dose rate was 37 cGy/hr. Mean tumor volume was 41 cc, range 5-187 cc. Mean volume of brain that received 60 cGy was 67 cc, range 11-184 cc. Of 20 patients treated after resection alone, 8 are alive, 3-43 months after implantation; median survival is 22 months. Of 36 patients treated at recurrence, 14 are alive, 0-19 months after implantation; median survival is 10 months. The most common side effect of the procedure, which occurred in five patients, was catheter misplacement. Twenty-four patients (43%) required 27 reoperations, 1-25 months after implantation. In 25 pathologic specimens available for review, microscopic tumor foci with substantial radiation necrosis were found in 18, radiation necrosis only was noted in 5, and glioma alone was seen in 2.
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PMID:Interstitial irradiation of malignant gliomas. 144 65

Radioresponse and prognosis of 91 malignant gliomas were studied to examine the efficacy of radiotherapy. There was no case of complete response. No statistically significant difference was observed among the prognoses of patients with various radiation methods. General survival rate was significantly higher than relapse-free survival rate both in astrocytoma grade III and in glioblastoma. This means that the retreatment after relapse is exceedingly important in any malignant glioma. In comparison with reported resection alone data, the efficiency of radiotherapy was evident in astrocytoma grade III and a part of glioblastoma; cases with minimal or no contrast enhanced area (CEA) in CT scans prior to irradiation. Poor radioresponders of glioblastoma with CEA should be reoperated.
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PMID:Radioresponse and prognosis of malignant glioma. 145 20

The aim of this study was to verify the tolerability and efficacy of therapeutic chemotherapy protocols, employing different combinations of cisplatin, carboplatin, etoposide and carmustine in primary glioblastoma patients. The purpose was focused on 2 end points: the response index to treatment, the TTP (tumor progression) and the ST (survival time). Eighty-four out of a group of 99 consecutive glioblastoma patients, entered this study. Patients were divided into 4 disparate treatment groups: (A) BCNU alone; (B) CDDP + VP-16; (C) CBDCA + BCNU; (D) CBDCA + BCNU + VP-16. The effectiveness and the TTP of the protocols differed, but differences were not statistically significant. Data concerning platinum treatment compare favorably with the best literature results. At 18 months more than half the carboplatin-treated patients are alive. Moreover these patients had a significantly longer ST than those treated with BCNU. We conclude that platinum-based chemotherapy has a beneficial effect on glial tumors.
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PMID:Carboplatin combined with carmustine and etoposide in the treatment of glioblastoma. 148 54


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