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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor and its receptor (EGFR) constitute an important and well-characterized mitogenic system in various ectodermal tissues including glial cells. Over-expression of the EGFR due to gene amplification has been reported in primary brain tumours of glial origin. Using a monoclonal antibody to the EGFR and immunohistochemical analysis, we examined the expression and distribution of EGFR in 103 astrocytic tumours. In addition, selected tumours were studied by Western blotting using a polyclonal antibody to EGFR and by Southern blot analysis. Glioblastomas (WHO grade IV) showed EGFR expression in 37% of cases, whereas pilocytic (WHO grade I), low-grade (WHO grade II) or anaplastic astrocytoma (WHO grade III) were invariably EGFR negative. Generally, there was a close correlation between the presence of EGFR gene amplification and over-expression of receptor protein. Different patterns of immunoreactive cells and significant intratumour heterogeneity of EGFR expression were observed in glioblastomas. The specific association of EGFR over-expression with glioblastoma may provide a useful diagnostic tool for distinguishing anaplastic astrocytoma (WHO grade III) and glioblastoma multiforme (WHO grade IV).
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PMID:Expression of the epidermal growth factor receptor in astrocytic tumours is specifically associated with glioblastoma multiforme. 131 48

Glioblastoma multiforme is one of the most resistant of human tumors to radiation whether used alone or in combination with surgery and/or chemotherapy. This resistance may be caused by one or more of several different factors. These include inherent cellular radiation sensitivity, an efficient repair of radiation damage, an increased number of clonogens per unit of volume, a high hypoxic fraction, high [GSH] concentration, and rapid proliferation between fractions. In the present study, we evaluate the intrinsic radiation sensitivity (surviving fraction at 2 Gy or mean inactivation dose) of malignant human glioma cells in vitro. The in vitro radiation sensitivity of 21 malignant glioma cell lines (early and long term passages) has been measured using colony formation as the end-point of cell viability. The survival curve parameters (SF2 measured and calculated, alpha, beta, D0, n and MID) have been determined for single dose irradiations of exponential phase cells (18-24 hr after plating) under aerobic conditions and growing on plastic. The mean SF2 of the 21 cell lines is 0.51 +/- 0.14 (with a range of 0.19 to 0.76). This value may be compared to the mean SF2 of 0.43-0.47 for SCC, 0.43 for melanoma, and 0.52 for glioblastoma as reported from other authors when using colony formation of cells in exponential phase on plastic. Although glioblastoma is almost invariably fatal, our data demonstrate a very wide range of intrinsic radiosensitivities. These broadly overlap the radiation sensitivities of cell lines from tumors that are often treated successfully. We conclude that standard in vitro measurements of cellular radiation sensitivity (SF2) do not yield values that track in a simple manner with local control probability at the clinical level and that, for at least some of the tumors, other parameters and/or physiological factors are more important.
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PMID:In vitro intrinsic radiation sensitivity of glioblastoma multiforme. 131 13

In order to determine the in vivo immune response in glioblastoma, monoclonal and polyclonal antibodies specific for inflammatory leukocytes and immunoregulatory products were utilized to stain tissue from four surgical specimens. The more activated the inflammatory cells, the more activated the tumors appeared to be. In the tumor with the largest infiltration (Case 3), inflammatory cells were stained for interferon-gamma, interleukin-2, interleukin-1 beta, lymphotoxin, tumor necrosis factor-alpha, and transforming growth factor-beta. The tumor cells also expressed interleukin-1 beta, interleukin-6, transforming growth factor-beta, tumor necrosis factor-alpha, and prostaglandin E. In contrast, in the tumor with the least inflammatory response (Case 1), the tumor cells did not express any cytokines. Expression of cytokines by glioma cells was modest in the two cases with modest inflammatory responses. Cellular inflammation, primarily consisting of T cells and macrophages with few or no B cells or natural killer cells, was two- to 15-fold greater outside the tumor than within. In contrast to leukocytes outside the tumor, which were activated and expressing class II major histocompatibility antigens, leukocytes within the tumor parenchyma or at the tumor's edge were negative for these antigens. In the four specimens studied here, the tumor cells themselves were also negative for class II major histocompatibility antigens. These findings, although preliminary, suggest that inflammatory cells within gliomas are inactivated and that glioma cells may increase the expression of immunosuppressive cytokines in response to an increased lymphocyte infiltrate. This observation, if corroborated by more extensive studies, may help to explain the failure of immune treatments in glioblastoma multiforme.
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PMID:Inflammatory leukocytes associated with increased immunosuppression by glioblastoma. 131 61

Although the loss of tumor suppressor genes and the activation of oncogenes have been established as two of the fundamental mechanisms of tumorigenesis in human cancer, little is known about the possible interactions between these two mechanisms. Loss of genetic material on chromosome 10 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequently reported genetic abnormalities in glioblastoma multiforme. In order to examine a possible correlation between these two genetic aberrations, the authors studied 106 gliomas (58 glioblastomas, 14 anaplastic astrocytomas, five astrocytomas, nine pilocytic astrocytomas, seven mixed gliomas, six oligodendrogliomas, two ependymomas, one subependymoma, one subependymal giant-cell astrocytoma, and three gangliogliomas) with Southern blot analysis for loss of heterozygosity on both arms of chromosome 10 and for amplification of the EGFR gene. Both the loss of genetic material on chromosome 10 and EGFR gene amplification were restricted to the glioblastomas. Of the 58 glioblastoma patients, 72% showed loss of chromosome 10 and 38% showed EGFR gene amplification. The remaining 28% had neither loss of chromosome 10 nor EGFR gene amplification. Without exception, the glioblastomas that exhibited EGFR gene amplification had also lost genetic material on chromosome 10 (p less than 0.001). This invariable association suggests a relationship between the two genetic events. Moreover, the presence of 15 cases of glioblastoma with loss of chromosome 10 but without EGFR gene amplification may further imply that the loss of a tumor suppressor gene (or genes) on chromosome 10 precedes EGFR gene amplification in glioblastoma tumorigenesis.
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PMID:Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. 132 Jun 66

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

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

The major function of a classification of neoplasms is to correlate with prognosis. During the 1980s two trends developed in the classification of gliomas: 1) the presence of necrosis in astrocytomas defines a subset with the worst prognosis (glioblastoma multiforme) and 2) no comparable subset of oligodendroglioma appears to exist, either histologically or prognostically. Even the worst of the oligodendrogliomas has a better prognosis than glioblastomas. These asymmetries must be kept in mind when one is considering the diagnosis of glioblastoma. The absence of a specific stain for oligodendrogliomas, the difficulty in differentiating small anaplastic cells from oligodendroglial cells and the common occurrence of mixtures of normal and/or reactive oligodendroglia and astrocytes in gliomas combine to create potentially confusing misclassification of many gliomas.
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PMID:Is necrosis helpful in the grading of gliomas? Editorial opinion. 153 37

Three cases of cerebral toxoplasmosis as the presenting manifestation of AIDS are reported. The initial diagnoses were brain tumors because of the cerebral mass lesions which resembled glioblastoma. In the light of the increasing occurrence of AIDS, attention is drawn to cerebral toxoplasmosis as a differential diagnosis from glioblastoma multiforme.
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PMID:[Cerebral toxoplasmosis primarily diagnosed as a tumor]. 154 73

Forty-five patients with malignant gliomas were treated after aggressive surgical resection with alternating intravenous carmustine and cisplatin both during and after radiation therapy. Thirty-three patients were considered evaluable for responses, 17 had glioblastoma multiforme (GBM), 14 had anaplastic astrocytoma (AA) and 2 had anaplastic oligodendroglioma (AO). The median age of the evaluable patients was 47 years. The median time to tumor progression was 34.5 weeks, and the median survival for the entire group was 76 weeks. Early progression occurred more frequently in patients with glioblastoma than in those with AA or AO. Seventeen patients (55%) were alive at 18 months (6 GBM, 9 AA, 2 AO). Toxicity was mainly hematologic, otic and tolerable. The results suggest that further trial is warranted to assess the efficacy of alternating carmustine and cisplatin in conjunction with radiation therapy postoperatively in patients with malignant gliomas.
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PMID:Adjuvant chemotherapy with carmustine and cisplatin for patients with malignant gliomas. 156 Feb 58

Between January 1982 and January 1990, 107 patients with unifocal, circumscribed malignant gliomas participated in a non-randomized trial testing brachytherapy in their initial treatment. Focal external irradiation (6000 cGy) was combined with an implant of high-activity iodine-125 (5000-6000 cGy) and six courses of procarbazine, lomustine, and vincristine. Of the 101 evaluable patients, 63 received implants. Of these, 29 had non-glioblastoma anaplastic gliomas, and 34 had glioblastoma multiforme. The other 38 did not receive implants, in most cases because radiation therapy failed to reduce the size of the tumor. The median survival was 165 weeks for all evaluable patients with non-glioblastoma anaplastic gliomas, 157 weeks for those with implants, 67 weeks for all evaluable glioblastoma patients, and 88 weeks for those with implants. Of the glioblastoma patients with implants, nine were alive after 2 years, and three were alive after 3 years. In each of the groups, nearly half the patients underwent reoperation for clinical deterioration, increasing steroid dependency, and increasing mass effect at the implantation site after 46.1 weeks (median) for glioblastoma multiforme and 41.3 weeks for non-glioblastoma patients. Karnofsky Performance Scores showed only a small decline in performance after brachytherapy. Patients receiving implants for non-glioblastoma anaplastic gliomas had a mean Karnofsky Performance Score of 91% (range 90-100%) after 1 month and 78% (range 60-100%) 30 months after brachytherapy. Those treated for glioblastoma multiforme had a mean Karnofsky Performance Score of 86% (range 60-100%) at 1 month and 75% (range 60-100%) at 24 months. The quality of life of treated patients appears to be satisfactory. On the basis of comparisons with previous studies, we conclude that a brachytherapy "boost" after external irradiation may be valuable for some patients with glioblastoma multiforme but not for those with non-glioblastoma anaplastic gliomas.
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PMID:External irradiation followed by an interstitial high activity iodine-125 implant "boost" in the initial treatment of malignant gliomas: NCOG study 6G-82-2. 165 2


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