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PubMed1996

Extradural extension of glioblastoma multiforme into the oral cavity: case report.

A rare case of glioblastoma multiforme with oral extension is presented in a 41-year-old female. She underwent two surgical treatments and both radiotherapy and chemotherapy for the right temporoparietal glioblastoma multiforme. A follow-up computed tomographic scan and magnetic resonance imaging demonstrated destruction of the temporal base and extradural extension of the tumor into the orbital, nasal, and oral cavities. This is the first report of the oral extension of glioblastoma multiforme. The mechanism for the extradural extension is discussed.

Adult↗

PubMed1997

Somatic mutations of PTEN in glioblastoma multiforme.

Alterations of the PTEN gene occur in glioblastoma multiforme. To determine the frequency of PTEN alteration, 34 consecutive glioblastomas were studied in detail. Sequencing each of the nine exons amplified from tumor DNA revealed 11 mutations. Analysis of polymorphic markers within and surrounding the PTEN gene identified an additional four homozygous deletion mutations. Loss of heterozygosity (LOH) was observed in 25 of 34 (74%) cases. All mutations occurred in the presence of LOH. PTEN was mutated in 44% (15 of 34) of all glioblastomas studied and 60% (15 of 25) of tumors with LOH on 10q. Thus, PTEN appears to be the major target of inactivation on chromosome 10q in glioblastoma multiforme.

Astrocytoma↗

PubMed2005

Fine needle aspiration diagnosis of extracranial glioblastoma multiforme: Case report and review of the literature.

BACKGROUND: Hitherto uncommon, the incidence of extracranial metastases of primary brain malignancies may increase, with improved treatment methods and longer patient survival. Fine needle aspiration biopsy is a simple, safe and reliable method to diagnose metastatic malignancy. It has definite advantages over tissue biopsy, which is more invasive and is of higher risk to the patient. Ours is a case of glioblastoma multiforme, which metastasized to the scalp and was diagnosed on fine needle aspiration biopsy. Only a few articles document the cytological features of extracranial glioblastoma multiforme, diagnosed by fine needle aspiration biopsy. CASE PRESENTATION: We report the case of an elderly female who presented with focal neurological symptoms. She was diagnosed radiologically with an intracranial lesion in the left temporal region, which was subsequently resected. Histology revealed a glioblastoma multiforme confirmed by immunohistochemistry. The tumor recurred subsequently and the patient was treated with chemotherapy, intraoperatively. At a later stage, she presented with a scalp mass on which fine needle aspiration biopsy was performed. The cytomorphological features aided by immunohistochemistry supported a diagnosis of metastatic glioblastoma multiforme. The mass was later resected and histology confirmed the fine needle aspiration diagnosis of glioblastoma multiforme. CONCLUSION: Reports of extracranial metastases of primary brain tumors are few. When they do occur, the primary cause is implantation during surgery or biopsy. However, spontaneous metastases to other organs do occur rarely. We believe fine needle aspiration biopsy to be very useful in the diagnosis of metastatic glioblastoma multiforme. The ability to use a cellblock for immunohistochemical studies is greatly advantageous and helpful in differentiating this tumor, from other malignancies that can occur in the scalp. A detailed discussion of the material obtained from fine needle aspiration biopsy of metastatic glioblastoma multiforme is presented, as well as a review of previous accounts in the literature.

Journal Article↗

PubMed2005

Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients.

PURPOSE: The epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% to 60% of glioblastoma multiforme tumors, and the most common EGFR mutant, EGFRvIII, is expressed in 24% to 67% of cases. We sought to determine whether glioblastoma multiforme expression of either overexpressed wild-type EGFR or the mutant EGFRvIII is an independent predictor of overall patient survival. EXPERIMENTAL DESIGN: Glioblastoma multiforme patients (n = 196) underwent a > or =95% volumetric tumor resection followed by conformal radiation. Their EGFR and EGFRvIII status was determined by immunohistochemistry and survival analyses were done. RESULTS: In our study of glioblastoma multiforme patients, 46% (n = 91) failed to express EGFR, 54% (n = 105) had overexpression of the wild-type EGFR, and 31% (n = 61) also expressed the EGFRvIII. Patients within groups expressing the EGFR, EGFRvIII, or lacking EGFR expression did not differ in age, sex, Karnofsky performance scale score, extent of tumor resection, or radiation. The median overall survival times for patients with tumors having EGFR expression absent, overexpressed only, or mutant (EGFRvIII) were 0.96, 0.98, and 1.07 years, respectively. However, for patients surviving > or =1 year, these values were 2.03, 2.02, and 1.21 years (P < 0.0001; log-rank test comparing EGFRvIII with all others). This effect remained significant in the multivariate analysis after adjustment for all other cofactors including age and Karnofsky performance scale score (rate ratio 4.34; 95% confidence interval, 2.21-8.51). CONCLUSIONS: Neither the overexpressed wild-type EGFR nor EGFRvIII was an independent predictor of median overall survival in this selected cohort of patients who underwent extensive tumor resection. However, in patients surviving > or =1 year, the expression of EGFRvIII was an independent negative prognostic indicator.

Adolescent↗

PubMed2005

Stereotactically guided fractionated re-irradiation in recurrent glioblastoma multiforme.

PURPOSE: To assess the feasibility, efficacy and toxicity of fractionated stereotactic radiotherapy in the treatment of recurrent glioblastoma multiforme. PATIENTS AND METHODS: From January 1995 to July 2003, 53 patients with histologically proven glioblastoma multiforme were treated at recurrence with fractionated stereotactic radiation therapy. A median dose of 36 Gy using a median fractionation of 5 x 2 Gy/week was applied. RESULTS: Median overall survival was 21 months, and median overall survival from the time point of re-irradiation was 8 months. The median time interval between primary and secondary radiation therapy was 10 months. In this patient population, no variables predicting longer overall survival could be determined. However, neurosurgical resection at relapse was associated with increased survival after re-irradiation (p=0.04), but left progression-free survival unaltered. Treatment was well-tolerated and no severe toxicities developed. CONCLUSION: Stereotactically guided fractionated re-irradiation is a safe and effective treatment modality in selected cases of recurring glioblastoma multiforme. Since this is not a randomized study, further evaluation in larger patient collectives is warranted. Also, based on recent results of radiochemotherapy in the treatment of primary glioblastoma multiforme, concomitant chemotherapy at relapse might be considered in the future.

Brain Neoplasms↗

PubMed1998

Establishment and characterization of a human glioblastoma multiforme cell line.

Cell lines provide a useful system for further understanding the biology of glioblastoma multiforme. In this study, a new glioblastoma multiforme cell line, GATAGM-96 (Gulhane Askeri Tip Akademisi-Gliblastoma Multiforme-96), was established from a tumor specimen removed from an 80-year-old male patient who underwent surgery for intracranial tumor. Morphologic examination, immunocytochemical staining, growth kinetics, and karyotypic characteristics of this cell line were studied. The cytoskeleton was positive for neuron-specific enolase, vimentin, and neurofilament, and it was negative for glial fibrillary acidic protein, S-100 protein, p53 protein, epidermal growth factor, and transforming growth factor alpha. Growth kinetic studies demonstrated an approximate population doubling time of 38 to 42 h and a colony forming efficiency of 83.3%. The karyotype of the cells demonstrated it as hyperdiploid, with a large subpopulation of polyploid cells. There were numerous structural and numerical chromosome aberrations; most of them were present as clonal events. The phenotypic and chromosomal features detailed on the GATAGM-96 cell line should make it a useful addition to the cell lines currently available for in vitro and in vivo studies of glioblastoma multiforme.

Aged↗

PubMed2005

Vitamin D(3) metabolism in human glioblastoma multiforme: functionality of CYP27B1 splice variants, metabolism of calcidiol, and effect of calcitriol.

PURPOSE: A better understanding of the vitamin D(3) metabolism is required to evaluate its potential therapeutic value for cancers. Here, we set out to contribute to the understanding of vitamin D(3) metabolism in glioblastoma multiforme. EXPERIMENTAL DESIGN: We did nested touchdown reverse transcription-PCR (RT-PCR) to identify CYP27B1 splice variants and real-time RT-PCR to quantify the expression of CYP27B1. A cell line was treated with calcitriol to determine the effect on the expression of CYP27B1, 1alpha,25-dihydroxyvitamin D(3)-24-hydroxylase (CYP24), and vitamin D(3) receptor (VDR). We generated three antibodies for the specific detection of CYP27B1 and splice variants. High-performance TLC was done to determine the endogenous CYP27B1 activity and the functionality of CYP27B1 splice variants. Using WST-1 assay, we determined the effect of vitamin D(3) metabolites on proliferation. RESULTS: We report a total of 16 splice variants of CYP27B1 in glioblastoma multiforme and a different expression of CYP27B1 and variants between glioblastoma multiforme and normal tissues. We found preliminary evidence for enzymatic activity of endogenous CYP27B1 in glioblastoma multiforme cell cultures but not for the functionality of the splice variants. By adding calcitriol, we found a proliferative effect for some cell lines depending on the dose of calcitriol. The administration of calcitriol led to an elevated expression of CYP27B1 and CYP24 but left the expression of the VDR unaltered. CONCLUSIONS: Our findings show that glioblastoma multiforme cell lines metabolize calcidiol. In addition, we show various effects mediated by calcitriol. We found a special vitamin D(3) metabolism and mode of action in glioblastoma multiforme that has to be taken into account in future vitamin D(3)-related therapies.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed1976

Glioblastoma multiforme in children.

Of 488 children with central nervous system neoplasms, 43 (8.8%) had glioblastomas, 22 of which were in the cerebral hemispheres, 16 in the brain stem, two in the cerebellum, and three in the spinal cord. The male to female ratio was 3:2. Glioblastoma multiforme of the cerebral hemispheres occurred at a mean age of 12.7 years, and the frontal lobe was the most commonly involved. Main presenting symptoms included headache (85%), nausea or vomiting (65%), and seizures (35%). Papilledema (45%) was the most common physical finding. The longest survivals were achieved by a combination of operation and radiation (22 months). Brain stem glioblastomas occurred at a mean age of 6.7 years, with the pons as the most frequent site. Nausea or vomiting (50%) and headache (36%) were the main presenting symptoms; the major physical findings were ataxia (43%), cranial nerve palsies (28%), and paresis (28%). The length of survival was greatest with radiation alone (10.5 months). The period of survival of children with glioblastoma multiforme was significantly increased with steroid therapy. Glioblastoma multiforme behaves similarly in children and adults. Intracranial glioblastomas have a more rapidly fatal course than that of other similarly situated gliomas in childhood.

Adolescent↗

PubMed2000

A study of concurrent radiochemotherapy with paclitaxel in glioblastoma multiforme.

Despite advances in neurosurgery and radiotherapy, the prognosis of patients with glioblastoma multiforme remains poor. Reports in the literature about the radiosensitizing properties of paclitaxel stimulated the authors to conduct a study using paclitaxel concurrently with radiation in a group of 18 patients who had residual disease postoperatively. Paclitaxel was delivered weekly as an intravenous infusion in a dose of 60 mg/m2 along with radiation to the primary lesion. A total of 108 cycles of paclitaxel was given. All the patients tolerated the treatment well. The main side effects were haematological, and neuropathy which was self-limiting. The overall 1-year survival rate was 70%, with 12 patients alive at 13 months. The median survival has not yet been reached although it is more than 13 months. Thus, paclitaxel can be safely delivered concomitantly with radiation in patients with glioblastoma multiforme. Larger, randomized trials are required to establish the comparative efficacy of paclitaxel as a radiosensitizer in glioblastoma multiforme.

Brain Neoplasms↗

PubMed1987

Halogenated pyrimidines as radiosensitizers in the treatment of glioblastoma multiforme.

Sixty patients with high-grade gliomas (including 50 patients with glioblastoma multiforme) were entered on four sequential Phase I trials combining continuous intravenous infusions of halogenated pyrimidines and high-dose brain irradiation. Patients received two 14-day infusions of bromodeoxyuridine (BUdR) or iododeoxyuridine (IUdR) during the initial wide field and later reduced field radiation treatment (total radiation dose 65-70 Gy). All patients were followed a minimum of 6 months or until death. The actuarial median survival was 13 months for the entire group, with an 18-month survival of 24%. No significant survival differences were observed based on BUdR versus IUdR, 12-h versus 24-h infusion schedule, degree of surgical resection, or sex. Good performance status and age under 50 years were significant favorable prognostic factors. Of interest, the 48 patients who completed planned treatment had a 14-month median survival, with a 30% 18-month survival. These survival observations are at least comparable to other combined modality trials in patients with glioblastoma multiforme. Ongoing and planned clinical trials using the halogenated pyrimidine analogs as radiosensitizers in patients with glioblastoma multiforme are discussed.

Astrocytoma↗

PubMed1998

Autopsy findings in a long-term survivor with glioblastoma multiforme--case report.

Autopsy detected no tumor tissues in a patient who died 6.5 years after the diagnosis of glioblastoma multiforme. A 54-year-old male developed left hemiparesis one month prior to admission. Computed tomography demonstrated a cystic lesion in the right frontal region with irregular ring-like enhancement. The tumor was extensively removed together with the surrounding tissue followed by irradiation (whole brain 32.4 Gy, local 28.8 Gy), and intravenous administration of interferon-beta. Histological examination confirmed the diagnosis of glioblastoma multiforme. He died of accidental head trauma 6.5 years after surgery. Autopsy of the brain detected no evidence of glioblastoma multiforme. The only findings were cerebral edema and hematoma caused by head trauma, as well as histological changes due to radiation damage. This case apparently confirms the histological disappearance of tumor tissue in a long-term survivor with glioblastoma multiforme.

Brain Neoplasms↗

PubMed2004

Primary presentation of glioblastoma multiforme with leptomeningeal metastasis in the absence of previous craniotomy: a case report.

Glioblastoma multiforme is a highly malignant glioma with a well-known tendency for intracranial spread but rarely for extracranial spread. We report a case of an adult woman who presented with symptoms of leptomeningeal metastasis from an intracranial glioblastoma multiforme located adjacent to the lateral ventricle. There have been very few cases of glioblastoma multiforme presenting with leptomeningeal metastasis in the absence of previous therapeutic intervention.

Cerebral Ventricle Neoplasms↗

PubMed1990

Glioblastoma multiforme with bone metastase and cauda equina syndrome.

Remote metastases, leptomeningeal dissemination and spreading of the tumor by infiltration are rare complications of glioblastoma multiforme. The existence of different forms of spreading simultaneously is very rare. We present a case of a young patient with glioblastoma multiforme who was operated and subsequently received radiation therapy and cytotoxic treatment. Eight months following the operation, the patient developed cauda equina syndrome. Bone metastases of vertebrae and ribs, and direct infiltration of the recurrent tumor mass into the ethmoidal and frontal sinuses were found. The described patient demonstrates a very rare combination of all forms of spreading metastases in glioblastoma multiforme. The infiltration of the tumor mass into the sinuses and the direct permeation of the meningeal and dural venous system and of the leptomeninges, may explain the mechanism of the development of distant metastases and leptomeningeal dissemination in glioblastoma multiforme.

Adult↗

PubMed1990

Secretion of alpha 2-macroglobulin, alpha 2-antiplasmin, and plasminogen activator inhibitor-1 by glioblastoma multiforme in primary organ culture.

Explants from a glioblastoma multiforme were maintained for 4 weeks in a three-dimensional Gelfoam matrix culture in order to study the synthesis of alpha 2-antiplasmin (alpha 2AP), alpha 2-macroglobulin (alpha 2M), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA). Since the organ culture system promotes cellular differentiation in gliomas with increasing time in vitro, secretion of the proteinase inhibitors and t-PA was examined at weekly intervals. Increased immunohistochemical staining for glial fibrillary acidic protein, a marker of astroglial differentiation, was observed in the explants with advancing time in culture. The proteinase inhibitors alpha 2AP and alpha 2M were secreted into the medium in all 4 weeks, while PAI-1 was detected at significant concentrations by an enzyme-linked immunosorbent assay (ELISA) in Weeks 3 and 4 only. The quantity of each inhibitor secreted into fresh medium during a 24-hour interval increased with the age of the tumor explants in the Gelfoam culture system. At no time was a sensitive ELISA able to detect t-PA in the culture medium. This study demonstrates that glioblastoma multiforme cells in primary organ culture can secrete three major fibrinolysis proteinase inhibitors. The appearance of PAI-1 only after extensive culturing of the explants suggests a possible correlation with neoplastic astroglial maturation.

Brain Neoplasms↗

PubMed2005

[Temozolomide in patients with a glioblastoma multiforme: new developments].

There are new scientific data concerning the treatment of patients with glioblastoma multiforme with concomitant and adjuvant temozolomide following surgery and radiotherapy. Patients have an improved survival rate, especially if they also have a methylated promoter of the methylguanine-DNA-methyltransferase (MGMT) gene. It is advisable to consider treating young patients with primary glioblastoma multiforme who are in good condition with concomitant and adjuvant temozolomide. Efficacy of temozolomide in recurrent glioblastoma multiforme is limited.

Antineoplastic Agents, Alkylating↗

PubMed1980

CCNU-chemotherapy of hemispheric supratentorial glioblastoma multiforme.

One hundred and three patients with hemispheric supratentorial glioblastoma multiforme were studied. All patients were operated on and a histologic diagnosis of glioblastoma multiforme was made. Patients were randomly placed in one of three treatment schedules within 3 weeks of surgery: Group A: combined radiation therapy and drug (CCNU) therapy (26 cases); Group B: CCNU given orally every 6-8 weeks (27 cases); Group C: standard radiation therapy alone (50 cases). All patients were periodically controlled by clinical and instrumental (EEG, scan, EMG, CAT) evaluations; laboratory data examinations were also frequently performed. The treatment results have been evaluated according to length of survival, social quality of life, and positive or negative response to chemotherapy. In our opinion the clinical findings are interesting but the statistical results are somewhat negative, especially when the groups of patients are not homogeneous.

Adolescent↗

PubMed1998

Interleukin-6-mediated autocrine growth promotion in human glioblastoma multiforme cell line U87MG.

Human glioblastoma multiforme cell lines, brain tumor biopsy tissue, and normal human fetal brain synthesize interleukin (IL)-6 and IL-6 receptor (IL-6R). Neither of these is expressed in human neurons or neuroblastoma cell lines in culture. Astrocytes from fetal brain grown in culture retain the ability to synthesize IL-6 but do not express IL-6R as inferred from RT-PCR and Southern blot studies. Coexpression of IL-6 and IL-6R in the glioblastoma cell line U87MG is confirmed by immunofluorescence staining. Both specific monoclonal antibodies against IL-6 and IL-6R and antisense oligonucleotide to IL-6 mRNA inhibit the growth of U87MG cells in culture, suggesting the existence of a functional autocrine growth loop. Anti-IL-6 antibodies also inhibit the growth of glioblastoma cell lines U373 and U118. The expression of IL-6 by human fetal astrocytes in culture is highly suggestive of its role as an oncofetal protein responsible for rapid proliferation of fetal and tumor cells but not cells of adult brain.

Animals↗

PubMed1979

Multiple pulmonary lesions in a patient treated with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) for glioblastoma multiforme.

A patient with a glioblastoma multiforme who was treated with BCNU, developed rapidly progressive pulmonary disease. The pulmonary changes were studied pathologically and included atypical alveolar cell hyperplasia, hyaline membranes, and interstitial fibrosis. These lesions contributed to the patient's demise and may be related to the administration of BCNU.

Brain Neoplasms↗