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

This article gives a toxicological risk analysis of occupational diseases in dentistry that are related to chronic exposure to inorganic mercury, especially metallic mercury vapour. Studies have indicated that dental work involving mercury may be an occupational hazard with respect to reproductive processes, glioblastoma (brain cancer), renal function changes, allergies and immunotoxicological effects. The correlation of chronic exposure to mercury in dentistry to the health situation of dental workers' health situation needs to be further studied.
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PMID:[Mercury in the dental office. Risk evaluation of the occupational environment in dental care]. 204 11

Anatomists are exposed to a wide range of solvents, stains, and preservatives used to prepare biologic specimens. One fixative, formaldehyde, has recently been shown to cause nasal cancer in laboratory rodents. A retrospective cohort study was conducted to assess whether anatomists have an increased risk of mortality from cancer, particularly from cancers of the respiratory tract. The cohort included 2,317 men who joined the American Association of Anatomists between 1888 and 1969 and who were living in the United States when they joined this association. Standardized mortality ratios were 0.3 for lung cancer [95% confidence interval (CI) = 0.1-0.5], 1.5 for leukemia (95% CI = 0.7-2.7), and 2.7 for brain cancer (95% CI = 1.3-5.0) when mortality rates for U.S. white males, available for 1925-79, were used as the referent. When rates for male members of the American Psychiatric Association, available for 1900-69, were used as the referent, standardized mortality ratios were 0.5 for lung cancer (95% CI = 0.2-1.1) and 6.0 for brain cancer (95% CI = 2.3-15.6). Each of the 10 anatomists who died of brain cancer between 1925 and 1979 had a neuroglial cell tumor (either astrocytoma or glioblastoma). The increased risk for leukemia was limited to the myeloid cell type. An etiologic agent associated with these increased risks was not identified.
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PMID:Brain cancer and other causes of death in anatomists. 346 14

The influence of parity on the risk of cancers of the female breast and reproductive organs is well established. However, non-reproductive sites have received less attention. Mail questionnaire data gathered from incident female cases (169 brain; 332 colon; 260 rectal; 145 kidney; and 169 pancreas cancers), and 821 population-based controls in Iowa (United States) were used to measure the effect of parity and age at first birth on risk of these malignancies. Relative to nulliparous women, ever-parous women were at significantly decreased risk of brain cancer (odds ratio [OR] = 0.44, 95 percent confidence interval [CI] = 0.3-0.7) and of colon cancer (OR = 0.67, CI = 0.5-0.97), after adjustment for age and other risk factors. The OR for the other sites did not differ significantly from 1.0. The lower risk of brain cancer among parous women was similar in younger and older age groups, in patients diagnosed with glioblastoma and astrocytoma, and among ever- and never-smokers. The findings for colon cancer are consistent with observations from other studies. In the context of limited laboratory and clinical evidence implicating hormones in brain neoplasia, these findings may suggest a role for hormonal factors in brain cancer etiology. Hormonal factors deserve more detailed future consideration as risk factors in brain cancer.
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PMID:Reproductive factors and risk of brain, colon, and other malignancies in Iowa (United States). 828 Aug 27

Glioblastoma multiforme is the most common form of malignant brain cancer in adults and, unfortunately, is not amenable to treatment with current therapeutic modalities. Human glioblastoma U-87 has many of the distinguishing phenotypic features of primary glioblastoma, including an autocrine form of proliferation, high levels of protein kinase C alpha (PKC alpha), and infiltration via white matter tracts. We show that treatment of mice bearing U-87 xenografts with an antisense phosphorothioate oligodeoxynucleotide (S-oligodeoxynucleotide) against the 3'-untranslated region of PKC alpha mRNA results in suppression of tumor growth. Growth was inhibited in both subcutaneous and intracranial tumors, and in the latter instance, treatment with the antisense PKC alpha S-oligodeoxynucleotide resulted in a doubling in median survival time ( > 80 days), with 40% long term survivors. The antisense S-oligodeoxynucleotide did not produce systemic toxicity in mice with subcutaneous or intracranial tumors after daily intraperitoneal injection for 21 or 80 days, respectively, and a scrambled S-oligodeoxynucleotide with the same nucleotide composition as the antisense S-oligodeoxynucleotide did not produce an antitumor effect. The intratumoral levels of both antisense and scrambled S-oligodeoxynucleotide in subcutaneous tumors were 2 microM after 21 daily doses of 20 mg/kg S-oligodeoxynucleotide. The antisense S-oligodeoxynucleotide selectively reduced the levels of PKC alpha in subcutaneous tumors but not those of protein kinase C epsilon or protein kinase C zeta. This is the first demonstration that the growth of glioblastoma multiforme can be suppressed by an antisense PKC alpha S-oligodeoxynucleotide and suggests that this may represent an effective therapy for this type of malignancy.
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PMID:Treatment of glioblastoma U-87 by systemic administration of an antisense protein kinase C-alpha phosphorothioate oligodeoxynucleotide. 870 Jan 29

Glioblastoma is a highly aggressive form of brain cancer characterized by uncontrolled cell growth resulting from a loss of cell cycle regulation. In this study we determined the antiproliferative effects of interferon gamma (IFNgamma) on the glioblastoma cell lines T98G, SNB-19 and U-373, focusing on the ability of IFNgamma to increase levels of p21WAF1/CIP1, an important negative regulator of cell cycle events. IFNgamma was found to inhibit the growth of all cell lines, with inhibition ranging from 82.2% to 45.4%. Flow cytometry analysis showed that IFNgamma treatment caused a cell cycle delay in the G1 or S phases. The strength of this delay varied, correlating with the degree by which IFNgamma inhibited proliferation of each cell line. IFNgamma treatment increased the production of the cyclin dependent kinase inhibitor (CKI) p21WAF1/ CIP1 in all cell lines, the level and kinetics of production of which correlated with the degree and stage of inhibition of cellular proliferation. Further, immunoprecipitation of p21WAF1/CIP1 in complexes of p21WAF1/CIP1/cyclin-dependent kinase 2 (cdk2)/cyclin showed that the amount of p21WAF1/CIP1 in the complexes and the inhibition of cdk2-cyclin kinase activity correlated with the level of p21WAF1/CIP1 produced in the cells by IFNgamma. These results show that IFNgamma has significant antiproliferative effects on the glioblastoma cell lines and suggest that p21WAF1/CIP1 plays a role in mediating these effects.
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PMID:IFNgamma inhibition of cell growth in glioblastomas correlates with increased levels of the cyclin dependent kinase inhibitor p21WAF1/CIP1. 988 99

About 12,000 Americans are diagnosed with malignant astrocytoma each year. Despite surgery, radiotherapy, and chemotherapy, the prognosis of these patients remains poor. Targeted toxins based on the identification of novel antigens or receptors provide a promising new approach to treating cancer. We have identified one such cell surface protein in the form of interleukin (IL)-4 receptors (IL-4R) on human malignant astrocytoma. Normal brain tissues from frontal cortex and temporal lobe cortex do not express IL-4R. To target IL-4R, we generated a chimeric fusion protein composed of IL-4 and Pseudomonas exotoxin (IL4-PE). This toxin is highly cytotoxic to IL-4R-bearing human brain cancer cells. Preclinical toxicologic experiments were performed in mice, rats, and guinea pigs to determine an maximum tolerated dose. Intrathecal administration in cynomolgus monkeys produced high cerebrospinal fluid levels without any central nervous system or other abnormalities. When IL4-PE was injected into the right frontal cortex of rats, localized necrosis was observed at 1,000 but not < or =100 microg/ml doses. Intravenous administration of this biologic to monkeys produced reversible grade 3 or grade 4 elevations of hepatic enzymes in a dose-dependent manner. These results indicate that localized administration can produce nontoxic levels of IL4-PE that may have significant activity against astrocytoma. In vivo experiments with nude mice have demonstrated that IL4-PE has significant antitumor activity against human glioblastoma tumor model. Intratumor administration of IL4-PE has been initiated for the treatment of malignant astrocytoma in a phase I clinical trial.
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PMID:Development of a recombinant interleukin-4-Pseudomonas exotoxin for therapy of glioblastoma. 1036 74

This study investigated whether or not home palliative care of brain tumor patients was possible and various ideas for accomplishing this, over the 2 1/2 years since our clinic was opened. There were 22 patients, aged 42-72 years, comprising 7 cases of glioblastoma, 14 cases of metastatic brain tumor, and 1 case of unknown origin. The control of intracranial hypertension and attacks of convulsion was possible with oral medication or suppositories, but not injection. The prognosis of cancer patients which changed home care showed no remarkable changes, and the home care rate was 53%. Malignant brain tumor patients were able to enjoy time with their families at home during the terminal stage, and die with dignity.
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PMID:[Home palliative care of brain tumor patients from our clinic]. 1063 Feb 35

Glioblastoma multiforme is one of the most aggressive and frequently occurring forms of brain cancer. It originates from astrocytes and is characterized by a loss of cell cycle control frequently involving mutations in tumor suppressor genes, such as p53 and p16. Nucleoside analogs, such as acyclovir (ACV), are currently being used in the treatment of viral diseases, such as those caused by members of the herpes family. Further, ACV in combination with type I interferons (IFN) has been shown to be more effective at lower doses in treatment of viral diseases. We show here that ACV at high concentrations (up to 500 microg/ml) inhibited growth in tissue culture of the human glioblastoma cell lines T98G, SNB-19, and U-373 by as much as 68.3% while inhibiting normal human astrocytes by only 38.3%. Related to this, the tumor cells were more than sevenfold more efficient in phosphorylation of ACV to the active phosphate form than normal human astrocytes. Analogous to treatment of virus-infected cells, suboptimal concentrations of ACV were as effective as high concentrations when used in conjunction with low concentrations of IFN-gamma in inhibition of tumor cell growth. At the cellular level, ACV and IFN-gamma inhibited the cell cycle in both the G1 and S phases. The cooperative effect of ACV and IFN-gamma against the glioblastomas appears to be due to direct inhibition of DNA synthesis by ACV in the S phase of the cell cycle and induction by IFN-gamma of the tumor suppressor gene p21wAF1/CIP1, which in turn acts at the level of proliferating cell nuclear antigen (PCNA) and cyclin E/cyclin-dependent kinase 2 (Cdk2) binding and inhibition of function. These studies show that the combination of IFN-gamma and ACV at suboptimal concentrations elicits significant antiproliferative effects on the glioblastoma cell lines T98G, SNB-19, and U-373 while having very little effect on normal human astrocyte cell proliferation.
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PMID:Inhibitory effects of IFN-gamma and acyclovir on the glioblastoma cell cycle. 1084 Oct 74

Astrocytomas are the leading cause of brain cancer in humans. Because these tumours are highly infiltrative, current treatments that rely on targeting the tumour mass are often ineffective. A mouse model for astrocytoma would be a powerful tool for dissecting tumour progression and testing therapeutics. Mouse models of astrocytoma have been designed to express oncogenic proteins in astrocytes, but have had limited success due to low tumour penetrance or limited tumour progression. We present here a mouse model of astrocytomas involving mutation of two tumour-suppressor genes, Nf1 and Trp53. Humans with mutations in NF1 develop neurofibromatosis type I (NF1) and have increased risk of optic gliomas, astrocytomas and glioblastomas. The TP53 tumour suppressor is often mutated in a subset of astrocytomas that develop at a young age and progress slowly to glioblastoma (termed secondary glioblastomas, in contrast to primary glioblastomas that develop rapidly de novo). This mouse model shows a range of astrocytoma stages, from low-grade astrocytoma to glioblastoma multiforme, and may accurately model human secondary glioblastoma involving TP53 loss. This is the first reported mouse model of astrocytoma initiated by loss of tumour suppressors, rather than overexpression of transgenic oncogenes.
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PMID:Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. 1097 61

Boron neutron capture therapy (BNCT) is an experimental, binary treatment for brain cancer which requires as the first step that tumor tissue is targeted with a boron-10 containing compound. Subsequent exposure to a thermal neutron flux results in destructive, short range nuclear reaction within 10 microm of the boron compound. The success of the therapy requires than the BNCT agents be well localized in tumor, rather than healthy tissue. The MEPHISTO spectromicroscope, which performs microchemical analysis by x-ray absorption near edge structure (XANES) spectroscopy from microscopic areas, has been used to study the distribution of trace quantities of boron in human brain cancer tissues surgically removed from patients first administered with the compound Na2B12H11SH (BSH). The interpretation of XANES spectra is complicated by interference from physiologically present sulfur and phosphorus, which contribute structure in the same energy range as boron. We addressed this problem with the present extensive set of spectra from S, B, and P in relevant compounds. We demonstrate that a linear combination of sulfate, phosphate and BSH XANES can be used to reproduce the spectra acquired on boron-treated human brain tumor tissues. We analyzed human glioblastoma tissue from two patients administered and one not administered with BSH. As well as weak signals attributed to BSH, x-ray absorption spectra acquired from tissue samples detected boron in a reduced chemical state with respect to boron in BSH. This chemical state was characterized by a sharp absorption peak at 188.3 eV. Complementary studies on BSH reference samples were not able to reproduce this chemical state of boron, indicating that it is not an artifact produced during sample preparation or x-ray exposure. These data demonstrate that the chemical state of BSH may be altered by in vivo metabolism.
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PMID:Spectromicroscopy of boron in human glioblastomas following administration of Na2B12H11SH. 1108 67


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