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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although primary brain tumors are relatively uncommon types of adult cancer, their location and resistance to treatment can significantly affect the patient's physical and cognitive function. Consequently, quality of life (QOL) issues are extremely important in the design and evaluation of clinical trials of high-grade glioma treatment. Although a number of studies have examined QOL in patients with primary brain tumors, very little is known about QOL in these patients. These studies often use either poorly validated instruments or tools, such as the Karnofsky performance scale, that do not fully evaluate the effects of the tumor on QOL. Recent attempts to better evaluate QOL in brain tumor patients have led to the development of brain tumor-specific QOL instruments, such as the European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire-Brain Cancer Module and the Functional Assessment of Cancer Therapy-Brain, which offer more insight into the QOL aspects of cancer and its treatment. Instruments such as quality time without symptoms or toxicity (Q-TWiST) provide a means of integrating both quality of time of survival and absence of symptoms or toxicity.
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PMID:Issues in assessing and interpreting quality of life in patients with malignant glioma. 1086 46

Glioblastoma multiforme (GBM) is a highly lethal brain cancer. Using cultures of rodent and human malignant glioma cell lines, we demonstrated that millimolar concentrations of acetylsalicylate, acetaminophen, and ibuprofen all significantly reduce cell numbers after several days of culture. However, their mechanisms of action may vary, as demonstrated by (1) differences in the morphological changes produced by these compounds; (2) varied responses to these drugs with respect to toxicity kinetics; and (3) respective rates of cell proliferation, DNA synthesis, and mitotic index. We studied the effects of acetaminophen on relative cell number further. Evidence is presented that acetaminophen induced cell death by an apoptotic mechanism after a brief burst of mitosis in which cell numbers increased transiently, followed by a reduction in cell number and an increase in DNA fragmentation, as evidenced by terminal deoxytransferase-mediated dUTP-biotin nick end labeling (TUNEL) analysis. Using cultures of adult human brain and embryonic rat brain, we demonstrated that glioma cells were several-fold more sensitive to acetaminophen than normal brain cells in culture. Finally, subtoxic doses of acetaminophen increased the sensitivity of the human glioma cells in culture to ionizing radiation. Taken together, these results suggest that acetaminophen may prove to be a useful therapeutic agent in the treatment of human brain tumors.
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PMID:Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture. 1090 53

A small proportion of brain tumors are attributed to a genetic predisposition; however, the hereditary proportion is undetermined. This study evaluates the degree of familial aggregation of cancer in a large series of brain tumor patients. Our study included 5,088 relatives of 639 probands (3,810 first- and 1,278 second-degree), diagnosed with a glioma between June 1992 and June 1995 at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, with diagnosis under age 65 years, and residents of the United States or Canada. We conducted an in-person or telephone interview with patients and/or their next-of-kin, and obtained family histories for the probands' first-degree (parents, siblings, offspring) and selected second-degree relatives (aunts, uncles, grandparents) using a sequential sampling strategy. Reported cancers were documented by medical records and/or death certificates (if the relative was deceased and medical records were unavailable). We conducted segregation analysis using the Pedigree Analysis Program (PAP). The analyses were divided into two categories: (1) all 639 families, and (2) a subset of families whose gliomas stained positive on p53 immunohistochemistry analysis. We demonstrated that a multifactorial Mendelian model was favored, while a model postulating a purely environmental cause of brain cancer was rejected. This study indicates that familial cancer in relatives of glioma patients are probably a result of multigenic action, and familial clustering of cancer among relatives of glioma patients may involve unknown environmental exposures.
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PMID:Segregation analysis of cancer in families of glioma patients. 1118 Apr 51

A number of occupations and industries have been inconsistently associated with the risk of brain cancer. To further explore possible relationships, we conducted a population-based case-control study of brain glioma in the state of Iowa, involving 375 histologically confirmed incident cases and 2434 population-based controls. Among men, the industries and/or occupations that had a significantly increased risk for employment of more than 10 years included roofing, siding, and sheet metalworking; newspaper work; rubber and plastics products, particularly tires and inner tubes; miscellaneous manufacturing industries; wholesale trade of durable goods, grain, and field beans; cleaning and building service occupations; miscellaneous mechanics and repairers; and janitors and cleaners. Subjects who worked in plumbing, heating, and air conditioning; electrical services; gasoline service stations; and military occupations also experienced a significantly increased risk. Among women, significant excess risk was observed for occupations in agricultural services and farming, apparel and textile products, electrical and electronic equipment manufacturing, various retail sales, record-keeping, and restaurant service. Workers in industries with a potential for gasoline or motor exhaust exposures experienced a non-significant excess risk of brain glioma.
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PMID:Occupational risk factors for brain cancer: a population-based case-control study in Iowa. 1132 92

In the United States and the San Francisco Bay Area, whites are nearly twice as likely as non-whites to develop brain cancer. To test whether prevalence and types of alterations in the p53 pathway in brain tumor development may explain some of this difference in risk, we have analyzed the p53 status of astrocytic gliomas from a population-based sample of cases within our San Francisco Bay Area Adult Glioma Study. We identified mutations in exons 5-8 of p53 using DNA extracted from formalin-fixed paraffin-embedded tissue blocks from 146 whites and 26 non-whites with astrocytic glioma by PCR-single-strand conformation polymorphism and direct sequencing. Tumor P53 protein (TP53) immunohistochemistry (IHC) available for 164 of these cases showed that tumors from 50% (13 of 26) of non-whites and 32% (44 of 138) of whites contained intense IHC staining for TP53, indicating persistence of TP53 protein. Irrespective of IHC status, tumors from 42% (11 of 26) of non-whites versus 13% (19 of 146) of whites contained p53 mutations (age/gender-adjusted odds ratio, 5.7; 95% confidence interval, 2.2-15.1; P = 0.0004). Patients with p53 mutation-positive tumors were also significantly younger than patients with mutation-negative tumors and somewhat more likely to be female. A higher proportion of tumors from non-whites than from whites had transition mutations, but there were similar proportions of transversion mutations in tumors from whites and non-whites. Whites and non-whites also had similar proportions of tumors with p53 mutations that stained intensely for TP53 (78 and 82%, respectively). Because whites have higher risk for glioma than non-whites in this population, that the gliomas from whites were less likely than those from non-whites to have p53 mutation suggests that whites may be more likely than non-whites to be at risk for the more common type of astrocytic gliomas, which do not contain p53 mutations.
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PMID:Ethnicity delineates different genetic pathways in malignant glioma. 1135 11

Cancers that arise from astrocytes in the adult CNS present as either anaplastic astrocytomas (AAs) or as more aggressive glioblastomas multiforme (GBMs). GBMs either form de novo or progress from AAs. We proposed to examine the molecular genetic relationship between these CNS tumors by conducting a genome-wide allelic imbalance analysis that included 70 loci on examples of AA and GBM. We found significant loss of heterozygosity (LOH) at 13 discrete chromosomal loci in both AAs and GBMs. Loss was significant in both AAs and GBMs at 9 of these loci. AAs show the highest rates of LOH at chromosomes 1p, 4q, 6p, 9p, 11p, 11q, 13q, 14q, 15p, 17p, 17q, and 19q. GBMs showed the greatest losses at 1p, 6q, 8p, 9p, 10p, 10q, 11p, 13q, 17p, 17q, 18p, 18q, and 19q. GBMs also demonstrated significant amplification at the epidermal growth factor receptor locus (7p12). These data suggest that there are three classes of loci involved in glioma evolution. First are loci that are likely involved in early events in the evolution of both AAs and GBMs. The second class consists of AA-specific loci, typified by higher LOH frequency than observed in GBMs (4q, 6p, 17p, 17q, 19q). The third class consists of GBM-specific loci (6q, 8p, 10, 18q). Damage at these loci may either lead to de novo GBMs or permit existing AAs to progress to GBMs. Glioma-related LOH profiles may have prognostic implications that could lead to better diagnosis and treatment of brain cancer patients.
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PMID:A study of loss of heterozygosity at 70 loci in anaplastic astrocytoma and glioblastoma multiforme with implications for tumor evolution. 1155 Mar 11

Membrane-type MMPs (MT-MMPs) constitute a growing subclass of recently identified matrix metalloproteinases (MMPs). In addition to the highly conserved MMP functional domains, the MT-MMPs have additional insertion sequences (IS) that confer unique functional roles. While most of the MMPs are secreted, the MT-MMPs are membrane associated and a number of these have cytoplasmic domains which may be important in cellular signaling. This membrane localization leads to focal areas of receptor recruitment and subsequent activity, thereby enhancing pericellular proteolysis in specific areas of contact within the brain interstitium. MT1-MMP is the best-characterized MT-MMP, the measure against which subsequently cloned homologues are compared. MT1-MMP activates proMMP2 via its interaction with TIMP2, which serves as an intermolecular bridge for proMMP2 binding to MT-MMPs. In addition to activation of proMMP2, MT-MMPs display intrinsic proteolytic activity towards extracellular matrix molecules (ECM), which is independent of MMP2 activation. The increased expression levels of several members of the MMP family have been shown to correlate with high-grade gliomas, including MTI-MMP. Despite improvements in the diagnosis and treatment of patients with glial tumors, they remain the most common and least curable brain cancer in adults. The ability of glioma cells to infiltrate surrounding brain tissue, and ultimately escape current therapeutic modalities, could potentially be minimized using anti-invasive therapies. Proteolysis is a necessary part of the invasion process, within which the MT-MMPs appear to play a central role. The development of pharmaceutical approaches that target expression and regulation of MT-MMPs may prove beneficial in targeting invading glioma cells.
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PMID:Membrane-type matrix metalloproteinases (MT-MMPs): expression and function during glioma invasion. 1171 70

NeoPharm, under license from the NIH and the FDA, is developing a chimeric human IL-13 fused in frame to a genetically engineered truncated Pseudomonas exotoxin (PE38QQR) molecule, for its potential as an antitumor agent [266296], [281418], [290480]. NeoPharm filed an IND in 1999 for renal cell carcinoma (RCC) and glioma [319690], [325001]; an additional IND was filed in March 2000 for the treatment of glioblastoma. In December 2000, NeoPharm initiated phase I/II trials of IL-13-PE38QQR involving patients with refractory glioblastoma multiforme. This trial was being conducted by the New Approaches to Brain Tumor Therapy, a research consortium sponsored by the NCI. At that time, the first patient with brain cancer had completed treatment with IL-13-PE38QQR [393197]. In October 1999, NeoPharm initiated phase I trials of hIL-13-PE38QQR for the treatment of patients with RCC [343878]. In February 2000, Dirks & Co estimated the potential US market for hIL-13-PE38QQR to be $5.8 billion [414515].
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PMID:hIL-13-PE38QQR. NeoPharm. 1171 20

Measurement of Health Related Quality of Life (HRQL) in brain tumour patients is important because brain tumours and brain tumour treatment usually affect physical, cognitive as well as emotional functioning. Measurement of HRQL is important for the understanding of disease burden and for the impact of specific tumour treatment. Quality of Life is a multidimensional concept consisting of physical, psychological and social phenomena. A large number of Quality of Life instruments have been developed. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the MOS Short-Form Health Survey are two frequently used general HRQL instruments. A specific brain tumour scale is the Brain Cancer Module, which is designed to be used in combination with general questionnaires. HRQL measurement and neuropsychological examination were used to investigate the impact of radiotherapy and surgery in low-grade glioma patients and the influence of tumour volume, tumour localization, performance status and age in both low-grade and high-grade glioma patients.
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PMID:Impact of brain tumour treatment on quality of life. 1219 37

The objective of our study was to investigate the possible interactive effect of occupational exposure to extremely low-frequency magnetic field (ELFMF) and to known or suspected carcinogenic chemicals on the incidence of the two main histological types of brain cancer, gliomas and meningiomas, in a cohort of male Swedish workers. The historical cohort of all Swedish men gainfully employed in 1970 were followed 19 years (1971-1989). Exposure to ELFMF and to nine chemicals were assessed using two Swedish job exposure matrices based on occupational codes and industrial activity. Relative risks adjusted for age, period, geographical area, and town size were computed using log-linear Poisson models. The main finding was the absence of ELFMF effect on glioma risk in the absence of a simultaneous exposure to chemical products. The effect of petroleum products was independent of the intensity of ELFMF exposure whereas solvents, lead, and pesticides/herbicides were only associated with glioma in workers also exposed to moderate or high levels of ELFMF. On the other hand, whereas ELFMF seemed to enhance the effect of specific chemicals in the causation of gliomas, we did not find a relationship between ELFMF exposure and meningiomas. The potential for ELFMF to act as an effect modifier of the association of chemical agents and glioma is an interesting new finding. It would be worthwhile to evaluate this hypothesis for other tumors. Also, it is necessary to confirm these results in epidemiological studies with individual exposure assessments, and in experimental studies that may elucidate whether there is a true causal mechanism for the results we observed.
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PMID:Interactive effect of chemical substances and occupational electromagnetic field exposure on the risk of gliomas and meningiomas in Swedish men. 1450 12


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