Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Racial patterns of childhood brain cancer by histologic type were studied using data from the Third National Cancer Survey and the Surveillance, Epidemiology, and End Results Program. Incidence rates for whites of all types combined and of astrocytic glioma and medulloblastoma were slightly higher than those for blacks. Proportionately more black than white cases of astrocytic glioma were diagnosed between the ages of 5-9 years; this difference corresponded to twofold-higher rates at ages of 0-4 and 10-14 years and similar rates at ages of 5-9 years among whites compared to rates among nonwhites. A real difference in age-incidence curves rather than diagnostic delay among blacks appeared to explain the differences. For medulloblastoma, the male-female rate ratio differed between whites (1.7) and blacks (1.0). Time trend analyses revealed statistically significant increases in medulloblastoma and glioma not otherwise specified (NOS) for incidences among blacks. The rate of microscopic confirmation was significantly higher among whites than among blacks, a difference apparently not explained by differences in the accessibility of tumors for biopsy. For avoidance of biased comparisons, differences in rates of microscopic confirmation and time trends for glioma NOS should be considered in studies of racial patterns of childhood brain cancer incidence by histologic type.
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PMID:Racial patterns of childhood brain cancer by histologic type. 347 96

The roles of diet and tobacco in the etiology of primary brain cancer are controversial. In this report, we compare dietary and cigarette smoking histories among 434 adults newly diagnosed with glioma in the San Francisco Bay Area (California, USA) between 1991 and 1994 with frequency age, gender, and ethnicity-matched population-based controls. Data were obtained on use of vitamin supplements and mean weekly consumption of each of 24 food groups. Adjusted for age, family income, and education, for both men and women, cases had higher mean weekly consumption of cured meats and other cured foods, lower consumption of high vitamin A and C fruits and vegetables, and higher average intakes of beer and other alcohol than controls. Men with brain cancer were twice as likely as control men to report high consumption of cured foods and low consumption of foods rich in vitamin C (odds ratio [OR] = 2.0, 95 percent confidence interval [CI] = 1.2-3.5). This association was less pronounced and not statistically significant in women (OR = 1.5, CI = 0.8-2.7). Similarly, men with brain cancer were twice as likely as controls to have high nitrite and low vitamin C consumption. Among men only, cases were 1.8 times more likely than controls to report smoking unfiltered cigarettes (CI = 0.9-3.4). Moreover, among smokers cases smoked unfiltered cigarettes almost twice as long as controls (P = 0.04) and cases' average total pack-years also significantly exceeded controls. Although these findings support the hypothesis that N-nitroso compounds might be a factor in adult glioma, they are compatible with other dietary hypotheses. In particular, these results also favor the hypothesis that total body burden of oxidants may play a role in brain cancer causation.
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PMID:Dietary and tobacco risk factors for adult onset glioma in the San Francisco Bay Area (California, USA) 905 16

The causes of glioma, the most common type of primary malignant brain tumor, are poorly understood. This study compared the personal and first-degree familial medical histories of 462 adults newly diagnosed with glioma in the San Francisco Bay Area between August 1, 1991, and March 31, 1994, with those of 443 controls who were frequency-matched on age, sex, and ethnicity. Cases and controls had equivalent personal histories of cancers other than brain cancer and most nervous system conditions, but they differed significantly regarding histories of epilepsy, seizures, or convulsions 3 or more years prior to diagnosis (odds ratio = 3.3, 95% confidence interval (CI) 1.4-7.9), chickenpox (odds ratio = 0.4, 95% CI 0.3-0.6), and shingles (odds ratio = 0.5, 95% CI 0.3-0.8). Four cases (less than 1%) and no controls had known genetic disorders (three had neurofibromatosis and one had tuberous sclerosis). Cases and controls had similar family histories of cancer and seizures. However, the odds ratio for a validated family history of primary brain tumor was 2.3 (95% CI 1.0-5.8). These results suggest that although family history of any cancer probably is not an important risk factor for adult glioma, a family history of brain tumors may play a role. Variation in exposure to or biologic response to common viral infections might play a greater role in the etiology of adult glioma than family history.
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PMID:Familial and personal medical history of cancer and nervous system conditions among adults with glioma and controls. 909 74

The retinoblastoma gene (RB) encodes a tumor suppressor that is inactivated in a number of different types of cancer. We searched for gross alterations of this gene in tumors of the central nervous system by using Southern blot hybridization. A common alteration was found in several tumors and was mapped to the region around exon 2. Nucleotide sequencing showed that the alteration was caused by a 799-bp deletion in intron 2 of the RB gene and was probably due to homologous recombination between two Alu repeats. Deletions of this type have not been found previously in the RB gene. The deletion turned out to be a polymorphism with an allele frequency estimated at 2.2% in 185 patients without cancer. The deletion was found in five of 48 patients with brain tumors (allele frequency of 5.2%). This difference is not statistically significant (P = 0.149, Fisher's exact test). Confining the analysis only to glioma brain tumors revealed a statistically significant difference compared with the cancer-free patient controls (P = 0.027, Fisher's exact test). Further study is needed to determine if the deletion is a weak brain cancer-predisposing mutation or a harmless polymorphism. Finding this mutation in a tumor and the germline DNA of a retinoblastoma patient could lead to incorrect estimation of the heritability of a tumor.
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PMID:A deletion polymorphism due to Alu-Alu recombination in intron 2 of the retinoblastoma gene: association with human gliomas. 921 Sep 53

Possible associations between childbearing and the risk of brain cancer were explored in a case-control study "nested" within a large nationwide cohort defined by the Swedish Fertility Registry. Among women born between 1925-1975, 1,088 patients with meningiomas and 1,657 patients with gliomas were identified in the Swedish Cancer Registry. For every woman diagnosed with brain tumor, 5 age-matched controls were selected among those in the Fertility Registry. Relative risks were estimated by odds ratios from conditional logistic regression. Ever-parous women were at a reduced risk of glioma compared to nulliparous women, while parity was unrelated to meningioma risk. Age at first birth was unrelated to both meningioma and glioma risk. The gradient in risk between ever-parous and nulliparous women for gliomas, but not meningiomas, is difficult to explain biologically. A possible explanation is that pregnancy-induced alterations in androgen levels reduce the risk of glioma in parous women. Alternatively, childlessness may represent a marker of an occult glioma, negatively affecting fecundity. Overall, our present results do not support the notion that hormonal changes, or other physiological changes induced by childbearing, play an important role in the development of brain tumors.
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PMID:Reproductive factors and the risk of brain tumors: a population-based study in Sweden. 924 78

The purpose of the study was to assess health-related quality of life (HQL) in patients with high-grade malignant glioma of the brain. The EORTC core Quality of Life Questionnaire (QLQ-C30) and a Brain Cancer Module (BCM20) were administered at baseline and several weeks later (follow-up) to 105 patients with either recently-diagnosed (n = 41) or recurrent (n = 64) malignant glioma. In addition, the attending neurologists completed a standard neurological examination, a modified Barthel Activities of Daily Living Index (BADLI) and the Karnofsky Performance Scale (KPS). In a preliminary step, the QLQ-C30 was found to have acceptable reliability (internal consistency and test-retest reliability). Newly-diagnosed patients and those with a KPS of 80-100 had significantly better physical, role and cognitive functioning and global quality of life with less fatigue, visual disorder, motor dysfunction, communication deficit, weakness of both legs and trouble controlling the bladder than did those with recurrent disease and those with a KPS of 50-70. Similarly, those capable of independent activities of daily living, as reported on the BADLI, had higher functioning scores and less fatigue than did those who were not independent. Patients with dysphasia, mental confusion or motor deficit on neurological examination reported significantly lower levels of physical, role, cognitive, emotional and social functioning and global quality of life than did patients not having these difficulties. They also had significantly more symptoms. In patients with deteriorating neurological status between baseline and follow-up, there was a marked decline in cognitive, physical, role, emotional and social functioning and global quality of life and an increase in fatigue. Thus, there are significant differences in HQL between patients with newly-diagnosed and recurrent brain cancer and between patients with differing KPS and BADLI scores. In addition, the HQL scores provide details not provided by the KPS and the BADLI. Deterioration in neurological function is accompanied by significant deterioration in a range of HQL domains and in global quality of life.
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PMID:Effect of neurological dysfunction on health-related quality of life in patients with high-grade glioma. 925 18

Direct in vivo tumor-targeting with "suicide" viral vectors is limited by either inefficient gene transfer (i.e., retroviral vectors) or indiscriminate transfer of a conditionally toxic gene to surrounding nonmalignant tissue (i.e., adenoviral vectors). Retrovectors pseudotyped with the vesicular stomatitis virus G protein (VSVG) may serve as a remedy to this conundrum. These retroviral particles differ from standard murine retroviruses by their very broad tropism and the capacity to be concentrated by ultracentrifugation without loss of activity. We propose that a VSVG-typed retrovector can be used for efficient and tumor-specific herpes simplex virus thymidine kinase (TK) gene delivery in vivo. To test this hypothesis, we developed a bicistronic retroviral vector that expresses TK and green fluorescence protein (pTKiGFP). The 293GPG packaging cell line was used to generate vTKiGFP retroparticles. In cytotoxicity assays, vTKiGFP-transduced human glioma cell lines were sensitized to the cytotoxic effects of gangciclovir (GCV) 10,000-fold. Subsequently, virus was concentrated by ultracentrifugation to a titer of 2.3 x 10(10) cfu/ml. We tested the antitumor activity of vTKiGFP retroparticles in a rat C6 glioma model of brain cancer. Concentrated retrovector stock (9 microl volume) was injected stereotactically in preestablished intracerebral tumor. Subsequently, rats were treated with GCV for 10 days. Control rats (no GCV) had a mean survival of 38 days (range, 20-52 days). Sections performed on postmortem brain tissue revealed large tumors with evidence of high efficiency retrovector transfer and expression (as assessed by GFP fluorescence). Fluorescence was restricted to malignant tissue. In the experimental group (GCV treated), 8 of 12 remain alive and well >120 days after glioma implantation. In conclusion, vTKiGFP is very efficient at transducing human glioma cell lines in vitro and leads to significant GCV sensitization. Recombinant retroviral particles can be concentrated to titers that allow in vivo intratumoral delivery of large viral doses. The therapeutic efficiency of this reagent has been demonstrated in a preclinical model of brain cancer.
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PMID:Vesicular stomatitis virus G pseudotyped retrovector mediates effective in vivo suicide gene delivery in experimental brain cancer. 1034 48

As a physician specializing in the treatment of cancer, I have had to watch hundreds of patients die from cancer because current treatments have limited benefit. I know of no disease that can strike a patient more tragically than cancer. However, I can say with absolute certainty that the medical and scientific communities are on the verge of major breakthroughs in our ability to control this dreadful disease. Unfortunately, I can also say with absolute certainty that tens of thousands of Americans will die because critical research remains unfunded or underfunded, slowing the development of new lifesaving treatments by years. Never in the history of mankind have we had such an opportunity in medicine. We are literally witnessing an explosion in our understanding of cancer. Every week, new genes which regulate the process of cancer are being discovered. We now have an incredible knowledge of cancer-what makes a cancer cell a cancer cell, what cancer cells need to thrive, and what signals cancer cells to self-destruct and die. With more research our knowledge will be even greater. We also now have the remarkable ability to manipulate genes within cells, to actually direct cells to do what we want them to do. This process, one of the many new treatments we now have, is called gene therapy. This combination of increased knowledge and powerful new techniques to manipulate cells provides opportunities we could only dream of just five years ago. Let me give you just one example of how we are now using this new knowledge. I specialize in the treatment of malignant brain tumors. The most common brain tumor, the malignant glioma, is responsible for 15,000 deaths in the United States each year. The median survival time from diagnosis to death without treatment is 12 to 16 weeks. With conventional cancer treatments, including surgery, radiation and chemotherapy, the median survival is 28 weeks. Because of new research findings, we now know that malignant brain tumors are able to grow in the brain and escape destruction by our immune system because they release a protein into the brain which suppresses or "turns off" the immune system. This protein is called transforming growth factor beta (TGF&bgr;). We are able to take tumor cells and genetically engineer them in our lab so that they can no longer make TGF&bgr;, thereby uncloaking these tumor cells to the immune system. We've shown in lab experiments that rats with untreated brain tumors all died. However, rats with brain tumors treated with the genetically modified vaccine all survived. We found that rats given the vaccine were able to develop immunity against these tumors and their brain cancer was completely eradicated. Based on these studies, we now have a clinical trial where tumor cells are removed from patients during surgery, genetically engineered to make a cancer vaccine, and then re-injected into patients with brain cancer. Six weeks ago we treated the first patient with the vaccine, a 36-year-old man with three young children whose brain tumor was growing despite two brain surgeries and radiation therapy. His tumor appeared to have stabilized after his first vaccine injection. This is just one of literally hundreds of novel approaches now under development for the treatment of cancer. When plans to start this experimental trial were first announced a year ago, my office received over two thousand phone calls, faxes, and e-mails from desperate patients hoping to participate in this trial because they had failed conventional treatments. Due partially to limited funding the trial started just six weeks ago. I would venture that most of the patients who called my office have now died. Even with the study under way, only twelve patients can be entered into the trial, out of potentially thousands who could be treated. This is the most painful reality, knowing that our patients will die because our country has not made cancer research a higher priority. To continue rapid progress requires increased funding for not only basic research to continue our understanding of cancer, but also for the translation of research into clinical trials for patient care. Our national budget for cancer research should be at least twice the current funding levels. We no longer wonder if we will find a cure for cancer but when. America has an incredible opportunity to conquer this deadly disease. Increasing funds for cancer research could now accelerate by years the development of new and more effective treatments for cancer, literally saving tens of thousands of American lives.
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PMID:The Cure for Cancer: Not If but When. 1038 68

The authors conducted a population-based case-control study in Iowa of 375 brain cancer patients and 2,434 controls. A postal questionnaire was used to gather information on lifetime residential history, sources of drinking water, beverage intake, and other potential risk factors. Exposure to chlorination byproducts in drinking water was estimated by combining questionnaire data with historical information from water utilities and trihalomethane levels in recent samples. The analysis included 291 cases (77.6%) and 1,983 controls (81.5%), for whom water quality information was available for at least 70% of lifetime years. Proxies represented 74.4% of cases. The mean number and mean duration of places of residence were comparable between direct and proxy respondents, suggesting little contribution to bias. After multivariate adjustment, odds ratios for brain cancer were 1.0, 1.1, 1.6, and 1.3 for exposure to chlorinated surface water of 0, 1-19, 20-39, and > or =40 years (p trend = 0.1). Among men, odds ratios were 1.0, 1.3, 1.7, and 2.5 (p trend = 0.04), and among women, 1.0, 1.0, 1.6, and 0.7 (p trend = 0.7)). Similar findings were found with estimates of average lifetime level of trihalomethanes. The association was stronger among men with above-median tap water consumption. These observations deserve further attention, especially in view of increasing glioma rates.
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PMID:Drinking water source and chlorination byproducts in Iowa. III. Risk of brain cancer. 1048 93

Loss of the tumor suppressor MMAC1 has been shown to be involved in breast, prostate and brain cancer. Consistent with its identification as a tumor suppressor, expression of MMAC1 has been demonstrated to reduce cell proliferation, tumorigenicity, and motility as well as affect cell-cell and cell-matrix interactions of malignant human glioma cells. Subsequently, MMAC1 was shown to have lipid phosphatase activity towards PIP3 and protein phosphatase activity against focal adhesion kinase (FAK). The lipid phosphatase activity of MMAC1 results in decreased activation of the PIP3-dependent, anti-apoptotic kinase, AKT. It is thought that this inhibition of AKT culminates with reduced glioma cell proliferation. In contrast, MMAC1's effects on cell motility, cell - cell and cell - matrix interactions are thought to be due to its protein phosphatase activity towards FAK. However, recent studies suggest that the lipid phosphatase activity of MMAC1 correlates with its ability to be a tumor suppressor. The high rate of mutation of MMAC1 in late stage metastatic tumors suggests that effects of MMAC1 on motility, cell - cell and cell - matrix interactions are due to its tumor suppressor activity. Therefore the lipid phosphatase activity of MMAC1 may affect PIP3 dependent signaling pathways and result in reduced motility and altered cell - cell and cell - matrix interactions. We demonstrate here that expression of MMAC1 in human glioma cells reduced intracellular levels of inositol trisphosphate and inhibited extracellular Ca2+ influx, suggesting that MMAC1 affects the phospholipase C signaling pathway. In addition, we show that MMAC1 expression inhibits integrin-linked kinase activity. Furthermore, we show that these effects require the catalytic activity of MMAC1. Our data thus provide a link of MMAC1 to PIP3 dependent signaling pathways that regulate cell - matrix and cell - cell interactions as well as motility. Lastly, we demonstrate that AKT3, an isoform of AKT highly expressed in the brain, is also a target for MMAC1 repression. These data suggest an important role for AKT3 in glioblastoma multiforme. We therefore propose that repression of multiple PIP3 dependent signaling pathways may be required for MMAC1 to act as a tumor suppressor.
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PMID:The MMAC1 tumor suppressor phosphatase inhibits phospholipase C and integrin-linked kinase activity. 1064 97


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