Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our objective was to review current literature pertaining to prenatal ultrasonography of various fetal intracranial neoplastic and non-neoplastic tumors. To this goal, all manuscripts published in the English language regarding this topic obtained from a MEDLINE search from 1966 through January 1998 were selected and reviewed. Additional sources were identified through cross-referencing. Intracranial fetal tumors are extremely rare and precise diagnosis is dependent on histology examination of tissue obtained at subsequent surgery or autopsy. Currently, prenatal ultrasonographic findings associated with the following fetal intracranial tumors have been described: teratomas; neuroepithelial tumors including: glioblastoma, astrocytoma, gangliocytoma, medulloblastoma, choroid plexus, and papilloma; and mesenchymal tumors. Non-neoplastic fetal intracranial tumors are even less frequent and include: unilateral megalencephaly, heterotopia, and lipoma of the corpus callosum. Cardinal ultrasonographic findings associated with fetal intracranial tumors include: echogenic and semicystic space occupying lesions with or without distortion of normal symmetrical intracranial (usually midline) structures, calcifications, craniomegaly, polyhydramnios, obstructive hydrocephaly, high-output cardiac failure (hydrops fetalis), the presence of other associated structural anomalies, and infrequently abnormal cerebral Doppler flow velocimetry.
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PMID:Prenatal ultrasonographic diagnosis of fetal intracranial tumors: a review. 964 39

Amiloride is a potassium-sparing diuretic that has been used as an anti-kaliuretic for the chronic management of hypertension and heart failure. Several studies have identified a potential anti-cancer role for amiloride, however the mechanisms underlying its anti-tumor effects remain to be fully delineated. Our group previously demonstrated that amiloride triggers caspase-independent cytotoxic cell death in human glioblastoma cell lines but not in primary astrocytes. To delineate the cellular mechanisms underlying amiloride's anti-cancer cytotoxicity, cell permeant and cell impermeant derivatives of amiloride were synthesized that exhibit markedly different potencies in cancer cell death assays. Here we compare the cytotoxicities of 5-benzylglycinyl amiloride (UCD38B) and its free acid 5-glycinyl amiloride (UCD74A) toward human breast cancer cells. UCD74A exhibits poor cell permeability and has very little cytotoxic activity, while UCD38B is cell permeant and induces the caspase-independent death of proliferating and non-proliferating breast cancer cells. UCD38B treatment of human breast cancer cells promotes autophagy reflected in LC3 conversion, and induces the dramatic swelling of the endoplasmic reticulum, however these events do not appear to be the cause of cell death. Surprisingly, UCD38B but not UCD74A induces efficient AIF translocation from the mitochondria to the nucleus, and AIF function is necessary for the efficient induction of cancer cell death. Our observations indicate that UCD38B induces programmed necrosis through AIF translocation, and suggest that its cytosolic accessibility may facilitate drug action.
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PMID:A cell-permeant amiloride derivative induces caspase-independent, AIF-mediated programmed necrotic death of breast cancer cells. 2364 72

Glioblastoma multiforme is the most lethal and aggressive astrocytoma among primary brain tumors in adults. However, most glioblastoma cells have been reported to be resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Here, we have shown that digitoxin (DT), a clinically approved cardiac glycoside for heart failure, can induce TRAIL-mediated apoptosis of glioblastoma cells. DT in noncytotoxic doses (20 nmol/l) can increase TRAIL-induced apoptosis in TRAIL-resistant U87MG glioblastoma cells. Treatment with DT led to apoptosis and a robust reduction in the levels of the antiapoptotic protein survivin by inducing its proteasomal degradation; however, it did not affect the levels of many other apoptosis regulators. Moreover, silencing survivin with small interfering RNAs sensitized glioma cells to TRAIL-induced apoptosis, underscoring the functional role of survivin depletion in the TRAIL-sensitizing actions of DT. We demonstrate that inactivation of survivin and death receptor 5 expression by DT is sufficient to restore TRAIL sensitivity in resistant glioma cells. Our results suggest that combining DT with TRAIL treatments may be useful in the treatment of TRAIL-resistant glioma cells.
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PMID:Digitoxin sensitizes glioma cells to TRAIL-mediated apoptosis by upregulation of death receptor 5 and downregulation of survivin. 2404 65

To inform clinical management of glioblastoma patients, we estimated the relative prevalence (present at glioblastoma diagnosis) and incidence (newly diagnosed) of comorbid conditions among these patients and their matched controls. We identified 2,424 glioblastoma patients registered in the Swedish National Cancer Registry between 1993 and 2006. Next, 12,120 randomly sampled population-based controls were individually matched to cases on age, sex and calendar year of diagnosis. We then evaluated patient discharge data for selected potential comorbid conditions. Seizures (odds ratio (OR) 31.6, 95% confidence interval (CI) 24.7-40.3) and cerebral edema (OR 25.0, 95% CI 5.5-114) were the most prevalent conditions at diagnosis. Beginning 30 days after diagnosis, increased risks of incident deep vein thrombosis (hazard ratio (HR) 119.7, 95% CI 60.8-211.0) and pulmonary embolism (HR 92.4, 95% CI 48.3-176.6) were observed. Risks of incident cardiovascular diseases including heart failure (HR 4.0, 95% CI 2.6-6.1), coronary artery disease (HR 2.3, 95% CI 1.7-3.2), and myocardial infarction (HR 1.9, 95% CI 1.1-3.4) were also elevated among glioblastoma patients. In this first population-based study of both prevalent and incident comorbid conditions among glioblastoma patients, we have quantified risk of those conditions related to the tumor and its treatment-based on nationwide registry data. However, for incident conditions we cannot distinguish between the effects of the tumor and the effects of treatment. A novel finding was the elevated risk of cardiovascular disease among glioblastoma patients; glioblastoma patients should be monitored for signs of cardiovascular disease.
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PMID:Comorbid conditions associated with glioblastoma. 2441 35

Glioblastoma is an uncommon and aggressive primary brain tumor with incidence of 3 per 100,000 annually. We report a 50-year-old woman diagnosed with glioblastoma within threeyears of induction of fingolimod therapy for relapsing-remitting multiple sclerosis. Fingolimod, an immunomodulating agent used in the treatment of relapsing-remitting multiple sclerosis, has also been suggested to impart a cardioprotective role in heart failure and arrhythmia via activation of P21-activated kinase-1 (Pak1). In the brain, Pak1 activation has been shown to correlate with decreased survival time amongst patients with glioblastoma. A molecular mechanism underlying a link between fingolimod use and glioblastoma development may involve activation of Pak1. To our knowledge, this is the first report of a potential association between fingolimod use and glioblastoma development.
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PMID:Glioblastoma following treatment with fingolimod for relapsing-remitting multiple sclerosis. 2697 Sep 35