Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously documented that the vast majority of high-grade gliomas over-express binding sites for interleukin 13 (IL13) in situ. We now extend this analysis to evaluate the distribution of the binding of IL13 among other brain tumors. Tumor specimens from patients with low-grade gliomas, oligodendrogliomas, ependymomas, pilocytic astrocytomas, gliosarcomas, medulloblastomas, meningiomas, and metastases to the brain were analyzed and compared to a new series of glioblastoma multiforme (GBM) samples. Serial tumor tissue sections were incubated with 125I-labeled (i) IL13, (ii) antibody against transferrin (Tf) receptor, and (iii) epidermal growth factor (EGF). Most (17/18) GBMs stained specifically for IL13 binding sites while sections from 3/11 low-grade gliomas, 5/5 high-grade gliomas (grade III), 3/5 oligodendrogliomas (all three were anaplastic), and 1/2 gliosarcomas also showed specific binding for IL13. We did not detect IL13 binding sites in medulloblastomas (0/4) and found them only in 2/20 meningiomas. Metastases to the brain (4/12, i.e., lung adenocarcinomas and renal cell carcinoma) showed some binding of 125I-IL13. The presence of receptors for Tf was ubiquitous among all studied tumors while EGF receptor expression was much more variable. Since it appears that primarily the least differentiated forms of gliomas possess IL13 binding sites in abundance, it is plausible that IL 13 receptor expressed in low-grade gliomas might be a prognostically significant marker associated with their progression to high-grade gliomas. Finally, we demonstrate that the glioma-associated IL13 receptor is truly more restrictive in nature also due to its selective representation among brain tumors of glial origin.
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PMID:Expression of a restrictive receptor for interleukin 13 is associated with glial transformation. 1108 73

We report about 50 patients with spontaneous intracerebral haematomas (ICH) caused by intracranial neoplasms to assess the underlying histological condition, their presentation on admission, diagnostic work-up, treatment, histological diagnosis, and clinical outcome. These patients were identified in a prospective series of 2041 patients with intracranial neoplasms and 692 patients with spontaneous ICH, which were both consecutively collected over a nine-year-period. The frequency of ICH in patients with intracranial neoplasms was 2.4%. The frequency of tumour related ICH in the ICH group was 7.2%. The leading cause of tumour related ICH were metastases of extracranial origin (n = 18; 36%), followed by glioblastoma multiforme (n = 15; 30%). Nine patients (18%) had benign primary intracranial neoplasms. On admission 18 patients were somnolent (36%) and 14 patients (28%) were comatose. In 29 cases (58%) ICH was the first clinical sign of neoplastic disease, while in 21 patients (42%) a malignant tumour was already known. We operated on 45 patients (90%), four patients (8%) were not operated on because of poor clinical condition and died, one patient refused surgical treatment. Six patients (12%) died despite surgery. This series confirms the importance of a proper neuroradiological and clinical work-up of patients with suspected tumour related ICH followed by operative treatment and histological confirmation of the diagnosis. This is supported by the fact that 18% of patients had prognostically favourable intracranial tumours which would not otherwise have been adequately treated.
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PMID:Spontaneous intracranial haematomas caused by neoplasms. 1108 6

A 31-year old female underwent subtotal resection of a spinal glioblastoma multiforme (GBM) at level D 10/11 in June 1997. Immunohistochemistry revealed increased MIB-1 labeling index and accumulation of p53 protein. Routine MRI in February 1998 showed multiple tumors of the lumbar spinal cord. At open biopsy, diffuse infiltration of multiple radices was seen. Histologically and immunohistochemically, the tumor was similar to the primary. In May 1998, MRI revealed multiple intracranial metastases and meningeal involvement. The patient died in June 1998, 13 months after the onset of symptoms. The lifes of patients with spinal gliomas are not endangered by direct compression of the brain stem, and systemic metastases are extremely uncommon with gliomas. Yet, survival times in the reported case and in the literature are not better than with cerebral localization. Analysis of the present case and a survey of the literature indicate that CSF involvement and consecutive intracranial seeding determine the prognosis of patients with spinal GBM. Thus, regular monitoring of CSF-cytology and/or spinal MRI appear to be advisable in spinal GBM.
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PMID:A case of spinal glioblastoma multiforme: immunohistochemical study and review of the literature. 1126 3

Although intrinsic tumours of the brain seldom metastasize to distant sites, their diffuse, infiltrative-invasive growth within the brain generally precludes successful surgical and adjuvant therapy. Hence, attention has now focused on novel therapeutic approaches to combat brain tumours that include the use of anti-invasive and anti-proliferative agents. The effect of four anti-invasive agents, swainsonine (a locoweed alkaloid), captopril (an anti-hypertensive drug), tangeretin and nobiletin (both citrus flavonoids), were investigated on various parameters of brain tumour invasion such as matrix metalloproteinase (MMP) secretion, migration, invasion and adhesion. A standard cytotoxicity assay was used to optimize working concentrations of the drugs on seven human brain tumour-derived cell lines of various histological type and grade of malignancy. A qualitative assessment by gelatin zymography revealed that the effect of these agents varied between the seven cell lines such that the low grade pilocytic astrocytoma was unaffected by three of the agents. In contrast, downregulation of the two gelatinases, MMP-2 and MMP-9 was seen in the grade 3 astrocytoma irrespective of which agent was used. Generally, swainsonine was the least effective whereas the citrus flavonoids, particularly nobiletin, showed the greatest downregulation of secretion of the MMPs. Furthermore, captopril and nobiletin were most efficient at inhibiting invasion, migration and adhesion in four representative cell lines (an ependymoma, a grade II oligoastrocytoma, an anaplastic astrocytoma and a glioblastoma multiforme). Yet again, the effects of the four agents varied between the four cell lines. Nobiletin was, nevertheless, the most effective agent used in these assays. In conclusion, the differential effects seen on the various parameters studied by these putative anti-invasive agents may be the result of interference with MMPs and other mechanisms underlying the invasive phenotype. From these pilot studies, it is possible that these agents, especially the citrus flavonoids, could be of future therapeutic value. However, further work is needed to validate this in a larger study.
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PMID:Evaluation of the effects of swainsonine, captopril, tangeretin and nobiletin on the biological behaviour of brain tumour cells in vitro. 1129

Stereotactic radiosurgery is being increasingly advocated as the primary modality for treatment of vestibular schwannomas (VS). This modality has been shown to arrest tumor growth, with few associated short-term morbidities, and with possibly better hearing and facial nerve preservation rates than microsurgery. Radiation-induced oncogenesis has long been recognized, although stereotactic radiosurgery de novo induction of a secondary tumor has never been clearly described. The authors report on a patient with a VS who did not have neurofibromatosis Type 2 and who underwent gamma knife surgery (GKS). This patient required microsurgical removal of the VS within 8 months because of development of a tumor cyst with associated brainstem compression and progressive hydrocephalus. The operation resulted in clinical stabilization and freedom from tumor recurrence. Seven and a half years after undergoing GKS, the patient presented with symptoms of raised intracranial pressure. Magnetic resonance imaging demonstrated a new ring-enhancing lesion in the inferior temporal lobe adjacent to the area of radiosurgery, which on craniotomy was confirmed to be a glioblastoma multiforme (GBM). Despite additional conventional external-beam radiation to the temporal lobe, the GBM has progressed. Whereas this first reported case of a GBM within the scatter field of GKS does not conclusively prove a direct causal link, it does fulfill all of Cahan's criteria for radiation-induced neoplasia, and demands increased vigilance for the potential long-term complications of stereotactic radiosurgery, and reporting of any similar cases.
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PMID:Glioblastoma multiforme occurring in a patient treated with gamma knife surgery. Case report and review of the literature. 1135 16

Extraneural metastases of glioblastoma multiforme (GBM) are a relatively rare occurrence which usually manifest after de novo GBM. We report a case of a patient with an oligodendroastrocytoma who developed over a period of 12 years malignant progression to glioblastoma followed by multiple cytologically confirmed bone metastases. No 1p deletions were detected in the original tumour. GBM cells disclosed the EGFr(+) and p53(-) immunophenotype more characteristic of a primary GBM.
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PMID:Bone metastases from secondary glioblastoma multiforme: a case report. 1150 13

Dissemination of malignant glioma to the fourth ventricle with metastatic deposits and intractable vomiting is rare. Leptomeningeal extension of malignant glioma is an uncommon condition that has been reported in patients with end-stage disease and is usually unresponsive to any treatment modality. We describe 3 patients with progressing recurrent glioblastoma multiforme in whom leptomeningeal invasion manifested itself as intractable vomiting due to tumor metastases in the floor of the fourth ventricle. All patients received additional radiation therapy focused to the posterior fossa, with complete resolution of vomiting occurring within 10 days after irradiation. The remission of symptoms in these patients persisted until their death 3-4 months after the repeat radiation therapy. These reports indicate that additional focused radiation should be considered because of its significant therapeutic effect in alleviating intractable nausea and vomiting in patients with glioma metastasized to the posterior fossa.
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PMID:Intractable vomiting from glioblastoma metastatic to the fourth ventricle: three case studies. 1191 5

In the United States, tumors of the central nervous system remain the third leading cancer-related cause of death in young adults with a median survival time of < 1 year. A recent case study suggested that Capecitabine (a novel, fluoropyrimidine prodrug) may be effective in the treatment of brain metastases. Pharmacogenomic studies have correlated the antitumor response to Capecitabine with the expression of the drug metabolizing enzymes thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). In the current study, we examined TP and DPD expression in normal human brain tissues and in glioblastoma multiforme, the most common and malignant type of brain tumor. Because previous reports suggest a tumor necrosis factor (TNF)-alpha-mediated increase in TP expression after irradiation (a current standard of care for glioblastoma multiforme), we also examined the effect of irradiation on the expression of TP, DPD, and TNF-alpha in both irradiated and lead-shielded contralateral U87MG glioma xenografts within the same animal. Expression levels were determined using real-time quantitative PCR as described previously. Results demonstrate an approximately 70-fold increase in TP mRNA levels 4 days after irradiation, relative to initial control levels. Interestingly, TP mRNA in the lead-shielded tumors (contralateral to irradiated tumors) increased approximately 60-fold by day 10 relative to initial control levels. Elevated TP levels were sustained for 20 days in irradiated xenografts but began to decrease after 15 days in the shielded/contralateral tumors, returning to baseline by 20 days. TP mRNA levels in normal mouse liver were unaltered, suggesting a tumor-associated effect. TNF-alpha mRNA levels did not increase after irradiation; therefore, mRNA expression of 11 additional cytokines [interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, and IFN-gamma] in both the irradiated and shielded xenografts was quantitated. Results demonstrated increased levels of IFN-gamma, IL-10, and IL-1 alpha by 6.3-, 3.7-, and 1.6-fold, respectively, in irradiated tumors only. DPD mRNA levels did not change after irradiation. The tumor-associated induction of TP in irradiated and lead-shielded tumors within the same animal may have significant implications for the combined modality treatment of cancer patients with Capecitabine in conjunction with radiotherapy and may apply to the treatment of distant tumors and or metastatic disease.
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PMID:Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. 1248 38

Glioblastoma multiforme is the most common adult malignant brain tumor but is notably less common in children. The authors describe the case of a child who presented for evaluation and treatment of neurologic signs caused by a brain stem glioma. Response to radiotherapy and chemotherapy with temozolomide was initially positive, but later extensive leptomeningeal metastasis developed. Biopsy proved the lesion to be glioblastoma multiforme. During salvage irradiation to the spine and unirradiated brain, the patient complained of hip and femur pain. Subsequent radiographs demonstrated multiple bony metastases. This pattern of spread is uncharacteristic and emphasizes the importance of adequate metastatic evaluation.
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PMID:Atypical presentation and progression of glioblastoma multiforme in a 6-year-old girl: multidisciplinary case report. 1262 Dec 45

Centers in Japan and the United States are extending boron neutron capture therapy (BNCT) to the treatment of malignant melanoma (MM). Positron emission tomography (PET) has been used to image glioblastoma multiforme with 18F-boronophenylalanine (18F-BPA) for the purpose of generating 10B distribution maps. These distribution maps can be used to improve the BNCT treatment planning. 18F-BPA was given to a patient with widely metastatic MM involving the thorax and brain. 18F-BPA PET scans of the chest and the head were obtained and compared to the computed tomograms (CT) and magnetic resonance (MR) images. The lung metastases seen on the chest CT images and intracranial metastases seen on CT and MR images were correlated with the PET images. The PET images clearly identified a brain lesion that was difficult to identify on MR and CT images. The 18F-BPA lung and peri-oral mucous gland activity was intense indicating a relatively high concentration of BPA. The intensity seen in the peri-oral mucous glands is consistent with the experiences in the BNCT clinical trials. These results have implications in the use of BNCT outside of the cranium. The PET images allow the generation of treatment plans that are consistent with the clinical findings. PET imaging with 18F-BPA can be used to identify potential tumors that may be amenable to BNCT and to improve treatment plans prior to BNCT.
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PMID:The use of positron emission tomography to develop boron neutron capture therapy treatment plans for metastatic malignant melanoma. 1274 13


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