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)

A pharmacokinetic one-compartment model for the cerebrospinal infusion for the brain tumor chemotherapy is described together with various parameters used for computer simulation. An antitumor protein, neocarzinostatin (NCS) as a prototype drug, has been utilized since it was found effective against glioblastoma cells at extremely low concentration (less than 5 ng/ml) and it is readily inactivated by serum. A very slow infusion velocity was found necessary for an appropriate dose regimen; for example, 0.25mg of the drug should be infused into CSF for about 40 min to attain a drug level of 8 ng/ml.
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PMID:[Part I. Theory and computer simulation for cerebrospinal infusion]. 622 92

The authors discuss the case of a 15-year-old girl suffering from intra-cranial hypertension. Neuroradiological examinations do not reveal any obstruction in the cerebral spinal fluid circulation. The CSF cylologic examination was the first to give etiological indications, showing the existence of malignant cells which the cerebral biopsy later enabled us to classify as glioblastoma. This case affords an opportunity to recall the three stages of the diagnosis: first, intra-cranial hypertension; secondly, chronic meningitis; thirdly, cytological difficulties in the examination of CSF in patients having undergone neuro-radiological examinations.
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PMID:[The interest of CSF examinations in the etiological diagnosis of intracranial hypertension (author's transl)]. 628 17

Phase I and phase II clinical studies of interferon (IFN) were conducted in malignant brain tumours (47 cases of glioblastoma, medulloblastoma and others) using three preparations of the drug. The drug was administered daily in doses 3.0 - 9.0 X 10(6) I.U. locally or intravenously (beta-type) or intramuscularly (alpha-type). The administration was continued as many days as possible, eight weeks being the shortest period. The efficacy of the therapy was assessed mainly by the CT findings (computed volume of the tumour). As for efficacy against glioblastomas, the highest effectiveness rate (40%) was obtained with Human Fibroblast IFN (HFIF) (beta-type) (Toray) (one case of complete remission and seven cases of partial remission out of 20 cases) as compared to Human Lymphoblastoid IFN (HLBI) (alpha a-type) (Wellcome) (one case of partial remission out of three cases) and recombinant IFN (rIFN-alpha A) (alpha-type) (Roche) (two cases of partial remission out of nine cases). The high rate of responsiveness of HFIF seems to be largely attributable to the local, rather than systemic, administration of the drug. Our pharmacokinetic study revealed that, by means of intrathecal administration a much higher IFN titre was detected in the cerebrospinal fluid, while by intravenous or intramuscular route, the IFN titre in the CSF was undetectably low. The generally lower incidence of side-effects with HFIF compared to other preparations was also largely ascribable to the route of administration. IFN therapy in combination with radiotherapy and/or chemotherapy should also be investigated.
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PMID:Clinical effect of interferon in malignant brain tumours. 637 11

Ten (23%) patients out of 43 with malignant glioma developed meningeal gliomatosis during the follow up period of at least one year. The duration between the first surgery and diagnosis of meningeal gliomatosis ranged from one to 78 weeks (median 45 weeks). In younger age group less than 20 years old, 5 (56%) out of 9 patients had meningeal gliomatosis, and on the contrary the incidence was lower in older age group above 20 years old (5 of 34, 15%). Seven (22%) out of 32 male and 3 (27%) out of 11 female patients developed meningeal gliomatosis. The primary tumor location were frontal lobe in 4 cases (including one bifrontal tumor), temporal in 2, parieto-occipital in 1, thalamus in 1, midbrain in 1, and cerebellar hemisphere in 1, respectively. Histologically, 7 tumors were anaplastic astrocytoma, and 3 were glioblastoma. The characteristic neurological findings observed during the course of meningeal gliomatosis were abnormal mental status (80%), cranial nerve palsies (50%), paraplegia (60%), stiff neck (80%), seizure (50%), and respiratory disturbance (80%), CSF cytology was positive in all 9 patients tested. CT scan demonstrated hydrocephalus (70%), and diffuse contrast enhancement of ventricular wall (60%) and basal cistern (10%). In 2 cases, block and irregular filling defect were seen by myelography. Six patients were treated by irradiation to the whole brain and/or spine, and 5, by intrathecal chemotherapy with methotrexate, cytosine arabinoside and bleomycin. However, all patients died of the tumor one to 46 weeks (median 18 weeks) after the diagnosis of meningeal gliomatosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical studies of meningeal gliomatosis]. 649 23

The clinical, surgical, and pathological data from 35 published cases of oligodendroglioma and of one personal case are analysed and compared with those from other tumours of the cord and from cerebral oligodendrogliomas. Oligodendroglioma of the cord has a slightly lower average age than other gliomas and is closer to that of glioblastoma. In oligodendroglioma of the cord, as of the brain, acute onset or aggravation of the symptoms and an oscillating course are frequent. Two correlated data are particularly worth noting: a) the mean CSF protein content in oligodendroglioma of the cord is higher than in any other glioma; b) intracranial hypertension, in the form of papilloedema or hydrocephalus, or both, was present in 31% of cases. This signifies cerebral oligodendrogliomatosis, which was found in 6 out of 10 necropsied cases. At operation most oligodendrogliomas of the cord appear as infiltrating "gelatinous" tumours, though a minority have a firm consistency and apparently clearcut contours, which seem to be associated with a better prognosis. Postoperative radiotherapy seems to be useful.
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PMID:Oligodendrogliomas of the spinal cord. 699 45

Granulocyte-colony-stimulating factor (G-CSF) is a hematopoietic cytokine that regulates the differentiation of myeloid progenitors and the function of mature neutrophils. It is produced in vitro by monocytes/macrophages, mesothelial cells, fibroblasts and endothelial cells after appropriate induction by inflammatory mediators like IL-1 and TNF. Normal as well as tumorous glial cells can also be induced to produce CSFs in vitro. However, little is yet known about the in vivo expression of G-CSF as a mediator in inflammation and malignancy within the human central nervous system. The aim of the present study was to investigate by immunostaining the expression of the G-CSF protein within non-tumorous and tumorous glial tissues, and primitive neuroectodermal tumors. Using the murine monoclonal anti-G-CSF TM 82/60 antibody, we found high G-CSF expression in astrocytoma WHO grades I and II and reactive brain tissue, low expression in astrocytoma WHO grade III, and none in glioblastoma, oligodendroglioma WHO grades II and III, and medulloblastoma. In consecutive sections of the tissue samples, G-CSF protein was localized in GFAP-positive glial cells, but not in macrophages/microglial cells, which expressed HLA-DR, detected by the antibody CR3/43. Computer-assisted microdensitometric evaluation of the intensity of immunostaining for G-CSF and statistic analysis of the data revealed significant differences between the diagnostic entities studied (p < 0.0001). We conclude that in vivo expression of G-CSF is a characteristic of reactive as well as tumorous astrocytes, with the latter losing this feature at higher degrees of dedifferentiation.
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PMID:Immunolocalization of granulocyte-colony-stimulating factor in human glial and primitive neuroectodermal tumors. 751 14

Tenascin, an extracellular matrix glycoprotein, has been reported to be expressed predominantly on glioma tissue in the CNS, both in a cell associated and an excreted form. Recently, a highly sensitive sandwich type enzyme immunoassay for quantitative determination of tenascin was developed. In the present study, the amount of tenascin in CSF was measured. An increase of tenascin in CSF (> 100 ng/ml) was found in patients with an astrocytic tumour. The concentration was significantly higher (> 300 ng/ml) in high grade astrocytoma (anaplastic astrocytoma and glioblastoma) and a further increase (> 1000 ng/ml) was found in cases of CSF dissemination of high grade astrocytoma. On the other hand, tenascin concentrations were less than 100 ng/ml in non-astrocytic tumours and non-neoplastic neurological diseases, except meningeal dissemination of tumour cells, meningeal stimulation by infection, and subarachnoid haemorrhage. In cases of treated astrocytomas in remission, tenascin was negligible (< 100 ng/ml) in the CSF. The measurement of tenascin in CSF is useful for differential diagnosis of brain tumours and monitoring of astrocytic tumours.
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PMID:Tenascin in cerebrospinal fluid is a useful biomarker for the diagnosis of brain tumour. 752 4

The c-myb protooncogene plays a major role in regulating the process of in vitro and in vivo hematopoiesis via its activity as transcriptional regulator in hematopoietic progenitor cells. Since the bone marrow microenvironment appears to regulate in vivo hematopoiesis by maintaining the growth of multipotent progenitors via secretion of specific cytokines, we asked whether c-myb is also required for the proliferation of and/or cytokine production by stromal cells that generate fibroblast-like colonies (fibroblast colony-forming units [CFU-F]). Using the reverse transcriptase polymerase chain reaction technique, we detected low levels of c-myb mRNA transcripts in human normal bone marrow fibroblasts. Treatment of these cells with c-myb antisense oligodeoxynucleotides caused downregulation of c-myb expression, decreased in the number of marrow CFU-F colonies (approximately 54% inhibition) and in the cell number within residual colonies (approximately 80%), and downregulation of granulocyte/macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) mRNA expression. Transfection of T98G glioblastoma cells, in which expression of c-myb, GM-CSF, and SCF mRNAs is undetectable or barely detectable, with a plasmid containing a full-length c-myb cDNA under the control of the SV40 promoter induced the expression of biologically active SCF and GM-CSF in these cells. Regulation of GM-CSF expression by c-myb was due in part to transactivation of the GM-CSF promoter. These results indicate that, in addition to regulating hematopoietic cell proliferation, c-myb is also required for proliferation of and cytokines synthesis by bone marrow fibroblasts.
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PMID:Regulation of proliferation and cytokine expression of bone marrow fibroblasts: role of c-myb. 768 94

Nitrosoureas are the drugs most effective in the treatment of patients with intracerebral malignant glioma. Their limiting toxicity is delayed myelosuppression. A prospective, randomised crossover study of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was performed in patients receiving BCNU for relapsed glioblastoma, to investigate whether the resulting haematological toxicity profile could be modified by rhGM-CSF. Adequate data for analysis were obtained in 13 patients. Following BCNU, the nadir neutrophil count was higher in 12 out of 13 patients during the rhGM-CSF-protected cycles compared with the unprotected cycles. The median nadir was also significantly higher (1.79, CI 0.76-3.52, P < 0.005). Five episodes of neutropenia (< 2 x 10(9) l-1) occurred during the unprotected cycles compared with none in the rhGM-CSF-protected cycles (P = 0.076). There was no evidence of any effect on platelets. This result shows that the haematological toxicity profile following therapeutic doses of BCNU can be modified. It suggests that rhGM-CSF and other growth factors should be investigated for clinical efficacy in chemotherapy using nitrosoureas.
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PMID:rhGM-CSF ameliorates neutropenia in patients with malignant glioma treated with BCNU. 812 85

More than 80% of malignant gliomas have been reported to recur locally after conventional chemoradiation therapy. This regional pattern of recurrence has encouraged the introduction of new treatments for local tumors. Since 1987 interstitial brachytherapy using Iridium-192 seeds has been carried out in our department for malignant brain tumors. The present study was designed to evaluate the patterns of recurrence following interstitial brachytherapy and to assess how this recurrence differs from that observed in patients treated by conventional means. Ten patients who satisfied the following criteria were selected among 41 patients treated with brachytherapy. The criteria were; 1) histologically diagnosed to be malignant glioma (astrocytoma grade III or glioblastoma), 2) followed up with MRI every month after the brachytherapy, 3) follow-up period was more than 6 months, and 4) the time of recurrence was confirmed. The patients were classified into 3 groups according to the patterns of tumor recurrence as follows; 1. Local recurrence group: The tumor recurred near the pretreatment tumor site. 2. Necrotomy group: Reoperation was performed because of neurological deterioration and radiographic evidence of increasing mass effect with surrounding edema. Neurological symptoms were unchanged or improving during the 6 months after the reoperation. 3. CSF seeding group: Primary tumor was well controlled, but seeding via cerebrospinal fluid was recognized on MRI. Local recurrence occurred in three patients, necrotomy was carried out in three patients, and CSF metastases were defined by both MRI and clinical symptoms in four patients. Median radiation does was 33 Gy in the local recurrence group, 57.6 Gy in the necrotomy group, and 43.2Gy in the CSF seeding group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Patterns of recurrence in malignant gliomas after brachytherapy]. 816 95


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