Although malignant gliomas are highly invasive tumors, a characteristic that contributes to the commonly observed therapeutic failures and local disease recurrences, the molecular events that ...regulate invasion in these tumors remain poorly understood. Because the transcription factor RelA/NF- mu B has been shown to regulate invasion during several cellular processes, we have examined immunohistochemically expression of the constitutively activated RelA/NF- mu B in tissues obtained from 49 astrocytic tumors 8 diffuse astrocytomas, 9 anaplastic astrocytomas (AAs) and 32 glioblastomas (GBMs). In addition, we examined the in vitro effects of antisense oligonucleotides and curcumin on the expression and activation of RelA/NF- mu B, urokinase-type plasminogen activator (u-PA) expression, migration, and invasion in the T98G glioma cell line. Expression of the constitutively activated RelA/NF- mu B was observed in 2 (25%) of 8 cases of diffuse astrocytomas, 5 (55.6%) of 9 cases of AAs, and 30 (93.8%) of 32 cases of GBMs. This expression was significantly correlated with the malignant potential in astrocytic tumors (P < 0.001). Moreover, antisense oligonucleotides and curcumin inhibited phorbol-12-myristate-13-acetate (PMA)-induced RelA/NF- mu B expression or activation (or both), down-regulated u-PA expression, and reduced the migration and invasive potentials of T98G glioma cells. Thus, the expression of constitutively activated RelA/NF- mu B is associated with malignancy potential in astrocytic tumors and may play a critical role in the regulation of u-PA expression and invasiveness in gliomas. RelA/NF- mu B may therefore be an intriguing candidate for studies aimed at understanding and prevention of the invasiveness of gliomas.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To determine the indication for early surgery of aneurysmal subarachnoid hemorrhage (SAH) in the elderly, we retrospectively correlated surgical outcome with Glasgow Coma Scale (GCS) score. Between ...Jan. 1989 and Dec. 2000, 1,885 of 3,447 patients admitted within 48 hours after SAH underwent clipping of aneurysms between Day 0 and Day 3. The incidence of severe SAH (GCS 3 to 6) on admission inversely correlated with age: 38.2% for patients aged ≥80 years, 27.4% for patients aged 70-79 years, 24.2% for those aged 60-69 years, and 20.6% for those aged <60 years. The rate of early surgery was 87 of 272 patients (32.0%) for those aged ≥80 years, 386 of 738 patients (52.3%) for those aged 70-79 years, 578 of 996 patients (58.0%) for those aged 60-69 years, and 834 of 1441 patients (57.9%) for those aged <60 years. At the 3-month evaluation, the overall incidence of favorable outcome (Good recovery and moderate disability) was 23.0% for those aged ≥80 years, 43.2% for those aged 70-79 years, 59.4% for those aged 60-69 years, and 74.9% for those aged <60 years. Among patients aged ≥80 years, the incidence of favorable outcome was 47.4% in GCS 15, 31.0% in GCS 13+14, 33.3% in GCS 11+12, and 0% in GCS≤10. For patients aged 70-79 years, the incidence of favorable outcome was 61.9% in GCS 15, 40-50% between GCS 7 and GCS 14, and less than 10% between GCS 4 and 6. Initial bleeding and systemic complications were the major risk factors for poor prognosis in the elderly. We concluded that lower limitation of GCS score for early surgery was 11 for patients aged ≥80 years, and 7 for those aged 70-79 years.
Three cases of cerebral deep venous thrombosis (CDVT) were reported with review of the literature. A 47-year-old female had taken estrogen-derived drug. The other two patients had no specific past ...history. On MRI, T2-weighted and fluid-attenuated inversion recovery (FLAIR) images showed high signal intensity lesions at basal ganglia and thalamus. Diffusion-weighted image (DWI) detected only slightly high signal spots but apparent diffusion coefficient (ADC) images indicated mild increases of the ADC value. MR venogram and cerebral angiogram revealed obliteration of internal cerebral veins, great vein of Galen, and straight sinus. The two severely impaired patients received systemic heparinization, in which one patient preceded percutaneous transvenous angioplasty of straight sinus. One patient suffered cognitive disturbance and the other two patients fully recovered from their illness. The high signal intensity lesions on both T2-weighted image and FLAIR image disappeared and deep cerebral veins reappeared. The diagnosis of CDVT based on clinical symptoms is not simple but modern technology of MRI is very useful for diagnosis of CDVT. Once CDVT is detected, appropriate therapy should be started as soon as possible to avoid devastating outcome.
To verify whether the monitoring of regional cerebral oxygen saturation (rSO2) with transcranial near-infrared spectroscopy would successfully reflect changes in intracranial hemodynamics but not ...changes in extracranial compartment, we measured rSO2 and regional cerebral blood flow (rCBF) simultaneously in seven patients with cerebral ischemia and five normal volunteers before and after acetazolamide administration.
The baseline values of rSO2 and rCBF were 64.2 +/- 5.6% and 53.9 +/- 11.1 mL/100 g per minute, respectively. rCBF increased by 44.4 +/- 23.3% and rSO2 significantly increased to 69.6 +/- 5.6% after acetazolamide administration. Bilateral simultaneous measurement of rSO2 indicated a tendency that the larger the delta rSO2, the greater the delta%rCBF. The relationship between rSO2 level and rCBF value fit significantly on the theoretical curve calculated from Fick's equation.
It is suggested that monitoring of rSO2 with INVOS-3100 could be a useful indicator in the evaluation of intracranial hemodynamic changes.
1. For a better understanding of the biological features of astrocytic tumors, we investigated apoptosis and its pathway, especially in the interaction between Fas and Fas ligand (FasL). 2. We ...examined the presence of apoptosis in human astrocytic brain tumors by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP-biotin nick end labeling (TUNEL) and then apoptotic index (AI) was calculated. We also examined the distribution of Fas and FasL-positive tumor cells immunohistochemically. Labeling index (LI) for Fas and FasL was calculated as Fas-LI and FasL-LI, respectively, and compared to AI. 3. Tumor cells expressing both Fas and FasL were TUNEL positive. Such cells were distributed sparsely in low-grade astrocytomas, but focally in glioblastomas. There was a close correlation among AI, Fas-LI, and FasL-LI, and astrocytic tumors with higher Al were associated with a longer survival time than that with lower Al. 4. It was concluded that the Fas system may be involved in the apoptosis of astrocytic tumors, and Al can be a useful parameter for assessing prognosis of astrocytic tumors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Drug resistance is one of the important factors that determine tumor response to chemotherapy. Several candidates for resistance to various chemotherapeutic agents have been elucidated. O
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...-methylguanineDNA methyltransferase (MGMT) removes methylation damage induced by nitrosourea from the O
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position of DNA guanines before cell injury. Glutathione-S-transferase (GST) π is also involved in nitrosourea resistance. We examined the expression of MGMT and GST π in 18 glioblastomas (GBM) using immunohistochemistry and compared the results with patients' survival after administration of 1-(4- amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-based chemotherapy. According to the Kaplan-Meier's method, although median progression free survival (PFS) of eight patients whose tumors retained high MGMT (3 +~ 2 + ), and 10 patients whose tumors showed low MGMT expression (1 +~ 0) were nine and 15 months, respectively ( p= 0.09), median overall survival (OS) of the two groups were 12 and 22 months, respectively, which were significantly different ( p= 0.01). GST π expression in GBM was not a prognostic factor. It is suggested that GBM with strong staining of MGMT activity may show more resistance to ACNU-based chemotherapy compared to that with low MGMT. The simple immunohistochemical analysis of MGMT in GBM can be a useful method to determine whether ACNU or another treatment regimen should be recommended.
Although malignant gliomas are highly invasive tumors, a characteristic that contributes to the commonly observed therapeutic failures and local disease recurrences, the molecular events that ...regulate invasion in these tumors remain poorly understood. Because the transcription factor RelA/NF-kappaB has been shown to regulate invasion during several cellular processes, we have examined immunohistochemically expression of the constitutively activated RelA/NF-kappaB in tissues obtained from 49 astrocytic tumors 8 diffuse astrocytomas, 9 anaplastic astrocytomas (AAs) and 32 glioblastomas (GBMs). In addition, we examined the in vitro effects of antisense oligonucleotides and curcumin on the expression and activation of RelA/NF-kappaB, urokinase-type plasminogen activator (u-PA) expression, migration, and invasion in the T98G glioma cell line. Expression of the constitutively activated RelA/NF-kappaB was observed in 2 (25%) of 8 cases of diffuse astrocytomas, 5 (55.6%) of 9 cases of AAs, and 30 (93.8%) of 32 cases of GBMs. This expression was significantly correlated with the malignant potential in astrocytic tumors (P < 0.001). Moreover, antisense oligonucleotides and curcumin inhibited phorbol-12-myristate-13-acetate (PMA)-induced RelA/NF-kappaB expression or activation (or both), down-regulated u-PA expression, and reduced the migration and invasive potentials of T98G glioma cells. Thus, the expression of constitutively activated RelA/NF-kappaB is associated with malignancy potential in astrocytic tumors and may play a critical role in the regulation of u-PA expression and invasiveness in gliomas. RelA/NF-kappaB may therefore be an intriguing candidate for studies aimed at understanding and prevention of the invasiveness of gliomas.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We evaluated the feasibility of using Split-dose iodine-123-IMP SPECT for identifying the hemodynamic status in patients with bilateral carotid artery occlusive diseases. We studied 8 patients with ...angiographically-confirmed bilateral severe occlusive lesions (occlusion or >70% stenosis) in the cervical carotid artery. Of these patients, we performed carotid artery stenting (CAS) for carotid artery stenosis in 4 patients with contralateral carotid occlusion and for the symptomatic side in 1 patient with bilateral carotid stenosis. The remaining 3 patients were medically treated. The rest regional cerebral blood flow (rCBF) and cerebrovascular reactivity (CVR) were quantitatively evaluated twice by the split dose method before and after CAS. CAS for 1 side in patients with bilateral carotid artery occlusive diseases improves cerebral hemodynamics not only on the side of CAS but also on the other side. Split-dose iodine-123I-IMP SPECT is useful for evaluating the hemodynamic status in bilateral carotid artery occlusive diseases.
Local distribution into brain tumor and the pharmacokinetics of 4-pyridoxate diammine hydroxy platinum (PyPt), a novel cisplatin derivative, were examined using rats implanted with 9L glioma and ...compared with cisplatin. PyPt (5.0 mg/kg) and cisplatin (3.5 mg/kg) were administered as selective intracarotid infusions for 30 min to the rats. Dialysates from extracellular fluid (ECF) in tumor and non-tumor brain tissues were collected by simultaneous microdialysis. The amount of platinum was determined by atomic absorption spectrophotometry, as representative of the drug administered. Plasma concentration of total and protein unbound platinum, and urinary excretion amount and tissue distribution of total platinum were also determined. Unbound platinum was accumulated preferentially in the brain tumor tissue ECF aftwer administration, while there was little distribution into normal tissue ECF of the brain. In the brain tumor, the values of the unbound platinum AUC and MRT, where AUC is the area under the concentration-time curve and MRT is the mean residence time, for PyPt were 1.7 and 1.3 times larger than with cisplatin, respectively. The brain tumor distribution coefficient (the ratio of brain tumor ECF platinum AUC to plasma protein unbound platinum AUC) for PyPt (0.85) was higher than that for cisplatin (0.69), indicating that the local amount of platinum distributed into the glioma is enhanced by PyPt rather than by cisplatin. The binding to plasma proteins of PyPt (23%) was lower than that of cisplatin (65%). The total platinum concentration in tissues after administration of PyPt was significantly lower than that of cisplatin in the kidney, liver and spleen. In addition, the urinary excretion amount of total platinum after the administration of PyPt was significantly larger than that of cisplatin. These results suggested that PyPt is easily eliminated by rapid urinary excretion because of its reduced interaction with plasma proteins and poor distribution to the kidney or reticuloendothelial tissues such as the liver and spleen.It is concluded that PyPt is an effective cisplatin derivative for the treatment of gliomas with the added advantage of enhancing local distribution of drug into the brain tumor and reducing its accumulation in the kidney, which has previously caused severe nephrotoxicity.
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