Induction of cyclooxygenase-2 expression by interleukin-1beta in human glioma cell line, U87MG.

Cyclooxygenase-2 (COX-2) is up-regulated in most high-grade gliomas, and high COX-2 expression is associated with aggressive character and poor prognosis. However, the effect of COX-2 in human glioma cell lines is not well known. This study examined the effect of several stimuli, including interleukin-1beta (IL-1beta) and carcinogens, on COX-2 induction in normal astrocyte cells and human glioma cell lines U87MG, A172, and T98G. IL-1beta-induced COX-2 expression strongly at both protein and messenger ribonucleic acid levels in only the U87MG cells of the glioma cell lines. Furthermore, carcinogen induced COX-2 expression. Similar findings were also observed in normal human astrocyte cells. The U87MG glioma cell line is a good model for COX-2 induction in glioma cell lines.

Metastasis of carcinoid to the arch of the axis in a multiple endocrine neoplasia patient: a case report.

BACKGROUND CONTEXT: Carcinoid tumors eventually metastasize to the spine, and epidural spinal cord compression is a relatively frequent neurologic complication of carcinoid. However, a case of multiple endocrine neoplasia type 1 (MEN1) presenting with spinal cord compression as a result of a metastatic carcinoid tumor has not been reported previously. PURPOSE: To report an extremely rare case of MEN1 presenting with spinal cord compression by metastatic carcinoid tumor. STUDY DESIGN: Case report. METHODS: A 51-year-old man, with a past history of thymoma, insulinoma, and gastric carcinoid presented with neck pain. Neuroradiological examination revealed that a tumor around the arch of the axis compressed the spinal cord with osteoblastic changes. RESULTS: After hemilaminectomy of the axis and removal of the tumor followed by irradiation, the patient returned to his previous job. Histological examination confirmed metastatic carcinoid tumor. CONCLUSIONS: Spinal metastasis of carcinoid tumor occurred in a multiple endocrine neoplasia patient, and it is significant to note that carcinoid metastasis is one of differential diagnoses for osteoblastic lesions.

Metastatic hemangiopericytoma to the cauda equina: a case report.

BACKGROUND CONTEXT: Hemangiopericytoma is an aggressive tumor associated with high recurrence and metastasis. Metastases are usually delayed, long after diagnosis of the primary lesion. Metastatic hemangiopericytoma to the spinal cord is especially rare. PURPOSE: To report a rare clinical presentation of a metastatic intradural, intramedullary hemangiopericytoma to the cauda equina from a cerebellar hemangiopericytoma. STUDY DESIGN: Case report with a review of the literature. METHODS: Clinical history, physical findings, and magnetic resonance imaging studies of a patient with a metastatic intradural, intramedullary hemangiopericytoma to the cauda equina are reported. RESULTS: A case report is presented of a female with an intradural, intramedullary lesion at the L4-S1 level, presenting initially with progressive pain and motor weakness affecting the left lower extremity. She had a history of a cerebellar hemangiopericytoma, which had been treated with total resection and radiotherapy 4 years earlier. This patient developed urinary urgency and frequency. Pathological analysis revealed a hemangiopericytoma, which had a similar character to a cerebellar lesion. After radiotherapy, the tumor was mostly diminished and her symptoms totally resolved. CONCLUSIONS: Hemangiopericytomas have a strong tendency to both local recurrence and metastasis. Common metastatic sites are the skeletal system, lung, liver, and abdominal cavity. To the authors' knowledge, there have been no reports of spinal intradural, intramedullary metastasis of hemangiopericytoma.

Cerebral venous sinus thrombosis associated with iron deficiency: two case reports.

Two patients presented with cerebral venous sinus thrombosis (CVST) associated with iron deficiency. A 14-year-old man had thrombosis extending from the end of the superior sagittal sinus to the left transverse sinus. Severe dehydration after competitive sport had induced CVST. The laboratory findings showed severe iron deficiency anemia which persisted for 1 year. A 47-year-old man had thrombosis in the entire superior sagittal sinus. Dehydration caused by poor nutrition had induced CVST. The laboratory findings showed transient iron deficiency in the acute phase. Both patients received conservative treatment for dehydration and iron supplementation. These two cases indicate that iron deficiency is a risk factor for CVST.

The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells.

The induction of cyclooxygenase-2 (COX-2) expression is associated with more aggressive gliomas and poor survival. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity and have antitumorigenic properties. In this report, our initial aim was to determine if indomethacin would alter gene expression as measured by suppression subtractive hybridization (SSH). Three up-regulated and four down-regulated genes by indomethacin treatment were identified. Laminin gamma1, an extracellular matrix molecule, was the most significantly repressed gene. The repression of laminin gamma1 by indomethacin was confirmed by Northern and Western blot analyses and occurred in a concentration- and time-dependent manner at the protein level. Among several NSAIDs tested, only sulindac sulfide and indomethacin suppressed laminin gamma1 protein expression, and this repression was observed in both COX-expressing and -deficient cell lines, suggesting that laminin gamma1 repression by COX inhibitors was independent of COX. Indomethacin, at a concentration that represses laminin gamma1, inhibited glioblastoma cell invasion that was partially restored with additional human laminin protein containing gamma1 chain. The repression of laminin gamma1 by NSAIDs may be related to attenuation of invasion of brain tumors. These findings are important in understanding the chemopreventive activity of some NSAIDs and could be relevant for designing therapeutic strategies against glioblastoma.

Transoral penetration of a half-split chopstick between the basion and the dens.

A 6-year-old girl was admitted for transoral penetrating injury by a half-split chopstick. Subsequent CT imaging examinations showed that the chopstick had passed between the basion and the dens and reached the subarachnoid space just at the medulla oblongata. A sagittal reconstructed CT scan was useful for the evaluation of the injury. Imaging findings and their clinical relevance are discussed.

Role of reactive oxygen species in LPS-induced production of prostaglandin E2 in microglia.

We determined the roles of reactive oxygen species (ROS) in the expression of cyclooxygenase-2 (COX-2) and the production of prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated microglia. LPS treatment increased intracellular ROS in rat microglia dose-dependently. Pre-treatment with superoxide dismutase (SOD)/catalase, or SOD/catalase mimetics that can scavenge intracellular ROS, significantly attenuated LPS-induced release in PGE2. Diphenylene iodonium (DPI), a non-specific NADPH oxidase inhibitor, decreased LPS-induced PGE2 production. In addition, microglia from NADPH oxidase-deficient mice produced less PGE2 than those from wild-type mice following LPS treatment. Furthermore, LPS-stimulated expression of COX-2 (determined by RT-PCR analysis of COX-2 mRNA and western blot for its protein) was significantly reduced by pre-treatment with SOD/catalase or SOD/catalase mimetics. SOD/catalase mimetics were more potent than SOD/catalase in reducing COX-2 expression and PGE2 production. As a comparison, scavenging ROS had no effect on LPS-induced nitric oxide production in microglia. These results suggest that ROS play a regulatory role in the expression of COX-2 and the subsequent production of PGE2 during the activation process of microglia. Thus, inhibiting NADPH oxidase activity and subsequent ROS generation in microglia can reduce COX-2 expression and PGE2 production. These findings suggest a potential therapeutic intervention strategy for the treatment of inflammation-mediated neurodegenerative diseases.

[A case of ruptured aneurysm of the middle cerebral artery associated with dural arteriovenous fistula in the anterior cranial fossa].

A 66-year-old man suffered from subarachnoid hemorrhage due to the rupture of a right middle cerebral artery aneurysm that was detected by 3D-CTA. He underwent an emergent clipping operation. Incidentally, postoperative DSA demonstrated dural arteriovenous fistula in the left anterior cranial fossa, which was fed by the left anterior ethmoidal artery and drained into the superior sagittal sinus via the cortical vein of the left frontal lobe. We performed electrocoagulation and division of the fistula at the second surgery. Subsequently, he underwent a ventriculo-peritoneal shunt and was discharged without any neurological deficits. We reviewed reported cases of rare association of ruptured cerebral aneurysm and dural arteriovenous fistula in the left anterior cranial fossa.

Aspirin and indomethacin exhibit antiproliferative effects and induce apoptosis in T98G human glioblastoma cells.

The in vitro antiproliferative and apoptosis inducing properties of the nonsteroidal anti-inflammatory drugs (NSAIDs) like acetyl salicylic acid (aspirin) and indomethacin were investigated in T98G human glioblastoma cells to explore their potential role in the chemoprevention of human glioma. The biological effects induced by aspirin and indomethacin on T98G cells, in which the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were confirmed by RT-PCR and immunostaining, were investigated by studying cell proliferation and apoptosis assays. The antiproliferative effects occurred in a dose- and time-dependent manner on T98G cells by the treatment with 0.1 -2 mM aspirin and 25-100 microM indomethacin. Moreover, aspirin displayed the greatest growth inhibition within 24 h. Approximately 90% growth inhibition occurred following treatment either with 2 mM aspirin or 100 microM indomethacin by 72 h and induction of apoptosis was confirmed by DNA laddering and TUNEL assay. Our in vitro findings indicate that aspirin and indomethacin have an antiproliferative effect on T98G human glioblastoma cells at toxic concentrations.

Transcriptional regulation of cyclooxygenase-1 by histone deacetylase inhibitors in normal human astrocyte cells.

While cyclooxygenase (COX)-2 is a highly inducible gene, COX-1 is widely known as a noninducible gene and is constitutively expressed in a variety of cell lines and human tissues. Recently, several reports have indicated that COX-1 is also regulated at the transcriptional level by various stimuli. We present evidence that histone deacetylase (HDAC) inhibitors induce COX-1 transcription and translation in normal human astrocyte (NHA) cells and glioma cell lines. HDAC inhibitors increased acetylated histone H4 protein expression in NHA cells. The levels of COX-1 mRNA and protein were maximal at 24 and 48 h, respectively, after treatment with the specific HDAC inhibitor, trichostatin A (TSA). In addition, TSA-treated NHA cells produced prostaglandin E(2) as determined by enzyme-linked immunosorbent assay after incubation with 10 microm exogenous arachidonic acid, indicating that the induced COX-1 is functionally active. In addition to NHA cells, this up-regulation of COX-1 after treatment with HDAC inhibitors was observed in 5 different glioma cell lines. The nucleotide sequence of the inducible COX-1 cDNA was confirmed identical to human COX-1 that was previously reported. HDAC inhibitors stimulated COX-1 promoter activity as measured by luciferase reporter assays, suggesting that the induction of COX-1 is regulated at the transcriptional level. Furthermore, mutation analysis of the COX-1 promoter suggests that TSA-responsive element exists in the proximal Sp1-binding site at +25 to +31. In conclusion, COX-1 is an inducible gene in glial-derived cells including immortalized cells, and appears to be transcriptionally regulated by a unique mechanism associated with histone acetylation.

Histone acetylation may suppress human glioma cell proliferation when p21 WAF/Cip1 and gelsolin are induced.

Histone deacetylase inhibitors that increase histone acetylation on transformed cells are being investigated as unique anticancer drugs. The aim of this investigation was to evaluate an antiproliferative activity of the histone deacetylase inhibitors sodium butyrate (NaBT) and trichostatin A on 5 glioma cell lines, T98G, A172, U-87 MG, U-118 MG, and U-373 MG, with the examination of the altered expressions in p21 and gelsolin genes. Treatment with 5-mM NaBT and 40 ng/ml trichostatin A for 48 h caused more than a 50% growth inhibition in 5 cell lines as measured by cell proliferation assays. An increase in histone acetylation was confirmed in each cell line. After treatment with 5 mM NaBT, T98G, A172, and U118 cells undergo apoptosis as indicated by DNA ladder formation. Treatment with NaBT and trichostatin A also decreased DNA synthesis as examined by the fluorescence-activated cell sorting analysis in T98G and U87 cells. In addition to the suppression of cell growth, the up regulation of p21 and gelsolin expression was observed after treatment with NaBT, especially in T98G cells. Maximum expression of p21 and gelsolin was observed within 24 h after treatment. Results from our in vitro studies indicate that the treatment of human glioma cells with one of the histone deacetylase inhibitors suppresses cell growth with decreasing DNA synthesis and stimulates apoptosis, and that associated molecular mechanisms responsible for these effects include increased histone acetylation as well as enhanced expression of p21 and gelsolin.