Effects of Sense and Antisense Expression of Protein Kinase Calpha on the Proliferation and Radiosensitization of U-87 Human Glioblastoma Cells

OBJECTIVE: It has been suggested that protein kinase C(PKC) may be one of a number of important regulatory enzymes influencing the tumor cell proliferation and intracellular sensitivity to irradiation. In this study, authors investigate the role of PKC in the growth and radiosensitization of glial brain tumors. METHODS: Human glioblastoma cell line U-87 was stably transfected with sense and antisense complementary deoxyribonucleic acid(cDNA) encoding PKCalpha. The effect of sense and antisense PKCalpha cDNA transfection on PKCalpha expression, PKC activity, cell proliferation, and radiosensitivity of tumor cells was determined. RESULTS: There was no significant difference in cell proliferation between control cells and cDNA(sense and antisense) transfected cells on thiazolyl blue(microculture tetrazolium, MTT) assay. PKC activity was increased by 68% in cells transfected with the sense PKCalpha cDNA(U-87/sPKCalpha), and was reduced by 32% in cells transfected with the antisense PKCalpha cDNA(U-87/aPKCalpha) compared to control cells(p<0.05). Western blotting with a polyclonal antibody against PKCalpha and scanning densitometric analysis of autoradiograms revealed that PKCalpha expression was enhanced by about 5 times of that of control cells in U-87/sPKCalpha cells and was suppressed by more than 30% of that of control cells in U-87/aPKCalpha cells. After exposure to 6 Gy irradiation, cell viability on MTT assay was increased by 43.7% in U-87/sPKCalpha cells and was reduced by 24.3% in U-87/aPKCalpha cells compared to control cells(p<0.001). CONCLUSION: The results of this study demonstrate that PKCalpha overexpression confers a relative radior-esistance and PKCalpha suppression enhances a radiosensitivity on U-87 cells. These observations suggest that PKCalpha plays an important role in regulating cell response to irradiation and a specific modulation of PKCalpha expression in malignant gliomas may influence the radiosensitivity of them.

Syringostomy Using Myringostomy Tube in Syringomyelia Associated Type I Chiari Malformation

We describe a case of syringomyelia associated with type I Chiari malformation treated with syringostomy using myringostomy tube. The syrinx was found at C2 to C5 level, and the patient presented with quadriparesis and both shoulder pain. We performed extensive suboccipital craniectomy, C1 laminectomy, duroplasty, and then syringostomy using myringostomy tube. Postoperatively, the clinical and neurological improvement was noted and MRI showed reduced size of syrinx.

The Relationship between Intracellular Protein Kinase C Concentration and Invasiveness in U-87 Malignant Glioma Cells

OBJECTIVES: Glioblastomas, the most common type of primary brain tumors, are highly invasive and cause massive tissue destruction at both the tumor invading edges and in areas that are not in direct contact with glioma cells. As a result, patients with high-grade gliomas are faced with a poor prognosis. Such grim statistics emphasize the need to better understand the mechanisms that underlie glioma invasion, as these may lead to the identification of novel targets in the therapy of high grade gliomas. Protein kinase C(PKC) is a family of serine/threonine kinases and an important signal transduction enzyme that conveys signals generated by ligand-receptor interaction at the cell surface to the nucleus. PKC appears to be critical in regulating many aspects of glioma biology. The purpose of this study was to assess accurately the role of PKC in the invasion regulation of human gliomas based on hypothesis that protein kinase C(PKC) is functional in the process of glial tumor cell invasion. METHOD: To test this hypothesis, U-87 malignant glioma cell line intracellular PKC levels were up and down regulated and their invasiveness was tested. Intracellular PKC level was characterized using PKC activity assays. Invasion assays including barrier migration and spheroid confrontation were used to study the relationship between PKC concentration and invasiveness. RESULT: The cell line which were treated by PKC inhibitor tamoxifen and hypericin exhibited decreased PKC activity and decreased invasive abilities dose dependently both in matrigel invasion assay and tumor spheroid fetal rat brain aggregates(FRBA) confrontation assay. However, the cell line that was treated by PKC activator 12-O-tetradecanylphorbol-13acetate(TPA) did not exhibit increases in either PKC activity or invasive ability. CONCLUSION: These studies suggest that PKC may be a useful molecular target for the chemotherapy of glioblastoma and other malignancies and that a therapeutic approach based on the ability of PKC inhibitors may be helpful in preventing invasion.

Bypass Graft for Cerebral Revascularization / 대한뇌혈관학회지

OBJECTIVE: The authors were performed bypass graft for cerebral revascularization in the treatment of hemodynamic cerebral ischemia and unclippable traumatic aneurysm, which acute sacrifice of the internal carotid artery is necessary. The aim of this study was to assess effectiveness bypass graft for cerebral revascularization. METHOD: Of 6 patients, Four patients were hemodynamic cerebral ischemia and two patients were traumatic cerebral aneurysm and traumatic carotid-cavernous fistula (CCF). Revascularization was performed external carotid artery (ECA) to middle cerebral artery (MCA) bypass with radial artery (n=1), ECA to MCA bypass with long saphenous vein (n=1), main trunk of superficial temporal artery (STA) to MCA with short saphenous vein (n=2), and internal carotid artery (ICA) to MCA with long saphenous vein (n=2). RESULTS: There were two graft occlusion, which one is recanalization case of preoperative MCA obstruction and the other is traumatic CCF. Four patients with good patiency through bypass showed significant increase of postoperative cerebral blood flow and good surgical outcome. There was not operative complication except for graft failure of 2 cases. CONCLUSION: Extracranial to intracranial bypass graft with radial artery or saphenous vein is thought to alternative method for cerebral revascularization in cases with unsuitable STA to bypass, and ICA reconstruction, which acute sacrifice of ICA is necessary.

Solitary Plasmacytoma of the Skull: A Case Report

No abstract available.

Surgical Results of Microvascular Decompression and Partial Sensory Rhizotomy in the Treatment of 154 Patients with Trigeminal Neuralgia

OBJECTIVE: To evaluate the efficacy of microvascular decompression(MVD) for trigeminal neuralgia(TN) and to discuss current understanding of the mechanism of MVD for this disorder. PATIENTS AND METHODS:Since 1987, 154 patients treated for trigeminal neuralgia(TN) had been followed for an average 4.3 years. Among these patients, 145 had vascular compression of the nerve and underwent microvascular decompression(MVD). Remaining 9 patients had no offending vessels, so partial sensory rhizotomy(PSR) was performed in these patients. RESULTS: Immediate pain relief was achieved in 95%(147/154) of all patients, but the rate dropped to 90%(140/154) during the follow-up period. Recurrence rate in the MVD group was 2% and in the PSR group 55%. Among those patients underwent MVD, permanent sequelae occurred in only 1 patient(sensorineural hearing loss) and transient complications(impaired hearing due to hemotympanum, minor sensory deficit etc.) were more frequent. There were no differences in the outcome, considering age, sex and the duration of symptoms. There was a close relationship between operative findings of arterial compression on the nerve and long-term complete pain relief. Prognosis for patients with severe arterial compression was better than that for patients with mild or venous compression. CONCLUSION: MVD provides a high rate of success with a minor risk of complications, and this study gives support to the hypothesis that in most cases of TN is caused by neurovascular compression.

Improvement of Cerebrovascular Reserve Capacity by Bypass Surgery in Patients with Hemodynamic Cerebral Ischemia

To study the effect of extracranial-intracranial(EC/IC) bypass on symptomatic patients with hemodynamic cerebral ischemia, we prospectively reviewed 14 patients who underwent EC/IC bypass surgery. A series of 14 patients treated in a 2 years period met the following criteria, 1) symptomatic internal carotid artery(ICA) or middle cerebral aetery(MCA) obstruction or stenosis over 80M, 2) decrease in basal cerebral blood flow(CBF) over 10%, 3) hyporeactivity to acetazolimide of CBF Amomg these, the type of ischemic episode was transient ischemic attack(TIA) or reversible ischemic neurological deficit(RIND) in 4, minor stroke in 8, and major stroke in 2. Of these, 10 patients had multiple episode of ischemic attack. CT or MRI were showed infarction of the MCA territory in 3, border zone infarction in 5, basal ganglia infarction in 2 and multiple lacunar infarction in 4. Based on our criteria, superficial temporal artery(STA)-MCA anastomosis was performed in 13 cases and EC-IC bypass grafting using radial artery in one. Average follow up period was 24 months. Postoperative course was uneventful in 12 patients. One patient suffered a postoperative stroke with complete recovery and another suffered operative wound infection. Of the 14 patients 12(85.7 % ) have had an excellent to good outcome with complete resolution or significant improvement of preoperative neurologic symptom, remaining two show no improvement of preoperative neurologic deficit. Bypass patency was confirmed by postoperative angiography in all cases except for one. Postoperative follow up studies of the basal CBF and response to the acetazolamide of the CBF showed significant increased CBF activity to acetazolamide in 12 cases(85. 7%) while the basal CBF was essentially unchanged in all cases except for two. In view of these finding, the authors suggest that EC-IC bypass surgery to be considered as an appropritate therapy for improvement of the cerebrovascular reserve capacity in patients with hemodynamic cerebral ischemia, defined using the strict selection criteria employed in this study.

Microvascular Decompression for Hemifacial Spasm

The authors analysed the results of 300 microvascular decompression(MVD) procedures for hemifacial spasm. The follow up period ranged from 6months to 3years. Of these, 70% were women(mean age 54). The vessel most frequently found to compress the facial nerve was the posterior inferior cerebellar artery(43.3%) followed by anterior inferior cerebellar artery(26.7%). For the surgical results, 210 patients(70%) had complete relief of spasm within 3 days after MVD, 65 patients(21.7%) subsequently experienced complete relief, noted in 4 days to 6 months after MVD, ten patients had delayed partial relief and remaining 15 patients showed no improvement. Twelve patients of these 15 unresponsive patients underwent reoperation without beneficial results. Recently the authors have monitored facial elctromyography(EMG) intraoperatively to observe the abnormal late response. There were few cases of permanant major complications, including two cases of ipsilateral hearing loss, ataxia and no operation-related death. These results suggest that MVD is a safe and definite treatment for hemifacial spasm, if performed by experienced surgeon with gentle operative technique, and with intraoperative monitoring such as auditory evoked potential and facial EMG, better surgical results with less complications can be expected.

Responses of Trigeminal Ganglion Neurons to Electrical and Mechanical Stimulation of the Middle Meningeal Artery, Superior Sagittal Sinus and Transverse Sinus in Rats

The intracranial blood vessels of the dura and the pia receive sensory afferent innervations from trigeminal nerve which has been believed to play a critical role in the mediation of vascular headache such as migraine. The purpose of this study was to discover the mechanism by which the interaction between trigeminal ganglion neurons and the function of cerebral blood vessels. Using electrophysiological recording, we studied the responses of trigeminal ganglion neurons to electrical stimulation of middle meningeal artery(MMA), superior sagittal sinus(SS) and transverse sinus(TS) in rats. Sumatriptan is a highly selective agonist for 5-HT1D receptor subtype which mediates vasoconstriction of cerebral blood vessels. We observed responses to electrical stimulation in trigeminal ganglion neurons and meningeal blood flow(MBF) after intravenous injection of sumatriptan. The results were as follows: 1) The presumed mean conduction velocities of the cells activated MMA, SS and TS by electrical stimulation were approximately 1.5, 2.9 and 2.9m/s, respectively. These were presumed to be nociceptive small myelinated or unmylinated sensory fibers. 2) The action potential discharges of trigeminal ganglion neurons on MMA, SS and TS in the experimental control groups were 671+/-39.49, 856+/-63.95 and 494+/-21.54microV, respectrely. The action potential discharges of sumatriptan groups on MMA, SS and TS(393+/-20.10, 562+/-32.26 and 262+/-18.94microV, respectively) were significantly decreased compared to that of the experimental control groups. 3) The mean MBF of normal control group was 63.29+/-7.54ml/100g/min. The mean MBF of the experimental control groups on MMA, SS and TS were 97.13+/-9.91, 104.28+/-12.54 and 91.82+/-6.41ml/100g/min, respectively(p<0.05). MBF of sumatriptan group before stimulation was significantly decreased(compared to normal: 37.17+/-4.76ml/100g /min vs 63.29+/-7.54ml/100g/min). The mean MBF of sumatriptan groups on MMA, SS and TS were 57.11+/-4.48, 66.56+/-6.23 and 56.07+/-5.00ml/100g/min, respectively. Compared to that of the experimental control groups, the MBF of the sumatriptan groups were significantly decreased. In conclusion, the activation of trigeminal sensory afferents by the electrical stimulation of the dural vessel may create vasodilatation and increase cerebral blood flow which may lead to vascular headaches via trigeminal ganglion to brain stem This pathway can be important for understanding the neural mechanism for the development of pharmacological and surgical approach to alleviate vascular headache.

Fractionated Stereotactic Radiation Therapy Using Linear Accolerator in Brain Tumor and Arteriovenous Malformation

With a frame-based system, stereotactic dose of radiation is delivered to the target in one day. The patient is uncomfortable with a frame based system and the staff is forced to produce a treatment plan under time pressure. And then a single dose of radiation is delivered. Our frameless fractionated conformal stereotactic radiotherapy system uses markers, permanently placed in the head. There is more time to prepare and perform the treatment. The point reference system is a frameless system, allowing a separation in time between all of the steps in a stereotactic procedure. And these reference points allow physician precisely to set up the patient again and again. Our system is made to spare normal cells within target volume by fractionating the tumor dose. We have treated 43 patients with multifraction regimen using 6-MV linear accelerator. All patient tolerated the treatment well and no significant complication were seen. Although small in number experienced, this technique seems to be feasible and safe for treating brain tumor and vascular malformation.

Intracranial Intraparenchymal Ostemoa: Case Report

A 55-years-old woman suffered from 5 years of persistent left temporo-parietal headache. She had no feature of raised intracranial pressure. Her headache was only partially relieved by analgesics. There was no history of head trauma nor systemic disease. Plain radiographs of the skull showed a dense round opaque lesion in the left parietal area. Computed-Tomography showed a hyperdense lesion in the same region suggestive of an osteoma. In operation, we found the bony hard mass in the subarachnoid space to be unattached to the dura or the skull. The mass was totally removed, and histologically it was an osteoma.