Seung Heon Cha

Role of ERK in Hydrogen Peroxide-Induced Cell Death of Human Glioma Cells

Oxidative stress is known to induce cell death in a wide variety of cell types, apparently by modulating intracellular signaling pathways. Activation of extracellular signal-regulated kinase (ERK) in oxidative stress remains controversial. In some cellular systems, the ERK activation is associated with protection against oxidative stress, while in other system, the ERK activation is involved in apoptotic cell death. The present study was undertaken to examine the role of ERK activation in H2O2-induced cell death of human glioma (A172) cells. H2O2 resulted in a time- and dose-dependent cell death, which was largely attributed to apoptosis. H2O2 treatment caused marked sustained activation of ERK. The ERK activation and cell death induced by H2O2 was prevented by catalase, the hydrogen peroxide scavenger, and U0126, an inhibitor of ERK upstream kinase MEK1/2. Transient transfection with constitutive active MEK1, an upstream activator of ERK1/2, increased H2O2-induced cell death, whereas transfection with dominant-negative mutants of MEK1 decreased the cell death. The ERK activation and cell death caused by H2O2 was inhibited by antioxidants (N-acetylcysteine and trolox), Ras inhibitor, and suramin. H2O2 produced depolarization of mitochondrial membrane potential and its effect was prevented by catalase and U0126. Taken together, these findings suggest that growth factor receptor/Ras/MEK/ERK signaling pathway plays an active role in mediating H2O2-induced apoptosis of human glioma cells and functions upstream of mitochondria-dependent pathway to initiate the apoptotic signal.

Potential identity of multi-potential cancer stem-like subpopulation after radiation of cultured brain glioma

BackgroundGlioblastoma multiforme (GBM) is the most frequently encountered brain cancer. Although the existence of cancer stem cells in GBM has been previously established, there is little evidence to explain the difference between cancer stem cells and radio-resistant cells in GBM. In an effort to increase our understanding of whether cellular radio-resistance is a characteristic associated with cancer stem cells, we developed a dissociated cell system of subpopulations derived from GBM, and demonstrated radiotherapy resistance therein.ResultsThe radio-resistant cancer cell subpopulations of GBM abundantly express CD133, CD117, CD71, and CD45 surface markers, and these radio-resistant cancer cell subpopulations have the capacity for extensive proliferation, self-renewal, and pluripotency. These radio-resistant cancer subpopulations have been shown to initiate tumorigenesis when transplanted into SCID mouse brains. Moreover, these tumors evidenced highly peculiar nest-like shapes harboring both vascular and cancerous tissue structures, which expressed the blood vessel specific marker, the von Willebrand factor. Accordingly, subpopulations of radio-resistant cells in GBM have been shown to be very similar to hematopoietic stem cells (HSCs) in the circulating blood. This similarity may contribute to increased tumor growth and GBM recurrence.ConclusionThe results of the present study provide further evidence for radio resistant subpopulations of cancer stem cells in GBM. Also, our results will assist in the identification and characterization of cancer stem cell populations in glioma, and will help to improve the therapeutic outcomes of GBM.

Allicin inhibits cell growth and induces apoptosis in U87MG human glioblastoma cells through an ERK-dependent pathway

Allicin, the main flavor compound in garlic, has anti-carcinogenic activities in a range of cancer cells, however, the underlying molecular mechanisms are not completely understood. This study examined the effect of allicin on the cell viability of U87MG human glioma cells along with its molecular mechanisms of induction of cell death. Apoptosis was determined by TUNEL and Hoechst 33258 staining as well as by western blot analysis. Allicin inhibited the cell viability of U87MG human glioma cells in a dose- and time-dependent manner. Allicin-induced inhibition of cell viability was due to apoptosis of cells. The mechanisms of apoptosis were found to involve the mitochondrial pathway of Bcl-2/Bax, the MAPK/ERK signaling pathway and antioxidant enzyme systems. These results suggest that allicin can serve as a novel chemotherapeutic candidate for the treatment of glioblastoma multiforme.

Hemorrhage Rates Associated with Two Methods of Ventriculostomy: External Ventricular Drainage vs. Ventriculoperitoneal Shunt Procedure

Cerebrospinal fluid (CSF) diversion is an essential component of neurosurgical care, but the rates and significance of hemorrhage associated with external ventricular drainage (EVD) and ventriculoperitoneal (VP) shunt procedures have not been well quantified. In this retrospective study, the authors examined the frequencies of hemorrhagic complications associated with EVD and VP shunt procedures, and attempted to identify associated risk factors. The treatment records of 370 EVDs in 276 patients and 102 VP shunts in 96 patients performed between 2008 and 2010 were retrospectively reviewed. Post-insertion computed tomographic (CT) scans were analyzed for any new hemorrhage related to the ventricular catheter. The effects of diagnosis at admission, endovascular treatment, anti-platelet medication, and a concurrent craniotomy operation were included in the analysis conducted to identify risk factors of ventricular catheter-related hemorrhage. Hemorrhage following EVD was detected on CT scans in 76 (20.5%) of the 370 cases. However, symptomatic hemorrhage occurred in only 5 cases (1.4% of all EVDs). VP shunt was associated with a higher incidence of ventricular catheter-related hemorrhage than EVD (hemorrhage rate: 43.1%) and the rate of detectable neurological change was 2.9%. Multivariate logistic-regression analysis of risk factors of EVD-related hemorrhage identified preoperative anti-platelet medication as the only significant factor (odds ratio, 3.583 [95% confidence interval, 1.353 to 9.486]; p = 0.010). Ventriculostomy-related hemorrhagic complications were more common than anticipated, especially for the VP shunt procedure. However, such hemorrhages are rarely large, rarely the cause of neurological deterioration, and rarely require surgical removal. Preoperative anti-platelet medication appears to affect EVD-related hemorrhage development.

C-arm assessment of cervical pedicle screw: screw coaxial fluoroscopy and oblique view.

Study Design. Oblique view and screw coaxial fluoroscopy were used to assess cervical pedicle screw position in human cadaveric spine, results of which were compared with those of direct visual inspection by an anatomist. Objectives. To determine whether clinicians can detect misplaced cervical pedicle screws with accurate sensitivity and specificity using conventional C-arm equipment. Summary of Background Data. In the cervical region, pedicle screws have not been used so popularly as in lumbar or in thoracic regions. The reasons are related to the risk of inserting screw in small pedicle. So far, no method has been studied to assess the position of cervical pedicle screw during the operation. Methods. Ten human cadavers were prepared for this study. Headed and nonheaded pedicle screws were inserted bilaterally from C3–C7. Using C-arm oblique and screw coaxial fluoroscopy, the depth of penetration was recorded in 2-dimension scale (superoinferior and mediolateral direction) by 6 different observers. The vertebrae were all harvested, and the penetration depth was recorded by an anatomist under direct visualization. The accuracy of C-arm measurements was analyzed. The results of nonheaded and headed screws also were compared. Results. A total of 98 pedicle screw positions were finally enrolled into the study. The oblique view can verify screw position with the sensitivity of 86.1% and specificity of 64.5%. Coaxial fluoroscopy had a sensitivity of 89.8% and a specificity of 56.9% in superoinferior direction. Mediolaterally coaxial fluoroscopy had a sensitivity of 70.0% and a specificity of 51.3%. Conclusion. C-arm assessment of pedicle position has acceptable accuracy. With C-arm swing motion of the coaxial fluoroscopy, headed screws were also inspected without any difference as nonheaded screws. Measurements for superoinferior direction showed better sensitivity than those for mediolateral direction, which are supposed to be related to be elliptical shape and thin lateral margin of cervical pedicle.

Neuroendoscopic removal of large choroid plexus cyst: a case report.

Choroid plexus cysts (CPCs) are the most commom neuroepithelial cysts, occuring in more than 50% of some autopsy series. They are typically small and asymptomatic and are discovered incidentally in older patients, usually in the trigone of the lateral ventricle. Symptomatic CPCs (usually exceptionally large, 2-8 cm) are rare. The authors report a case of large symptomatic choroid plexus cyst, located in the trigone of the right lateral ventricle in a 26-yr-old man who presented with headache and vomiting. The patient underwent endoscopic removal through a burr hole placed 3 cm from the midline and just behind the hair line. The histological examination of the cyst wall was consistent with choroid epithelium. Despite of postoperative intraventricular hemorrhage and catheter infection, he discharged home without neurologic deficits. The endoscopic fenestration rather than excision should be considered as the first surgical procedure because the goal of treatment is shrinkage of the cyst until normal cerebrospinal fluid flow is restored.

Crossing Y-stent technique with dual open-cell stents for coiling of wide-necked bifurcation aneurysms

OBJECTIVE Double stenting in a Y-configuration is a promising therapeutic option for wide-necked cerebral aneurysms not amenable to reconstruction with a single stent. We retrospectively evaluated the efficacy and safety of the crossing Y-stent technique for coiling of wide-necked bifurcation aneurysms. METHODS By collecting clinical and radiological data we evaluated from January 2007 through December 2013, 20 wide-necked bifurcation aneurysms. RESULTS Twelve unruptured and eight ruptured aneurysms in 20 patients were treated with crossing Y-stent-assisted coiling. Aneurysm size and neck size ranged from 3.2 to 28.2mm (mean 7.5mm) and from 1.9 to 9.1mm (mean 4.5mm). A Y-configuration was established successfully in all 20 patients. All aneurysms were treated with a pair of Neuroform stents. The immediate angiographic results were total occlusion in 17 aneurysms, residual neck in two, and residual sac in one. Peri-operative morbidity was only 5%. Fifteen of 18 surviving patients underwent follow-up conventional angiography (mean, 10.9 months). The result showed stable occlusion in all 15 aneurysms and asymptomatic in-stent occlusion in one branch artery. At the end of the observation period (mean, 33.5 months), all 12 patients without subarachnoid hemorrhage had excellent clinical outcomes (mRS 0), except one (mRS 2). Of eight patients with subarachnoid hemorrhage, four remained symptom free (mRS 0), while the other four had were dependent or dead (mRS score, 3-6). CONCLUSION In this report on 20 patients, crossing Y-stent technique for coiling of wide-necked bifurcation aneurysms showed a good technical safety and favorable clinical and angiographic outcome.

Recurrent intracranial germinoma along the endoscopic ventriculostomy tract

The authors report a case of a recurrent intracranial germinoma along the site of an endoscopic third ventriculostomy (ETV) after complete local tumor control using 3D conformal radiation therapy. A 13-year-old girl presented with sudden left upward gaze limitation for 4 days. A pineal region tumor and obstructive hydrocephalus were noted on magnetic resonance (MR) images. An ETV and tumor biopsy procedure were performed, which revealed the lesion to be a germinoma. The patients visual symptoms and hydrocephalus disappeared postoperatively. Chemotherapy using cisplatin, etoposide, vincristine, and cyclophosphamide was initiated on postoperative Day 10. An MR image obtained 10 weeks after surgery and 2 weeks after chemotherapy revealed a significant (> 50%) reduction of the lesion. Radiation therapy was administered at 50.4 Gy to the target and 36 Gy to the periphery. Ten months after surgery, an MR image revealed further shrinkage of the tumor mass. One year after surgery, follow-up MR imaging demonstrated a small mass lesion at the entry site of the ETV, measuring 1.0 x 1.4 x 1.5 cm. An operation was performed to remove the small lesion, and pathological findings revealed it to be of the same histology as the primary tumor.

Epidermoid Tumors in the Cerebellopontine Angle Presenting with Trigeminal Neuralgia

OBJECTIVE The purpose of this study is to evaluate the clinical characteristics and surgical outcome of cerebellopontine angle (CPA) epidermoids presenting with trigeminal neuralgia. METHODS Between 1996 and 2004, 10 patients with typical symptoms of trigeminal neuralgia were found to have cerebellopontine angle epidermoids and treated surgically at our hospital. We retrospectively analyzed the clinico-radiological records of the patients. RESULTS Total resection was done in 6 patients (60%). Surgical removal of tumor and microvascular decompression of the trigeminal nerve were performed simultaneously in one case. One patient died due to postoperative aseptic meningitis. The others showed total relief from pain. During follow-up, no patients experienced recurrence of their trigeminal neuralgia (TN). CONCLUSION The clinical features of TN from CPA epidermoids are characterized by symptom onset at a younger age compared to TN from vascular causes. In addition to removal of the tumor, the possibility of vascular compression at the root entry zone of the trigeminal nerve should be kept in mind. If it exists, a microvascular decompression (MVD) should be performed. Recurrence of tumor is rare in both total and subtotal removal cases, but long-term follow-up is required.

Isolated Recurrence of Intracranial Granulocytic Sarcoma Mimicking a Falx Meningioma in Acute Myeloblastic Leukemia

Intracranial granulocytic sarcomas are rare tumors, which are composed of immature granulocytic cells. Although it has been well known that these tumors are associated with acute myeloblastic leukemia (AML), they have been almost always related to bone marrow relapse. However, isolated recurrence of granulocytic sarcoma following complete remission from prior AML is extremely rare, especially in the central nervous system. A 44-year-old male presented with isolated recurrence of granulocytic sarcoma mimicking a falx meningioma two years after complete remission by allogenic peripheral blood stem cell transfusion (PBSCT) in the acute myelomonoblastic leukemia (FAB, M4). Because of depressed mental state and mass effect, total surgical resection was performed. Pathological findings were compatible with the granulocytic sarcoma. There was no evidence of leukemic relapse in the peripheral blood. We suggest that this phenomenon can be explained by the hypothesis that a certain barrier effect such as blood brain barrier might lead to the proliferation of intracranial leukemic cells which metastasized before PBSCT.