• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.353-360
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• 2019

Epilepsy surgery that eliminates the epileptogenic focus or disconnects the epileptic network has the potential to significantly improve seizure control in patients with medically intractable epilepsy. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been an established option for epilepsy surgery since the US Food and Drug Administration cleared the use of MRgLITT in neurosurgery in 2007. MRgLITT is an ablative stereotactic procedure utilizing heat that is converted from laser energy, and the temperature of the tissue is monitored in real-time by MR thermography. Real-time quantitative thermal monitoring enables titration of laser energy for cellular injury, and it also estimates the extent of tissue damage. MRgLITT is applicable for lesion ablation in cases that the epileptogenic foci are localized and/or deep-seated such as in the mesial temporal lobe epilepsy and hypothalamic hamartoma. Seizure-free outcomes after MRgLITT are comparable to those of open surgery in well-selected patients such as those with mesial temporal sclerosis. Particularly in patients with hypothalamic hamartoma. In addition, MRgLITT can also be applied to ablate multiple discrete lesions of focal cortical dysplasia and tuberous sclerosis complex without the need for multiple craniotomies, as well as disconnection surgery such as corpus callosotomy. Careful planning of the target, the optimal trajectory of the laser probe, and the appropriate parameters for energy delivery are paramount to improve the seizure outcome and to reduce the complication caused by the thermal damage to the surrounding critical structures.

• Journal of Chest Surgery
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• v.30 no.2
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• pp.205-208
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• 1997

Cardiac rhabdomyomas are the moil common primary tumor in infancy and childhood and are frequently associated with tuberous sclerosis. Although spontaneous regression of cardiac rhabdomyoma has been reported, prognosis of this tumor associated with subaortic stenosis is still considered to be poor and surgery continues to be indicated. A 4-day-old female was admitted due to tachypnea and cyanosis. Single rhabdomyoma arising from the interventricular septum associated with severe subaortic stcnosls as partially removed under cardiopulmonary bypass. Excised tumor sizc was 0.7$\times$0.9$\times$0.4cm in dimension. The postoperative course was uneventful and the infant discharged on the 14th postoperative day.

• Journal of Yeungnam Medical Science
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• v.27 no.1
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• pp.63-68
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• 2010

Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease that is associated with mutation in the tuberous sclerosis genes, renal angiomyolipomas, lymphatic spread and a remarkable female gender predilection. The pathology of LAM is represented by the proliferation of immature smooth muscle cells in the walls of airways, and venules and lymphatic vessels in the lung. The clinical course of LAM is characterized by progressive dyspnea on exertion, recurrent pneumothorax and collections of chylous fluid. The diagnosis of pulmonary LAM can be made on chest X-ray, a high-resolution CT scan and lung biopsy. We experienced a case of pulmonary lymphangioleiomyomatosis in a 28-years-old female patient who had suffered from progressive dyspnea on exertion, so we report on it along with a brief review of the relevant literature.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.506-518
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• 2021

The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3'-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the three-dimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

• BMB Reports
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• v.55 no.5
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• pp.244-249
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• 2022

Characterized by abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), neointima hyperplasia is a hallmark of vascular restenosis after percutaneous vascular interventions. Vaccinia-related kinase 1 (VRK1) is a stress adaption-associated ser/thr protein kinase that can induce the proliferation of various types of cells. However, the role of VRK1 in the proliferation and migration of VSMCs and neointima hyperplasia after vascular injury remains unknown. We observed increased expression of VRK1 in VSMCs subjected to platelet-derived growth factor (PDGF)-BB by western blotting. Silencing VRK1 by shVrk1 reduced the number of Ki-67-positive VSMCs and attenuated the migration of VSMCs. Mechanistically, we found that relative expression levels of β-catenin and effectors of mTOR complex 1 (mTORC1) such as phospho (p)-mammalian target of rapamycin (mTOR), p-S6, and p-4EBP1 were decreased after silencing VRK1. Restoration of β-catenin expression by SKL2001 and re-activation of mTORC1 by Tuberous sclerosis 1 siRNA (siTsc1) both abolished shVrk1-mediated inhibitory effect on VSMC proliferation and migration. siTsc1 also rescued the reduced expression of β-catenin caused by VRK1 inhibition. Furthermore, mTORC1 re-activation failed to recover the attenuated proliferation and migration of VSMC resulting from shVrk1 after silencing β-catenin. We also found that the vascular expression of VRK1 was increased after injury. VRK1 inactivation in vivo inhibited vascular injury-induced neointima hyperplasia in a β-catenin-dependent manner. These results demonstrate that inhibition of VRK1 can suppress the proliferation and migration of VSMC and neointima hyperplasia after vascular injury via mTORC1/β-catenin pathway.

• Journal of Korean Neurosurgical Society
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• v.29 no.2
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• pp.222-230
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• 2000

Purpose : Resection of the epileptogenic zone in the parietal and occipital lobes may be relevant although only few studies have been reported. Methods : Eight patients with parietal epilepsy and nine patients with occipital epilepsy were included for this study. Preoperatively, all had video-EEG monitoring with extracranial electrodes, MRI, 3D-surface rendering of MRI using Allegro(ISG Technologies Inc., Toronto, Canada), and PET scans. Sixteen patients underwent invasive recording with subdural grid. Eight had parietal resection including the sensory cortex in two. Seven had partial occipital resection. Two underwent total unilateral occipital lobectomy. The extent of the resection was made based mainly on the data of invasive EEG recordings, MRI, and 3D-surface rendering of MRI, not on the intraoperative electrocorticographic findings as usually done. During resection, electrocortical stimulation was performed on the motor cortex and speech area. Results : Out of eight patients with parietal epilepsy, three had sensory aura, two had gustatory aura, and two had visual aura. Six of nine patients with occipital epilepsy had visual auras. All had complex partial seizures with lateralizing signs in 15 patients. Four had quadrantopsia. One had mild right hemiparesis. Abnormality in MRI was noticed in six out of eight parietal epilepsy and in eight out of nine occipital epilepsy. 3D-surface rendering of MRI visualized volumetric abnormality with geometric spatial relationships adjacent to the normal brain, in all of parietal and occipital epilepsy. Surface EEG recording was not reliable in localizing the epileptogenic zone in any patient. The subdural grid electrodes can be implanted on the core of the structural abnormality in 3D-reconstructed brain. Ictal onset zone was localized accurately by subdural grid EEGs in 16 patients. Motor cortex in nine and sensory speech area in two were identified by electrocortical stimulation. Histopathologic findings revealed cortical dysplasia in 10 patients ; tuberous sclerosis was combined in two, hamartoma and ganglioglioma in one each, and subpial gliosis in six. Eleven patients were seizure free at follow-up of 6 months to 37 months(mean 19.7 months) after surgery. Seizures recurred in two and were unchanged in one. Six produced transient sensory loss and one developed hemiparesis and tactile agnosia. One revealed transient apraxia. Two patients with preoperative quadrantopsia developed homonymous hemianopsia. Conclusion : This study suggests that surgical treatment was relevant in parietal and occipital epilepsies with good surgical outcome, without significant neurologic sequelae. Neuroimaging studies including conventional MRI, 3Dsurface rendering of MRI were necessary in identifying the epileptogenic zone. In particular, 3D-surface rendering of MRI was very helpful in presuming the epileptogenic zone in patients with unidentifiable lesion in the conventional MRI, in planning surgical approach to lesions, and also in making a decision of the extent of the epileptogenic zone in patients with identifiable lesion in conventional MRI. Invasive EEG recording with the subdural grid electrodes helped to confirm a core of the epileptogenic zone which was revealed in 3D-surface rendered brain.

• The Journal of the Korean life insurance medical association
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• v.29 no.2
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• pp.29-32
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• 2010

Moyamoya disease (MMD) is a progressive occlusive disease of the cerebral vasculature with particular involvement of the circle of Willis and the arteries that feed it. MMD is one of cerebrovacular accident,which is treated with sugical maeuver in pediatic neurosurgery. Moyamoya (ie, Japanese for "puff of smoke") characterizes the appearance on angiography of abnormal vascular collateral networks that develop adjacent to the stenotic vessels. The steno-occlusive areas are usually bilateral, but unilateral involvement does not exclude the diagnosis. The exact etiology of moyamoya disease is unknown. Some genetic predisposition is apparent because it is familial 10% of the time. The disease may be hereditary and multifactorial. It may occur by itself in a previously healthy individual. However, many disease states have been reported in association with moyamoya disease, including the following: 1) Immunological - Graves disease/thyrotoxicosis 2) Infections - Leptospirosis and tuberculosis 3) Hematologic disorders - Aplastic anemia, Fanconi anemia, sickle cell anemia, and lupus 4) Congenital syndromes - Apert syndrome, Down syndrome, Marfan syndrome, tuberous sclerosis, Turner syndrome, von Recklinghausen disease, and Hirschsprung disease 5) Vascular diseases - Atherosclerotic disease, coarctation of the aorta and fibromuscular dysplasia, 6)cranial trauma, radiation injury, parasellar tumors, and hypertension etc. These associations may not necessarily be causative but do warrant consideration due to impact on treatment.(Mainly neurosurgical operation.) The incidence of moyamoya disease is highest in Japan. The prevalence of MMD is 1 person per 100,000 population. The prevalence and incidence of moyamoya disease in Japan has been reported to be 3.16 cases and 0.35 case per 100,000 people, respectively. With regard to sex, the female-to-male ratio is 1.4:1. A bimodal peak of incidence is noted, with symptoms occurring either in the first decade(5-10yr) or in the third and fourth decades (30-40yr)of life. Mortality rates of moyamoya disease are approximately 10% in adults and 4.3% in children. Death is usually from hemorrhage. In aspect of life insurance, MR is 1700%, EDR is 16 per 1000 persons. Children and adults with moyamoya disease (MMD) may have different clinical presentations. The symptoms and clinical course vary widely from asymptomatic to transient events to severe neurologic deficits. Adults experience hemorrhage more commonly; cerebral ischemic events are more common in children. Children may have hemiparesis, monoparesis, sensory impairment, involuntary movements, headaches, dizziness, or seizures. Mental retardation or persistent neurologic deficits may be present. Adults may have symptoms and signs similar to those in children, but intraventricular, subarachnoid, or intracerebral hemorrhage of sudden onset is more common in adults. Recently increasing diagnosis of MMD with MRI, followed by surgical operation is noted. MMD needs to be considered as the "CI" state now in life insurance fields.

• Clinical and Experimental Pediatrics
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• v.45 no.2
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• pp.232-239
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• 2002

Purpose : Renal cystic diseases comprise a mixed group of heritable, developmental and acquired disorders. Recently the use of imaging modalities such as ultrasonography and radionuclide scanning has increased the detection rate of renal cystic diseases. We studied to review the clinical features and treatment of renal cystic diseases in children. Methods : This study was performed in 95 children with renal cystic diseases in the Department of Pediatrics, Asan Medical Center from October 1989 to June 2001. Results : In 95 patients, there were 55 cases(58.0%) with multicystic dysplastic kidney(MCDK), 19 cases(20.0%) with simple renal cysts, 13 cases(13.7%) with hereditary polycystic kidney diseases( 7 with autosomal recessive type, 5 with autosomal dominant type, 1 with undetermined), 6 cases(6.3%) with renal cysts in tuberous sclerosis and 1 case(1.0%) with medullary cystic disease. All MCDK patients had no renal dysfunction and hypertension during the follow-up period. Three out of 13 with polycystic kidney diseases had progressed to end-stage renal disease during the follow-up period. One case with a simple cyst underwent laparoscopic malsupialization for decompression. Conclusion : Renal cystic diseases have diverse clinicopathologic features and variable prognosis. We emphasize that routine follow-up should be performed to prevent and to detect early treatable complication in renal cystic diseases. Therefore, their natural history and treatment need further investigation and long term follow-up is required.

• Tuberculosis and Respiratory Diseases
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• v.40 no.5
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• pp.519-531
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• 1993

Background: Lymphangioleiomyomatosis(LAM) is a very rare disease occurring in women of reproductive age and leading to progressive respiratory failure despite therapy. But the natural history of this disease is uncertain and although anti-estrogenic agents have been used for more than twenty years, it's efficacy is still in debate. This study was performed to enhance understanding of this fatal disease in Korea by examining clinical, radiological, and pathologic findings of all the previously reported cases of LAM on Korea along with four new cases of LAM whom we report in this paper. Method: Out of twlve cases of LAM previously unpublished and published in domestic papers, two cases whose diagnoses were considered doubtful after review of clinical, radiological, and pathologic findings at "Asian Congress on Lymphangioleiomyomatosis" at Kyoto, Japan in feburary of 1993 were excluded from this study. Six cases which were reported previously and four new cases of LAM whom we report in this paper were analysed for the clinical, radiological, and pathologic characteristics. Results: All ten patients were women with mean age of $33{\pm}7$. The most common symptom was exertional dyspnea and most patients had history of pneumothoraces. Pulmonary function tests showed decreased diffusing capacity. on high resolution computed tomography(HRCT), all the cases had characteristic cysts. Most of the patients did not respond to hormonal therapy. Conclusion: In women of reproductive age, presenting with dyspnea who has a history of pneumothorax, LAM should always be considered as one of the diagnostic possibilities. If suspected, HRCT should be done to look for characteristic cysts and if needed, open lung biopsy should be done to confirm the diagnosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.9
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• pp.1257-1264
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• 2016

Extracts from Artemisia annua $Linn\acute{e}$ (AAE) have various functions (anti-malaria, anti-virus, and anti-oxidant). However, the mechanism of the effects of AAE is not well known. Thus, we determined the apoptotic effects of AAE in AGS human gastric carcinoma cells. In this study, we suggested that AAE may exert cancer cell apoptosis through the Akt/mammalian target of rapamycin (mTOR)/glycogen synthase kinase (GSK)-$3{\beta}$ signal pathway and mitochondria-mediated apoptotic proteins. Activation by Akt phosphorylation resulted in cell proliferation through phosphorylation of tuberous sclerosis complex 2 (TSC2), mTOR, and GSK-$3{\beta}$. Thus, de-phosphorylation of Akt inhibited cell proliferation and induced apoptosis through inhibition of Akt, mTOR, phosphorylation of GSK-$3{\beta}$ at serine9, and control of Bcl-2 family members. Inhibition of GSK-$3{\beta}$ attenuated loss of mitochondrial membrane potential and release of cytochrome C. Bax and pro-apoptotic proteins were activated by their translocation into mitochondria from the cytosol. Translocation of Bax induced outer membrane transmission and generated apoptosis through cytochrome C release and caspase activity. We also measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase assay, Hoechst 33342 staining, Annexin V-PI staining, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide staining, and Western blotting. Accordingly, our study showed that AAE treatment to AGS cells resulted in inhibition of Akt, TSC2, GSK-$3{\beta}$-phosphorylated, Bim, Bcl-2, and pro-caspase 3 as well as activation of Bax and Bak expression. These results indicate that AAE induced apoptosis via a mitochondrial event through regulation of the Akt/mTOR/GSK-$3{\beta}$ signaling pathways.