• 대한한방내과학회지
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• 제35권3호
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• pp.298-308
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• 2014

Objectives: In this study we made an effort to investigate the protective effect of SSMT on the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced cytotoxicity of SH-SY5Y cells. Methods: The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MMT) assay. The fluorescence intensity was measured by using a dye and then with propidium iodide (PI) DNA flow cytometry analysis of the effects on the cell cycle of the SH-SY5Y cells and were used to measure the fluorescence of intracellular reactive oxygen species generation by MPTP. Results: Pretreatment of SSMT significantly suppressed MPTP-induced cytotoxicity, which was revealed as apoptosis characterized by the reduction of cell viability, the increase of ROS production, and the loss of mitochondrial membrane potential in SH-SY5Y cells. Conclusions: These findings suggest that SSMT exerts neuroprotective effects on human neuroblastoma SH-SY5Y cells by MPTP-induced dopaminergic neurodegeneration.

• 대한한의학회지
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• 제25권2호
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• pp.138-150
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• 2004

Objectives : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. Although a variety of oriental prescriptions, including Sesim-tang, have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. The present study investigated the effects of Sesim-tang on apoptotic cell death induced by CT105 (carboxy terminal 105 amino acid peptide fragment of APP) overexpression in SK-N-SH neuroblastoma cell lines. Methods: We studied the regenerative and inhibitory effects on Alzheimer's disease in CT105-induced SK-N-SH cell lines by Sesim-tang water extract. We examined for cell morphological pattern, DNA fragmentation, LDH activity assay, zymography assay, and immunohistochemistric analysis. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. Results: Findings from our experiments have shown that Sesim-tang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in the cell line. In addition, pretreatment with Sesim-tang ($>50\mu\textrm{g}/ml$ for 12 hours) partially prevented CT105-induced cytotoxicity in SK-N-SH cell lines. SK-N-SH cell lines overexpressed with CT105 exhibited remarkable apoptotic cell damage. Based on morphological observations by phase-contrast microscope and LDH activity measurements in the culture media, the CT105-induced cell death was significantly inhibited by Sesim-tang water extract. Sesim-tang was found to reduce the expression of APP and caspase-3 induced by CT105 in SK-N-SH cell lines and in rat hippocampus. Conclusions: As the result of this study, in the Sesim-tang group, apoptosis in the nervous system is inhibited, the repair against the degeneration of SK-N-SH cell lines by CT105 expression is promoted. Hence, Sesim-tang may be beneficial for the treatment of AD.

• Advances in pediatric surgery
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• 제5권2호
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• pp.146-151
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• 1999

Neurocristopathy originates from aberrant development of the neural crest by genetic abnormality. Dysgenetic or neoplastic neurocristopathy mayor may not combine at one or more organs. Congenital central hypoventilation syndrome (Ondine's curse) is characterized by the respiratory depression during sleep, although showing normal ventilation while awake, because the baby does not responde to hypercapnea or hypoxia. One newborn girl, full-term, 3,020 g of birth weight with neurocristopathy is reported. It showed poor respiration at birth, and temporary Improvement with oxygen and respiratory stimulations. Abdomen was distended. Abdominal x-ray revealed small bowel obstruction and calcified opacity at the right lower quadrant. Because transitional zone was noticed at the distal jejunum during laparotomy, jejunostomy was performed. Several times trial of extubation have failed becaused of the repeated apneas. Brain sonography and echocardiogram were normal. The patient died of sepsis at 37 days of age. Para-aortic ganglioneuroblastoma was found at autopsy. In this case, congenital central hypoventilation syndrome, Hirschsprung's disease and congenital ganglioneuroblastoma are combined as a neurocristopathy.

• Advances in pediatric surgery
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• 제15권1호
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• pp.38-43
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• 2009

With the widespread use of the obstetrical ultrasound, identification of a fetal suprarenal mass becomes more common. Most of these masses prove to be congenital neuroblastomas (CNB) postnatally. However, the diagnosis is often confused with other benign lesions and the post-natal management remains controversial. The medical records of 13 patients that underwent primary surgical excision for an antenatally detected adrenal CNB, between January 1995 and April 2009, were reviewed retrospectively. The clinical, radiological, surgical, and pathological data on the suprarenal mass were collected. Staging evaluation was performed after histological confirmation of the CNB. Most of the CNBs were stage I (N=11), with 1 stage IV and 1 stage IV-S. Four patients (3 stage I and 1 stage IV-S) had N-myc gene amplification. The stage I patients were cured by surgery alone, and stage IV patients underwent 9 cycles of adjuvant chemotherapy and currently have no evidence of disease after 39 months of follow-up. The patient with stage IV-S is currently receiving chemotherapy. There were no post-operative complications. For early diagnosis and treatment, surgical excision should be considered as the primary therapy for an adrenal CNB detected before birth. The surgery can be safely performed during the neonatal period and provides a cure in most cases. Surgical diagnosis and treatment of CNB is recommended in neonatal period.

• Advances in pediatric surgery
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• 제15권1호
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• pp.27-37
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• 2009

Neuroblastoma is the most common extracranial solid tumor in children. We retrospectively analyzed the results of neuroblastoma treatment of 191 patients (116 males and 75 females) treated between January 1986 and December 2005 at the Department of Pediatric Surgery and the Department of Pediatrics, Seoul National University Children's Hospital. The mean age at diagnosis was 3.1 years (0.1 yrs - 13.5 yrs). Forty-seven patients were under 1 year of age. The mean follow-up period was 57.3 months (24 days - 19.1 yrs). Patients were classified into two groups according to the completeness of resection of the primary tumor; (1) gross total resection (GTR) and (2) incomplete resection (IR). The number of patients in stages I, II, III, IV, IV-S were 17 (8.9 %), 12 (6.3 %), 43 (22.5 %), 114 (59.7 %), 4 (2.1 %), respectively. GTR was achieved in 120 patients and IR in 71 (22 stage III, 47 stage IV, 1 stage IV-S, 1 brain). Overall survival (OS) was 65.2 % and event-free survival (EFS) was 48.6 %. EFS were 100 %, 75 %, 66.8 %, 31.3 %, 75 % at stage I, II, III, IV, IV-S, respectively. There was no significant difference in EFS according to the completeness of resection. EFS was improved in GTR group (p=ns) of stage III, but by contrast, stage IV patients showed worse EFS in GTR group. EFS was improved significantly after the introduction of autologous stem cell transplantation (ASCT) (58.1% vs. 40.6%, p=.029). The EFS improved significantly after the introduction of ASCT in IR group (p=.009) rather than GTR group (p=ns). The EFS of the patients under 1 year of age (N=47) was better than the patients over 1 year of age (N=144) significantly (75.5 % vs. 39.4 %, p=.0034). The prognosis of neuroblastoma was related to the INSS stage and age at diagnosis. The survival of IR group significantly improved after ASCT.

• 대한한방내과학회지
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• 제25권3호
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• pp.482-491
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• 2004

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD may be the biggest problem in public health service. Although a variety of oriental therapies in the study of Jimitang have been traditionally utilized for the treatment of AD, their pharmacological effects and active mechanisms have not been fully elucidated. This study in an investigation of effects of Jimitang on apoptotic cell death induced by CT105 overexpression in SK-N-SH neuroblastoma cell lines. DNA fragmentation, neurite outgrowth assay and LDH activity assay were examined. The regeneratory and inhibitory effects on Alzheimer's disease in pCT105-induced neuroblastoma cell lines by Jimitang water extract were examined. Findings from these experiments have shown that Jimitang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in cell lines. In addition, pretreatment of $Jimitang(>50\;{\mu}g/mL\;for\;12\;hours)$ partially prevented CT(105)-induced cytotoxicity in SK-N-SH cell lines, and were inhibited by pretreatment. $Jimitang(>50\;{\mu}g/mL\;for\;12\;hours)$ repaired CT(105)-induced neurite outgrowth when SK-N-SH cell lines were transfected with CT(105). Results of this study show that. in the Jimitang group, the apoptosis in the nervous system in inhibited, the repair against the degerneration of neuroblastoma cells by CT105 expression is promoted. In addition, Jimitang was found to inhibit DNA fragmentation induced by CT105 overexpression, and promote neurite outgrowth. These findings suggest that Jimitang is beneficial for the treatment of AD.

• Advances in pediatric surgery
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• 제11권2호
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• pp.99-106
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• 2005

Neuroblastoma treatment remains challenging, but treatment has become more effective due to the establishment of clinical and biological variables that determine prognostic risks. Initially, stage and age were the prime determinants of survival used in clinical practice. Risk-based therapy currently is the hallmark of neuroblastoma treatment. This study reviews one center's experience with the management of neuroblastoma. Sixty-three patients with neuroblastoma were treated from 1989 to 2003. All patients were graded according to the International Neuroblastoma Staging System (INSS) at diagnosis. There were 37 boys and 26 girls. The median age was 2.14 years (range, 33 days-10.2years). The primary site was the adrenal gland in 47, dumbbell shape extending into spinal canal in 6, retroperitoneum in 5, mediastinum in 3, and other sites in 2. The probability of 5-year overall survival (OS) and event free survival (EFS) were 46.7 % and 44.2 % by Kaplan-Meier method. According to INSS, there were stage 1 in 2 cases, stage 2 in 5, stage 3 in 12, stage 4 in 42, and stage 4s in 2. There were statistically significant differences in the survival rates between patients with stage1, 2 and stage 3, 4(P<0.05). For the stage 3 and 4, the extents of surgical resection, determined from the operative records and pathologies, were complete resection in 17 cases, minimal residual in 15, and partial resection 11, and the 5-year OS rate was 57.8, 51.4, and 13.6 %, respectively. There is a trend toward higher OS with more complete resection (P<0.05). We conclude that age and stage at diagnosis are prognostic factors, and complete excision of the primary tumor can provide better prognosis for patients with stage 3 and 4 neuroblastoma.

• Advances in pediatric surgery
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• 제8권2호
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• pp.101-106
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• 2002

The antiangiogenic effects of novel agent KJ3, Betulinic acid, and Fumagillin on the neovascularization were studied by examining ultrastructural alterations in the vasculature of synthetic gelform and mouse neuroblastoma C1300. Small pieces of gelform with 0.4% agar were introduced subcutaneously (s.c.) in 7 week old male CH3/HeJ mice. After the $LD_{50}s$ were determined by FACS analysis, a third of $LD_{50}$ of three drugs were injected either locally or intraperitoneally every other day for 14 days. A/J mice were inoculated s.c. with the C1300 neuroblastoma cell line, then either saline or three drugs were injected in the same manner. The antiangiogenic effects of three drugs were studied by measuring the histologic changes in tumors, and immunostaining for CD34, VIII/vWF, CD105, and thymidine phosphorylase. In the drug treated groups, the number of vessels in gelform experiments and C1300 neuroblastoma experiments were lower than the corresponding values in the control. The histologic findings were significantly different in drug treated groups on day 7, but these were not significant on day 14. These results imply that antiangiogenic agents were effective when the tumor burden is minimal.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제22권4호
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• pp.302-306
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• 2011

Objectives : To investigate the cognitive functions of pediatric cancer patients and to test the hypotheses that the impairment of processing speed and working memory are more prevalent in children with medulloblastoma (MBL) compared to children with neuroblastoma (NBL). Methods : We gave the Korean version of the Wechsler Intelligent Scale for Children-III to 21 children with MBL and 24 children with NBL during outpatient follow-up after the treatment was completed. Results : Children with MBL showed below average performance across most of the sub-tests. The full scale IQ, verbal IQ, and performance IQ of children with MBL were significantly lower than those of children with NBL. There were significant differences between two groups in coding and Digit Span subtest scores. Children with MBL performed especially poorly in the coding subtest. Conclusion : These findings support previous reports of generally low IQ and the dysfunction of processing speed and working memory among children with MBL, a kind of central nervous system tumor. Further investigation is needed to determine how the deficit of processing speed and working memory affect neurocognitive development and general intelligent functions.

• 동의생리병리학회지
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• 제20권6호
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• pp.1548-1555
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• 2006

Bujeonghangam-tang(BHT) has been used as an anticancer agent in oriental medicine, but the mechanism by which it induces cell death in cancer cells is still unclear. To investigate cell death mechanism by BHT in cancer cells, the activities of apoptosis signaling pathway were tested in human neuroblastoma cell line LAN5. Viability of LAN5 cells was markedly decreased by treatment of the water extract of BHT in a dose-dependent manner. BHT induced cell death was confirmed as apoptosis characterized by chromatin condensation. We tested whether the water extract of BHT affects the anti-apoptotic protein such as Bcl-2 and Bcl-XL, and the pro-apoptotic protein such as Bax. Both Bcl-2 and Bcl-XL were gradually decreased but Bas was increased in a time-dependent manner after the addition of the water extract of BHT. Cleavage of Bid by activation of caspase-8 protease was also observed in LAN-5 cells by the treatment of the water extract of BHT. Taken together, these results suggest that the water extract of BHT exerts anti-cancer effects on human neuroblastoma LAN-5 cells by inducing the apoptotic death via down-regulation of anti-apoptotic proteins such as Bcl-2 and Bcl-XL, up-regulation of pro-apoptotic protein such as Bax, and activation of intrinsic caspase cascades.