• Nutrition Research and Practice
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• 제4권6호
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• pp.455-461
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• 2010

The tumor microenvironment, particularly sufficient nutrition and oxygen supply, is important for tumor cell survival. Nutrition deprivation causes cancer cell death. Since apoptosis is a major mechanism of neuronal loss, we explored neuronal apoptosis in various microenvironment conditions employing neuroblastoma (NB) cells. To investigate the effects of tumor malignancy and differentiation on apoptosis, the cells were exposed to poor microenvironments characterized as serum-free, low-glucose, and hypoxia. Incubation of the cells in serum-free and low-glucose environments significantly increased apoptosis in less malignant and more differentiated N-type IMR32 cells, whereas more malignant and less differentiated I-type BE(2)C cells were not affected by those treatments. In contrast, hypoxia (1 % $O_2$) did not affect apoptosis despite cell malignancy. It is suggested that DLK1 constitutes an important stem cell pathway for regulating self-renewal, clonogenicity, and tumorigenicity. This raises questions about the role of DLK1 in the cellular resistance of cancer cells under poor microenvironments, which cancer cells normally encounter. In the present study, DLK1 overexpression resulted in marked protection from apoptosis induced by nutrient deprivation. This in vitro model demonstrated that increasing severity of nutrition deprivation and knock-down of DLK1 caused greater apoptotic death, which could be a useful strategy for targeted therapies in fighting NB as well as for evaluating how nutrient deprived cells respond to therapeutic manipulation.

• 대한한의학회지
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• 제26권4호
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• pp.74-86
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• 2005

Background: There are increasing neuro-degenerative disorders with aging. Paeoniae Radix(PR) possesses various pharmacological effects such as sedative, analgesic, anti-inflammatory, anti-stress and neuro-protective actions. Also antiaging and anti-cancer effects of PR were reported. Our purpose was to investigate whether PR is useful on the treatment of Parkinson's disease, one of the neuro-degenerative disorders. Objective: We investigated whether Paeonia Radix possesses a protective effect against 1-methyl-4 phenylpyridine(MPP+)-induced cytotoxicity in neuronal cells. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, flow cytometry, DNA fragmentation assay, reverse transcription-polymerase chain reaction(RT-PCR), and Western blotting were performed on SK-N-MC neuroblastoma cells. Results: Cells treated with MPP+ exhibited several apoptotic features, while cells pre-treated with Paeonia Radix prior to MPP+ exposure showed s decrease in the occurrence of apoptotic features. Conclusions: These results suggest that Paeonia Radix may exert a protective effect against MPP+-induced apoptosis in SK-N-MC neuroblastoma cells.

• The Korean Journal of Physiology and Pharmacology
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• 제13권4호
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• pp.281-285
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• 2009

Rotenone, a mitochondrial complex I inhibitor, can induce the pathological features of Parkinson's disease (PD). In the present study, naringin, a grapefruit flavonoid, inhibited rotenone-induced cell death in human neuroblastoma SH-SY5Y cells. We assessed cell death and apoptosis by measuring mitogen-activated protein kinase (MAPKs) and caspase (CASPs) activities and by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Naringin also blocked rotenone-induced phosphorylation of Jun NH2-terminal protein kinase (JNK) and P38, and prevented changes in B-cell CLL/lymphoma 2 (BCL2) and BCL2-associated X protein (BAX) expression levels. In addition, naringin reduced the enzyme activity of caspase 3 and cleavages of caspase 9, poly (ADP-ribose) polymerase (PARP), and caspase 3. These results suggest that naringin has a neuroprotective effect on rotenone-induced cell death in human neuroblastoma SH-SY5Y cells.

• 대한본초학회지
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• 제21권4호
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• pp.77-84
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• 2006

Objectives : To evaluate the neuroprotective effects of modified Bo-Yang-Hwan-O-Tang (BHT), we investigated the neuronal death protection effects to oxidative damages in N2a neuroblastoma cells. Methods : To study the cytotoxic effect of BHT on N2a neuronal cells, the cell viability was determined by MTT assay. To investigate the neuronal death protection of BHT, N2a neuronal cells were induced oxidative damages by H2O2, and assayed the cell viability and DNA fragmentation. We also investigated DPPH free radical scavenging effects of BHT by tube test. Results : In MTT assay, $500{\mu}g/ml$ of BHT was not showed cytotoxic effect on N2a neuronal cells. BHT protected N2a neuronal cells from H2O2-induced cell death in a dose-dependent manner. BHT also protected N2a neuronal cells from H2O2-induced DNA fragmentation. BHT scavenged DPPH free radicals in a dose-dependent manner. Conclusion : These data suggest that BHT may have strong anti-oxidant effects through the free radical scavenging and neuroprotective effects in neuronal cells.

• Clinical and Experimental Pediatrics
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• 제55권4호
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• pp.115-120
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• 2012

Although high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) have improved the prognosis for patients with high-risk neuroblastoma (NB), event-free survival rates remain in the range of 30 to 40%, which is unsatisfactory. To further improve outcomes, several clinical trials, including tandem HDCT/autoSCT, high-dose $^{131}I$-metaiodobenzylguanidine treatment, and immunotherapy with NB specific antibody, have been undertaken and pilot studies have reported encouraging results. Nonetheless, about half of high-risk NB patients still experience treatment failure and have no realistic chance for cure with conventional treatment options alone after relapse. Therefore, a new modality of treatment is warranted for these patients. In recent years, several groups of investigators have examined the feasibility and effectiveness of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) for the treatment of relapsed/progressed NB. Although a graft-versus-tumor effect has not yet been convincingly demonstrated in the setting of relapsed NB, the strategy of employing RI alloSCT has provided hope that treatment-related mortality will be reduced and a therapeutic benefit will emerge. However, alloSCT for NB is still investigational and there remain many issues to be elucidated in many areas. At present, alloSCT is reserved for specific clinical trials testing the immunomodulatory effect against NB.

• Molecular & Cellular Toxicology
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• 제2권1호
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• pp.60-66
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• 2006

Methylmercury (MeHg), one of the heavy metal compounds, can cause severe damage to the central nervous system in humans. Many reports have shown that MeHg is poisonous to human body through contaminated foods and has released into the environment. Despite many studies on the pathogenesis of MeHg-induced central neuropathy, no useful mechanism of toxicity has been established so far. This study, using of suppression subtractive hybridization (SSH) method, was peformed to identify differentially expressed genes by MeHg in SH-SY5Y human neuroblastoma cell line. We prepared to total RNA from SH-SY5Y cells treated with solvent (DMSO) and $6.25\;{\mu}M\;(IC_{50})$ MeHg and performed forward and reverse SSH. Differentially expressed cDNA clones were screened by dot blot, sequenced and confirmed that individual clones indeed represent differentially expressed genes with real time RT-PCR. These sequences were identified by BLAST homology search to known genes or expressed sequence tags (ESTs). Analysis of these sequences may provide an insight into the biological effects of MeHg in the pathogenesis of neurodegenerative disease and a possibility to develop more efficient and exact monitoring system of heavy metals as ubiquitous environmental pollutants.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5391-5397
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• 2012

Background: Neuroblastoma (NB), like most human cancers, is characterized by genomic instability, manifested at the chromosomal level as allelic gain, loss or rearrangement. Genetics methods, as well as conventional and molecular cytogenetics may provide valuable clues for the identification of target loci and successful search for major genes in neuroblastoma. We aimed to investigate AURKA and MYCN gene rearrangements and the chromosomal aberrations (CAs) to determine the prognosis of neuroblastoma. Methods: We performed cytogenetic analysis by G-banding in 25 cases [11 girls (44%) and 14 boys (66%)] and in 25 controls. Fluorescence in situ hybridization (FISH) with AURKA and MYCN gene probes was also used on interphase nuclei to screen for alterations. Results: Some 18.4% of patient cells exhibited CAs., with a significant difference between patient and control groups in the frequencies (P<0.0001). Some 72% of the cells had structural aberrations, and only 28% had numerical chnages in patients. Structural aberrations consisted of deletions, translocations, breaks and fragility in various chromosomes, 84% and 52% of the patients having deletions and translocations, respectively. Among these expressed CAs, there was a higher frequency at 1q21, 1q32, 2q21, 2q31, 2p24, 4q31, 9q11, 9q22, 13q14, 14q11.2, 14q24, and 15q22 in patients. 32% of the patients had chromosome breaks, most frequently in chromosomes 1, 2, 3, 4, 5, 8, 9, 11, 12, 19 and X. The number of cells with breaks and the genomic damage frequencies were higher in patients (p<0.001). Aneuploidies in chromosomes X, 22, 3, 17 and 18 were most frequently observed. Numerical chromosome abnormalities were distinctive in 10.7% of sex chromosomes. Fragile sites were observed in 16% of our patients. Conclusion: Our data confirmed that there is a close correlation between amplification of the two genes, amplification of MYCN possibly contributing significantly to the oncogenic properties of AURKA. The high frequencies of chromosomal aberrations and amplifications of AURKA and MYCN genes indicate prognostic value in children with neuroblastomas and may point to contributing factors in their development.

• 대한세포병리학회지
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• 제4권1호
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• pp.45-51
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• 1993

말초성 신경아세포종은 예후가 나쁘고 희귀한 종양으로 이 종양의 세침흡인 세포학적 소견에 관한 보고는 세계 문헌상 1988년 Neuhold에 의해 처음 기술된 1례가 있을 따름이다. 최근 저자들은 30세 여자의 우측 상박의 연부조직 종괴로 부터 세침흡인 세포 검사를 시행하여 진단된 말초성 신경아세포종을 경험하여 그 세침흡인 세포학적 소견을 기술하는 바이다. 환자는 1개월전 부터 우측 상박에 서서히 자라는 종괴를 주소로 내원하였다. 우측 상박 X-선 및 초음파 촬영술에서 주위와 잘 경계지어진 방추형의 연부조직 종괴가 관찰되었고 주변조직으로 침윤하는 소견은 관찰할 수 없었으며 상완골은 정상이었다. 종괴의 세침흡인 도말은 세포밀도가 매우 높았고 작고 둥근 세포들이 뭉쳐있거나 산재되어 있었다. 세포간의 크기나 모양의 차이는 아주 미약하였고 유사분열은 거의 관찰되지 않았다. 종양세포들의 집단은 간혹 모세혈관을 중심으로 뭉치거나, 로제트 형태를 보이며 그 세포질은 가늘고 긴 돌기를 보였다. 핵은 뚜렷한 핵막과 미세하게 뭉친 염색질 및 작고 뚜렷한 핵 소체를 갖고 있었다. 이상의 소견은 작고 둥근 세포로 된 악성 종양 중 말초성 신경아세포종에 매우 합당하였으나 골외 Ewing 육종과의 감별은 불가능하였다. 단순 절제술이 시행되었고 종양은 조직학적으로 말초성 신경아세포종임이 확인되었다.

• 대한방사선협회지
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• 제25권1호
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• pp.85.2-85.2
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• 1999

• 대한두경부종양학회:학술대회논문집
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• 대한두경부종양학회 2007년도 추계학술대회 논문집
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• pp.209-209
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• 2007