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ABSTRACT: Medulloblastoma (MBL), the most common malignant pediatric brain tumor, is incurable in about one-third of patients and can lead to long-term disabilities despite current multimodal treatments. The purpose of this study was to demonstrate in vitro biological effects of neurotrophins-3 (NT-3) on MBL cells and to evaluate the growth-inhibitory effect of neurotrophin-3 (NT-3)-secreting stem cells on tumor cells. We confirmed by western blotting that D283-MED cells express tyrosine kinase C, a specific receptor for NT-3. Analyzing the biological effects of NT-3 on MBL cells, we evaluated autophagy, apoptosis, senescence, and differentiation of tumor cells with NT-3. The NT-3 induced a concentration-dependent increase in apoptosis in the tumor cell line (P < 0.001). The high concentrations of NT-3 increased the expression of class III β-tubulin (P < 0.001) and decreased the expression of Nestin (P < 0.05). NT-3-secreting stem cells were produced by nucleofecting pIRES2.EGFP-NT3 into human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and their tropic property toward MBL cells was confirmed by migration assay. Double-layered co-culture experiments with the NT-3-secreting hAT-MSCs and D283-MED MBL cells were performed, and NT-3-induced cell death was studied by 3-(4,5-dimethylathiazol-2-yl)-2,5-dephenyl-tetrazolium bromide (MTT) assay. Consequently, the high concentrations of NT-3-secreting hAT-MSCs significantly (P < 0.05) increased the death of D283-MED cells in vitro. The present study demonstrated that both apoptotic cell death and neuronal differentiation of tumor cells were the mechanisms of growth-inhibitory effect of NT-3-secreting hAT-MSCs on MBL cell line.
Journal of Neuro-Oncology 07/2011; 106(1):89-98. · 3.21 Impact Factor
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Kyung-A Lee,
Kwang-Min Sohn, Seung-Hee Cho,
Hyokkee Hwang,
Sun Woo Kim,
Hong-Hee Won,
Hee-Jin Kim,
Min Ji Kim,
Sang Sun Cho,
Jun Hee Park,
Jong-Won Kim
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ABSTRACT: It has been suggested that the haplotypic relationship between microsatellite markers and single nucleotide polymorphisms (SNPs) is of considerable importance, as microsatellite markers can potentially be incorporated into haplotypes containing SNPs to increase marker density across a region of interest. However, SNPs and microsatellite markers have different mutation rates and durations, and it is conceivable that the linkage disequilibrium (LD) patterns between the genetic markers may considerably differ. We assessed the LD patterns using 1,661 SNPs and 65 microsatellite markers along chromosome 22 and investigated whether common patterns of LD between the two genetic markers are deduced from the results. The results demonstrated that the patterns of LD among microsatellite markers varied considerably and the LD runs of SNPs and microsatellite markers showed distinct patterns. Microsatellite markers have a much higher mutation rate and the evolution of microsatellite markers is a more complex process which has distinct mutation properties from those of SNPs. We consider that these might contribute to the different LD patterns between the two genetic markers. Therefore, it would seem inadvisable to make assumptions about persistence of LD across even a relatively small genetic distance among microsatellite markers and to construct mixed marker haplotypes/LD maps employing microsatellite markers.
Journal of Korean Medical Science 07/2007; 22(3):425-30. · 0.99 Impact Factor
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ABSTRACT: Chromosome 8p21-12 has been reported to be a susceptibility locus for schizophrenia based on genome-wide linkage scans. After neuregulin 1 (NRG1) was identified as a positional candidate gene for schizophrenia in this locus, several independent association studies have reported controversial results. To determine whether genetic variations in this locus are associated with schizophrenia in the Korean population, we investigated multiplex families and unrelated patients using linkage and association analyses. Seven microsatellite markers in 8p21-12 were genotyped for 40 families with schizophrenia, and a non-parametric linkage analysis was applied. The association study was performed with 242 unrelated schizophrenia patients and the same number of normal controls for three single nucleotide polymorphisms (SNPs), two microsatellite markers and their haplotypes. A significant linkage signal was observed on D8S1769, which is located 352 kb upstream of the 5' end of the first exon of NRG1 for two ("narrow" and "narrow with auditory hallucination (AH)") of the three adopted phenotype classes. In the association study, the G allele of SNP8NRG241930 was significantly in excess in the subgroup of patients with AHs. We also found haplotypes which were associated with schizophrenia with a protective effect. This study provides additional suggestive evidence for both the linkage and association of genetic variations on 8p12, a locus of NRG1, with schizophrenia. NRG1 might either play a role in the predisposition to schizophrenia or be in linkage disequilibrium (LD) with a causal locus of this illness.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 05/2006; 141B(3):281-6. · 3.70 Impact Factor
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ABSTRACT: Graves' disease (GD) is a complex autoimmune thyroid disease with a strong genetic component. The cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene, which encodes a negative regulator of the T-lymphocyte immune response, has been reported to be associated and/or linked to GD. Therefore, in order to determine the contribution of CTLA-4 in GD in Koreans, we genotyped the five single nucleotide Polymorphisms (SNPs) of the CTLA-4 gene, including +49, CT60, JO31, JO30, and JO27-1 in Korean spatients with GD and healthy controls. Two hundred seventy-eight Korean patients with GD from the Thyroid Clinic and 472 healthy controls from the Health Screening Center of Samsung Medical Center were enrolled in this study. The +49A/G polymorphism of the CTLA-4 gene exon 1 was sequenced directly and the genotyping of the remaining 4 SNPs was accomplished using a Snapshot. In addition, the association of haplotypes with a combination of the above markers was also examined in 278 Korean patients with GD and 472 controls. The results showed that there was no significant positive association between any individual SNP or haplotype comprising of the four 3 untranslated region (UTR) SNPs (CT60, JO31, JO30, and JO27-1) and GD. These data provide little support for CTLA-4 to play a role in the genetic predisposition to GD in Koreans. However, it will be necessary to validate or replicate this association in other independent large-size ethnic groups.
Thyroid 04/2006; 16(3):237-41. · 4.79 Impact Factor
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Eun Young Cho,
Yu Sang Lee,
Kyeong Sook Choi,
Yong Lee Jang, Seung Hee Cho,
Hyun Ok Jeun,
Jong Won Kim,
Sue Kyung,
M D Hong,
Correspondence : Kyung,
Sue Hong
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ABSTRACT: Objectives Chromosome 8p21-12 has been identified as a susceptibility locus for schizophrenia based on several genomewide linkage scans with Caucasian families. The purpose of this study is to investigate the linkage of this locus to schizophrenia i n Korean families. Materials and Methods We recruited ninety-one family members from twenty-seven multiplex schizophrenia families. Fifty-nine of them were affected individuals. Seven microsatellite markers of this region with 3cM intervals were genotyped. Non-parametric linkage analysis was performed by evaluating the levels of allele sharing between the affected relative pairs. Results In the multi-point analysis, all the points tested within this area showed positive but non-significant non-parametric lod (NPL) scores with the peak occurring between D8S1820 and D8S1769. In the single point analysis, statistically significant allele sharing was observed at D8S1769 (NPL=1.65, p=0.049). Higher levels of NPL scores (the highest single point NPL=1.98, p=0.025) were observed when the same analyses were applied to a subgroup of families in which all of the affected individuals showed auditory hallucination. Conclusions These findings support the previous evidence from Caucasian families for a locus predisposing to schizophrenia at 8p21-12. Further studies designed to screen positional candidate genes and their SNPs at this locus are warranted, in order to identify the specific causative genetic variation of schizophrenia.
