• Journal of Gastric Cancer
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• v.3 no.4
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• pp.214-220
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• 2003

Purpose: The aim of this study was to investigate the frequency of loss of heterozygosity and the microsatellite instability at multiple tumor suppressor gene loci in gastric adenocarcinomas. Materials and Methods: Loss of heterozygosity and the microsatellite instability at several tumor suppressor gene loci were analyzed in 29 primary gastric carcinomas by using microdissection and the polymerase chain reaction. Results: Twenty-three ($79\%$) of the 29 cases demonstrated loss of heterozygosity at one or more loci. The frequency of loss of heterozygosity at the p53 locus was the highest ($63\%$) and those at the VHL, APC, p16, Rb, MEN1, BRCA1, DPC4, 3p21, and 16p13 region were $41\%,\;36\%,\;19\%,\;29\%,\;33\%,\;26\%,\;21\%,\;32\%,\;and\;11\%$, respectively. Compared with histological type, loss of heterozygosity was more common in diffuse-type gastric cancer (P<0.01). Interestingly, 9 of 10 tumors with allelic deletion at the p53 locus showed loss of heterozygosity at other tumor suppressor gene loci. The microsatellite instability was also detected in 6 ($20\%$) of the 29 cases at one or more loci. Conclusion: These data suggest that frequent loss of heterozygosity and the microsatellite instability at multiple tumor suppressor genes might be required for the development and the progression of gastric carcinomas and that p53 allelic loss may be the most frequent event in the development of gastric carcinomas.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.495-503
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• 2008

Background: Epigenetic alterations in certain genes are now known as at least important as genetic mutation in pathogenesis of cancer. Especially abnormal hypermethylation in or near promoter region of tumor suppressor genes (TSGs) are known to result in gene silencing and loss of gene function eventually. The authors tried to search for new lung cancer-specific TSGs which have CpG islands and HpaII sites, and are thought to be involved in carcinogenesis by epigenetic mechanism. Methods: Tumor tissue and corresponding adjacent normal tissue were obtained from 10 patients who diagnosed with non small cell lung cancer (NSCLC) and underwent surgery in Konyang university hospital in 2005. Methylation profiles of promoter region of 21 genes in tumor tissue & non-tumor tissue were examined with HpaII-MspI methylation microarray (Methyl-Scan DNA chip$^{(R)}$, Genomic tree, Inc, South Korea). The rates of hypermethylation were compared in tumor and non-tumor group, and as a normal control, we obtained lung tissue from two young patients with pneumothorax during bullectomies, methylation profiles were examined in the same way. Results: Among the 21 genes, 10 genes were commonly methylated in tumor, non-tumor, and control group. The 6 genes of APC, AR, RAR-b, HTR1B, EPHA3, and CFTR, among the rest of 11 genes were not methylated in control, and more frequently hypermethylated in tumor tissue than non-tumor tissue. Conclusion: In the present study, HTR1B, EPHA3, and CFTR are suggested as possible novel TSGs of NSCLC by epigenetic mechanism.

• Proceedings of the Microbiological Society of Korea Conference
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• 2005.05a
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• pp.110-113
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• 2005

Under the condition of nutritional deprivation, actively growing cells prepare to enter $G_0$-like stationary phase. Protein modification by phosphorylation/dephosphorylation or ubiqutination contributes to transfer cells from active cell cycle to dormant stage. We show here that Psp1/Sds23, which functions in association with the 20S cyclosome/APC (1) and is essential for cell cycle progression in Schizosaccharomyces pombe (2), is phosphorylated by stress-activated MAP kinase Sty1 and protein kinase A, as well as Cdc2/cyclinB, upon entry into stationary phase. Three serines at the positions 18,333 and 391 are phosphorylated and overexpression of Psp1 mutated on these sites causes cell death in stationary phase. These modifications are required for the binding of Spufd2, a S.pombe homolog of multiubiquitin chain assembly factor E4 in ubiquitin fusion degradation pathway. Deletion of Spufd2 gene led to increase cell viability in stationary phase, indicating that S. pombe Ufd2 functions to inhibit cell growth at this stage to maintain cell viability. Moreover, Psp1 enhances the multiubiquitination function of Ufd2, suggesting that Psp1 phosphorylated by sty1 and PKA kinases is associated with the Ufd2-dependent protein degradation pathway, which is linked to stress tolerance, to maintain cell viability in the $G_0$-like stationary phase.

• Journal of Life Science
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• v.27 no.10
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• pp.1215-1224
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• 2017

Until now, various oncogenic pathways were idenfied. The accumulation of DNA mutation induces genomic instability in the cell, and it makes cancer. The development of bioinformatics and genomics, to find the precise and reliable biomarker is available. This biomarker could be applied the early-dignosis, prediction and convalescence of cancer. Recently, Transposable elements (TEs) have been attracted as the regulator of genes, because they occupy a half of human genome, and the cause of various diseases. TEs induce DNA mutation, as well as the regulation of gene expression, that makes to cancer development. So, we confirmed the relationship between TEs and colon cancer, and provided the clue for colon cancer biomarker. First, we confirmed long interspersed nuclear element-1 (LINE-1), Alu, and long terminal repeats (LTRs) and their relationship to colon cancer. Because these elements have large composition and enormous effect to the human genome. Interestingly, colon cancer specific patterns were detected, such as the hypomethylation of LINE-1, LINE-1 insertion in the APC gene, hypo- or hypermethylation of Alu, and isoform derived from LTR insertion. Moreover, hypomethylation of LINE-1 in proto-oncogene is used as the biomarker of colon cancer metastasis, and MLH1 mutation induced by Alu is detected in familial or hereditary colon cancer. The genes, effected by TEs, were analyzed their expression patterns by in silico analysis. Then, we provided tissue- and gender-specific expression patterns. This information can provide reliable cancer biomarker, and apply to prediction and diagnosis of colon cancer.

• KSBB Journal
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• v.24 no.1
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• pp.80-88
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• 2009

Human prostatic acid phosphatase (PAP), with comprehensive homology to glandular kallikrein, are representative serum biomarkers of prostate cancer. Dendritic cell (DC), which is the potent antigen-presenting cells(APC) in the immune system, can induce strong T cell responses against viruses, microbial pathogens, and tumors. Therefore, the immunization using DC loaded with tumor-associated antigens is a powerful method for inducing anti-tumor immunity. The CTP (Cytoplasmic Transduction Peptide) technology developed by Creagene which can transport attached bio-polymers like nucleic acids or proteins into the cell with high permeation efficiency. As the active forms of PAP can mediate apoptotic processing, we used multimer forms of PAP as an inactive form for antigen pulsing of DCs. In this study, multimeric forms of CTP-rhPAP was obtained according to the advanced purification process and subsequently confirmed by gel filtration chromatography, western blot and Dynamic Light Scattering. Therefore, CTP-conjugated PA multimers transduced into the cytoplasm were efficiently presented on the cell surface without any harm effect on cells via MHC class I molecules and result in induction of a large number of effector cell.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.41-48
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• 2002

Background: Viral antigens presented on the cell surface in association with MHC class I molecules are recognized by CD8+ T cells. MHC restricted peptides are important in eliciting cellular immune responses. As peptide antigens have a weak immunigenicity, pH-sensitive liposomes were used for peptide delivery to induce effective cytotoxic T lymphocyte (CTL) responses. In the previous study, as the HBx peptides could induce specific CTLs in vitro, we tested whether the HLA-A2/$K^b$ transgenic mice that were immunized by HBx-derived peptides could be protected from a viral challenge. Methods: HBx-peptides encapsulated by pH-sensitive liposomes were prepared. $A2K^b$ transgenic mice were immunized i.m. on days one and seven with the indicated concentrations of liposome-encapsulated peptides. Three weeks later, mice were infected with $1{\times}10^7pfu$/head of recombinant vaccinia virus (rVV)-HBx via i.p. administration. The ovaries were extracted from the mice, and the presence of rVV-HBx in the ovaries was analyzed using human TK-143B cells. IFN-${\gamma}$ secretion by these cells was directly assessed using a peptide-pulsed target cell stimulation assay with either peptide-pulsed antigen presenting cells (APCs), concanavalin A ($2{\mu}g/ml$), or a vehicle. To generate peptide-specific CTLs, splenocytes obtained from the immunized mice were stimulated with $20{\mu}g/ml$ of each peptide and restimulated with peptide-pulsed APC four times. The cytotoxic activity of the CTLs was assessed by standard $^{51}Cr$-release assay and intracellular IFN-${\gamma}$ assay. Results: Immunization of these peptides as a mixture in pH-sensitive liposomes to transgenic mice induced a good protective effect from a viral challenge by inducing the peptide-specific CD8+ T cells. Mice immunized with $50{\mu}g/head$ were much better protected against viral challenge compared to those immunized with $5{\mu}g$/head, whereas the mice immunized with empty liposomes were not protected at all. After in vitro CTL culture by peptide stimulation, however, specific cytotoxicity was much higher in the CTLs from mice immunized with $5{\mu}g/head$ than $50{\mu}g/head$ group. Increase of the number of cells that intracellular IFN-${\gamma}$ secreting cell among CD8+ T cells showed similar result. Conclusion: Mice immunized with XEPs within pH-sensitive liposome were protected against viral challenge. The protective effect depended on the amount of antigen used during immunization. XEP-3-specific CTLs could be induced by peptide stimulation in vitro from splenocytes obtained from immunized mice. The cytotoxic effect of CTLs was measured by $^{51}Cr$-release assay and the percentage of accumulated intracellular IFN-${\gamma}$ secreting cells after in vitro restimulation was measured by flow cytometric analysis. The result of $^{51}Cr$-release cytotoxicity test was well correlated with that of the flow cytometric analysis. Viral protection was effective in immunized group of $50{\mu}g/head$, while in the in vitro restimulation, it showed more spectific response in $5{\mu}g$/head group.