• Journal of Life Science
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• v.19 no.8
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• pp.1164-1169
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• 2009

Aberrant DNA methylation plays an important role in the development of cancer. It has been reported recently that DNA hypermethylation is involved in the maintenance of cancer stem cells. The present study was designed to test the hypothesis that the demethylating agent, 5-aza-2'-deoxycytidine (AZA), can inhibit the potential for maintenance of cancer stem cells. To validate this hypothesis, we used 4T1 syngeneic mouse models of breast cancer. The AZA pre-treated 4T1 cells showed a dramatic inhibition of tumorsphere formation, compared to their counterparts in vitro. In addition, the AZA treatment significantly suppressed the expression of stem regulator genes, such as oct-4, nanog and sox2, compared to counterparts in vivo. Therefore, selective inhibition of DNA methylation may be useful for stem-specific cancer therapy.

• Journal of Microbiology and Biotechnology
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• v.28 no.6
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• pp.1007-1021
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• 2018

Cancer represents one of the most significant threats to human health on a global scale. Hence, the development of effective cancer prevention strategies, as well as the discovery of novel therapeutic agents against cancer, is urgently required. In light of this challenge, this research aimed to evaluate the effects of several potent bioactive peptides and proteins contained in crocodile white blood cell extract (cWBC) against LU-1, LNCaP, PC-3, MCF-7, and CaCo-2 cancer cell lines. The results demonstrate that 25, 50, 100, and $200{\mu}g/ml$ cWBC exhibits a strong cytotoxic effect against all investigated cell lines ($IC_{50}$ $70.34-101.0{\mu}g/ml$), while showing no signs of cytotoxicity towards noncancerous Vero and HaCaT cells. Specifically, cWBC treatment caused a significant reduction in the cancerous cells' colony forming ability. A remarkable suppression of cancerous cell migration was observed after treatment with cWBC, indicating potent antimetastatic properties. The mechanism involved in the cancer cell cytotoxicity of cWBC may be related to apoptosis induction, as evidenced by typical apoptotic morphology features. Moreover, certain cWBC concentrations induced significant overproduction of ROS and significantly inhibited the $S-G_2/M$ transition in the cancer cell. The molecular mechanisms of cWBC in apoptosis induction were to decrease Bcl-2 and XIAP expression levels and increase the expression levels of caspase-3, caspase-8, and p53. These led to a decrease in the expression level of the cell cycle-associated gene cyclin-B1 and the arrest of cell population growth. Consequently, these findings demonstrate the prospect of the use of cWBC for cancer therapy.

• Tuberculosis and Respiratory Diseases
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• v.55 no.4
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• pp.402-407
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• 2003

Mesoblastic nephroma is a neoplasm of the kidney which is characterized by interlacing bundles of spindle mesenchymal cells. It is usually diagnosed during the first six months of life and is mostly benign. Incidence in adults is exceedingly rare. In most cases, only total excision is required without postoperative adjuvant therapy, and the rare cases of local recurrence have usually been related to incomplete removal. However, mesoblastic nephroma may behave aggressively, in contrast to a congenital mesoblastic nephroma. Several cases of metastatic mesoblastic nephroma have been previously described. We report herein a case of a 42-year-old woman with mesoblastic nephroma which recurred as a large metastatic lung mass seven years after the nephrectomy. The patient presented with chest wall discomfort for four days. Seven years previously, total nephrectomy had been performed because of a right renal tumor which had been diagnosed as a mesoblastic nephroma. There had been no evidence of recurrence for five years, after which she discontinued follow-up. On readmission two years later, chest X-ray and CT scan revealed a large lung mass in the left upper lobe. It was completely excised and the pathologic examination was identical with that of the original renal tumor. Synovial sarcoma was excluded because the fusion transcripts of the SYT-SSX fusion gene associated with the t(X;18) translocation were negative. The final diagnosis was a lung metastasis of mesoblastic nephroma and the patient remained free of disease for 7 months postoperatively.

• Journal of the korean academy of Pediatric Dentistry
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• v.27 no.3
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• pp.394-399
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• 2000

Odontoma is defined as a benign odontogenic tumor containing enmel, dentin as well as cementum. It has come to mean a growth in which both the epithelial and the mesenchymal cells exhibit complete differentiation. Most authorities accept the view today that the odontoma represents a hamartomatous malformation rather than a true neoplasm. The etiology of odontomas is uncertain but hypothesized to involve local trauma, infection, inheritance or mutant gene. The odontomas often cause various disturbances in the eruption and position of the teeth. The steps in removal of an odontoma in close relation to an adjacent impacted normal tooth should comprise 1) removal of odontoma and 2) exposure of the impacted tooth. Orthodontic therapy may be applied. Before treatment, the necessary space for the impacted tooth should be evaluated. If there is lack of space in the dental arch, orthodontic treatment should be carried out before operation.

• BMB Reports
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• v.41 no.7
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• pp.537-541
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• 2008

Epilepsy is characterized by the presence of spontaneous episodes of abnormal neuronal discharges and its pathogenic mechanisms remain poorly understood. Recently, we found that the expression of creatine kinase (CK) was markedly decreased in an epilepsy animal model using proteomic analysis. A human CK gene was fused with a HIV-1 Tat peptide to generate an in-frame Tat-CK fusion protein. The purified Tat-CK fusion protein was efficiently transduced into PC12 cells in a time- and dose-dependent manner when added exogenously to culture media. Once inside the cells, the transduced Tat-CK fusion protein was stable for 48 h. Moreover, the Tat-CK fusion protein markedly increased endogenous CK activity levels within the cells. These results suggest that Tat-CK provides a strategy for the therapeutic delivery of proteins in various human diseases including the delivery of CK for potential epilepsy treatment.

• Molecules and Cells
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• v.41 no.6
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• pp.515-522
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• 2018

Patients with head and neck cancer are treated with therapeutic irradiation, which can result in irreversible salivary gland dysfunction. Because there is no complete cure for such patients, stem cell therapy is an emerging alternative for functional restoration of salivary glands. In this study, we investigated in vitro characteristics of primarily isolated epithelial cells from human salivary gland (Epi-SGs) and in vivo formation of acini-like structures by Epi-SGs. Primarily isolated Epi-SGs showed typical epithelial cell-like morphology and expressed E-cadherin but not N-cadherin. Epi-SGs expressed epithelial stem cell (EpiSC) and embryonic stem cell (ESC) markers. During long-term culture, the expression of EpiSC and ESC markers was highly detected and maintained within the core population with small size and low cytoplasmic complexity. The core population expressed cytokeratin 7 and cytokeratin 14, known as duct markers indicating that Epi-SGs might be originated from the duct. When Epi-SGs were transplanted in vivo with Matrigel, acini-like structures were readily formed at 4 days after transplantation and they were maintained at 7 days after transplantation. Taken together, our data suggested that Epi-SGs might contain stem cells which were positive for EpiSC and ESC markers, and Epi-SGs might contribute to the regeneration of acini-like structures in vivo. We expect that Epi-SGs will be useful source for the functional restoration of damaged salivary gland.

• Journal of Embryo Transfer
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• v.18 no.3
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• pp.243-248
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• 2003

Sperrnatogenesis, the process by which the male germ-line stem cells(GSCs; type A spermatogonia) divide and differentiate to produce the mature spermatozoa, occurs in the seminiferous tubules of the testis. The GSCs proliferate actively to produce two types of cells: other GSCs and differentiating spermatogonia. GSCs have unipotentcy, devoted solely to the generation of sperm. The function of GSCs has broad implications for development, disease, and evolution. Spermatogenesis is fundamental for propagation of species and the defects of this system can result in infertility or disease. The ability to identify, isolate, culture, and alter GSCs will allow powerful new approaches in animal transgenesis and human gene therapy relating to infertility. Until recently, research on stem cells in the testis has been limited because of technical difficulties in isolating and identifying these cell populations. Here, we were trying to find out optimal conditions for in vitro culture of GSCs for identifying and isolating GSCs. We collected mouse GSCs from 3-days old mouse by two-step enzyme digestion method. GSCs were plated and grown on mouse embryonic fibroblasts in Dulbecco's modified Eagle's medium (DMEM) containing 15％ fatal bovine serum, 10 mM 2-mercaptoethanol, 1％ non-essential amino acids, 1 ng/$m\ell$ bFGF, 10 $\mu$M forskolin, 1500 U/$m\ell$ human recombinant leukemia inhibitory factor (LIF). Over a period 3∼5 days, GSCs gave rise to large multicellular colonies resembling those of mouse pluripotent stem cells. After 5th passages, cells within the colonies continued to be alkaline phosphatase and Oct-4 positive and tested positive against a panel of two immunological markers(Integrin $\alpha$ 6 and Integrin $\beta$ 1) that have been recognized generally to characterize GSCs. SSEA-1, SSEA-3, and SSEA-4 also showed positive signals. Based on our data, these GSCs-derived cultures meet the criteria for GSCs itself and even other pluripotent stem cells. We reported here the establishment of in vitro cultures from mouse male GSCs.

• Korean Journal of Environmental Biology
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• v.27 no.1
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• pp.58-65
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• 2009

The chemopreventive effects of naringenin derived from citrus on tumor migration and the possible mechanisms involved in this protection were investigated in HT-1080 tumor cells. In this study, we found that naringenin reduced phorbol 12-myristate 13-acetate (PMA)-enhanced matrix metalloproteinases (MMP)-9 activation in a dose-dependant manner and further inhibited HT-1080 cell migration. In addition, naringenin suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of nuclear factor $\kappa$B (NF-$\kappa$B) activation and activator protein-1 (AP-1) translocation without changing tissue inhibitor of metalloproteinase (TIMP)-1 level. Therefore, our results suggested that the inhibitory effects of naringenin on MMP-9 activation, relation of tumor migration in vitro possibly involve mechanisms related to its ability to suppress PMA-enhanced MMP-9 gene and protein expression through NF-$\kappa$B activation and AP-1 translocation. Overall, naringenin may be a valuable anti-invasive drug candidate for cancer therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.459-466
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• 2016

Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than $Lnk^{-/-}$ MSCs. An ex vivo adipogenic differentiation assay showed that $Lnk^{-/-}$ MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma ($PPAR-{\gamma}$) and its adipogenic target genes (LPL and FABP4) significantly decreased in $Lnk^{-/-}$ MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the $IGF-1/Akt/PPAR-{\gamma}$ pathway.

• Journal of Life Science
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• v.17 no.12
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• pp.1654-1659
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• 2007

We examined total body irradiation (TBI)-induced effects by complete blood count (CBC) and fluorescence-activated cell sorter analysis (FACS) in the piglet following radiation irritation. A CBC included red blood cell count, white blood cell count, and platelet cell count. Four piglets were examined in this study and each piglet was divided by irradiation dose, two piglets with 4 Gy, two with 6 Gy, one with 8 Gy. All piglets showed leukopenia, thrombocytopenia after irradiation. In 6 and 8 Gy group, three piglets showed severe hemostatic disorder and gastrointestinal disorder suchas diarrhea and anorexia, and they died between 10 and 15 days after radiation irritation. In 4 Gy, two piglets showed no clinical sign after radiation injury, but persistent leukopenia was shown in blood examination. We suggest that a single TBI dose less than 6 Gy is adequate for conditioning piglet for bone marrow transplantation.