• Journal of Life Science
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• v.27 no.1
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• pp.1-7
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• 2017

Abnormal actin remodeling is a typical characteristic of tumor cells. Thymosin ${\beta}_{10}$ (TB10) and profilin-1 (PFN-1) are actin-binding proteins and essential regulators of actin polymerization. We previously showed that TB10 induced death in ovarian cancer cells by sequestering F-actin, but the underlying mechanisms of this induction have not been explored. In this study, we identified TB10 as a novel regulator of PFN-1 and demonstrated its novel function as a tumor suppressor in ovarian cancer cell lines. The present study investigated protein expression profiles through polyacrylamide gel electrophoresis (PAGE) and liquid chromatography-mass spectroscopy (LC-MS/MS) in SKOV3 cells, an ovarian cancer cell line, that were transiently transfected with TB10. PFN-1 was highly overexpressed in response to TB10, and overexpression of PFN-1 resulted in inhibition of cell proliferation and migration and promotion of cellular apoptosis in ovarian cancer cells. Furthermore, transiently transfected PFN-1 appeared to deactivate the Erk signaling pathway, followed by decreased expression of Elk-1 and Egr-1 in human ovarian cancer cells. Interestingly, PFN-1 did not affect the activation of Akt. The results demonstrated that PFN-1 induced apoptotic cell death and inhibited proliferation and migration in ovarian cancer cells, suggesting that PFN-1 may be valuable in anti-cancer therapy.

• Journal of Life Science
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• v.27 no.8
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• pp.958-964
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• 2017

Autophagy plays an important role in cellular homeostasis and survival for cell recycling and various stresses within the cell. Recent studies have shown that autophagy activity modulates the expression of oncogene and tumor suppressor genes, leading to the development or suppression of cancer. Induction of autophagy is involved in preventing cancer development in normal cells and plays an important role in prompting a specific cell death mechanism in cancer cells with damaged cell death function. It is also known that autophagy inhibition increases the therapeutic efficacy by sensitizing cancer cells that are resistant to chemotherapy. However, the role of autophagy has not yet been fully understood in cancer treatment. Oral squamous cell carcinoma accounts for more than 90% of oral cancer and is the sixth most common cancer in the world. The incidence of oral cancer has increased by 50% over the last 20 years and the mortality rate is over 40% within 5 years after the onset. In oral cancers, the role of autophagy are described to look for tumor inhibitory in the early stages of tumor formation, like other cancers, indicating the dual functions involved in tumor cell survival include tumor progression stages. This review summarizes the various roles of autophagy in cancer cells and suggests the possibility of autophagy as a promising target for effective oral cancer therapy.

• Reproductive and Developmental Biology
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• v.34 no.3
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• pp.143-151
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• 2010

Pluripotency of human embryonic stem cell (hESC) is one of the most valuable ability of hESCs for applying cell therapy field, but also showing side effect, for example teratoma formation. When transplant multipotent stem cell, such as mesnchymal stem cell (MSC) which retains similar differentiation ability, they do not form teratoma in vivo, but there exist limitation of cellular source supply. Accordingly, differentiation of hESC into MSC will be promising cellular source with strong points of both hESC and MSC line. In this study, we described the derivation of MSC like cell population from feeder free cultured hESC (hESC-MSC) using direct differentiation system. Cells population, hESC-MSC and bone marrow derived MSC (BM-MSC) retained similar characteristics in vitro, such as morphology, MSC specific marker expression and differentiation capacity. At the point of differentiation of both cell populations, differentiation rate was slower in hESC-MSC than BM-MSC. As these reason, to verify differentially expressed molecular condition of both cell population which bring out different differentiation rate, we compare the molecular condition of hESC-MSC and BM-MSC using 2-D proteomic analysis tool. In the proteomic analysis, we identified 49 differentially expressed proteins in hESC-MSC and BM-MSC, and they involved in different biological process such as positive regulation of molecular function, biological process, cellular metabolic process, nitrogen compound metabolic process, macromolecule metabolic process, metabolic process, molecular function, and positive regulation of molecular function and regulation of ubiquitin protein ligase activity during mitotic cell cycle, cellular response to stress, and RNA localization. As the related function of differentially expressed proteins, we sought to these proteins were key regulators which contribute to their differentiation rate, developmental process and cell proliferation. Our results suggest that the expressions of these proteins between the hESC-MSC and BM-MSC, could give to us further evidence for hESC differentiation into the mesenchymal stem cell is associated with a differentiation factor. As the initial step to understand fundamental difference of hESC-MSC and BM-MSC, we sought to investigate different protein expression profile. And the grafting of hESC differentiation into MSC and their comparative proteomic analysis will be positively contribute to cell therapy without cellular source limitation, also with exact background of their molecular condition.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.5
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• pp.758-763
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• 2003

Amino acid transporters play an important role in supplying nutrients to normal and cancer cells for cell proliferation. System L is a major transport system responsible for the N $a^{＋}$-independent, large neutral amino acids including several essential amino acids. L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed presumably to support their continuous growth and proliferation in malignant tumors. 2-Aminobicyclo- (2,2,1) -heptane-2-carboxylic acid (BCH) is a model compound for study of amino acid transporter as a system L selective inhibitor. In the present study, we examined whether BCH induced growth inhibition in KB human oral squamous carcinoma cell line or not. The uptake of L-［$^{14}$ C］leucine by KB cells is inhibited by BCH in a concentration dependent manner with a Ι $C_{50}$ value of 75.3$\pm$6.2 ${\mu}{\textrm}{m}$ and a $K_{i}$ value of 98.7$\pm$ 4.1 ${\mu}{\textrm}{m}$. The growth of KB cells is inhibited by BCH in time dependent manner and concentration dependent manner with a Ι $C_{50}$ value of 11.1 $\pm$0.8 mM. In the DNA of KB cells treated with the various concentrations and various periods of BCH, the characteristic ladders associated with DNA fragmentation were not observed. These results suggest that BCH inhibits the growth of KB oral epidermoid carcinoma cells through the inhibition of transport of neutral amino acids into cells without DNA break down. This phenomenon will be a new rationale for anti-cancer therapy.y.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4353-4358
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• 2014

Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

• Reproductive and Developmental Biology
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• v.32 no.1
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• pp.9-14
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• 2008

Efficient gene transfer into hematopoietic stem cells is a great tool for gene therapy of hematopoietic disease. Retrovirus have been extensively used for gene delivery and gene therapy. However, current in vitro gene transfer has some obstacles suck as induction of differentiation loss of self-renewal capacity, and down-regulation of homing efficiency for in vitro hematopoietic stem cells transplantation. To overcome these problems, we developed efficient in vitro retroviral transfer technique by direct intra-bone marrow injection (IBM). We identified effective retrovirus gene transfer in bone marrow hematopoietic cells in vitro. Two weeks after retrovirus transfer via IBM injection, we observed stable EGFP gene expression in bone marrow, lymph node, spleen, and liver cells. In addition, $6.4{\pm}2.7%$ of hematopoietic stem/progenitor cells were expressed EGFP transgene from flow cytometry analysis. Our results demonstrate that in vitro retrovirus gene transfer via IBM injection can provide a viable alternative to current or moo gene transfer approach.

• The Journal of Internal Korean Medicine
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• v.10 no.1
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• pp.65-80
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• 1989

About Oui-Ga-Sil(胃家實) in order to considerate the contents recorded in Nai-Gyung Sang-Han-Lon and latter literature, definition, etiopathology, syndrome, differential diagnosis, therapy, Prognosis and prevention were classified. And the results were as follows: 1. Oui-Ga(胃家)was a term which indicated the whole digestive system such as stomach, small intestine, large intestine, rectum and anus. Sil(實)could be defined as the peculiar concept pertaining to the acute and last stage which was invaded to inside bowels because of abundance with evil influence. 2. Eliology of Oui-Ga-Sil was abunt gastric fever originally, injured mucus because of mistreatment, the invasion to inside of outside evil influence through meridian. Pathology was the opening and shutting appearance of gastric abundance with intestinal emptiness, and intestinal abundance with gastric emptiness, Oui-Ga-Sil could be occurred because of gastric abundant dryness and splenic humidifying capacity decrease. 3. Symptom of Oui-Ga-Sil was classified as for the sunlight outside syndrome and the inside abundant syndrome. The sunlight outside syndrome was body fever, sweating, no chilling, on the contrary hatred of fever. The chief complaint of inside abundant syndrome was daily fever, talking in delirium, hand and foot sweating, abdominal distention, difficult defection and those could be pertained to sunlight bowel syndrome. 4. Diagnostic views of Oui-Ga-Sil were that pulse was descending abundant large strong and smooth quick, a coated tongue was yellow, deep yellow, old yellow, thick, scorching dry rough or gray black. On abdominal diagnosis, pressing by hand, patient was conscious of pain, excessive pain, rejection against press, impossible press or intermittent abdominal pain and bowel cutting pain without press. 5. Differential diagnosis was that the sunlight of Nai-Gyung-Fever-Theory was outside desease making meridian the prime object, Baik-Ho-Tang syndrome was making figureless abundant fever the pivotal point. And important differential standard of splenic shrink syndrome was that a daily fever, an irritation with fever were not occurred. 6. Theory of Oui-Ga-Sil was that Seng-Gi-Tang classes had been used in attacking downward or making balance, and moxibustion on Jung-Wan, honey boiling induction theory had been also used. Attacking downward therapy was invigorating method to preserve mucus, and if mucus had been exausted with complicating emptiness prognosis had been appeared badly. 7. Preventing from Oui-Ga-Sil diet by rule, fitness to cold and warmth may be needed to prevent outside evil influence attack and inside evil influence occurrence. Prudence with being very busy, fatigue, wine and woman may be also needed not to be an injury to splanic and gastric spirit.

• Journal of the Korean Society of Physical Medicine
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• v.9 no.2
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• pp.151-159
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• 2014

PURPOSE: The purpose of this study was to evaluate whether light-emitting diodes (LED) irradiation could be effective in a noninvasive, therapeutic device for the treatment of osteoarthritis(OA). METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: Vehicle control (saline); monosodium iodoacetate-injection (MIA); LED irradiation after MIA injection (MIA-LED); indomethacin-treatment after MIA injection (MIA-IMT). OA was induced by intra-articular injection of 3 mg MIA through the patellar ligament of the right knee. Vehicle control rats were injected with an equivalent volume of saline. The LED was irradiated for 15 min/day for a week after 7 days of MIA treatment. To compare with the effect of LED irradiation, the indomethacin was administrated 20 mg/kg twice a week orally after 7 days of MIA treatment. Knee joints were removed and fixed overnight in 10% neutral buffered formalin and decalcified by EDTA for 2 week before being embedded in paraffin. The assessment of OA induction were monitored by knee movement and radiographic finding. Histologic analysis were performed following staining with hematoxylin and eosin, safranin O-fast green, or toluidine blue, picrosirius red, and histologic changes were scored according to a modified Mankin system. Apoptotic cell in tissue sections was detected using TUNEL method. RESULTS: Radiographic examination could not show the differences between the MIA-treated and the MIA-LED-treated rats. In the histologic analysis, however, LED irradiation prevented cartilage damage and subchondral bone destruction, and significantly reduced mononuclear inflammatory cell infiltration and pannus formation. LED irradiation also reduced apoptosis of cartilage cells, but it prevented apoptosis of infiltrated inflammatory cells in synovium. In addition, LED irradiation showed an increase of collagen production in the meniscus. CONCLUSION: These results suggest that the 840 nm LED irradiation would be a suitable non-thermal phototherapy for the treatment of OA, as a cartilage protection and anti-inflammatory modality.

• Korean Journal of Head & Neck Oncology
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• v.34 no.2
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• pp.11-15
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• 2018

Background/Objectives: The efficacy of radiotherapy alone versus chemoradiotherapy has been studied in patients with T2N0M0 laryngeal squamous cell carcinoma. Materials & Methods: Thirty nine patients with newly diagnosed T2N0M0 laryngeal squamous cell carcinoma were treated with either radiotherapy(RT group, 66-70Gy) or chemoradiotherapy(CRT group, cisplatin based concurrent chemoradiation with or without 2 cycles induction chemotherapy including cisplatin, $5-FU{\pm}$ docetaxel / radiation therapy same with above mentioned). The mean follow-up was 73.5 months. Results: The overall survival (OS), disease specific survival (DSS), disease free survival (DFS), and larynx preservation survival (LPS) at 5 years were 70%, 79%, 67%, and 71%. The complete response rate was 82.4% in RT group, and was 95.5% in CRT group. OS (57% vs 80%), DSS (69% vs 86%), DFS (52% vs 77%), and LPS (63% vs 77%) at 5 years were higher in CRT group than RT group, but it was not statistically significant. In subsite analysis, CRT group tends to improve DFS, compared to RT group, in glottic cancer (p=0.06). The toxicities were tolerable and no fatal case was observed in both groups. Conclusion: Chemoradiotherapy is effective as primary therapy for T2 laryngeal squamous cell carcinoma and showed manageable treatment induced toxicity.

• Journal of Nutrition and Health
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• v.57 no.1
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• pp.27-42
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• 2024

Purpose: This study examined whether regular moderate-intensity treadmill exercise (Ex) and Syzygium aromaticum L. (SA) administration can influence lipid and muscle metabolism in obese rats induced by a 60% high-fat diet (HFD). Methods: Rats, except those in the Normal group, were exposed to a 60% HFD for 4 weeks to induce obesity. The obese rats were assigned randomly to three groups: HFD control group, HFD+Ex group, and HFD+Ex+SA group. Treadmill exercise was conducted five times a week for 4 weeks, with a 5° incline and a speed of 18 m/min (Week 1: 20 minutes; Weeks 2: 25 minutes; Weeks 3-4: 30 minutes). Serum analysis was performed. Western blot analysis was conducted on the liver and soleus muscle, and histopathological analysis was carried out on the liver and adipose tissues. Results: The body weight change in the Ex groups was significantly lower than in the HFD control group, while the soleus muscle weight in the HFD+Ex group increased significantly. The histopathological examination in the Ex groups revealed a marked reduction in liver lipid accumulation and a decrease in adipocyte size in adipose tissue. Obesity induction increased leptin levels substantially, but Ex notably reversed these changes. Ex resulted in significant inhibition of ROS and ONOO^-, whereas the serum inflammatory cytokine, IL-1β, and total cholesterol were reduced only by SA administration. Furthermore, the inflammatory proteins in the liver were inhibited more effectively when Ex was supplemented with SA. The expression of the muscle synthesis-related proteins and degradation proteins were modulated by Ex and Ex+SA. Conclusion: Ex significantly affected lipid and muscle metabolism, and adding SA alleviated the inflammation.