• Biomedical Science Letters
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• v.20 no.2
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• pp.85-95
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• 2014

Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the head and neck tumors. To investigate the mechanism of antiproliferation to EGFR inhibition in oral cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$). We have demonstrated that ZD1839 induces growth arrest and apotosis in oral cancer cell lines by independent of EGFR-mediated signaling. An exposure of oral cancer cells to ZD1839 resulted in a dose dependent up-regulation of the cyclin-dependent kinase inhibitor p21 and p27, down regulation of cyclin D1, inactivation of GSK-$3{\beta}$ and of active MAPK. In resistant cells, GSK-$3{\beta}$ is constitutively active and its activity is negatively regulated primarily through Ser 9 phosphorylation and further enhanced by Tyr216 phosphorylation. These results showed that the resistance to the antiproliferative effects of ZD1839, in vitro was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-$3{\beta}$ activation and degradation of its target cyclin D1 were indicators of high cell sensitivity to ZD1839. In conclusion, our data show that the uncoupling of EGFR with mitogenic pathways can cause resistance to EGFR inhibition in oral cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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• pp.54-61
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• 2011

Introduction: Bisphosphonates is used widely for the treatment of the Paget's disease, multiple myeloma, bone metastases of malignant tumors with the prevention of pain and their pathological fracture. However, it was recently suggested that bisphosphonates related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate use. Materials and Methods: Twenty-four individuals, who were referred to the Department of Oral and Maxillofacial surgery, Dankook University Dental Hospital, were selected from those who had exposed bone associated with bisphosphonates from January, 2005 to December, 2009 according to the criteria of American Association of Oral and Maxillofacial Surgeons (AAOMS) for BRONJ. The patients group consisted of 7 males and 17 females between the age of 46 to 78 years (average 61.8 years). Each patient had panoramic imaging, computed tomography (CT), whole body bone scanning performed for a diagnosis and biopsy sampling from the necrotizing tissue. C-terminal cross-linking telopeptide of type I collagen (CTX) level of patients who had undergone surgical intervention was measured 7 days before surgery. Results: The main cause of bone exposure was post-extraction (15), chronic periodontitis (4), persistent irritation of the denture (3). Twenty people had undergone BRONJ treatment for two to eight months except for 4 people who had to maintain the bisphosphonates treatment to prevent a metastasis and bone trabecular pain with medical treatment. When the bisphosphonate treatment was suspended at least for 3 months and followed up according to the AAOMS protocols, the exposed necrotizing bones were found to be covered by soft tissue. Conclusion: Prevention therapy, interruption of bisphophonates for at least 3 months and cooperation with the physician for conservative treatment are the essential for treating BRONJ patient with high risk factors. The CTX level of BRONJ patients should be checked before undergoing surgical intervention. Surgical treatments should be delayed in the case of a CTX level <150 pg/mL.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.481-491
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• 2018

Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised $CD4^+CD25^+Fox3^+$ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. $NF-{\kappa}B$ and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.

• Journal of Korean Orthopaedic Sports Medicine
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• v.5 no.2
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• pp.135-140
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• 2006

Purpose: To investigate the risk exposure, risk of injury, and injury pattern of football players in seasonal variation. We purposed to expect the injury and its' prevention. Material and Methods: The professional football club(45 players) in Seoul were followed prospectively throughout 2005, January to 2005, December. Injury pattern and incidence were recorded. Results: Total 157 injuries were recorded. Major injuries which could not attend to game and training were 87 cases. Most severe month was June about 16 injuries(18.4%). And, the competitive season injuries were 46(52.9%) in March, April, August and September. Especially, ankle sprain and contusion injuries were common cause of absence in game. And, thigh muscle group injuries had a high risk of reinjury, because of treat insufficiently. Conclusions: We enhance the ability of the soccer team by prevention and education for injuries, especially in season.

• Archives of Plastic Surgery
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• v.37 no.1
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• pp.71-74
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• 2010

Purpose: Nowadays spinal cord stimulator is frequently used for the patients diagnosed as complex regional pain syndrome. The lead is placed above the spinal cord and connected to the stimulation generator, which is mostly placed in the subcutaneous layer of the abdomen. When the complication occurs in the generator inserted site, such as infection or generator exposure, replacement of the new generator to another site or pocket of the abdomen would be the classical choice. The objective of our study is to present our experience of the effective replacement of the existing stimulation generator from subcutaneous layer to another layer in same site after the wound infection at inexpensive cost and avoidance of new scar formation. Methods: A 50-year-old man who was diagnosed as complex regional pain syndrome after traffic accident received spinal cord stimulator, Synergy$^{(R)}$ (Medtronic, Minneapolis, USA) insertion 1 month ago by anesthetist. The patient was referred to our department for wound infection management. The patient was presented with erythema, swelling, thick discharge and wound disruption in the left upper quadrant of the abdomen. After surgical debridement of the capsule, the existing generator replacement beneath the anterior layer of rectus sheath was performed after sterilization by alcohol. Results: Patient's postoperative course was uneventful without any complication and had no evidence of infection for 3 months follow-up period. Conclusion: Replacement of existing spinal cord stimulation generator after sterilization between the anterior layer of rectus sheath and rectus abdominis muscle in the abdomen will be an alternative treatment in wound infection of stimulator generator.

• Korean Journal of Pharmacognosy
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• v.32 no.3 s.126
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• pp.226-232
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• 2001

To explore the possible cancer therapeutic application of "Bo-yang-hwan-oh-tang" (BH), a herbal medicinal recipe used for improvement of blood stasis, we have examined its direct cytotoxicity against tumor cell, and induction of cytotoxic activity of lymphocytes. Water extract of BH alone did not exhibit direct cytotoxicity to Yac-1 target cells even with high concentrations (10 mg/ml). By exposure for 3 days, BH did not induce any nonspecific cytotoxic activity of mouse spleen cells, either, when assessed in a 4 hr $^{51}Cr-release$ assay. However, when BH was added during CD3 stimulation of non-adherent spleen cells, non-specific CTL activity was markedly promoted in a dose dependent manner. In contrast, BH did not alter activated NK cell activity following IL-2 stimulation. These data suggest that BH does not induce but upregulates non-specific CTL effecter function and that activated NK cell does not respond to BH. For elucidation of the mechanism underlying this function of BH, time kinetic study for IL-2 production using ELISA was undertaken. IL-2 production following CD3 stimulation was significantly augmented and higher level of IL-2 is sustained over 3 days in the culture medium by BH treatment. Moreover, addition of exogenous IL-2 during CD3 stimulation resulted in a similar level of cytotoxicity between control and BH-treated culture. These data indicate that the BH-mediated upregulation of non-specific CTL activity is contributed by augmentation of IL-2 production. Our data imply the possible application of BH for combination therapy of cancer with non-specific activator.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.690-696
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• 2006

Houttuynia cordata Thunb, well known as 'E-Sung-Cho' in Korea, is a traditional medicinal plant generally used in Oriental medicine therapy. In the present study, we investigated the effect of water extract of H. cordafa (WEHC) on the growth of human breast carcinoma MCF-7 cells. Exposure of MCF-7 cells to WEHC resulted in growth inhibition and apoptosis in a dose-dependent manner as measured by MTT assay and fluorescent microscope. The anti-proliferative effect of WEHC was associated with a dose-dependent up-regulation of cyclin-dependent kinase inhibitor p21 in a p53-independent fashion. We found WEHC decreased the levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthease (iNOS) expression without significant changes in the expression of COX-1 , which was correlated with a decrease in prostaglandin $E_2{\;}(PGE_2)$ synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. cordata.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.701-709
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• 2006

The Rhus verniciflua Stokes (乾漆-RVS) has been used in traditional East Asia medicine for the therapy of gastritis, stomach cancer, although the mechanism for the biological activity is unclear. In the present study aims to investigate RVS extract contributes to growth inhibitory effect and it's the molecular mechanism on the human gastric cancer cells. AGS (gastric cancer cells) and RIEI (normal cells) were treated to different concentrations and periods of RVS extract $(10{\;}{\sim{{\;}100{\;}ug/mil)$. Growth inhibitory effect was analyzed by measuring FACS study and MTS assay. Cell cycle inhibition was confirmed by measuring CDK2 kinase activity by immunoprecipitation and kinase assay. And apoptosis was confirmed by surveying caspase cascades activation using a pan caspase inhibitor Exposure to RVS extract (50 ug/mll) resulted in a synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was related with the inhibition of proliferation and induction of apoptosis. The extract induces Gl -cell cycle arrest through the regulation of cyclins, the induction of p27kip1, and the decrease CDK2 kinase activity. And upregulated p27kip1 level is caused by protein stability increment by the reduction of S-phase kinase-associated protein 2 (Skp2), a key molecule related with p27kip1 ubiquitination and degradation, and do novo protein synthesis. Besides, 乾漆 extract induces apoptosis through the expression of Bax, poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract induces Gl -cell cycle arrest via accumulation of p27kip1 and apoptosis in human gastric cancer cells but not in normal cells, therefore we suggest that the extract can be used as a novel class of anti-cancer drugs.

• Toxicological Research
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• v.29 no.1
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• pp.35-42
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• 2013

Quantum dots (QDs) have received considerable attention due to their potential role in photosensitization during photodynamic therapy. Although QDS are attractive nanomaterials due to their novel and unique physicochemical properties, concerns about their toxicity remain. We suggest a combination strategy, CdSe/ZnS QDs together with curcumin, a natural yellow pigment from turmeric, to reduce QD-induced cytotoxicity. The aim of this study was to explore a potentially effective cancer treatment: co-exposure of HL-60 cells and human normal lymphocytes to CdSe/ZnS QDs and curcumin. Cell viability, apoptosis, reactive oxygen species (ROS) generation, and DNA damage induced by QDs and/or curcumin with or without ultraviolet A (UVA) irradiation were evaluated in both HL-60 cells and normal lymphocytes. In HL-60 cells, cell death, apoptosis, ROS generation, and single/double DNA strand breaks induced by QDs were enhanced by treatment with curcumin and UVA irradiation. The protective effects of curcumin on cell viability, apoptosis, and ROS generation were observed in normal lymphocytes, but not leukemia cells. These results demonstrated that treatment with QD combined with curcumin increased cell death in HL-60 cells, which was mediated by ROS generation. However, curcumin acted as an antioxidant in cultured human normal lymphocytes.

• Archives of Reconstructive Microsurgery
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• v.16 no.2
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• pp.93-99
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• 2007

Purpose: To report the clinical results and efficacies of one stage reverse lateral supramalleolar adipofascial flap for soft tissue reconstruction of the foot and ankle joint. Material and Methods: We performed 5 cases of one stage reverse lateral supramalleolar adipofascial flap from Jan 2005 to Sept 2005. All patients were males and mean age was 50(36~59) years old. The causes of soft tissue defects were 1 diabetic foot, 2 crushing injuries of the foot, 1 open fracture of the calcaneus, and 1 chronic osteomyelitis of the medial cuneiform bone. Average size of the flap was 3.6(3~4)${\times}$4.6(4~6) cm. All flaps were harvested as adipofascial flap and were performed with the split-thickness skin grafts (STSG) above the flaps simultaneously. Results: All flap survived completely and good taking of STSG on the flap was achieved in all cases. There were no venous congestion and marginal necrosis of the flap. In diabetic foot case, wound was healed at 4 weeks after surgery due to wound infection. There was no contracture on the grafted sites. Ankle and toe motion were not restricted at last follow up. All patients did not have difficulty in wearing shoes. Conclusion: The reverse lateral supramalleolar adipofascial flap and STSG offers a valuable option for repair of exposure of the tendon and bone around the ankle and foot. Also one stage procedure with STSG can give more advantages than second stage with FTSG, such as good and fast take-up, early ambulation and physical therapy, and good functional result.