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Bisphosphonates-related osteonecrosis of the jaw in Korea: a preliminary report

  • Lee, Jeong Keun;Kim, Kyung-Wook;Choi, Jin-Young;Moon, Seong-Yong;Kim, Su-Gwan;Kim, Chul-Hwan;Kim, Hyeon-Min;Kwon, Yong-Dae;Kim, Yong-Deok;Lee, Dong-Keun;Min, Seung-Ki;Park, In-Sook;Park, Young-Wook;Kook, Min-Suk;Park, Hong-Ju;Baek, Jin-A;Park, Jun-Woo;Kwon, Tae-Geon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.39 no.1
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    • pp.9-13
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    • 2013
  • Objectives: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. Materials and Methods: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. Results: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was $70.0{\pm}10.1$ years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. Conclusion: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea.

Role of Tumor Necrosis Factor-Producing Mesenchymal Stem Cells on Apoptosis of Chronic B-lymphocytic Tumor Cells Resistant to Fludarabine-based Chemotherapy

  • Valizadeh, Armita;Ahmadzadeh, Ahmad;Saki, Ghasem;Khodadadi, Ali;Teimoori, Ali
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8533-8539
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    • 2016
  • Background: B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine-based chemotherapy. Materials and Methods: In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL. Results: Observed apoptosis rates were: group 1, $42{\pm}1.04%$; group 2, $21{\pm}0.57%$; group 3, $19{\pm}2.6%$; and group 4, % $0.01{\pm}0.01$. The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of $63{\pm}1.6%$, which was again higher than in other groups. Conclusions: In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis.

Prognosis of Eight Chinese Cases of Primary Vaginal Yolk Sac Tumor with a Review of the Literature

  • Tang, Qiong-Lan;Jiang, Xue-Feng;Yuan, Xiao-Ping;Liu, Yong;Zhang, Lin;Tang, Xiao-Feng;Zhou, Jia-Jia;Li, Hai-Gang;Fang, Jian-Pei;Xue, Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9395-9404
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    • 2014
  • Background: Primary vaginal yolk sac tumor is a rare malignancy in the pediatric population, and a diagnostic challenge and appropriate initial treatment remains unsolved. The aim of this study was to investigate the clinicopathologic features, treatment and prognosis of this tumor. Materials and Methods: Eight cases of primary vaginal yolk sac tumor were reported with a literature review. Results: There were 4 pure yolk sac tumor cases and four mixed germ cell tumors containing yolk sac tumor element, including two cases with embryonal carcinoma and two cases with embryonal carcinoma and dysgerminoma. Partial vaginectomy was performed in four cases and all patients received chemotherapy. 85 cases in literatures were reviewed and 9 cases were misdiagnosed. Follow-up data was available in 77 cases and 5-year overall survival rate was 87.6%. 5-year survival rate of biopsy with chemotherapy, conservative surgery with chemotherapy and radical surgery with chemotherapy was 91.1%, 100% and 28.6%, respectively (p<0.001). Compared to cases without relapse or metastasis after initial treatment, patients with relapse or metastasis had a shorter overall survival (35.6% vs 96.6%, p<0.001). Conclusions: Mixed germ cell tumor containing yolk sac tumor element was not uncommon and partial vaginectomy may be a good choice for primary vaginal mixed yolk sac tumor type to eradicate local tumor cells and provide complete information for pathological diagnosis and postoperative adjuvant therapy.

Development of Respiratory Training System Using Individual Characteristic Guiding Waveform (환자고유의 호흡 패턴을 적용한 호흡 연습장치 개발 및 유용성 평가)

  • Kang, Seong-Hee;Yoon, Jai-Woong;Kim, Tae-Ho;Suh, Tae-Suk
    • Progress in Medical Physics
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    • v.23 no.1
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    • pp.1-7
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    • 2012
  • The purpose of this study was to develop the respiratory training system using individual characteristic guiding waveform to reduce the impact of respiratory motion that causes artifact in radiotherapy. In order to evaluate the improvement of respiratory regularity, 5 volunteers were included and their respiratory signals were acquired using the in-house developed belt-type sensor. Respiratory training system needs 10 free breathing cycles of each volunteer to make individual characteristic guiding waveform based on Fourier series and it guides patient's next breathing. For each volunteer, free breathing and guided breathing which uses individual characteristic guiding waveform were performed to acquire the respiratory cycles for 3 min. The root mean square error (RMSE) was computed to analyze improvement of respiratory regularity in period and displacement. It was found that respiratory regularity was improved by using respiratory training system. RMSE of guided breathing decreased up to 40% in displacement and 76% in period compared with free breathing. In conclusion, since the guiding waveform was easy to follow for the volunteers, the respiratory regularity was significantly improved by using in-house developed respiratory training system. So it would be helpful to improve accuracy and efficiency during 4D-RT, 4D-CT.

Mechanism of Growth Inhibition by BCH in HEp2 Human Head and Neck Squamous Cell Carcinoma (사람 두경부 편평세포암종 HEp2 세포에서 BCH에 의한 세포성장 억제기전)

  • Choi, Bong-Kyu;Jung, Kyu-Yong;Cho, Seon-Ho;Kim, Chun-Sung;Kim, Do-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.5
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    • pp.555-560
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    • 2008
  • Amino acid transporters are essential for the growth and proliferation in all living cells. Among the amino acid transporters, the system L amino acid transporters are the major nutrient transport system responsible for the $Na^+$-independent transport of neutral amino acids including several essential amino acids. The L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed in cancer cells to support their continuous growth and proliferation. 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) is a model compound for the study of amino acid transporter as a system L selective inhibitor. We have examined the effect and mechanism of BCH on cell growth suppression in HEp2 human head and neck squamous cell carcinoma. The BCH inhibited the L-leucine transport in a concentration-dependent manner with a $IC_{50}$ value of $51.2{\pm}3.8{\mu}M$ in HEp2 cells. The growth of HEp2 cells was inhibited by BCH in the timeand concentration-dependent manners. The formation of DNA ladder was not observed with BCH treatment in the cells. Furthermore, the proteolytic processing of caspase-3 and caspase-7 in the cells were not detected by BCH treatment. These results suggest that the BCH inhibits the growth of HEp2 human head and neck squamous cell carcinoma through the intracellular depletion of neutral amino acids for cell growth without apoptotic processing.

AN EXPERIMENTAL STUDY OF ELECTROPHYSIOLOGICAL AND HISTOLOGICAL ASSESSMENT ON THE INJURY TYPES IN RABBIT INFERIOR ALVEOLAR NERVE (가토의 하치조 신경 손상 형태에 따른 전기생리학적 및 조직학적 변화에 관한 실험적 연구)

  • Lee, Jae-Eun;Lee, Dong-Keun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.18 no.4
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    • pp.679-700
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    • 1996
  • Inferior alveolar nerve dysfunction may be the result of trauma, disease, or iatrogenic injury. Inferior alveolar nerve injury is inherent risk in endodontic therapy, orthognathic surgery of the mandible, and extraction of mandibular teeth, particularly the third molars. The sensory disturbances of inferior alveolar nerve associated with such injury have been well documented clinical problem that is commonly evaluated by several clinical sensory test including Tinels sign, Von Frey test(static light touch detection), directional discrimination, two-point discrimination, pin pressure nociceptive discrimination, and thermal test. These methods used to detect and assess inferior alveolar nerve injury have been subjective in nature, relying on the cooperation of the patients. In addition, many of these techniques are sensitive to differences in the examiners experience and skill with the particular technique. Data obtained at different times or by different examiners are therefore difficult to compare. Prior experimental studies have used electro diagnostic methods(sensory evoked potential) to objectively evaluate inferior alveolar nerve after nerve injury. This study was designed with inferior alveolar nerve of rabbit. Several types of injury including mind, moderate, severe compression and perforation with 19 gauze, 21 gauze needle and 6mm, 10mm traction were applied for taking the sesory evoked ppterntial. Latency and amplitude of injury rabbit inferior alveolar nerve were investigated with sensory evoked potential using unpaired t-test. The results were as follows : 1. Intensity of threshold (T1) was $128{\pm}16{\mu}A$ : latency, $0.87{\pm}0.07$ microsecond : amplitude, $0.4{\pm}0.1{\mu}V$ : conduction velocity, 23.3 m/s in sensory evoked potential of uninjured rabbit inferior alveolar nerve. 2. Rabbit inferior alveolar nerve consists of type II and III sensory nerve fiber. 3. Latency was increased and amplitude was decreased in compression injury. The more injured, the more changed in latency and amplitude. 4. Findings in perforation injury was similar to compression injury. Waveform for sensory evoked potential improved by increasing postinjured time. 5. Increasing latency was prominent in traction injury rabbit inferior alveolar nerve. 6. In microscopic histopathological findings, significant degeneration and disorganization of the internal architecture were seen in nerve facicle of severe compression and 10mm traction group. From the above findings, electrophysiological assessment(sensory evoked potential) of rabbit injured inferior alveolar nerve is reliable technique in diagnosis and prognosis of nerve injury.

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Effects of Dichloromethane Fraction of Phlomidis Radix on Bone Formation in Human Fetal Osteoblasts (속단의 dichloromethane 분획물이 태아골모세포의 골형성 유도에 미치는 효과)

  • Lee, Young-Joon;Choi, Hee-In;Kim, Yun-Chul;Shin, Hyung-Shik;You, Hyung-Keun
    • Journal of Periodontal and Implant Science
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    • v.33 no.2
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    • pp.259-269
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    • 2003
  • The ideal goal of periodontal therapy is the regeneration of periodontal tissue repair of function. Although is very difficult to attain the goal, recent advances in periodontal wound healing concepts encourage hope reaching it. Recently many efforts are concentrated on the regeneration potential of material used in traditional Korean medicine. Phlomidis Radix has been used for the treatment of blood stasis, bone fracture and osteoporosis in traditional Korean medicine. The purpose of this study is to examine effects of dichloromethane fraction Phlomidis Radix on Bone Formation in Human Fetal Osteoblasts. Human fetal osteoblastic cell line(hFOB1 1.19 ;American Type Culture Collection, Manassas, VA) were used and cells were cultured containing DMEM and dichloromethane fraction Phlomidis Radix(100 ng/ml , 1 ${\mu}$/ml, 10 ${\mu}$/ml) at 34$^{\circ}C$ with 5% $CO_2$ in 100% humidity. MTT was performed to examine the viability of the cell, and alkaline phosphatase activity was analyzed to examine the mineralization. Also bone calcification nodules were evaluated. The cellular activity of hFOB1 was increased in 100 ng/ml, 1 ${\mu}$/ml , 10 ${\mu}$/ml of dichloromethane fraction of Phlomidis Radix and especially significant increation was showed in 100 ng/ml of dichloromethane fraction of Phlomidis Radix at 6days (p <0.05). ALP level of hFOB1 was significantly increased in 100 ng/ml , 1 ${\mu}$/ml, 10 ${\mu}$/ml of dichloromethane fraction of Phlomidis Radix and especially more increation was showed in 10 ${\mu}$/ml of dichloromethane fraction of Phlomidis Radix (p <0,05). Calcification nodules of hFOB1 significantly increased in 10 ${\mu]$/ml of dichloromethane fraction of Phlomidis Radix at 21 days of incubation(p<0.05). The results indicate that dicholoromethane fraction of Phlomidis Radix has excellent effects on mineralization of hFOB1.

Recurrence of Early Gastric Cancer (조기위암의 재발)

  • Ahn Jung-Sik;Bang Ho-Yoon;Lee Jong-Inn;Noh Woo-Chul;Hwang Dae-Yong;Choi Dong-Wook;Paik Nam-Sun;Moon Nan-Mo;Choi Tae-Inn
    • Journal of Gastric Cancer
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    • v.1 no.3
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    • pp.180-186
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    • 2001
  • Purpose: The prognosis for early gastric cancer (EGC) is favorable, and the 10-year disease-specific survival rate is reported to be around $90\%$. The absolute number of recurred EGC is too small to assess the risk factors, so recruitment of a large number of cases for statistical analysis is very difficult. We carried out this study to analyze the incidence and the patterns of recurrence of EGC and to identify the clinicopathological risk factors for recurrence of EGC. Materials and Methods: The authors retrospectively investigated the follow-up records of 1418 patients who underwent a curative resection for EGC from Jan. 1984 to Dec. 1999 at the Korea Cancer Center Hospital and analyzed them with special reference to cancer recurrence. Results: In this retrospective study of 1418 cases, 43 patients died of a recurrence of gastric cancer, and 105 patients died of unrelated causes. The five-year and the ten-year overall survival rates were $89.6\%$ and $81.7\%$, respectively, while the five-year and the ten-year diseasespecific survival rates were $96.5\%$ and $94.3\%$, respectively. The recurrence patterns of the 45 recurred EGC were hematogenous metastasis (19 cases), lymph node (L/N) metastasis (8 cases), locoregional recurrence (2 cases), peritoneal seeding (3 cases), and combined form (13 cases). The mean time interval to recurrence was 38.6 months, and the number of delayed recurred cases after 5 years was 10 ($22.2\%$). Of the clinicopathologic factors, depth of invasion, L/N metastasis, macroscopic type, lymphatic invasion, and vessel invasion, were significant risk factors in the univariate analysis. However, in the multivariate analysis, only L/N metastasis was an independent prognostic factor. Conclusion: Based on the results of this study, L/N metastasis is an independent prognostic factor. Thus, in patients with node-positive disease, adjuvant therapy might be considered, and long-term close follow-up might facilitate early detection and treatment of recurrent disease due to delayed recurrence.

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Twenty Four Cases of Idiopathic Bronchiolitis Obliterans Organizing Pneumonia, Reported in Korea and a Review of Literatures (국내 보고된 특발성 폐쇄성세기관지염 기질화폐렴 24예와 문헌 고찰)

  • Chang, Jung-Hyun;Park, Sa-Yong
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.709-717
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    • 1999
  • Background & Method : Bronchiolitis obliterans organizing pneumonia(BOOP) is a specific clinicopathologic condition characterized by chronic inflammatory interstitial infiltrates. Cryptogenic form of BOOP presents subacute clinical course of flu-like illness, such as cough, fever, dyspnea with exertion and other constitutional symptoms. Pathologically it shows the presence of granulation tissue filling the lumen of terminal and respiratory bronchioles, extending into distal airspaces. Recently, we reviewed 24 cases of idiopathic type of BOOP, 5 cases of our hospital and another 19 cases on Korean literatures, and compared with reviewed data from foreign literatures. Results : Mean age was 54 years old and there was female preponderance in domestic reports. Their common presenting symptoms were dyspnea and cough, and mean duration of illness was 41 days. On chest examination, inspiratory crackle was a common finding. The laboratory findings were nonspecific except hypoxemia. Lung function studies revealed restrictive defect or combined obstructive and restrictive pattern in most patients. Bilateral patchy and nonsegmental alveolar opacities constituted characterized radiographic finding, highlighted on high resolution computed tomogram. It showed a favorable prognosis with an excellent responsiveness to corticosteroid therapy. The clinical features and laboratory findings were similar between domestic and foreign cases except female preponderance in Korean cases. Conclusion : If the clinical course is atypical or pregressive under proper treatment, clinicians should reevaluate clinical features and radiographic findings under the consideration of BOOP. Tissue confirmation would be recommended for the definitive diagnosis of BOOP.

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Disulfiram Suppresses Invasive Ability of Osteosarcoma Cells Via the Inhibition of MMP-2 and MMP-9 Expression

  • Cho, Hyun-Ji;Lee, Tae-Sung;Park, Jae-Bok;Park, Kwan-Kyu;Choe, Jung-Yoon;Sin, Doo-Il;Park, Yoon-Yub;Moon, Yong-Suk;Lee, Kwang-Gill;Yeo, Joo-Hong;Han, Sang-Mi;Cho, Young-Su;Choi, Myeong-Rak;Park, Nam-Gyu;Lee, Yun-Sik;Chang, Young-Chae
    • BMB Reports
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    • v.40 no.6
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    • pp.1069-1076
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    • 2007
  • Cancer cells, characterized by local invasion and distant metastasis, are very much dependant on the extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we reported the effects of disulfiram, a clinically used anti-alcoholism drug, on tumor invasion suppression, as well as its effects on the activity of MMP-2 and MMP-9 in human osteosarcoma cells (U2OS). Disulfiram has been used for alcohol aversion therapy. However, recent reports have shown that disulfiram may have potential in the treatment of human cancers. Herewith, we showed that the anti-tumor effects of disulfiram, in an invasion assay using U2OS cells and that disulfiram has a type IV collagenase inhibitory activity that inhibits expression of genes and proteins responsible for both cell and non-cell mediated invasion on pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9 and it regulated the invasion of human osteosarcoma cells. These observations raise the possibility of disulfiram being used clinical for the inhibition of cancer invasion.