• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.5
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• pp.404-416
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• 2001

Purpose : Traditionally, the treatement of choice has been a bone grafting procedure to increase the length of bone in case of actual length discrepancy. But, bone grafting procedure has many disadvantages, for example, graft resorption, donor site morbidity, and so on. So, many trials have been performed to avert the use of autogenous bone graft via introducing new materials or methods. And, one of those trials has been realized by the development of a technique inducing bone lengthening by osteotomy (or corticotomy) and slow gradual distraction of the osteotomized segments. This new technique of bone lengthening dates back to the early 20th century. But, the majority of information concerning the biology of new bone formation during bone lengthening and technical details of the procedure were produced by extensive clinical and experimental studies performed by Ilizarov, a Russian surgeon. According to Ilizarov, with adequate blood supply, preservation of periosteum, rigid fixation of the osteotomized segments, and proper rate and rhythm of distraction, intramembranous bone rapidly develops within the distraction gap in the limb lengthening procedure. In the limb lengthening, many orthopedic surgeons try to observe the biologic and clinical principles recommended by Ilizarov. In the oral and maxillofacial region, however, not a few studies must be performed to apply this surgical technique in the clinical cases. Besides, the mechanism of bone formation in the distraction gap is not clear, yet. The purpose of this experiment was to scrutinize serially the histological changes in the elongated bone affected by osteodistraction of the mandibular body in an adult canine model. In addition, it was performed to confirm the presence of specific region(s) which was important in the bone formation in the gap through the observation of the expression pattern of osteocalcin and osteonectin with the immunohistochemical examination. Materials and Methods : The experimental and control specimens were obtained from seven adult male mongrel dogs weighing over 20kg. The distractors were custom-made linear extraoral devices and bicortical fixation screws were 2.3mm in diameter, 50mm in total length, 15mm in screw length. The distractors were devised to produce a linear gap of 0.75mm between two bony segments every $360^{\circ}$ turn of the rotation rod of the device. The mandibular body of the right side of each animal was corticotomized perpendicular to the occlusal plane and then two bony segments were separated completely by careful manipulation of the segments with bone forceps. The left side of each animal was left intact. This side was served as control. At sixth day after osteotomy and fixation of the segments were performed, distraction of the segments was commenced with a rate of 1.1mm/day and a rhythm of two/day for ensuing 7 days. The animals were euthanized at the 16th. 29th, and 44th day after the osteotomy. The bony specimens were decalcified, embedded in paraffin, sectioned $5{\mu}m$ thick and stained with H&E. The prepared specimens were examined under the light microscope. And, immunohistochemical examinations using anti-osteocalcin antibody (OC1, Biodesign, USA) and anti-osteonectin antibody (Haematologic Technologies Inc., Essex, VT) to locate the expressions of osteocalcin and osteonectin, respectively, were performed. Results : 1. New bone was observed already at the 16th. day after osteotomy. This suggests that new bone formation in osteodistraction was commenced at an early stage of the regenerative process. But, radiologically and microscopically, bony union was not completed in the distraction gap at the 44th. day after osteotomy. Therefore, rigid fixation must be maintained between the bony fragments till the complete bony union is confirmed clinically rather than one month or so after the completion of distraction.

• Yonsei Medical Journal
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• v.63 no.3
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• pp.259-264
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• 2022

Purpose Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. ¹⁸F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer's disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ-) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer's disease pathophysiology. Accordingly, we investigated associations between ¹⁸F-THK5351 PET positivity and cognitive decline among Aβ- aMCI patients. Materials and Methods The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: ¹⁸F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of ¹⁸F-THK5351 PET positivity on cognitive prognosis among Aβ- aMCI patients. Results Among the 25 Aβ- aMCI patients, 10 (40.0%) were ¹⁸F-THK5351 positive. The patients in the ¹⁸F-THK5351-positive group were older than those in the ¹⁸F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the ¹⁸F-THK5351-positive group deteriorated at a faster rate than those of the ¹⁸F-THK5351-negative group (B=0.003, p=0.033). Conclusion The results of the present study suggest that increased ¹⁸F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ- aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).

• Radiation Oncology Journal
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• v.31 no.2
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• pp.57-65
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• 2013

Beta-lapachone (${\beta}$-Lap; 3,4-dihydro-2, 2-dimethyl-2H-naphthol[1, 2-b]pyran-5,6-dione) is a novel anti-cancer drug under phase I/II clinical trials. ${\beta}$-Lap has been demonstrated to cause apoptotic and necrotic death in a variety of human cancer cells in vitro and in vivo. The mechanisms underlying the ${\beta}$-Lap toxicity against cancer cells has been controversial. The most recent view is that ${\beta}$-Lap, which is a quinone compound, undergoes two-electron reduction to hydroquinone form utilizing NAD(P)H or NADH as electron source. This two-electron reduction of ${\beta}$-Lap is mediated by NAD(P)H:quinone oxidoreductase (NQO1), which is known to mediate the reduction of many quinone compounds. The hydroquinone forms of ${\beta}$-Lap then spontaneously oxidizes back to the original oxidized ${\beta}$-Lap, creating futile cycling between the oxidized and reduced forms of ${\beta}$-Lap. It is proposed that the futile recycling between oxidized and reduced forms of ${\beta}$-Lap leads to two distinct cell death pathways. First one is that the two-electron reduced ${\beta}$-Lap is converted first to one-electron reduced ${\beta}$-Lap, i.e., semiquinone ${\beta}$-Lap $(SQ)^{{\cdot}-}$ causing production of reactive oxygen species (ROS), which then causes apoptotic cell death. The second mechanism is that severe depletion of NAD(P)H and NADH as a result of futile cycling between the quinone and hydroquinone forms of ${\beta}$-Lap causes severe disturbance in cellular metabolism leading to apoptosis and necrosis. The relative importance of the aforementioned two mechanisms, i.e., generation of ROS or depletion of NAD(P)H/NADH, may vary depending on cell type and environment. Importantly, the NQO1 level in cancer cells has been found to be higher than that in normal cells indicating that ${\beta}$-Lap may be preferentially toxic to cancer cells relative to non-cancer cells. The cellular level of NQO1 has been found to be significantly increased by divergent physical and chemical stresses including ionizing radiation. Recent reports clearly demonstrated that ${\beta}$-Lap and ionizing radiation kill cancer cells in a synergistic manner. Indications are that irradiation of cancer cells causes long-lasting elevation of NQO1, thereby sensitizing the cells to ${\beta}$-Lap. In addition, ${\beta}$-Lap has been shown to inhibit the repair of sublethal radiation damage. Treating experimental tumors growing in the legs of mice with irradiation and intraperitoneal injection of ${\beta}$-Lap suppressed the growth of the tumors in a manner more than additive. Collectively, ${\beta}$-Lap is a potentially useful anti-cancer drug, particularly in combination with radiotherapy.

• Journal of Yeungnam Medical Science
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• v.11 no.1
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• pp.115-126
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• 1994

The recent availability of recombinant human erythropoietin has opened new perspectives in the management of a variety of anemias. Clinical trials have been initiated in several countries using different approaches and methodology. We randomly assigned twelve premature infants(gestational age < 32 week) at high risk of requiring erythrocyte transfusion for anemia of prematurity with either subcutaneous recombinant human erythropoietin or a placebo. Treatment with rHuEPO was initiated at a dose of 100 units/kg day for 3 days a week. All patients were given supplemental oral iron therapy at a dose of 3 mg/kg per day, as tolerated and oral vitamin E at a dose of 25 units per day. Treated and control babies did not differ with respect to weight, hematocrit, overall mean reticulocyte count or rate of growth respectively. However, reticulocyte counts increased earlier in patients given rHuEPO. We conclude that rHuEPO administration is safe and feasible at the dose studied.

• Herbal Formula Science
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• v.26 no.1
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• pp.65-80
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• 2018

Objectives : This study aims to sort out prescription candidates for four major symptoms of Parkinson's disease from Korean traditional medical publication, "Dongeuibogam". Methods : Medical terms related to four major symptoms of Parkinson's disease were primarily selected from "Dongeuibogam". Prescriptions that include at least one or more medical terms which are selected above were classified by the four major symptoms of Parkinson's disease, and finally analyzed to sort the most effective candidates. Results & Conclusions : 1. There are 18 medical terms in efficacy ($ch{\grave{i}}$ $z{\grave{o}}ng$, $j{\bar{u}}$ $lu{\acute{a}}n$, $j{\bar{i}}ng$${\check{u}}$ $ju{\check{a}}n$($ju{\check{a}}n$, $qu{\acute{a}}n$) $lu{\acute{a}}n$, $j{\bar{i}}ng$${\check{u}}$ $lu{\acute{a}}n$($lu{\acute{a}}n$) $t{\grave{o}}ng$, $j{\bar{i}}n$ $lu{\acute{a}}n$, $j{\bar{i}}n$ $t{\grave{i}}$, $sh{\check{o}}u$ $zh{\grave{e}}n$, $y{\acute{a}}ng$ $sh{\check{o}}u$, $lu{\acute{a}}n$ $j{\acute{i}}$, $lu{\acute{a}}n$ $b{\grave{i}}$, $r{\grave{o}}u$ $r{\acute{u}}n$, $zh{\grave{a}}n$ $di{\grave{a}}o$, $zh{\grave{a}}n$ $y{\acute{a}}o$, $zh{\grave{i}}$ $z{\acute{u}}$, $ch{\grave{e}}$ $t{\grave{o}}ng$, $ch{\bar{o}u}$ $ch{\grave{e}}$, $f{\bar{e}}ng$ $ch{\grave{u}}$, $ch{\grave{u}}$ $nu{\grave{o}}$) related to tremor, one of four major symptoms of Parkinson's disease. 2. There are 9 medical terms in efficacy ($qi{\acute{a}}ng$ $j{\acute{i}}$, $qi{\acute{a}}ng$ $zh{\acute{i}}$, $qi{\acute{a}}ng$ $t{\grave{o}}ng$, $j{\bar{u}}$ $j{\acute{i}}$, $j{\bar{i}}n$ $j{\acute{i}}$, $sh{\bar{e}}n$ $qi{\acute{a}}ng$, $lu{\acute{a}}n$ $j{\acute{i}}$, $y{\bar{a}}o$ $j{\acute{i}}$ $qi{\acute{a}}ng$, $xi{\grave{a}}ng$ $qi{\acute{a}}ng$) related to rigidity, one of four major symptoms of Parkinson's disease. 3. 38 prescription candidates (jiaweishouxingyuan, jiaweilonghusan, gehuajiexingtang, qiangfutang, qianghuoxuduantang, dawugongsan, duhuojishengtang, mahuangzuojingtang, fangfengbaizhumulitang, fangfengtongshengsan, baizhutang, buxinwan, fulingtang, binsusan, xieqingwan, sanbitang, shengdiqinliantang, shujinbaoansan, xingxiangsan, xiaotanfulingwan, shengjunwan, shenmizuojingtang, wuyaoshunqisan, yuzhenwan, wenjingyiyuantang, yiziqingjinsan, ziyinningshentang, shaoyaogancaotang, dingtongsan, zhushazhijiasan, cangzusan, chuanxiongfulingtang, tiedanyuan, choubaowan, duomingsan, xuanhusuosan, xuefengtang, huoluodan) were selected for tremor, one of the four major symptoms of Parkinson's disease. 4. 21 prescription candidates (qianghuoshengshitang, guizhiqianghuotang, guizhifuzitang, jiuweiqianghuotang(qianghuochonghetang), xiongzhixiangsusan, daqianghuotang, mahuangguizhitang, muguajian, fuzilizhongtang, shenzhusan, lianqiaobaidusan, yuzhensan, niuhuangjinhudan, renshenbaidusan, shaoyaogancaotang, jiuzhumuguazhou, cangzusan, shenxiangtianmatang, xiangjiaosan, xuefengtang, huishousan) were selected for rigidity, one of the four major symptoms of Parkinson's disease. 5. The results in this study ought to be verified by subsequent studies and clinical trials.

• Journal of Yeungnam Medical Science
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• v.9 no.2
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• pp.312-320
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• 1992

Radiotherapeutically, nasopharyngeal cancer is an important disease in korea. Because of its blind anatomic location, early detection is relatively uncommon. Clinically, most of cases are locally advanced and nodal involvement are common. Recently better understanding of nature of the disease and improvement of radio-therapy technique permit better treatment results, including locoregional control and survival rate, and minimal normal tissue damages comparing with previously published data. We analyzed 31 patients of pathologically proven and previously untreated naso-pharyngeal carcinoma with different treatment techniques, retrospectively. Minimal and maximal follow up period of the survuor is 6 months and 68 months, respectively. Thirteen patients with squamous cell carcinoma are included in this analysis. The median age is 49 years(range from 20 to 64 years). Twenty two patients are stage III. Eleven patients are treated with radiotherapy alone and 20 are treated with comblined modalities treatment. The degree of responses after radiotherapy are categorized by 3-classes, i.e. complete response, partial response. In spite of simioarities of complete response rate and 1-year survival rate between two different treatment techniques, those patients with undifferentiated carcinoma appear to benefit from the adjuvant chemotherapy. In addition, systemic failure is more prominant in radiotherapy alone group than in combined modalities treatment group. These results suggest that adjuvant therapy in the radiotherapeutic management of nasopharyngeal cancers needs additional research according to histologic types and future extensive clinical trials.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.117-123
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• 2011

Loxoprofen sodium, a 2-phenylpropionate non-steroidal anti-inflammatory drug (NSAID), has marked analgesic and antipyretic activities and relatively weak gastrointestinal ulcerogenicity. The purpose of the present study was to evaluate the bioequivalence of two loxoprofen sodium tablets, Hana loxoprofen sodium tablet (Hana Pharm. Co., Ltd.) and Dongwha Loxonin$^{(R)}$ tablet (Dongwha Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of loxoprofen from the two loxoprofen sodium formulations was tested using KP IX Apparatus II method with various dissolution media. Twenty four healthy Korean male volunteers, $22.83{\pm}1.862$ years in age and $69.92{\pm}9.14$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 60 mg as loxoprofen sodium was orally administered, blood samples were taken at predetermined time intervals and the concentrations of loxoprofen in serum were determined using a online column-switching HPLC method with UV/Vis detection. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC^t$, $C_{max}$ and $T_{max}$ were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and un-transformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Dongwha Loxonin$^{(R)}$ tablet, were 2.03, 2.99 and -9.49% for $AUC_t$, $C_{max}$, and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log0.8 to log1.25 (e.g., log0.9831~log1.0535 and log0.9455~log1.1386 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Hana loxoprofen sodium tablet was bioequivalent to Dongwha Loxonin$^{(R)}$ tablet.

• Journal of Gastric Cancer
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• v.18 no.2
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• pp.118-133
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• 2018

Purpose: Exercise intervention after surgery has been found to improve physical fitness and quality of life (QOL). The purpose of this study was to investigate the feasibility and effects of a postoperative recovery exercise program developed specifically for gastric cancer patients (PREP-GC) undergoing minimally invasive gastrectomy. Materials and Methods: Twenty-four patients treated surgically for early gastric cancer were enrolled in the PREP-GC. The exercise program comprised sessions of In-hospital Exercise (1 week), Home Exercise (1 week), and Fitness Improvement Exercise (8 weeks). Adherence and compliance to PREP-GC were evaluated. In addition, body composition, physical fitness, and QOL were assessed during the preoperative period, after the postoperative recovery (2 weeks after surgery), and upon completing the PREP-GC (10 weeks after surgery). Results: Of the 24 enrolled patients, 20 completed the study without any adverse events related to the PREP-GC. Adherence and compliance rates to the Fitness Improvement Exercise were 79.4% and 99.4%, respectively. Upon completing the PREP-GC, patients also exhibited restored cardiopulmonary function and muscular strength, with improved muscular endurance and flexibility (P<0.05). Compared to those in the preoperative period, no differences were found in symptom scale scores measured using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and Quality of Life Questionnaire-Stomach Cancer-Specific Module (QLQ-STO22); however, higher scores for global health status and emotional functioning were observed after completing the PREP-GC (P<0.05). Conclusions: In gastric cancer patients undergoing minimally invasive gastrectomy, PREP-GC was found to be feasible and safe, with high adherence and compliance. Although randomized studies evaluating the benefits of exercise intervention during postoperative recovery are needed, surgeons should encourage patients to participate in systematic exercise intervention programs in the early postoperative period (Registered at the ClinicalTrials.gov, NCT01751880).

• Journal of Gastric Cancer
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• v.22 no.2
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• pp.107-119
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• 2022

Purpose: We aimed to explore whether the prognosis of patients treated with capecitabine and oxaliplatin (XELOX) or S-1 and oxaliplatin (SOX) regimens who received fewer cycles of chemotherapy after D2 radical resection for gastric cancer (GC) would be non-inferior to that of patients who received the standard number of cycles of chemotherapy. Materials and Methods: Data on patients who received XELOX or SOX chemotherapy after undergoing D2 radical resection at Harbin Medical University Cancer Hospital between January 2011 and May 2016 were collected. Results: In patients who received 4, 6, and 8 cycles of chemotherapy, the 5-year overall survival (OS) rates were 59.4%, 64.8%, and 62.7%, respectively. Compared to patients who received 4 cycles of chemotherapy, those who received 6 cycles (hazard ratio [HR], 0.882; 95% confidence interval [CI], 0.599-1.299; P=0.52) or 8 cycles (HR, 0.882; 95% CI, 0.533-1.458; P=0.62) of chemotherapy did not exhibit significantly prolonged OS. The 3-year disease-free survival (DFS) rate of patients who received 4, 6, and 8 cycles of chemotherapy was 62.1%, 67.2%, and 60.8%, respectively. Compared to patients who received 4 cycles of chemotherapy, those who received 6 cycles (HR, 0.835; 95% CI, 0.572-1.221; P=0.35) or 8 cycles (HR, 0.972; 95% CI, 0.606-1.558; P=0.91) of chemotherapy did not show significantly prolonged DFS. However, the 3-year DFS and 5-year OS rates of patients who received 6 cycles of chemotherapy appeared to be superior to those of patients who received 4 and 8 cycles of chemotherapy. Conclusions: For patients with stage III GC, 4 to 6 cycles of XELOX or SOX chemotherapy may be a favorable option. This study provides a rationale for further randomized clinical trials.

• Journal of Gastric Cancer
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• v.23 no.4
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• pp.609-621
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• 2023

Purpose: Determination of optimal treatment strategies for HER2-positive advanced gastric cancer (AGC) in randomized trials is necessary despite difficulties in direct comparison between trastuzumab deruxtecan (T-DXd) and nivolumab as third or later-line treatments. Materials and Methods: This single-institution, retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as ≥ third line treatments for HER2-positive AGC between March 2016 and May 2022. Overall, 58 patients (median age, 64 years; 69% male) were eligible for the study (T-DXd group, n=20; nivolumab group, n=38). Results: Most patients exhibited a HER2 3+ status (72%) and presented metastatic disease at diagnosis (66%). The response rates of 41 patients with measurable lesions in the T-DXd and nivolumab groups were 50% and 15%, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval [CI], 3.3, 7.0) and 2.3 months (95% CI, 1.5, 3.5), median overall survival (OS) of 10.8 months (95% CI, 6.9, 23.8) and 11.7 months (95% CI, 7.6, 17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% patients received subsequent treatment. Among 23 patients who received both regimens, the T-DXd-nivolumab and nivolumab-T-DXd groups had a median OS of 14.0 months (95% CI, 5.0, not reached) and 19.3 months (95% CI, 9.5, 25.1), respectively. Conclusions: T-DXd and nivolumab showed distinct efficacy and toxicity profiles as ≥ third line treatments for HER2-positive AGC. Considering the distinct features of each regimen, they may help clinicians personalize optimal treatment approaches for these patients.