• 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 Korean Neurosurgical Society
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• v.29 no.6
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• pp.731-737
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• 2000

Objective : Growth factor receptors on the tumor cells are known to be expressed highly allowing the tumor cells to bind growth factors to stimulate cellular division. Immunotoxin therapy is one of the novel approaches to the primary malignant brain tumor, and expression of cell-surface receptor is essential for the immunotoxin to have specific anti-tumor activity. Despite promising cytotoxic activity of immunotoxin, tumor responses are not curative on clinical trials, and additional studies are needed regarding various factors influencing the efficacy of the immunotoxin. The purpose of this study is to detect the expression of various growth factor receptors on brain tumor cell lines which are going to be used in these studies. Materials and Methods : The authors detected transferrin receptor(TR), insulin-like growth factor-1 receptor(IGF-1R), and interleukin-4 receptor(IL-4R) on medulloblastoma cell line(Daoy) and glioblastoma cell lines(U373 MG and T98 G) by flow cytometric analysis. Results : TR was expressed on Daoy, U373 MG, and T98 G. IGF-1R was expressed on Daoy and U373 MG, but not on T98 G. IL-4R was expressed on all cell lines tested. Conclusion : The transferrin and interleukin-4 receptors might be good targets for immunotoxin therapy. The results should be considered in additional in vitro and in vivo studies regarding immunotoxin and in establishing the proper treatment model of the immunotoxin therapy including selection of the adequate immunotoxin.

• YAKHAK HOEJI
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• v.53 no.2
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• pp.83-88
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• 2009

Warfarin is the most widely used oral anticoagulant in the world but maintenance of proper therapeutic range and prevention of adverse drug events always need to be careful. Especially, in Korea, warfarin dosing for patients with cerebral infarction is currently based on the nomogram which is done by foreign clinical trials not for the Korean. Therefore we evaluate warfarin dose of patients in the neurology and eventually get the base data of warfarin nomogram for Korean with stroke. We performed this study retrospectively on reviewing the medical charts to evaluate the prescribed loading dose (LD) and maintenance dose (MD) of warfarin and each responding International Normalized Ratio (INR) with any bleeding adverse drug reaction including of patient's characteristics for total 75 patients with stroke in the department of neurology of Kangnam ST. Mary's Hospital from January 2005 to June 2008. All evaluated patients should not be treated with warfarin in the past at all and should be initiated warfarin therapy first.ly at this time. All evaluated patients were divided as two classes by wafarin LD which is; 1) HDG - a high loading dosing group prescribed over 5mg, and 2) LDG - a low loading dosing group prescribed 5mg or below. As a result, average LD was $9.34{\pm}0.22$ mg (p=0.000) in HDG and $4.25{\pm}0.39$ mg (p=0.000) in LDG. Average baseline INR was $0.91{\pm}0.05$ (p=0.161) in HDG and $1.26{\pm}0.14$ (p=0.002) in LDG. On the first and second week, daily MD was $4.21{\pm}0.14$ mg (p=0.000) and $2.96{\pm}0.19$ mg (p=0.696) in HDG and also in LDG, $2.95{\pm}0.29$ mg (p=0.000) and $3.14{\pm}0.36$ mg (p=0.696). Also average reacting daily INR was respectively $2.53{\pm}0.12$ (p=0.141) and $2.51{\pm}0.16$ (p=0.678) in HDG, and in LDG, $2.11{\pm}0.17$ (p=0.141) and $2.42{\pm}0.14$ (p=0.678). After the second week, INR was not measured in regularly. Also most of underlying diseases were hypertension (n=38), diabetes mellitus (n=14), dyslipidemia (n=8) in order. Four ADRs with simple hemorrhage were occurred and those were due to drug interaction by comedication. In the conclusion, proper starting LD for Korean with stroke is 10 mg if baseline INR is around 1.0 or 5 mg if over 1.3. Proper MD need to be more evaluated in the future for setting up warfarin nomogram to make prospective study.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9367-9373
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• 2014

In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are requentlyused lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4791-4795
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• 2015

Purpose: This study was conducted to observe the efficacy and safety of pemetrexed based chemotherapy in treating patients with locally advanced or metastatic cancers as first-line, second-line or third-line therapy. Materials and Methods: From May 2011 to January 2015, we recruited 29 patients with advanced breast cancer, 19 patients with advanced ovary cancer, 17 patients with advanced esophageal cancer,5 patients with advanced gallbladder cancer,5 patients with advanced cervical cancer and 1 patient with advanced tongue cancer in Jiangsu Cancer Hospital and Research Institute.All of them were pathologically confirmed and treated with pemetrexed based chemotherapy. After two cycles of treatment,efficacy and safety can be evaluated. Results: For pemetrexed based regimens,including 76 patients with 6 kinds of advanced cancer were considered eligible for inclusion. Complete remission represents CR, partial remission represents PR, stable disease represents SD, progressive disease represents PD. Among 29 patients with advanced breast cancer, 4 patients chose pemetrexed based regimens as second-line treatment,1 of them was PR,the other 3 got SD. The last 25 patients made use of this chemotherapy as third-line treatment, except one patient could not be assessed, 2 of them got PR,6 of them got SD,the remaining 16 of them finally were PD.19 patients with advanced ovary cancer,5 patients used this regimens as second-line treatment, 3 of them got PD,the remaining patients got SD, respectively. The last 14 patients made use of pemetrexed based regimens as third-line treatment,. RR (CR+PR) was 28.5%. Among 17 patients with advanced esophageal cancer, 2 patients made use of pemetrexed based regimens as first-line treatment,both of them got PR.4 of them used this chemotherapy as second-line regimen, except 2 patients could not be assessed,the remaining 2 was PD at last. The last 11 patients was third-line users, RR (CR+PR) was 18.2%. Among 5 patients with advanced gallbladder cancer, pemetrexed based regimens was used in 1 patient as first-line treatment and 1 patient as second-line treatment. The curative effect was SD and PD, respectively. 3 patients accepted pemetrexed based regimens as third-line treatment, 2 of them got PD as results and another was SD. Among 5 patients with advanced cervical cancer, just 1 patient adopted pemetrexed based regimens as first-line treatment, whose curative effect was PR.2 patients chose this chemotherapy regimens as second-line treatment. Both of them got PD as their consequence. The last 2 patients made use of the regimens as third-line treatment, the effect of them was PD and SD, respectively. The one who with advanced tongue cancer, pemetrexed based regimens was used as second-line treatment, and the consequence was PD. About 71.1% patients experienced bone marrow suppression. Among them, 5 patients reached 4 grade. Other toxicity of pemetrexed were neurotoxicity, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusions: Pemetrexed based chemotherapy has considerable effect in patients with advanced cancers such as breast cancer,esophageal cancer and ovary cancer. More randomly clinical trials are needed to verify the results.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1677-1680
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• 2013

Background: Areas of Iran have among the highest incidences of esophageal cancer in the world. Definitive chemo-radiotherapy (DCRT) is used for locally advanced esophageal cancer and for inoperable tumors asan alternative to surgical treatment. Materials and Methods: This retrospective study was conducted in North-West Iran 2006-2011, including 267 consecutive patients with non-metastatic esophageal cancer. Eligible inoperable patients were treated with DCRT or definitive radiotherapy (DRT) alone. Radiotherapy (RT) was delivered at 1.8-2 Gy/day for five consecutive days in a given week. Chemotherapy (CT) consisted of cisplatin and 5-fluorouracil. Results: The median survival was 12.7 months with 1, 3 and 5 year survival rates of 55%, 18% and 11%, respectively. On univariate analysis, relations with age at diagnosis (p=0.015), N-stage (p=0.04), total dose of RT (p=0.001), fraction (p<0.001), Gap status (p=0.025), chemotherapeutic regimens (P=0.027), and 5-Fu $Mg/m^2$ (P=0.004) were apparent. Comparing DCRT to DRT, there was a significant difference in survival. Multivariate analysis was performed for comparison between DCRT and DRT showed significant association with age group ${\geq}65$ to <65 (P=0.02; OR: 1.46), the total RT dose (Gy) ${\geq}50$ to <50 (P=0.01; OR: 0.65) and the fraction group ${\geq}25$ to <25 (P=<0.001; OR: 0.54). Conclusions: The survival rates of esophageal cancer treated with DCRT in North West of Iran is poor; therefore, early detection and improved treatment methods, with clinical trials are a high priority.

• Journal of the Korean Arthroscopy Society
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• v.3 no.1
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• pp.54-61
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• 1999

The current treatment of extensive meniscal injuries has resulted in numerous investigations and clinical trials to restore normal meniscal functions. A cryopreserved meniscal allograft transplantation is one of the successful methods available to restore the meniscus. All the procedures of 26 cases were performed in an minimal open fashion, though initial four cases were done with the aid of arthroscope. In all of the grafts, we used a bone bridge which was attached to meniscus for better stability and healing. Anterior cruciate ligament reconstructions were also performed simultaneously with the meniscal procedures. We attempted to minimize articular cartilage by employing so called the "Key-hole technique" for the medial meniscus transplantation. First, the meniscal cartilage bone bridge was shaped into a cylinder and a bone tunnel was made just beside the medial border of the anterior criciate ligament insertion of the recipient knee joint, and the bone bridge of the meniscal cartilage was push to press-fit. The inserted meniscal cartilage was sutured by the usually employed technique under arthroscopic control. The lateral meniscus was shaped different to the medial meniscus in that the bone bridge was semicylindrical and the bone trough was made beside the lateral border of the anterior criciate ligament insertion of the recipient knee joint. The meniscus was put into the bone trough and the leading suture was extracted anterior to the tibia and tied the knot. The inserted meniscus was sutured in the same manner as the medial meniscus transplantation. By the above described method, the authors were able to minimize the articular cartilage invasion and transplant the meniscus with relative accuracy.

• Journal of the korean academy of Pediatric Dentistry
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• v.35 no.1
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• pp.73-82
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• 2008

Dental caries is an infectious disease caused by mutans streptococci, and is a primary etiologic agent of dental caries in humans. The molecular pathogenesis of mutans streptococcal-associated dental caries occurs in three phases. Firstly, S. mutans attaches to tooth surface via a cell surface adhesion termed antigen I/II. In the second phase, the glucosyltransferase(GTFs) synthesize polymers like glucans in the presence of sucrose. In the third phase, the multivalent glucans interacts with glucan binding proteins (GBPs) and they make dental plaque and accumulation of microorganisms. Many studies and clinical trials have indicated that a mucosal immune response to these antigens(Ag I/II, GTFs, GBPs) of S. mutans can influence the pathogenesis of dental caries. So these antigens can be important vaccine candidates for immunologic intervention against dental caries. In this study, we cloned the genes for GTFb, GTFc, GTFd from S. mutans GS-5 and did the nucleotide sequence analysis. And the recombinant proteins of GTFd and N-terminus of GTFd were expressed. Intact GTF which we get from this experiment can be used for antibody production specific for any GTF activity domain through animal experiment.

• 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).

• Korean Journal of Biological Psychiatry
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• v.20 no.3
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• pp.111-117
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• 2013

Objectives We investigated the effectiveness and safety when treated in schizophrenics with paliperidone palmitate, a long acting injectable antipsychotic. Methods This was a 24-week open-label study, performed at one center in Korea. The eligible patients with schizophrenia diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria were enrolled. Patients received long-acting paliperidone palmitate injection (234 mg, baseline; 156 mg, week 1 ; then once 4 weeks flexible dosing). Effectiveness assessments were measured by the Positive and Negative Syndrome Scale (PANSS), The Clinical Global Impression Severity Scale (CGI-S), The Personal and Social Performance (PSP) at baseline, week 1, every 4 weeks untill 24 weeks or endpoint. Safety assessments were measured by The Extrapyramidal Symptom Rating Scale (ESRS), body weight (BW) and incidence of adverse events. Oral antipsychotics were stopped or tapered off within next 14 days. Results Of 20 patients recruited, 9 patients (45%) completed the study. Paliperidone palmitate produced a significant improvement in PANSS total score from baseline to endpoint. The response rate was 75% [mean change (${\pm}SD$) $-25.9{\pm}14.4$, all p < 0.001]. The CGI-S and PSP total scores significantly improved during 24 weeks (All p < 0.001). Eighty percent of patients reported adverse events and most common adverse events (${\geq}10%$) in paliperidone palmitate were anticholinergic adverse event, extrapyramidal symptoms, weight gain, akathisia, insomnia, headache, agitation, anxiety and GI trouble. ESRS score is not statistically significant, but tends to get better at the end of the study when compared to baseline. Conclusions Our study results demonstrated maintained effectiveness and safety of paliperidone palmitate treatment in schizophrenics. And provides both clinicians and patients with a new choice of treatment that can improve the outcome of long term therapy. Their potential effectiveness and safety should be better addressed by future randomized-controlled trials.