• Title/Summary/Keyword: Clinical Trials

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Screening of Phenolic Compounds with Inhibitory Activities against HMG-CoA Reductase (페놀 화합물로부터 HMG-CoA reductase 저해 활성 물질 탐색)

  • Son, Kun Ho;Lee, Ju Yeon;Lee, Jeong Soon;Kang, Sam Sik;Sohn, Ho Yong;Kwon, Chong Suk
    • Journal of Life Science
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    • v.27 no.3
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    • pp.325-333
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    • 2017
  • High level of plasma cholesterol is strongly associated with the development of atherosclerosis and coronary heart disease. Clinical trials designed to reduce plasma cholesterol level by diet or pharmacological intervention have resulted in marked reduction of disease incidence. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which reduces cholesterol biosynthesis in the liver is the key enzyme of the mevalonate pathway that produces cholesterol. In this study, 71 naturally occurring phenolic compounds were tested for inhibitory activities against HMG-CoA reductase. Eleven compounds out of 71 showed inhibitory activities: three hydrolyzable tannin (geraniin, acetonyl geraniin and pentagalloyl ${\beta}-D-glucose$), four benzoic acid derivatives (benzoic acid, trans-cinnamic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid), and four naphthoquinone derivatives (1,2-naphthoquinone, 1,4-naphthoquinone, plumbagin and shikonin). At the concentration of $10{\mu}g/ml$, 1,4-naphthoquinone inhibited HMG-CoA reductase by 99.4%, and then plumbagin 91.4%, pentagalloyl ${\beta}-D-glucose$ 46.6%, 2,4-dihydroxybenzoic acid 40.9%, shikonin 37.7%, 1,2-naphthoquinone 36.6%, trans-cinnamic acid 32.0%, acetonyl geraniin 30.2%, benzoic acid 28.5%, geraniin 28.3% and 2,5-dihydroxybenzoic acid 22.3%, respectively. $IC_{50}$ values of 1,4-naphthoquinone and plumbagin was $2.1{\mu}g/ml$ and $5.8{\mu}g/ml$, respectively.

The Structural and Functional Role of p53 as a Cancer Therapeutic Target (암 치료 표적으로서 p53의 구조적 및 기능적 역할)

  • Han, Chang Woo;Park, So Young;Jeong, Mi Suk;Jang, Se Bok
    • Journal of Life Science
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    • v.28 no.4
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    • pp.488-495
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    • 2018
  • The p53 gene plays a critical role in the transcriptional regulation of cellular response to stress, DNA damage, hypoxia, and tumor development. Keeping in mind the recently discovered manifold physiological functions of p53, its involvement in the regulation of cancer is not surprising. In about 50% of all human cancers, inactivation of p53's protein function occurs either through mutations in the gene itself or defects in the mechanisms that activate it. This disorder plays a crucial role in tumor evolution by allowing the evasion of a p53-dependent response. Many recent studies have focused on directly targeting p53 mutants by identifying selective, small molecular compounds to deplete them or to restore their tumor-suppressive function. These small molecules should effectively regulate various interactions while maintaining good drug-like properties. Among them, the discovery of the key p53-negative regulator, MDM2, has led to the design of new small molecule inhibitors that block the interaction between p53 and MDM2. Some of these small molecule compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, more personalized anti-carcinogenic medicines. Here, we review the structural and functional consequences of wild type and mutant p53 as well as the development of therapeutic agents that directly target this gene, and compounds that inhibit the interaction between it and MDM2.

Eleocharis kuroguwai Ohwi Ameliorates LPS-mediated Inflammation by Suppressing MAPKs Signaling (LPS로 유도된 염증 상태 내에서 MAPKs 세포신호 전달체계를 저해하는 올방개의 항염증 효과)

  • Kim, Kang-Hoon;Bae, Eun Young;Lim, Hyun Goo;Kim, Mi Heui;Oh, Tae-Seok;Lee, Seung Woong
    • Journal of Life Science
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    • v.30 no.5
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    • pp.476-482
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    • 2020
  • In rice agriculture, Eleocharis kuroguwai Ohwi (olbanggae) is a target for herbicidal intervention as a problem weed although it has also long been used clinically as a traditional medicine for jaundice, fever, and blood flow. E. kuroguwai has been evaluated in many clinical trials, but its molecular biological advantages are still unknown. Here, we investigate the anti-inflammatory effects of E. kuroguwai 80% ethanol extracts by screening NO production in LPS-induced macrophage activation. To find the most effective fractions, we partitioned five sub-fractions using HP20 column chromatography, namely 20%, 40%, 60%, 80%, and 100%. Of these, the 60% and 80% sub-fractions were found to significantly inhibit NO production; there were no toxicological effects at any concentration. In addition, the 80% sub-fraction inhibited significantly the iNOS and the mRNA of the pro-inflammatory mediators IL-6, TNF-α, and IL-1β by inhibiting the phosphorylation of JNK and ERK pathways associated with MAPKs signaling. Our results suggest that the 80% E. kuroguwai sub-fraction has the most significant anti-inflammatory effects of inhibiting iNOS and pro-inflammatory mediators and suppressing the phosphorylation of JNK and ERK. Therefore, the 80% sub-fraction of E. kuroguwai extract may be a therapeutic candidate for inflammatory diseases associated with the overexpression of MAPKs.

An Appropriateness Evaluation of Cesarean Section, Cholecystectomy, and Admission in Pediatric Pneumonia (입원과 수술시행의 적정성 평가)

  • Kim, Chang-Yup;Ahn, Hyeong-Sik;Lee, Young-Seong;Kwon, Young-Dae;Kim, Yong-Ik;Shin, Young-Soo
    • Journal of Preventive Medicine and Public Health
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    • v.25 no.4 s.40
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    • pp.413-428
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    • 1992
  • The aim of this study was to evaluate the appropriateness of some kinds of surgery and admission, such as cesarean section (C/S), cholecystectomy, and pediatric pneumonia. For appropriateness evaluation, we ourselves developed some criteria, which were included in the category of explicit and linear criteria, with the assistance of specialists of relevant clinical field. The evaluation of appropriateness was performed by two family physicians. The major findings were as follows: 1. For cesarean section, 77.6% of deliveries were determined to be 'appropriate', but the level of appropriateness was not significantly different among hospitals and between hospital groups by size. The most freqeunt indication of C/S was repeated operation, followed by cephalopelvic disproportion (CPD). The labor trials for vaginal delivery among repeated C/S and CPD cases were performed in 24.5% of pertinent deliveries. 2. About 73.8% of cholecystectomy cases was appropriate to one of the surgical indications, without significant differences among hospitals. Of surgical indications, 'sufficiently frequent and intense symptom recurrence' was the most frequent, and 'confirmed acute cholecystitis' was the second. 3. Of children admitted due to pneumonia, only 57.4% of cases satisfied admission criteria, and the level of appropriateness of admission was different among hospitals. The common reasons fur admission were 'failure to initial treatment', 'suspected bacterial pneumonia', 'young infant', etc. We could find that there were differences of quality among hospitals in some procedures, especially in the pediatric pneumonia and labor trial before C/S, which suggested that the implementation of quality assurance activiteis would be necessary in this country. In this study, we used some simple and primitive research tools and the numbers of subjects and tracer procedures were limited. So advanced studios with plentiful subjects and more representative diseases or procedures should be tried.

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Current Trends and Recent Advances in Diagnosis, Therapy, and Prevention of Hepatocellular Carcinoma

  • Wang, Chun-Hsiang;Wey, Keh-Cherng;Mo, Lein-Ray;Chang, Kuo-Kwan;Lin, Ruey-Chang;Kuo, Jen-Juan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3595-3604
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    • 2015
  • Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

Feasibility Study of Case-Finding for Breast Cancer by Community Health Workers in Rural Bangladesh

  • Chowdhury, Touhidul Imran;Love, Richard Reed;Chowdhury, Mohammad Touhidul Imran;Artif, Abu Saeem;Ahsan, Hasib;Mamun, Anwarul;Khanam, Tahmina;Woods, James;Salim, Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7853-7857
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    • 2015
  • Background: Mortality from breast cancer is high in low- and middle-income countries, in part because most patients have advanced stage disease when first diagnosed. Case-finding may be one approach to changing this situation. Materials and Methods: We conducted a pilot study to explore the feasibility of population-based case finding for breast cancer by community health workers (CHWs) using different data collection methods and approaches to management of women found to have breast abnormalities. After training 8 CHWs in breast problem recognition, manual paper data collection and operation of a cell-phone software platform for reporting demographic, history and physical finding information, these CHWs visited 3150 women >age 18 and over they could find-- from 2356 households in 8 villages in rural Bangladesh. By 4 random assignments of villages, data were collected manually (Group 1), or with the cell-phone program alone (Group 2) or with management algorithms (Groups 3 and 4), and women adjudged to have a serious breast problem were shown a motivational video (Group 3), or navigated/accompanied to a breast problem center for evaluation (Group 4). Results: Only three visited women refused evaluation. The manual data acquisition group (1) had missing data in 80% of cases, and took an average of 5 minutes longer to acquire, versus no missing data in the cell phone-reporting groups (2,3 and 4). One woman was identified with stage III breast cancer, and was appropriately treated. Conclusions: Among very poor rural Bangladeshi women, there was very limited reluctance to undergo breast evaluation. The estimated rarity of clinical breast cancer is supported by these population-based findings. The feasibility and efficient use of mobile technology in this setting is supported. Successor studies may most appropriately be trials focusing on improving the suggested benefits of motivation and navigation, on increasing the numbers of cases found, and on stage of disease at diagnosis as the primary endpoint.

Comparison of Survival Prediction of Rats with Hemorrhagic Shocks Using Artificial Neural Network and Support Vector Machine (출혈성 쇼크를 일으킨 흰쥐에서 인공신경망과 지원벡터기계를 이용한 생존율 비교)

  • Jang, Kyung-Hwan;Yoo, Tae-Keun;Nam, Ki-Chang;Choi, Jae-Rim;Kwon, Min-Kyung;Kim, Deok-Won
    • Journal of the Institute of Electronics Engineers of Korea SC
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    • v.48 no.2
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    • pp.47-55
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    • 2011
  • Hemorrhagic shock is a cause of one third of death resulting from injury in the world. Early diagnosis of hemorrhagic shock makes it possible for physician to treat successfully. The objective of this paper was to select an optimal classifier model using physiological signals from rats measured during hemorrhagic experiment. This data set was used to train and predict survival rate using artificial neural network (ANN) and support vector machine (SVM). To avoid over-fitting, we chose the best classifier according to performance measured by a 10-fold cross validation method. As a result, we selected ANN having three hidden nodes with one hidden layer and SVM with Gaussian kernel function as trained prediction model, and the ANN showed 88.9 % of sensitivity, 96.7 % of specificity, 92.0 % of accuracy and the SVM provided 97.8 % of sensitivity, 95.0 % of specificity, 96.7 % of accuracy. Therefore, SVM was better than ANN for survival prediction.

A Study of the Effects of Gold and Stone Therapies on Changes in Body Size in the Neck, Back and Shoulder (골드테라피와 스톤테라피가 목, 등, 어깨 부위 신체 치수 변화에 미치는 영향 연구)

  • Lee, Jin-Young;Jeong, Yeon-Jeong;Li, Shun-Hua
    • Journal of Digital Convergence
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    • v.15 no.8
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    • pp.465-476
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    • 2017
  • This study attempted to investigate the effects of gold therapy on myofascial pain syndrome(MPS) in the neck, back and shoulder in comparison to stone therapy and verify its availability as an efficient nursing mediator in clinical trials. For this, therapy was given to a total of 20 women in two groups (gold therapy group, stone therapy group: 10 persons each) living in the capital region three times a week (40 min. at a time) for two weeks. In both groups, a statistically significant decrease was found in the following after the treatment: neck circumference, shoulder width, width of the inferior angle of scapula, shoulder thickness and waist circumference (p<0.001). In terms of differences, the gold therapy group was greater than the stone therapy group. In both groups, a statistically significant increase was observed after treatment in the following: cervical lateral bending (right), cervical lateral bending (left), cervical flexion and cervical extension angle (p<0.001). In terms of differences, the gold therapy group was greater than the stone therapy group. In conclusion, this study seems to show that gold therapy is a nursing intervention option having effective fascial relaxation and pain relief for the neck, back and shoulder. Therefore, it would be valuable as safe, non-invasive therapy.

The Burden of Atopic Dermatitis on Children and Their Families : Quality of Life and Financial Impact in Seoul Area (서울 지역을 대상으로 모집된 유.소아기 아토피피부염 환아의 삶의 질과 경제적 비용 부담에 관한 조사)

  • Yu, Seung-Min;Choi, In-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.3
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    • pp.122-137
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    • 2010
  • Objective : Atopic dermatitis (AD) in children may profoundly affect the quality of life (QOL), and also cause financial burden, to the families of those suffering from this ailment. The aim of our study was to examine the quality of life and the financial burden of atopic dermatitis in children and their families to evaluate this relationship with the degree of AD. Methods : 37 infant and child atopic dermatitis patients were included and evaluated using the SCORing of Atopic Dermatitis (SCORAD) Index and Eczema Area and Severity Index (EASI). Patients and carers were asked to fill in the questionnaires about their quality of life and financial costs during the past year. Data about sleep disturbance and pruritus were also obtained. Pearson's correlation was used for statistical analysis. Results : 1. The mean score of Children's Dermatology Life Quality Index (CDLQI) was $10.52{\pm}4.82$, Infants' Dermatologic Quality of Life (IDQOL) was $8.21{\pm}3.95$. 2. The mean score of Family Dermatology Life Quality Index (FDLQI) was $13.30{\pm}5.72$, Dermatitis Family Impact (DFI) was $12.5{\pm}4.98$. 3. By analyzing the questionnaire, the monthly average cost was determined to be 730,800 won for each patient : the direct cost was 283,500 won, and the indirect cost was 447,300 won. 4. By analyzing the correlation between the severity of AD and QOL, subjective SCORAD were significantly and positively correlated with QOL(IDQOL, FDLQI, DFI, CDLQI). 5. By analyzing the correlation between the severity of AD and any economic impact, EASI were significantly and positively correlated with the direct cost. Conclusion : The above results show that the QOL of the patients and carers is significantly related to their disease severity. Atopic dermatitis patients pay an average of 730,800 won a month, and the economic impact on the patients is significantly related to their disease severity. The CDLQI, IDQOL, FDLQI and DFImay potentially be of value to help in the appropriate management of AD and can be used as an added measurement in clinical trials involving AD management.

Effects of Integrated Palliative Care Intervention on Quality of Life in Terminal Cancer Patients: A Meta-analysis (통합적 완화 돌봄 중재가 말기암환자의 삶의 질에 미치는 효과: 메타분석)

  • Jo, Kae Hwa;Park, Ae Ran;Lee, Jin Ju
    • Journal of Hospice and Palliative Care
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    • v.18 no.2
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    • pp.136-147
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    • 2015
  • Purpose: This study was conducted to evaluate the effects of integrated palliative care intervention on quality of life in terminally ill patients. Methods: A comprehensive literature search was performed via PubMed, Cochrane Library CENTRAL, LWW (Ovid), CINAHL and several Korean databases. The main search strategy was to combine terms indicating palliative care intervention, presence of terminal illness and study design. Methodological quality was assessed using Cochrane's Risk of Bias for randomized studies and Risk of Bias Assessment tool for non-randomized studies. Data were analyzed by the Stata 10 program. Results: Eight clinical trials met the inclusion criteria with a total of 356 participants. Integrated palliative care interventions were administered for a mean of 6.5 weeks, 5.6 sessions and an average of 47.8 minutes per session. Effect sizes were heterogeneous, and subgroup analysis was done. Integrated palliative care interventions had a significant effect on quality of life (ES=1.83, P=0.018, $l^2=92%$), spiritual well-being (ES=0.78, P=0.040, $l^2=0$), depression (ES=0.86, P<0.001, $l^2=32$) and anxiety (ES=0.69, P=0.041, $l^2=71.1$). But integrated palliative care interventions had no significant effect on pain (ES=0.365, P=0.230, $l^2=69.8$). Conclusion: Results support findings that integrated palliative care interventions were helpful in lessening depression and anxiety and improving quality of life and spiritual well-being, however, the interventions did not assist pain management in terminal cancer patients. These findings suggest that various integrated palliative care interventions can assist terminal cancer patients with better quality of life in the socio-psycho-spiritual dimension.