• Title/Summary/Keyword: Precision medicine

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Cantharidin Overcomes Imatinib Resistance by Depleting BCR-ABL in Chronic Myeloid Leukemia

  • Sun, Xiaoyan;Cai, Xueting;Yang, Jie;Chen, Jiao;Guo, Caixia;Cao, Peng
    • Molecules and Cells
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    • v.39 no.12
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    • pp.869-876
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    • 2016
  • Cantharidin (CTD) is an active compound isolated from the traditional Chinese medicine blister beetle and displayed anticancer properties against various types of cancer cells. However, little is known about its effect on human chronic myeloid leukemia (CML) cells, including imatinib-resistant CML cells. The objective of this study was to investigate whether CTD could overcome imatinib resistance in imatinib-resistant CML cells and to explore the possible underlying mechanisms associated with the effect. Our results showed that CTD strongly inhibited the growth of both imatinib-sensitive and imatinib-resistant CML cells. CTD induced cell cycle arrest at mitotic phase and triggered DNA damage in CML cells. The ATM/ATR inhibitor CGK733 abrogated CTD-induced mitotic arrest but promoted the cytotoxic effects of CTD. In addition, we demonstrated that CTD downregulated the expression of the BCR-ABL protein and suppressed its downstream signal transduction. Real-time quantitative PCR revealed that CTD inhibited BCR-ABL at transcriptional level. Knockdown of BCR-ABL increased the cell-killing effects of CTD in K562 cells. These findings indicated that CTD overcomes imatinib resistance through depletion of BCR-ABL. Taken together, CTD is an important new candidate agent for CML therapy.

Comparison of formaldehyde concentration in working environment between passive sampling method and impinger sampling method (능동포집법과 확산포집법에 의한 작업환경 중 포름알데히드 농도 비교)

  • Ham, Seong-Ae;Mun, Deok-Hwan
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.16 no.4
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    • pp.346-355
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    • 2006
  • The purpose of this study was conducted to ascertain the difference between impinger and passive sampling methods in the process of sampling and analyzing on airborne formaldehyde. Formaldehyde generating workplaces included in this study comprised four types of manufacturing industry such as two workplaces of products of wood, cork, straw and plaiting materials manufacturing industries, one casting metal manufacturing industry, and one parts and accessories for motor vehicles and it′s engines manufacturing industry. Workplaces contained in this study were located in some manufacturing area of Busan industrial complex and this study was carried out during a period from January 2003 to December 2004. Analytical accuracy, precision and detection limit of two methods was compared. Exposure level of its airborne concentration was evaluated in formaldehyde generating workplaces those were classified by types of industry, working process, and time. The results were as follows ; 1. A rate of recovery was 107.1% in impinger method and 101.8% in passive method, and precision was 7.79% in impinger method and 4.40% in passive method. There was no statistical significance in analytical accuracy and precision between two methods. A limitation of detection was 0.011 ppm in passive method which was lower than that of impinger method (0.020 ppm) by 1.8 times. 2. Airborne formaldehyde concentration of impinger method was different from passive method. It′s concentration by passive method was higher by 5.1 times than that by impinger method in the parts and accessories for motor vehicles and it′s engines manufacturing industry (P<0.05). Only in molding process among several types of processes, formaldehyde concentration in passive method was higher by 5.1 times than that in impinger method (P<0.05). Furthermore, formaldehyde concentration in passive method was higher by 1.7 times than that in impinger method (P<0.05) in the first half of year 2003. 3. The geometric mean of formaldehyde concentration in impinger method was lower than that in passive method, but there was no statistical significance of formaldehyde concentration by the difference of sampling method. In conclusion, it is difficult to conclude which is better between the two sampling methods because of no statistical significance for the difference of concentration. Because of lacks of certified passive sampling and analytical method, at present situation, studies on verification of accuracy and precision, obstructive reaction against validity on its exposure assessment, and research to develop domestically manufactured passive sampler in terms of cost-effectiveness should be continuously carried out.

Development of Sequential Sampling Plan for Bemisia tabaci in Paprika Greenhouses (파프리카 온실에서 담배가루이의 축차표본조사법 개발)

  • Choi, Wonseok;Park, Jung-Joon
    • Korean journal of applied entomology
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    • v.54 no.3
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    • pp.159-167
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    • 2015
  • In order to establish B. tabaci control in paprika greenhouses a fixed-precision-level sampling plan was developed. The sampling plan consisted of spatial distribution analysis, a sampling stop line, and decision making. Sampling was conducted simultaneously in two independent greenhouses (GH 1, GH 2). GH 1 and 2 were surveyed every week for 22 consecutive weeks, using 19 sampling locations in GH 1 and 9 sampling locations in GH 2. The plant in both greenhouses were divided into top (180-220 cm from the ground), middle (80-120 cm from the ground) and bottom (30-70 cm from the ground) sections and B. tabaci adults and pupae were observed on three paprika leaves at each position and recorded separately. GH 2 data were used to validate the fixed-precision sampling plan, which was developed using GH 1 data. In this study, spatial distribution analysis was performed using Taylor's power law with the pooled data of the top and bottom position (B. tabaci adults), and the middle and bottom positions (B. tabaci pupae), based on a 1-leaf sampling unit. Decision making was undertaken using the maximum of action threshold in accordance with previously published method, and the value was decided by the price of the plants. Using the results obtained in the greenhouse, simulated validation of the developed sampling plan by RVSP (Resampling Validation for Sampling Plan) indicated a reasonable level of precision.

Analysis Study on the Detection and Classification of COVID-19 in Chest X-ray Images using Artificial Intelligence (인공지능을 활용한 흉부 엑스선 영상의 코로나19 검출 및 분류에 대한 분석 연구)

  • Yoon, Myeong-Seong;Kwon, Chae-Rim;Kim, Sung-Min;Kim, Su-In;Jo, Sung-Jun;Choi, Yu-Chan;Kim, Sang-Hyun
    • Journal of the Korean Society of Radiology
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    • v.16 no.5
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    • pp.661-672
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    • 2022
  • After the outbreak of the SARS-CoV2 virus that causes COVID-19, it spreads around the world with the number of infections and deaths rising rapidly caused a shortage of medical resources. As a way to solve this problem, chest X-ray diagnosis using Artificial Intelligence(AI) received attention as a primary diagnostic method. The purpose of this study is to comprehensively analyze the detection of COVID-19 via AI. To achieve this purpose, 292 studies were collected through a series of Classification methods. Based on these data, performance measurement information including Accuracy, Precision, Area Under Cover(AUC), Sensitivity, Specificity, F1-score, Recall, K-fold, Architecture and Class were analyzed. As a result, the average Accuracy, Precision, AUC, Sensitivity and Specificity were achieved as 95.2%, 94.81%, 94.01%, 93.5%, and 93.92%, respectively. Although the performance measurement information on a year-on-year basis gradually increased, furthermore, we conducted a study on the rate of change according to the number of Class and image data, the ratio of use of Architecture and about the K-fold. Currently, diagnosis of COVID-19 using AI has several problems to be used independently, however, it is expected that it will be sufficient to be used as a doctor's assistant.

Accuracy of FDG-PET/CT for Detection of Incidental Pre-Malignant and Malignant Colonic Lesions - Correlation with Colonoscopic and Histopathologic Findings

  • Kunawudhi, Anchisa;Wong, Alexandra K;Alkasab, Tarik K;Mahmood, Umar
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.4143-4147
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    • 2016
  • Purpose: We evaluated all PET/CTs acquired for patients without a primary diagnosis of colorectal cancer, and compared results for those who had subsequent colonoscopy within 6 months, to assess the accuracy of FDG PET/CT for detection of incidental pre-malignant polyps and malignant colon cancers. Materials and Methods: Medical records of 9,545 patients who underwent F-18 FDG PET/CT studies over 3.5 years were retrospectively reviewed. Due to pre-existing diagnosis of colorectal cancer, 818 patients were excluded. Of the remainder, 157 patients had colonoscopy within 6 months (79 males; mean age 61). We divided the colon into 4 regions and compared PET/CT results for each region with colonoscopy and histopathologic findings. True positive lesions included colorectal cancer, villous adenoma, tubulovillous adenoma, tubular adenoma and serrated hyperplastic polyp/hyperplastic polyposis. Results: Of 157 patients, 44 had incidental colonic uptake on PET/CT (28%). Of those, 25 had true positive (TP) uptake, yielding a 48% positive predictive value (PPV); 9% (4/44) were adenocarcinoma. There were 23 false positive (FP) lesions of which 4 were hyperplastic polyp, one was juvenile polyp and 7 were explained by diverticulitis. Fifty eight patients had false negative PET scans but colonoscopy revealed true pre-malignant and malignant pathology, yielding 23% sensitivity. The specificity, negiative predictive value (NPV) and accuracy were 96%, 90% and 87%, respectively. The average SUVmax values of TP, FP and FN lesions were 7.25, 6.11 and 2.76, respectively. There were no significant difference between SUVmax of TP lesions and FP lesions (p>0.95) but significantly higher than in FN lesions (p<0.001). The average size (by histopathology and colonoscopy) of TP lesions was 18.1 mm, statistically different from that of FN lesions which was 5.9 mm (p<0.001). Fifty-one percent of FN lesions were smaller than 5 mm (29/57) and 88% smaller than 10 mm (50/57). Conclusions: The high positive predictive value of incidental focal colonic FDG uptake of 48% for colonic neoplasia suggests that colonoscopy follow-up is warranted with this finding. We observed a low sensitivity of standardly acquired FDG-PET/CT for detecting small polyps, especially those less than 5 mm. Clinician and radiologists should be aware of the high PPV of focal colonic uptake reflecting pre-malignant and malignant lesions, and the need for appropriate follow up.

Cycle-Consistent Generative Adversarial Network: Effect on Radiation Dose Reduction and Image Quality Improvement in Ultralow-Dose CT for Evaluation of Pulmonary Tuberculosis

  • Chenggong Yan;Jie Lin;Haixia Li;Jun Xu;Tianjing Zhang;Hao Chen;Henry C. Woodruff;Guangyao Wu;Siqi Zhang;Yikai Xu;Philippe Lambin
    • Korean Journal of Radiology
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    • v.22 no.6
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    • pp.983-993
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    • 2021
  • Objective: To investigate the image quality of ultralow-dose CT (ULDCT) of the chest reconstructed using a cycle-consistent generative adversarial network (CycleGAN)-based deep learning method in the evaluation of pulmonary tuberculosis. Materials and Methods: Between June 2019 and November 2019, 103 patients (mean age, 40.8 ± 13.6 years; 61 men and 42 women) with pulmonary tuberculosis were prospectively enrolled to undergo standard-dose CT (120 kVp with automated exposure control), followed immediately by ULDCT (80 kVp and 10 mAs). The images of the two successive scans were used to train the CycleGAN framework for image-to-image translation. The denoising efficacy of the CycleGAN algorithm was compared with that of hybrid and model-based iterative reconstruction. Repeated-measures analysis of variance and Wilcoxon signed-rank test were performed to compare the objective measurements and the subjective image quality scores, respectively. Results: With the optimized CycleGAN denoising model, using the ULDCT images as input, the peak signal-to-noise ratio and structural similarity index improved by 2.0 dB and 0.21, respectively. The CycleGAN-generated denoised ULDCT images typically provided satisfactory image quality for optimal visibility of anatomic structures and pathological findings, with a lower level of image noise (mean ± standard deviation [SD], 19.5 ± 3.0 Hounsfield unit [HU]) than that of the hybrid (66.3 ± 10.5 HU, p < 0.001) and a similar noise level to model-based iterative reconstruction (19.6 ± 2.6 HU, p > 0.908). The CycleGAN-generated images showed the highest contrast-to-noise ratios for the pulmonary lesions, followed by the model-based and hybrid iterative reconstruction. The mean effective radiation dose of ULDCT was 0.12 mSv with a mean 93.9% reduction compared to standard-dose CT. Conclusion: The optimized CycleGAN technique may allow the synthesis of diagnostically acceptable images from ULDCT of the chest for the evaluation of pulmonary tuberculosis.

Evolution of Radiological Treatment Response Assessments for Cancer Immunotherapy: From iRECIST to Radiomics and Artificial Intelligence

  • Nari Kim;Eun Sung Lee;Sang Eun Won;Mihyun Yang;Amy Junghyun Lee;Youngbin Shin;Yousun Ko;Junhee Pyo;Hyo Jung Park;Kyung Won, Kim
    • Korean Journal of Radiology
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    • v.23 no.11
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    • pp.1089-1101
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    • 2022
  • Immunotherapy has revolutionized and opened a new paradigm for cancer treatment. In the era of immunotherapy and molecular targeted therapy, precision medicine has gained emphasis, and an early response assessment is a key element of this approach. Treatment response assessment for immunotherapy is challenging for radiologists because of the rapid development of immunotherapeutic agents, from immune checkpoint inhibitors to chimeric antigen receptor-T cells, with which many radiologists may not be familiar, and the atypical responses to therapy, such as pseudoprogression and hyperprogression. Therefore, new response assessment methods such as immune response assessment, functional/molecular imaging biomarkers, and artificial intelligence (including radiomics and machine learning approaches) have been developed and investigated. Radiologists should be aware of recent trends in immunotherapy development and new response assessment methods.

Comparison Study of AAS and ISE Method in the Lithium Analysis of Serum and Urine (혈액 및 소변의 Lithium치 측정에 있어서 AAS법과 ISE법의 비교)

  • Lee, Soo-In;Lee, Chae-Hoon;Kim, Kyung-Dong;Kim, Chung-Sook
    • Journal of Yeungnam Medical Science
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    • v.10 no.2
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    • pp.409-416
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    • 1993
  • In the method for lithium (Li) analysis, flame emission photometry and atomic absorption spectrophotometry (AAS) have been used most frequently. In addition, lithium can be analyzed by ion-selective electrode (ISE) or fluorscence polarization immunoassay. We evaluated the comparison between AAS method based on the principle of absorption of light at 670.8 nm by Li and ISE method based on the principle of voltage difference generated by Li in contact with lithium ionophore. We compared with those obtained by AAS (AA/AE Spectrophotometer 551, Instrumentation Laboratory Co.) and ISE(CSYNCHRON EL-ISE, Beckman Co.) in the serum and urine of 6 patients and evaluated time-related changes of serum lithium concentration after dosing in both methods. The results are summarized as follows : 1. In within-run precision study for lithium concentration, coefficient variations (CVs, %) ranged from 1.34 to 2.17 for AAS and from 0.34 to 0.85 for ISE method. In between-run precision study for lithium concentration, CVs ranged from 1.23 to 1.72 for AAS and from 0.61 to 1.38 for ISE method. 2. The correlation study between AAS and ISE method resulted in Y=0.946X+0.137 (N=32, r=0.933, X=AAS, Y=ISE) for serum lithium and Y=1.092X+0.977 (N=28, r=0.943, X=AAS, Y=ISE) for urine lithium. 3. Time-related changes of serum lithium concentration in both AAS and ISE method resulted in peak serum levels about 2 hours after dosing and then rapidly decreased after the peak serum level and finally arrived at nearly initial levels about 9 hours after dosing. 4. The reference range of serum lithium was found as undetectable level for both AAS and ISE method and the reference range of urine lithium to the urine creatinine was 0-0.00014 mmol/mg(mean 0.00002 mmol/mg) for AAS method.

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Simultaneous Determination of Seven Compounds by HPLC-PDA and Cytotoxicity of Samchulkunbi-tang (삼출건비탕의 HPLC-PDA 동시 분석법 설정 및 세포독성)

  • Seo, Chang-Seob;Lee, Mee-Young;Kim, Jung-Hoon;Lee, Jin-Ah;Shin, Hyeun-Kyoo
    • The Korea Journal of Herbology
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    • v.25 no.3
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    • pp.65-71
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    • 2010
  • Objectives:To develop and validate HPLC-PDA methods for simultaneous determination of seven constituents in Samchulkunbi-tang (SKT). Additionally, we investigated the cytotoxicity against BEAS-2B cell line and splenocytes of SKT. Methods:Reverse-phase chromatography using a Gemini $C_{18}$ column operating at $40^{\circ}C$, and photodiode array (PDA) detection at 230, 254 and 280 nm, were used for quantification of the three marker components of SKT. The mobile phase using a gradient flow consisted of two solvent systems. Solvent A was 1.0% (v/v) aqueous acetic acid and solvent B was acetonitrile with 1.0% (v/v) acetic acid. The cytotoxicity of SKT were measured by the CCK-8 assay method. Results:Calibration curves were acquired with $r^2$>0.9999, and the relative standard deviation (RSD) values (%) for intra- and inter-day precision were less than 6.0%. The recovery rate of each compound was in the range of 86.89-109.78%, with an RSD less than 4.0%. The contents of seven compounds in SKT were 1.39-6.84 mg/g. SKT had no cytotoxicity effect at 50-200 ${\mu}g$/mL concentrations. Conclusions:The established method will be helpful to improve quality control and in vitro efficacy study of SKT.

Weighting Method based on Experts Opinions for Obesity Syndrome Differentiation Questionnaire (전문가 가중치 부여를 통한 비만변증설문지 적용)

  • Moon, Jin-Seok;Kang, Byung-Kab;Kang, Kyung-Won;Shin, Woo-Jin;Shin, Mi-Sook;Choi, Sun-Mi
    • Journal of Korean Medicine for Obesity Research
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    • v.8 no.1
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    • pp.53-61
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    • 2008
  • Objectives We have investigated a questionnaire on syndrome differentiation pertaining to obesity. To calculate data from this questionnaire, we can simply sum up the degree of symptoms. However, this does not reflect the difference in contribution of syndrome differentiation. In order to improve the level of precision of this questionnaire, we gather the weight of each symptom from experts and apply them to overweight persons. Method Nine Experts from The Society of Korean Medicine for Obesity Research nominated weights for the symptoms. We created a program based on weight survey results and applied to 1487 overweight persons and 26 oriental medical doctors. The concordance rate between the result obtained from the oriental medical doctors and that obtained using three methods was analyzed. Results 1. The reliability of this questionnaire is very high (Cronbach' ${\alpha}$=0.963). 2. The concordance level between diagnosis by oriental medical doctors and the result of general calculation is 0.347, between diagnosis by oriental medical doctors and the result of weighted calculation by syndrome differentiation is 0.362, between diagnosis by oriental medical doctors and the result of weighted calculation by symptoms is 0.1. Conclusions Weighted calculation by syndrome differentiation is relative more appropriate among three methods studied.

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