• Title/Summary/Keyword: Precision medicine

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CDKN2 expression is a potential biomarker for T cell exhaustion in hepatocellular carcinoma

  • Shibo Wei;Yan Zhang;Baeki E. Kang;Wonyoung Park;He Guo;Seungyoon Nam;Jong-Sun Kang;Jee-Heon Jeong;Yunju Jo;Dongryeol Ryu;Yikun Jiang;Ki-Tae Ha
    • BMB Reports
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    • v.57 no.6
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    • pp.287-292
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    • 2024
  • Hepatocellular Carcinoma (HCC), the predominant primary hepatic malignancy, is the prime contributor to mortality. Despite the availability of multiple surgical interventions, patient outcomes remain suboptimal. Immunotherapies have emerged as effective strategies for HCC treatment with multiple clinical advantages. However, their curative efficacy is not always satisfactory, limited by the dysfunctional T cell status. Thus, there is a pressing need to discover novel potential biomarkers indicative of T cell exhaustion (Tex) for personalized immunotherapies. One promising target is Cyclin-dependent kinase inhibitor 2 (CDKN2) gene, a key cell cycle regulator with aberrant expression in HCC. However, its specific involvement remains unclear. Herein, we assessed the potential of CDKN2 expression as a promising biomarker for HCC progression, particularly for exhausted T cells. Our transcriptome analysis of CDKN2 in HCC revealed its significant role involving in HCC development. Remarkably, single-cell transcriptomic analysis revealed a notable correlation between CDKN2 expression, particularly CDKN2A, and Tex markers, which was further validated by a human cohort study using human HCC tissue microarray, highlighting CDKN2 expression as a potential biomarker for Tex within the intricate landscape of HCC progression. These findings provide novel perspectives that hold promise for addressing the unmet therapeutic need within HCC treatment.

Experimental studies of validation and stability of Sweet Bee Venom using HPLC (Sweet BV의 조제물 농도분석 및 안정성 확인을 위한 시험적 연구)

  • Kang, Kye-Sung;Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.12 no.4
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    • pp.33-50
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    • 2009
  • Objectives : This study was conducted to confirm validation and stability of concentration analysis method of pure melittin (Sweet Bee Venom-Sweet BV) extracted from the bee venom by utilizing protein isolation method of gel filtration. Methods : All experiments were conducted at Biotoxtech, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP). Standard solutions of melittin (SIGMA, USA) and test substances were dispensed and were analyzed with HPLC for Sweet BV to secure the validation of analysis. Results : 1. Measurement of system suitability of Sweet BV satisfied criterion of below 3%. 2. Confirming Linearity of Sweet BV in 10-200${\mu}g/m\ell$ solution yielded correlation coefficient (r) of 0.995 and accuracy of 85-115% which satisfy criterion. 3. Measurement of Specificity of Sweet BV didn't yield any substance affecting the peak of test substances, but detected at 21.22min verified as the test substance. 4. Confirming Intra-day of Sweet BV, accuracy and precision of 0.1, 100${\mu}g/m\ell$ were 105.70, 95.81 and 0.66, 0.73, respectively, satisfying both criteria of accuracy (85-115%) and precision (within 10%). 5. To measure Stability in autosampler, all samples used in Intra-day reproducibility sat in the autosampler for five hours and were re-analyzed. Both variability and precision satisfied the criteria. 6. Homogeneity of Sweet BV (0.1, 100${\mu}g/m\ell$) at upper, middle, and lower layers all satisfied the accuracy and precision criteria. 7. Stability of Sweet BV (0.1, 100${\mu}g/m\ell$) at room temperature for four hours and refrigerated for 7 days all satisfied the criterion. 8. For the measurement of Quality control, QC samples measured on the first and eighth day all satisfied accuracy and precision criteria. Conclusion : Above experiment data satisfies validation and stability of concentration analysis method of Sweet BV.

Treatment strategies targeting specific genetic etiologies in epilepsy

  • Kim, Hyo Jeong;Kang, Hoon-Chul
    • Journal of Genetic Medicine
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    • v.18 no.1
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    • pp.8-15
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    • 2021
  • Recent genetic advances allow for identification of the genetic etiologies of epilepsy within individual patients earlier and more frequently than ever. Specific targeted treatments have emerged from improvements in understanding of the underlying epileptogenic pathophysiology. These targeted treatment strategies include modifications of ion channels or other cellular receptors and their function, mechanistic target of rapamycin signaling pathways, and substitutive therapies in hereditary metabolic epilepsies. In this review, we explore targeted treatments based on underlying pathophysiologic mechanisms in specific genetic epilepsies.

POSSIBILITY OF NONDESTRUCTIVE ANALYSIS OF CHOLESTEROL AND COLLAGEN IN ATHEROSCLEROTIC PLAQUES USING NIRS

  • Neumeister, Volker;Lattke, Peter;Schuh, Dieter;Knuschke, Peter;Reber, Friedemann;Steiner, Gerald;Jaross, Werner
    • Proceedings of the Korean Society of Near Infrared Spectroscopy Conference
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    • 2001.06a
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    • pp.4103-4103
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    • 2001
  • The aim of this study was to examine whether near infrared spectroscopy (NIRS) is an acceptable tool to determine cholesterol and collagen in human atherosclerotic plaque without destruction of the analyzed areas and without danger the endothelial cells - three preconditions for the development of a NIR-heart-catheter. The questions were: Can the cholesterol and collagen content of the arterial intima be estimated with acceptable precision in vitro by NIRS despite the matrix inhomogeneity of the plaques and their anatomic variability\ulcorner How deep can such NIR radiation penetrate into arterial tissue without danger for endothelial cells\ulcorner Is this penetration sufficient for information on the lipid and collagen accumulation\ulcorner Using NIRS, cholesterol and collagen can be determined with acceptable precision in model mixtures and human aortic specimens (r=0,896 to 0,957). The chemical reference method was HPLC. The energy dose was 71 mW/$cm^{-2}$ using a fiber optic strand with a length of 1.5m and an optical window of d=4mm. This dose appears to be not dangerous for endothelial cells, It will be attenuated to 50% by a arterial tissue of about 170-$200\mu\textrm{m}$ thickness. The results are also acceptable using a thin coronary catheter-like fiber optic strand (d=1mm).

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The Precision Test Based on States of Bone Mineral Density (골밀도 상태에 따른 검사자의 재현성 평가)

  • Yoo, Jae-Sook;Kim, Eun-Hye;Kim, Ho-Seong;Shin, Sang-Ki;Cho, Si-Man
    • The Korean Journal of Nuclear Medicine Technology
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    • v.13 no.1
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    • pp.67-72
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    • 2009
  • Purpose: ISCD (International Society for Clinical Densitometry) requests that users perform mandatory Precision test to raise their quality even though there is no recommendation about patient selection for the test. Thus, we investigated the effect on precision test by measuring reproducibility of 3 bone density groups (normal, osteopenia, osteoporosis). Materials and Methods: 4 users performed precision test with 420 patients (age: $57.8{\pm}9.02$) for BMD in Asan Medical Center (JAN-2008 ~ JUN-2008). In first group (A), 4 users selected 30 patient respectively regardless of bone density condition and measured 2 part (L-spine, femur) in twice. In second group (B), 4 users measured bone density of 10 patients respectively in the same manner of first group (A) users but dividing patient into 3 stages (normal, osteopenia, osteoporosis). In third group (C), 2 users measured 30 patients respectively in the same manner of first group (A) users considering bone density condition. We used GE Lunar Prodigy Advance (Encore. V11.4) and analyzed the result by comparing %CV to LSC using precision tool from ISCD. Check back was done using SPSS. Results: In group A, the %CV calculated by 4 users (a, b, c, d) were 1.16, 1.01, 1.19, 0.65 g/$cm^2$ in L-spine and 0.69, 0.58, 0.97, 0.47 g/$cm^2$ in femur. In group B, the %CV calculated by 4 users (a, b, c, d) were 1.01, 1.19, 0.83, 1.37 g/$cm^2$ in L-spine and 1.03, 0.54, 0.69, 0.58 g/$cm^2$ in femur. When comparing results (group A, B), we found no considerable differences. In group C, the user_1's %CV of normal, osteopenia and osteoporosis were 1.26, 0.94, 0.94 g/$cm^2$ in L-spine and 0.94, 0.79, 1.01 g/$cm^2$ in femur. And the user_2's %CV were 0.97, 0.83, 0.72 g/$cm^2$ L-spine and 0.65, 0.65, 1.05 g/$cm^2$ in femur. When analyzing the result, we figured out that the difference of reproducibility was almost not found but the differences of two users' several result values have effect on total reproducibility. Conclusions: Precision test is a important factor of bone density follow up. When Machine and user's reproducibility is getting better, it’s useful in clinics because of low range of deviation. Users have to check machine's reproducibility before the test and keep the same mind doing BMD test for patient. In precision test, the difference of measured value is usually found for ROI change caused by patient position. In case of osteoporosis patient, there is difficult to make initial ROI accurately more than normal and osteopenia patient due to lack of bone recognition even though ROI is made automatically by computer software. However, initial ROI is very important and users have to make coherent ROI because we use ROI Copy function in a follow up. In this study, we performed precision test considering bone density condition and found LSC value was stayed within 3%. There was no considerable difference. Thus, patient selection could be done regardless of bone density condition.

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Usefulness of Manual Analysis of Bone Mineral Density Using Dual Energy X-ray Absorptiometry (이중에너지엑스선흡수기(Dual energy X-ray Absorptiometry: DXA)를 이용한 골밀도검사 결과분석에서 수동분석법의 유용성 평가)

  • Kim, Eun Hye;Kwak, Jong Gil;Kim, Ho Sung
    • Journal of Radiation Industry
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    • v.12 no.4
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    • pp.317-324
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    • 2018
  • The results of bone mineral density analysis using DXA were compared between automatic and manual methods. The purpose of this paper is to verify the range of errors of each analysis method in the same patient and select a proper method to minimize errors. Comparisons between automatic and manual analysis methods were made using BMD, BMC and AREA. Basal and follow up examinations were performed with the patients of normal, osteopenia and osteoporosis. In the basal examinations, the precision errors between automatic and manual method showed 1.9% in normal, 3.1% in osteopenia and 3.8% in osteoporosis. In case of follow up studies, the precision errors between automatic and manual method showed 2.3% in normal, 3.2% in osteopenia and 3.5% in osteoporosis. BMC and AREA also showed a tendency to increase precision errors on osteopenia and osteoporosis. Therefore, a manual method would be a better option to minimize errors in patients with osteopenia and osteoporosis.

Comparison of F-18 FDG Radioacitivity to Determine Accurate Dose Calibrator Activity Measurements (방사능 측정기를 이용한 F-18 FDG 방사능의 비교)

  • Jin, Gye-Hwan;Kweon, Dae-Cheol;Oh, Ki-Baek;Park, Hoon-Hee;Kim, Jung-Yul;Park, Min-Soo;Park, Dae-Sung
    • Progress in Medical Physics
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    • v.20 no.3
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    • pp.159-166
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    • 2009
  • Obviously, the administration of the prescribed amount of activity to the patient requires proper operation of the dose calibrator, which shall be verified by implementing the required quality control on the instrument. This investigation examined the accuracy and precision of dose calibrator activity measurement of the radiopharmaceutical F-18 FDG. To investigate the status of the nuclear medicine centers in Korea for the performance of dose calibrators, 10 centers providing PET/CT system services in Korea were inspected in 2008. We measured accuracy and precision in 10 equipments in consideration of PET/CT model, installation area, and installation time. According to the results of comparative analysis of 10 dose calibrators used to measure radioactivity of F-18 FDG, accuracy was -5.00~4.50% and precision was 0.05~0.45%, satisfying the international standards, which are accuracy ${\pm}$10% and precision ${\pm}$5%. This study demonstrated that, for accurate measurements, no adjustment is necessary for a dose calibrator setting when measuring different dose calibrators of F-18 FDG activity prescriptions.

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Clinical Utility and Cross-Reactivity of Insulin and C-Peptide Assays by the Lumipulse G1200 System

  • Oh, Jongwon;Kim, Jae Hyeon;Park, Hyung-Doo
    • Annals of Laboratory Medicine
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    • v.38 no.6
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    • pp.530-537
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    • 2018
  • Background: Measurement of insulin and C-peptide concentrations is important for deciding whether insulin treatment is required in diabetic patients. We aimed to investigate the analytical performance of insulin and C-peptide assays using the Lumipulse G1200 system (Fujirebio Inc., Tokyo, Japan). Methods: We examined the precision, linearity, and cross-reactivity of insulin and C-peptide using five insulin analogues and purified proinsulin. A method comparison was conducted between the Lumipulse G1200 and Roche E170 (Roche Diagnostics, Mannheim, Germany) systems in 200 diabetic patients on insulin treatment. Reference intervals for insulin and C-peptide concentrations were determined in 279 healthy individuals. Results: For insulin and C-peptide assays, within-laboratory precision (% CV) was 3.78-4.14 and 2.89-3.35%, respectively. The linearity of the insulin assay in the range of 0-2,778 pmol/L was $R^2=0.9997$, and that of the C-peptide assay in the range of 0-10 nmol/L was $R^2=0.9996$. The correlation coefficient (r) between the Roche E170 and Lumipulse G1200 results was 0.943 (P <0.001) for insulin and 0.996 (P <0.001) for C-peptide. The mean differences in insulin and C-peptide between Lumipulse G1200 and the Roche E170 were 19.4 pmol/L and 0.2 nmol/L, respectively. None of the insulin analogues or proinsulin showed significant cross-reactivity with the Lumipulse G1200. Reference intervals of insulin and C-peptide were 7.64-70.14 pmol/L and 0.17-0.85 nmol/L, respectively. Conclusions: Insulin and C-peptide tests on the Lumipulse G1200 show adequate analytical performance and are expected to be acceptable for use in clinical areas.