• Title/Summary/Keyword: Clinical biomarker

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Automated radiosynthesis for the routine production of [18F]FPEB for imaging metabotropic glutamate receptor 5 (mGluRS)

  • Kyung Rok Nam;Sang Jin Han;Kyo Chul Lee;Jae Yong Choi
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.8 no.1
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    • pp.3-8
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    • 2022
  • Alteration of the mGluR5 density is closely related to various brain diseases including schizophrenia, depression, Parkinson's disease, and Alzheimer's disease. Therefore, mGluR5 is considered as a valuable imaging biomarker for brain disease and many radiopharmaceuticals have been developed so far. Among them, [18F]FPEB has favorable pharmacokinetic characteristics, and this is the most frequently used radiopharmaceutical for preclinical and clinical studies. In the present study, we want to introduce the optimized radiosynthetic method for the routine production of [18F]FPEB using a GE TRACERlabTM FXFN pro module. In addition, the entire process was monitored with a webcam to solve the problems arising from the synthetic process. As a result, [18F]FPEB was prepared by nucleophilic substitution from its nitro- precursor at 120℃ for 20 min in dimethyl sulfoxide. Radiochemical yield was 13.7 ± 5.1% (decay-corrected, n = 91) with the molar activity of 84 ± 17 GBq/µmol at the end of synthesis. The radiochemical purity was determined to be above 96%. The manufactured [18F]FPEB injection for quality controls were carried out in accordance with an KIRAMS approved protocol, as per ICH and USP guidelines.

Emerging Targets for Systemic Treatment of Gastric Cancer: HER2 and Beyond

  • In-Ho Kim
    • Journal of Gastric Cancer
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    • v.24 no.1
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    • pp.29-56
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    • 2024
  • In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

SARS-CoV-2 infection induces expression and secretion of lipocalin-2 and regulates iron in a human lung cancer xenograft model

  • Sangkyu Park;Dongbum Kim;Jinsoo Kim;Hyung-Joo Kwon;Younghee Lee
    • BMB Reports
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    • v.56 no.12
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    • pp.669-674
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    • 2023
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to various clinical symptoms including anemia. Lipocalin-2 has various biological functions, including defense against bacterial infections through iron sequestration, and it serves as a biomarker for kidney injury. In a human protein array, we observed increased lipocalin-2 expression due to parental SARS-CoV-2 infection in the Calu-3 human lung cancer cell line. The secretion of lipocalin-2 was also elevated in response to parental SARS-CoV-2 infection, and the SARS-CoV-2 Alpha, Beta, and Delta variants similarly induced this phenomenon. In a Calu-3 implanted mouse xenograft model, parental SARSCoV-2 and Delta variant induced lipocalin-2 expression and secretion. Additionally, the iron concentration increased in the Calu-3 tumor tissues and decreased in the serum due to infection. In conclusion, SARS-CoV-2 infection induces the production and secretion of lipocalin-2, potentially resulting in a decrease in iron concentration in serum. Because the concentration of iron ions in the blood is associated with anemia, this phenomenon could contribute to developing anemia in COVID-19 patients.

Development and Evaluation of Integrated Management Program for Hemodialysis Patients (혈액투석 환자를 위한 통합적 관리 프로그램의 개발 및 효과)

  • Kim, Bora;Yoo, Hana
    • Journal of Home Health Care Nursing
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    • v.31 no.1
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    • pp.66-76
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    • 2024
  • Purpose: This study aimed to develop and evaluate an integrated management program to enhance self-efficacy, compliance with sick-role behaviors, symptom management, and biomarker indication in hemodialysis patients. Methods: The integrated management program was developed through a systematic review of literature, analysis of relevant online data, and expert validation. It comprised 480 min of video-based education delivered eight times over four weeks, supplemented by weekly phone consultations and text message support from a nurse. To evaluate the program's effectiveness, it was administered to 44 patients with hemodialysis in a single group in a pre-post test experimental study. Changes in self-efficacy, sick-role behavior compliance, dialysis symptom index, and biomarkers were assessed. Results: The program yielded statistically significant improvements in self-efficacy (t=-7.13, p<.001), sick-role behavioral compliance (t=-7.35, p<.001), dialysis symptom index (t=4.32, p<.001), and blood urea nitrogen levels (t=2.55, p=.014) among the participants. Conclusion: The integrated management program is an effective intervention for improving hemodialysis patients' self-efficacy, compliance with sick-role behaviors, and experience of symptoms. Additionally, it is considered an intervention with high clinical applicability and efficiency through video reproducibility.

The Pallidal Index in Patients with Acute-on-Chronic Liver Disease: Is It a Predictor of Severe Hepatic Encephalopathy?

  • Lee, Dong Hyun;Lee, Hui Joong;Hahm, Myong Hun
    • Investigative Magnetic Resonance Imaging
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    • v.21 no.3
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    • pp.125-130
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    • 2017
  • Purpose: To evaluate the clinical significance of T1 high signal intensity on the globus pallidus as a predictor of severe hepatic encephalopathy in patients with acute-on-chronic liver failure (ACLF), which is a distinct syndrome characterized by multi-organ dysfunction including cerebral failure. Materials and Methods: From January 2002 to April 2014, we retrospectively reviewed the magnetic resonance imaging (MRI) findings and clinical and magnetic resonance (MR) features of 74 consecutive patients (44 men and 30 women; mean age, 59.5 years) with liver cirrhosis. The chronic liver failure-sequential organ failure assessment score was used to diagnose ACLF. The pallidal index (PI), calculated by dividing the mean signal intensity of the globus pallidus by that of the subcortical frontal white matter were compared according to ACLF. The PI was compared with the Model for End-Stage Liver Disease (MELD) score in predicting the development of ACLF. Results: Fifteen patients who were diagnosed with ACLF had higher hepatic encephalopathy grades (initial, P = 0.024; follow-up, P = 0.002), MELD scores (P < 0.001), and PI (P = 0.048). In the ACLF group, the mean PI in patients with cerebral failure was significantly higher than that in the patients without cerebral failure (1.33 vs. 1.20, P = 0.039). In patients with ACLF, the area under the curve (AUC) for PI was 0.680 (95% confidence intervals [CI], 0.52-0.85), which was significantly lower than that for the MELD score (AUC, 0.88; 95% CI, 0.77-0.99) (P = 0.04). Conclusion: The PI can be an ancillary biomarker for predicting the development of ACLF and severe hepatic encephalopathy.

Age-adjusted plasma N-terminal pro-brain natriuretic peptide level in Kawasaki disease

  • Jun, Heul;Ko, Kyung Ok;Lim, Jae Woo;Yoon, Jung Min;Lee, Gyung Min;Cheon, Eun Jung
    • Clinical and Experimental Pediatrics
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    • v.59 no.7
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    • pp.298-302
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    • 2016
  • Purpose: Recent reports showed that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) could be a useful biomarker of intravenous immunoglobulin (IVIG) unresponsiveness and coronary artery lesion (CAL) development in Kawasaki disease (KD). The levels of these peptides are critically influenced by age; hence, the normal range and upper limits for infants and children are different. We performed an age-adjusted analysis of plasma NT-proBNP level to validate its clinical use in the diagnosis of KD. Methods: The data of 131 patients with KD were retrospectively analyzed. The patients were divided into 2 groups-group I (high NT-proBNP group) and group II (normal NT-proBNP group)-comprising patients with NT-proBNP concentrations higher and lower than the 95th percentile of the reference value, respectively. We compared the laboratory data, responsiveness to IVIG, and the risk of CAL in both groups. Results: Group I showed significantly higher white blood cell count, absolute neutrophil count, C-reactive protein level, aspartate aminotransferase level, and troponin-I level than group II (P<0.05). The risk of CAL was also significantly higher in group I (odds ratio, 5.78; P=0.012). IVIG unresponsiveness in group I was three times that in group II (odds ratio, 3.35; P= 0.005). Conclusion: Age-adjusted analysis of plasma NT-proBNP level could be helpful in predicting IVIG unresponsiveness and risk of CAL development in patients with KD.

Aspect of Blood Pressure after Oral Administration of Alcohol : Effect of Dissolved Oxygen on Blood Pressure (알코올 투여에 따른 혈압의 변화 양상 : 용존산소량에 따른 혈압 변화)

  • Song, Byung-Jeong;Lee, Byung-Yo;Chae, Jung-Woo;An, Jung-Hwa;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.3
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    • pp.228-233
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    • 2012
  • Purpose: The purpose of this study was to elucidate the effect of dissolved oxygen in alcohol to blood pressure of healthy persons. Methods: Subjects (n=30) were randomized in a double blind crossover study to receive 120 mL, 240 mL, 360 mL of alcohol (Korean spirit, 19.59 v/v%, dissolved oxygen is 8 ppm and 20 ppm). Blood alcohol concentration (BAC) and blood pressure were measured applying Lion SD-400 Alcolmeter$^{(R)}$ Breathalyser and Tensoval duo control. Pharmacokinetic parameters ($C_{max}$, $T_{max}$, $AUC_{last}$, $K_{el}$, $V_d$, Clearance) were calculated using Winnonlin$^{(R)}$ program. The difference of parameters and values were analysed by student t-test using Microsoft$^{(R)}$ Excel program. Results: The $AUC_{last}$ values of 8 ppm group and 20 ppm group in 240 ml administration were $6.15{\pm}2.60cg{\cdot}min/ml$, $5.33{\pm}1.84cg{\cdot}min/ml$ (p<0.05) and those in 360 mL were $11.93{\pm}5.70cg{\cdot}min/ml$, $10.33{\pm}4.60cg{\cdot}min/ml$ (p < 0.01), respectively. Thus, the $AUC_{last}$ was significantly decreased. On the other hands, there was a significant change in systolic blood pressure (SBP) after alcohol administration. All measured value after 360 mL of alcohol administration was significantly decreased (p < 0.01). Conclusions: The dissolved oxygen in alcoholic beverage has no effect on blood pressures but the alcohol administration has an effect on blood pressure. Thus, SBP can be used as a biomarker of alcohol administration and utilized in PK/PD modeling of alcohol.

Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

  • Tang, Qing-Feng;Ji, Qing;Tang, Yu;Hu, Song-Jiao;Bao, Yi-Jie;Peng, Wen;Yin, Pei-Hao
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5747-5751
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    • 2013
  • Golgi phosphoprotein 2 (GOLPH2) is a very important biomarker in a variety of diseases. Its biological function is not clear, particularly in gastric cancer. To investigate the role of GOLPH2 in human gastric cancer, and determine its effect on the Th1 lymphocyte response, its expression and that of IL-12A were measured by real-time PCR and immunohistochemistry. The relationship between GOLPH2 and IL-12A was analysed statistically. The effect of GOLPH2 on the Th1 lymphocyte response was investigated with an in vitro co-culture system. The results showed that in human gastric cancer, the expression of GOLPH2 was significantly higher and the expression of IL-12A was lower than in normal gastric mucosal tissues, and the expression levels of GOLPH2 and IL-12A were negatively correlated. In addition, obvious down-regulation of the Th1 response was observed when lymphocytes were co-cultured with gastric cancer SGC7901 cells over-expressing GOLPH2. GOLPH2 down-regulated the expression of IL-12A, and inhibited the expression of TNF-${\alpha}$ and IFN-${\gamma}$. The results indicated that GOLPH2 down-regulates the Th1 response via suppression of IL-12A in human gastric cancer, and this might provide a target for the prevention and treatment.

Substrate reduction therapy in three patients with Gaucher disease

  • Kim, Soo Hyun;Kang, Eungu;Kim, Yoon-Myung;Kim, Gu-Hwan;Choi, In-Hee;Choi, Jin-Ho;Yoo, Han-Wook;Lee, Beom Hee
    • Journal of Genetic Medicine
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    • v.13 no.2
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    • pp.72-77
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    • 2016
  • Purpose: Gaucher disease (GD) is the most common lysosomal storage disease caused by beta-glucocerebrosidase (GBA) deficiency. Oral substrate reduction therapy with miglustat ($Zavesca^{(R)}$) was approved for the treatment of adults with GD type 1, for whom enzyme replacement therapy (ERT) is unsuitable or not a therapeutic option. In this study, we report the effect of miglustat ($Zavesca^{(R)}$) in three Korean GD patients. Materials and Methods: Clinical findings comprising age at diagnosis, presenting signs, laboratory findings at diagnosis, GBA activity and mutations, and clinical courses of the three patients were reviewed. Results: Miglustat was administered to three patients who reported allergic reactions during intravenous imiglucerase infusions. One patient withdrew after 15 months of miglustat administration owing to continuous elevation of disease biomarker levels (chitotriosidase, acid phosphatase, and angiotensin-converting enzyme). Poor adherence to medication was suspected but was denied by the patient. In the other two patients, platelet count and levels of hemoglobin and other biomarkers remained stable during miglustat administration. However, they suffered from severe diarrhea and weight loss, which led to miglustat discontinuation after 1 and 12 months of administration. Conclusion: Our study shows that although miglustat is suggested to GD patients as an alternative treatment to ERT, significant adverse reactions may lead to discontinuation of miglustat. In addition, it is difficult to monitor the drug adherence.

MicroRNAs and periodontal disease: a qualitative systematic review of human studies

  • Mico-Martinez, Pablo;Alminana-Pastor, Pedro J.;Alpiste-Illueca, Francisco;Lopez-Roldan, Andres
    • Journal of Periodontal and Implant Science
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    • v.51 no.6
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    • pp.386-397
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    • 2021
  • Purpose: MicroRNAs (miRNAs) are epigenetic post-transcriptional regulators that modulate gene expression and have been identified as biomarkers for several diseases, including cancer. This study aimed to systematically review the relationship between miRNAs and periodontal disease in humans, and to evaluate the potential of miRNAs as diagnostic and prognostic biomarkers of disease. Methods: The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (reference number CRD42020180683). The MEDLINE, Scopus, Cochrane Library, Embase, Web of Science, and SciELO databases were searched for clinical studies conducted in humans investigating periodontal diseases and miRNAs. Expression levels of miRNAs across the different groups were analysed using the collected data. Results: A total of 1,299 references were identified in the initial literature search, and 23 articles were finally included in the review. The study designs were heterogeneous, which prevented a meta-analysis of the data. Most of the studies compared miRNA expression levels between patients with periodontitis and healthy controls. The most widely researched miRNA in periodontal diseases was miR-146a. Most studies reported higher expression levels of miR-146a in patients with periodontitis than in healthy controls. In addition, many studies also focused on identifying target genes of the differentially expressed miRNAs that were significantly related to periodontal inflammation. Conclusions: The results of the studies that we analysed are promising, but diagnostic tests are needed to confirm the use of miRNAs as biomarkers to monitor and aid in the early diagnosis of periodontitis in clinical practice.